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Conserved domains on  [gi|431822377|ref|NP_001258929|]
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dedicator of cytokinesis protein 7 isoform 3 [Homo sapiens]

Protein Classification

dedicator of cytokinesis protein 7( domain architecture ID 10570938)

dedicator of cytokinesis protein 7 functions as a guanine nucleotide exchange factor (GEF), which activates Rac1 and Rac3 Rho small GTPases by exchanging bound GDP for free GTP

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
DHR2_DOCK7 cd11703
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 7; Dock7, also ...
1604-2078 0e+00

Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 7; Dock7, also called Zizimin-related 2 (Zir2), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPases Rac1 and Cdc42 by exchanging bound GDP for free GTP. It plays a critical role in the initial specification of axon formation in hippocampal neurons. It affects neuronal polarity by regulating microtubule dynamics. Dock7 also plays a role in controlling myelination by Schwann cells. It may also play important roles in the function and distribution of dermal and follicular melanocytes. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class C includes Dock6, 7 and 8. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock7, which contains the catalytic GEF activity for Rac and/or Cdc42.


:

Pssm-ID: 212576  Cd Length: 473  Bit Score: 960.69  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1604 DLVFNLHMILSDTVKMKEHQEDPEMLIDLMYRIAKGYQTSPDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLS 1683
Cdd:cd11703     1 DLVFNLHMILSDTVKMKEHQEDPEMLIDLMYRIAKGYQTSPDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLS 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1684 MLEDRKYLPVGCVTFQNISSNVLEESAVSDDVVSPDEEGICSGKYFTESGLVGLLEQAAASFSMAGMYEAVNEVYKVLIP 1763
Cdd:cd11703    81 MLEDRKYLPVGCVTFQNISSNVLEESAVSDDVVSPDEEGICSGKYFTEAGLVGLLEQAAASFSMAGMYEAVNEVYKVLIP 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1764 IHEANRDAKKLSTIHGKLQEAFSKIVHQSTGweRMFGTYFRVGFYGTKFGDLDEQEFVYKEPAITKLAEISHRLEGFYGE 1843
Cdd:cd11703   161 IHEANRDAKKLATIHGKLQEAFSKIVHQDGK--RMFGTYFRVGFYGTKFGDLDEQEFVYKEPAITKLAEISHRLEGFYGE 238
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1844 RFGEDVVEVIKDSNPVDKCKLDPNKAYIQITYVEPYFDTYEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKR 1923
Cdd:cd11703   239 RFGEDVVEVIKDSNPVDKCKLDPNKAFIQITYVEPYFDTYEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKR 318
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1924 KTILTTSHAFPYIKTRVNVTHKEEIILTPIEVAIEDMQKKTQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQV 2003
Cdd:cd11703   319 KTILTTSHAFPYIKTRINVIHKEEIILTPIEVAIEDMQKKTQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQV 398
                         410       420       430       440       450       460       470
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 431822377 2004 FLSEIPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSLIGPDQKEYQRELERNYHRLKEALQPLINRKIPQLYK 2078
Cdd:cd11703   399 FLSEIPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSLIGPDQKEYQRELERNYHRLKEALQPLINRKIPQLYK 473
C2_Dock-C cd08696
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 ...
560-737 2.14e-115

C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 classes of Dock family proteins. The members here include: Dock6/Zir1, Dock7/Zir2, and Dock8/Zir3. Dock-C members are GEFs for both Rac and Cdc42. In addition to the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker), which all Dock180-related proteins have, Dock-C members contain a functionally uncharacterized domain upstream of the C2 domain. DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


:

Pssm-ID: 176078  Cd Length: 179  Bit Score: 362.83  E-value: 2.14e-115
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377  560 YRNLLYIYPQSLNFANRQGSARNITVKVQFMYGEDPSNAMPVIFGKSSCSEFSKEAYTAVVYHNRSPDFHEEIKVKLPAT 639
Cdd:cd08696     1 YRNLLYVYPQSLNFSNRLGSARNIAVKVQLMSGEDESQALPVIFKGSSPEEFLTEAYTAVTYHNKSPDFYDEIKIKLPAD 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377  640 LTDHHHLLFTFYHVSCQQKQ-NTPLETPVGYTWIPMLQNGRLKTGQFCLPVSLEKPPQAYSVLSPEVPLPGMKWVDNHKG 718
Cdd:cd08696    81 LTDNHHLLFTFYHISCQKKQeGGSVETPIGYTWLPLLRNGRLQSGEFNLPVSLEKPPSNYSPDSPEVKLPGTKWVDNHKG 160
                         170
                  ....*....|....*....
gi 431822377  719 VFNVEVVAVSSIHTQDPYL 737
Cdd:cd08696   161 VFSVSVEAVSSVHTQDSYL 179
DUF3398 pfam11878
Domain of unknown function (DUF3398); This domain is functionally uncharacterized. This domain ...
52-161 2.20e-50

Domain of unknown function (DUF3398); This domain is functionally uncharacterized. This domain is found in eukaryotes. This presumed domain is about 100 amino acids in length.


:

Pssm-ID: 432155  Cd Length: 112  Bit Score: 174.00  E-value: 2.20e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377    52 TEAVDPVDLEDYLITHPLAVDSGPLRDLIEFPPDDIEVVYSPRDCRTLVSAVPEE--SEMDPHVRDCIRSYTEDWAIVIR 129
Cdd:pfam11878    1 PKLVEPLDYEEFISQHLTQLDNDPLRDLLLFPDDDVEVATLPRECRTLQPTVPEEaeKEADSLVRECIKTYTSDWHVVNY 80
                           90       100       110
                   ....*....|....*....|....*....|..
gi 431822377   130 KYHKLGTGFNPNTLDKQKERQKGLPKQVFESD 161
Cdd:pfam11878   81 KYEDYSGDFRQLPRNKRRERPEKLPKQVFEID 112
 
Name Accession Description Interval E-value
DHR2_DOCK7 cd11703
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 7; Dock7, also ...
1604-2078 0e+00

Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 7; Dock7, also called Zizimin-related 2 (Zir2), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPases Rac1 and Cdc42 by exchanging bound GDP for free GTP. It plays a critical role in the initial specification of axon formation in hippocampal neurons. It affects neuronal polarity by regulating microtubule dynamics. Dock7 also plays a role in controlling myelination by Schwann cells. It may also play important roles in the function and distribution of dermal and follicular melanocytes. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class C includes Dock6, 7 and 8. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock7, which contains the catalytic GEF activity for Rac and/or Cdc42.


Pssm-ID: 212576  Cd Length: 473  Bit Score: 960.69  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1604 DLVFNLHMILSDTVKMKEHQEDPEMLIDLMYRIAKGYQTSPDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLS 1683
Cdd:cd11703     1 DLVFNLHMILSDTVKMKEHQEDPEMLIDLMYRIAKGYQTSPDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLS 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1684 MLEDRKYLPVGCVTFQNISSNVLEESAVSDDVVSPDEEGICSGKYFTESGLVGLLEQAAASFSMAGMYEAVNEVYKVLIP 1763
Cdd:cd11703    81 MLEDRKYLPVGCVTFQNISSNVLEESAVSDDVVSPDEEGICSGKYFTEAGLVGLLEQAAASFSMAGMYEAVNEVYKVLIP 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1764 IHEANRDAKKLSTIHGKLQEAFSKIVHQSTGweRMFGTYFRVGFYGTKFGDLDEQEFVYKEPAITKLAEISHRLEGFYGE 1843
Cdd:cd11703   161 IHEANRDAKKLATIHGKLQEAFSKIVHQDGK--RMFGTYFRVGFYGTKFGDLDEQEFVYKEPAITKLAEISHRLEGFYGE 238
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1844 RFGEDVVEVIKDSNPVDKCKLDPNKAYIQITYVEPYFDTYEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKR 1923
Cdd:cd11703   239 RFGEDVVEVIKDSNPVDKCKLDPNKAFIQITYVEPYFDTYEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKR 318
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1924 KTILTTSHAFPYIKTRVNVTHKEEIILTPIEVAIEDMQKKTQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQV 2003
Cdd:cd11703   319 KTILTTSHAFPYIKTRINVIHKEEIILTPIEVAIEDMQKKTQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQV 398
                         410       420       430       440       450       460       470
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 431822377 2004 FLSEIPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSLIGPDQKEYQRELERNYHRLKEALQPLINRKIPQLYK 2078
Cdd:cd11703   399 FLSEIPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSLIGPDQKEYQRELERNYHRLKEALQPLINRKIPQLYK 473
DHR-2 pfam06920
Dock homology region 2; This family represents a conserved region within a number of ...
1541-2067 0e+00

Dock homology region 2; This family represents a conserved region within a number of eukaryotic dedicator of cytokinesis proteins. These are potential guanine nucleotide exchange factors, which activate some small GTPases by exchanging bound GDP for free GTP. This region interacts with RAC1 and ELMO1.


Pssm-ID: 429192 [Multi-domain]  Cd Length: 526  Bit Score: 832.30  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377  1541 RQNFEIG--NNFARVKMQVTMSLSSLVGTSQNFNEEFLRRSLKTILTYAEEDLELRETTFPDQVQDLVFNLHMILSDTVK 1618
Cdd:pfam06920    1 RSNFELTkyKNFTRVKLQVIIALSQLVGEEQGLNEERLRRSLKTINSYAKSDKAMKSTGFPSQVKDLTKRLRTILMDTVK 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377  1619 MKEHQEDPEMLIDLMYRIAKGYQTSPDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLSMLeDRKYLPVGCVTF 1698
Cdd:pfam06920   81 MKEHKEDPEMLADLQYSLANSYKSSPDLRLTWLENLAEKHLENGNFSEAAQCLIHIAALIAEYLKLL-GKIPNPFGASAF 159
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377  1699 QNISSNVLEESAVSDDVVSpDEEGICSGKYFTESGLVGLLEQAAASFSMAGMYEAVNEVYKVLIPIHEANRDAKKLSTIH 1778
Cdd:pfam06920  160 EKISPNILSEESLTSSALK-DDVGVCDSPHFTEDGLVGLLEEAIDYLDKAERYELAIELYKLLIPIYESRRDYKKLSEIH 238
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377  1779 GKLQEAFSKIVHQSTGWeRMFGTYFRVGFYGTKFGDLDEQEFVYKEPAITKLAEISHRLEGFYGERFGEDVVEVIKDSNP 1858
Cdd:pfam06920  239 KKLAEAYEKIVEQNRSG-KLFGTYFRVGFYGKKFEELDGKEFIYKEPKLTRLSEISERLLNQYSEKFGSENVEIIKDSNP 317
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377  1859 VDKCKLDPNKAYIQITYVEPYFDTYEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKRKTILTTSHAFPYIKT 1938
Cdd:pfam06920  318 VDPSELDPDKAYIQITSVEPYFDEEELKERITSFERNNNVNRFMFETPFTKSGKAQGSLEEQWKRRTILTTENSFPYIKK 397
                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377  1939 RVNVTHKEEIILTPIEVAIEDMQKKTQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQVFLSEIPSDPKLFRHH 2018
Cdd:pfam06920  398 RIEVVSKEEIELSPIEVAIEEIEKKTEELEEAINQEPPDIKTLQMVLQGSVDVQVNAGPLEYAEAFLSEKKVPNYPAEHV 477
                          490       500       510       520
                   ....*....|....*....|....*....|....*....|....*....
gi 431822377  2019 NKLRLCFKDFTKRCEDALRKNKSLIGPDQKEYQRELERNYHRLKEALQP 2067
Cdd:pfam06920  478 EKLKEAFRDFLKVCGEALELNKRLISEDQREYQEELEEGFEKLKEKLSP 526
C2_Dock-C cd08696
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 ...
560-737 2.14e-115

C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 classes of Dock family proteins. The members here include: Dock6/Zir1, Dock7/Zir2, and Dock8/Zir3. Dock-C members are GEFs for both Rac and Cdc42. In addition to the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker), which all Dock180-related proteins have, Dock-C members contain a functionally uncharacterized domain upstream of the C2 domain. DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176078  Cd Length: 179  Bit Score: 362.83  E-value: 2.14e-115
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377  560 YRNLLYIYPQSLNFANRQGSARNITVKVQFMYGEDPSNAMPVIFGKSSCSEFSKEAYTAVVYHNRSPDFHEEIKVKLPAT 639
Cdd:cd08696     1 YRNLLYVYPQSLNFSNRLGSARNIAVKVQLMSGEDESQALPVIFKGSSPEEFLTEAYTAVTYHNKSPDFYDEIKIKLPAD 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377  640 LTDHHHLLFTFYHVSCQQKQ-NTPLETPVGYTWIPMLQNGRLKTGQFCLPVSLEKPPQAYSVLSPEVPLPGMKWVDNHKG 718
Cdd:cd08696    81 LTDNHHLLFTFYHISCQKKQeGGSVETPIGYTWLPLLRNGRLQSGEFNLPVSLEKPPSNYSPDSPEVKLPGTKWVDNHKG 160
                         170
                  ....*....|....*....
gi 431822377  719 VFNVEVVAVSSIHTQDPYL 737
Cdd:cd08696   161 VFSVSVEAVSSVHTQDSYL 179
DOCK-C2 pfam14429
C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical ...
557-736 1.69e-66

C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical GTP/GDP exchange factors for the small GTPases Rac and Cdc42 and are implicated cell-migration and phagocytosis. Across all Dock180 proteins, two regions are conserved: C-terminus termed CZH2 or DHR2 (or the Dedicator of cytokinesis) whereas CZH1/DHR1 contain a new family of the C2 domain.


Pssm-ID: 433949  Cd Length: 185  Bit Score: 222.84  E-value: 1.69e-66
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377   557 NTTYRNLLYIYPQSLNFANR-QGSARNITVKVQFMYGEdpSNAMP-VIFGKSSCsEFSKEAYTAVVYHNRSPDFHEEIKV 634
Cdd:pfam14429    1 PGDYRNDLYVTPKSGNFSKGkKSSARNIEVTVEVRDSD--GEPLPnCIYGGSGG-PLVTEFKSTVYYHNKSPTWYEEIKI 77
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377   635 KLPATLTDHHHLLFTFYHVSCQQKqNTPLETPVGYTWIPMLQNGR--LKTGQFCLPVSL-EKPPQAYSVLS-------PE 704
Cdd:pfam14429   78 ALPIELTPKHHLLFTFYHVSCQKK-KDKVEKPFGYAFLPLLDDDGafLRDGEHTLPVYKyDELPPGYLSLPwskggekES 156
                          170       180       190
                   ....*....|....*....|....*....|..
gi 431822377   705 VPLPGMKwvdNHKGVFNVEVVAVSSIHTQDPY 736
Cdd:pfam14429  157 SALPGLK---GHKDVFKVRTLLCSTKLTQDPH 185
DUF3398 pfam11878
Domain of unknown function (DUF3398); This domain is functionally uncharacterized. This domain ...
52-161 2.20e-50

Domain of unknown function (DUF3398); This domain is functionally uncharacterized. This domain is found in eukaryotes. This presumed domain is about 100 amino acids in length.


Pssm-ID: 432155  Cd Length: 112  Bit Score: 174.00  E-value: 2.20e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377    52 TEAVDPVDLEDYLITHPLAVDSGPLRDLIEFPPDDIEVVYSPRDCRTLVSAVPEE--SEMDPHVRDCIRSYTEDWAIVIR 129
Cdd:pfam11878    1 PKLVEPLDYEEFISQHLTQLDNDPLRDLLLFPDDDVEVATLPRECRTLQPTVPEEaeKEADSLVRECIKTYTSDWHVVNY 80
                           90       100       110
                   ....*....|....*....|....*....|..
gi 431822377   130 KYHKLGTGFNPNTLDKQKERQKGLPKQVFESD 161
Cdd:pfam11878   81 KYEDYSGDFRQLPRNKRRERPEKLPKQVFEID 112
 
Name Accession Description Interval E-value
DHR2_DOCK7 cd11703
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 7; Dock7, also ...
1604-2078 0e+00

Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 7; Dock7, also called Zizimin-related 2 (Zir2), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPases Rac1 and Cdc42 by exchanging bound GDP for free GTP. It plays a critical role in the initial specification of axon formation in hippocampal neurons. It affects neuronal polarity by regulating microtubule dynamics. Dock7 also plays a role in controlling myelination by Schwann cells. It may also play important roles in the function and distribution of dermal and follicular melanocytes. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class C includes Dock6, 7 and 8. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock7, which contains the catalytic GEF activity for Rac and/or Cdc42.


Pssm-ID: 212576  Cd Length: 473  Bit Score: 960.69  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1604 DLVFNLHMILSDTVKMKEHQEDPEMLIDLMYRIAKGYQTSPDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLS 1683
Cdd:cd11703     1 DLVFNLHMILSDTVKMKEHQEDPEMLIDLMYRIAKGYQTSPDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLS 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1684 MLEDRKYLPVGCVTFQNISSNVLEESAVSDDVVSPDEEGICSGKYFTESGLVGLLEQAAASFSMAGMYEAVNEVYKVLIP 1763
Cdd:cd11703    81 MLEDRKYLPVGCVTFQNISSNVLEESAVSDDVVSPDEEGICSGKYFTEAGLVGLLEQAAASFSMAGMYEAVNEVYKVLIP 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1764 IHEANRDAKKLSTIHGKLQEAFSKIVHQSTGweRMFGTYFRVGFYGTKFGDLDEQEFVYKEPAITKLAEISHRLEGFYGE 1843
Cdd:cd11703   161 IHEANRDAKKLATIHGKLQEAFSKIVHQDGK--RMFGTYFRVGFYGTKFGDLDEQEFVYKEPAITKLAEISHRLEGFYGE 238
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1844 RFGEDVVEVIKDSNPVDKCKLDPNKAYIQITYVEPYFDTYEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKR 1923
Cdd:cd11703   239 RFGEDVVEVIKDSNPVDKCKLDPNKAFIQITYVEPYFDTYEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKR 318
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1924 KTILTTSHAFPYIKTRVNVTHKEEIILTPIEVAIEDMQKKTQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQV 2003
Cdd:cd11703   319 KTILTTSHAFPYIKTRINVIHKEEIILTPIEVAIEDMQKKTQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQV 398
                         410       420       430       440       450       460       470
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 431822377 2004 FLSEIPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSLIGPDQKEYQRELERNYHRLKEALQPLINRKIPQLYK 2078
Cdd:cd11703   399 FLSEIPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSLIGPDQKEYQRELERNYHRLKEALQPLINRKIPQLYK 473
DHR2_DOCK6 cd11702
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 6; Dock6, also ...
1643-2065 0e+00

Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 6; Dock6, also called Zizimin-related 1 (Zir1), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPases Rac and Cdc42 by exchanging bound GDP for free GTP. It is widely expressed and shows highest expression in the dorsal root ganglion and the brain. It regulates neurite outgrowth. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class C includes Dock6, 7 and 8. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock6, which contains the catalytic GEF activity for Rac and/or Cdc42.


Pssm-ID: 212575  Cd Length: 423  Bit Score: 914.01  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1643 SPDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLSMLEDRKYLPVGCVTFQNISSNVLEESAVSDDVVSPDEEG 1722
Cdd:cd11702     1 SPDLRLTWLQNMAGKHSERGNHAEAAHCLVHSAALVAEYLSMLEDCRHLPVGCVSFQNISSNVLEESAVSDDILSPDEEG 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1723 ICSGKYFTESGLVGLLEQAAASFSMAGMYEAVNEVYKVLIPIHEANRDAKKLSTIHGKLQEAFSKIVHQSTGWERMFGTY 1802
Cdd:cd11702    81 ICSGKYFTELGLVGLLEQAAASFNMGGLYEAVNEVYKILIPIHEANRDYKKLAVVHGKLQEAFNKITNQSSGWERMFGTY 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1803 FRVGFYGTKFGDLDEQEFVYKEPAITKLAEISHRLEGFYGERFGEDVVEVIKDSNPVDKCKLDPNKAYIQITYVEPYFDT 1882
Cdd:cd11702   161 FRVGFYGCKFGDLDEQEFVYKEPSITKLAEISHRLEEFYTERFGDEVVEIIKDSNPVDKSKLDPNKAYIQITYVEPFFDT 240
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1883 YEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKRKTILTTSHAFPYIKTRVNVTHKEEIILTPIEVAIEDMQK 1962
Cdd:cd11702   241 YELKDRVTYFDKNYNLRTFLFCTPFTLDGRAHGELHEQYKRKTILTTSHAFPYIKTRINVLHREEIVLIPVEVAIEDMQK 320
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1963 KTQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQVFLSEIPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSL 2042
Cdd:cd11702   321 KTQELAFATHQDPADAKMLQMVLQGCVGTTVNQGPLEVAQVFLSEIPEDPKLFRHHNKLRLCFKDFTKRCEDALRKNKAL 400
                         410       420
                  ....*....|....*....|...
gi 431822377 2043 IGPDQKEYQRELERNYHRLKEAL 2065
Cdd:cd11702   401 IGPDQKEYHRELERNYQRLREAL 423
DHR-2 pfam06920
Dock homology region 2; This family represents a conserved region within a number of ...
1541-2067 0e+00

Dock homology region 2; This family represents a conserved region within a number of eukaryotic dedicator of cytokinesis proteins. These are potential guanine nucleotide exchange factors, which activate some small GTPases by exchanging bound GDP for free GTP. This region interacts with RAC1 and ELMO1.


Pssm-ID: 429192 [Multi-domain]  Cd Length: 526  Bit Score: 832.30  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377  1541 RQNFEIG--NNFARVKMQVTMSLSSLVGTSQNFNEEFLRRSLKTILTYAEEDLELRETTFPDQVQDLVFNLHMILSDTVK 1618
Cdd:pfam06920    1 RSNFELTkyKNFTRVKLQVIIALSQLVGEEQGLNEERLRRSLKTINSYAKSDKAMKSTGFPSQVKDLTKRLRTILMDTVK 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377  1619 MKEHQEDPEMLIDLMYRIAKGYQTSPDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLSMLeDRKYLPVGCVTF 1698
Cdd:pfam06920   81 MKEHKEDPEMLADLQYSLANSYKSSPDLRLTWLENLAEKHLENGNFSEAAQCLIHIAALIAEYLKLL-GKIPNPFGASAF 159
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377  1699 QNISSNVLEESAVSDDVVSpDEEGICSGKYFTESGLVGLLEQAAASFSMAGMYEAVNEVYKVLIPIHEANRDAKKLSTIH 1778
Cdd:pfam06920  160 EKISPNILSEESLTSSALK-DDVGVCDSPHFTEDGLVGLLEEAIDYLDKAERYELAIELYKLLIPIYESRRDYKKLSEIH 238
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377  1779 GKLQEAFSKIVHQSTGWeRMFGTYFRVGFYGTKFGDLDEQEFVYKEPAITKLAEISHRLEGFYGERFGEDVVEVIKDSNP 1858
Cdd:pfam06920  239 KKLAEAYEKIVEQNRSG-KLFGTYFRVGFYGKKFEELDGKEFIYKEPKLTRLSEISERLLNQYSEKFGSENVEIIKDSNP 317
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377  1859 VDKCKLDPNKAYIQITYVEPYFDTYEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKRKTILTTSHAFPYIKT 1938
Cdd:pfam06920  318 VDPSELDPDKAYIQITSVEPYFDEEELKERITSFERNNNVNRFMFETPFTKSGKAQGSLEEQWKRRTILTTENSFPYIKK 397
                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377  1939 RVNVTHKEEIILTPIEVAIEDMQKKTQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQVFLSEIPSDPKLFRHH 2018
Cdd:pfam06920  398 RIEVVSKEEIELSPIEVAIEEIEKKTEELEEAINQEPPDIKTLQMVLQGSVDVQVNAGPLEYAEAFLSEKKVPNYPAEHV 477
                          490       500       510       520
                   ....*....|....*....|....*....|....*....|....*....
gi 431822377  2019 NKLRLCFKDFTKRCEDALRKNKSLIGPDQKEYQRELERNYHRLKEALQP 2067
Cdd:pfam06920  478 EKLKEAFRDFLKVCGEALELNKRLISEDQREYQEELEEGFEKLKEKLSP 526
DHR2_DOCK8 cd11701
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 8; Dock8, also ...
1642-2065 0e+00

Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 8; Dock8, also called Zizimin-related 3 (Zir3), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPases Rac1 and Cdc42 by exchanging bound GDP for free GTP. Dock8 is highly expressed in the immune system and it regulates T and B cell numbers and functions. It plays essential roles in humoral immune responses and the proper formation of B cell immunological synapses. Dock8 deficiency is a primary immune deficiency that results in extreme susceptibility to cutaneous viral infections, elevated IgE levels, and eosinophilia. It was originally described as an autosomal recessive form of hyper IgE syndrome (AR-HIES). DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class C includes Dock6, 7 and 8. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock8, which contains the catalytic GEF activity for Rac and/or Cdc42.


Pssm-ID: 212574  Cd Length: 422  Bit Score: 781.53  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1642 TSPDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLSMLEDRKYLPVGCVTFQNISSNVLEESAVSDDVVSPDEE 1721
Cdd:cd11701     1 TSPDLRLTWLQNMAEKHTKRKCFTEAAMCLVHAAALVAEYLSMLEDHSYLPVGSVSFQNISSNVLEESAVSDDILSPDED 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1722 GICSGKYFTESGLVGLLEQAAASFSMAGMYEAVNEVYKVLIPIHEANRDAKKLSTIHGKLQEAFSKIVHQstGWERMFGT 1801
Cdd:cd11701    81 GVCSGRYFTENGLVGLLEQAAELFSTGGLYETVNEVYKIVIPILEAHRDFRKLASTHDKLQKAFDNIINK--GHKRMFGT 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1802 YFRVGFYGTKFGDLDEQEFVYKEPAITKLAEISHRLEGFYGERFGEDVVEVIKDSNPVDKCKLDPNKAYIQITYVEPYFD 1881
Cdd:cd11701   159 YFRVGFYGSKFGDLDEQEFIYKEPAITKLPEISHRLEGFYGQCFGDDVVEVIKDSTPVDKSKLDPNKAYIQITFVEPYFD 238
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1882 TYEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKRKTILTTSHAFPYIKTRVNVTHKEEIILTPIEVAIEDMQ 1961
Cdd:cd11701   239 DYEMKDRVTYFEKNFNLRRFMYTTPFTLDGRPRGELSEQYKRKTILTTMHAFPYIKTRINVIQKEEFDLTPIEVAIEDMQ 318
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1962 KKTQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQVFLSEIPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKS 2041
Cdd:cd11701   319 KKTRELAEATHQEPPDAKMLQMVLQGSVGATVNQGPLEVAQVFLAEIPADPKLYRHHNKLRLCFKEFIMRCGEAVEKNKR 398
                         410       420
                  ....*....|....*....|....
gi 431822377 2042 LIGPDQKEYQRELERNYHRLKEAL 2065
Cdd:cd11701   399 LITADQREYQQELKKNYNKLRENL 422
DHR2_DOCK_C cd11695
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis proteins; DOCK ...
1643-2065 0e+00

Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. As GEFs, they activate small GTPases by exchanging bound GDP for free GTP. They are divided into four classes (A-D) based on sequence similarity and domain architecture; class C, also called the Zizimin-related (Zir) subfamily, includes Dock6, 7 and 8. Class C DOCKs have been shown to have GEF activity for both Rac and Cdc42. Dock6 regulates neurite outgrowth. Dock7 plays a critical roles in the early stages of axon formation, neuronal polarity, and myelination. Dock8 regulates T and B cell numbers and functions, and plays essential roles in humoral immune responses and the proper formation of B cell immunological synapses. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Class C Docks, which contains the catalytic GEF activity for Rac and Cdc42.


Pssm-ID: 212568  Cd Length: 368  Bit Score: 749.13  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1643 SPDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALvaeylsmledrkylpvgcvtfqnissnvleesavsddvvspdeeg 1722
Cdd:cd11695     1 SPDLRLTWLQNMAEKHYERKNFAEAAQCLVHAAAL--------------------------------------------- 35
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1723 icsgkyftesGLVGLLEQAAASFSMAGMYEAVNEVYKVLIPIHEANRDAKKLSTIHGKLQEAFSKIVHQStGWERMFGTY 1802
Cdd:cd11695    36 ----------GLVGLLEQAAESFSKAGMYEAVNEVYKLLIPILEANRDYKKLAEIHGKLQDAFTKIEKQQ-GGKRMFGTY 104
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1803 FRVGFYGTKFGDLDEQEFVYKEPAITKLAEISHRLEGFYGERFGEDVVEVIKDSNPVDKCKLDPNKAYIQITYVEPYFDT 1882
Cdd:cd11695   105 FRVGFYGSKFGDLDGKEFIYKEPAITKLPEISHRLETFYGERFGEERVEVIKDSNPVDTSKLDPDKAYIQITYVEPYFDE 184
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1883 YEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKRKTILTTSHAFPYIKTRVNVTHKEEIILTPIEVAIEDMQK 1962
Cdd:cd11695   185 YELKERTTYFERNYNLRRFMYATPFTPDGKAHGELAEQYKRKTILTTENSFPYVKTRLQVVNREEIVLTPIEVAIEDVQK 264
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1963 KTQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQVFLSEIPSDPK-LFRHHNKLRLCFKDFTKRCEDALRKNKS 2041
Cdd:cd11695   265 KTRELAAATTQEPPDPKMLQMVLQGSIGTTVNQGPLEVANVFLSDIPLDPKeLDRHQNKLRLCFKEFSKKCYDALEKNKE 344
                         410       420
                  ....*....|....*....|....
gi 431822377 2042 LIGPDQKEYQRELERNYHRLKEAL 2065
Cdd:cd11695   345 LIGPDQKEYQKELERNYENFKEKL 368
DHR2_DOCK_D cd11694
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis proteins; DOCK ...
1645-2065 2.95e-129

Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. As GEFs, they activate small GTPases by exchanging bound GDP for free GTP. They are divided into four classes (A-D) based on sequence similarity and domain architecture; class D, also called the Zizimin subfamily, includes Dock9, 10 and 11. Class D Docks are specific GEFs for Cdc42. Dock9 plays important roles in spine formation and dendritic growth. Dock10 and Dock11 are preferentially expressed in lymphocytes. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of class D DOCKs, which contains the catalytic GEF activity for Cdc42. Class D DOCKs also contain a Pleckstrin homology (PH) domain at the N-terminus.


Pssm-ID: 212567  Cd Length: 376  Bit Score: 410.96  E-value: 2.95e-129
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1645 DLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLSmledRKYLpvgcvtfqnissnvleesavsddvvspdeegic 1724
Cdd:cd11694     1 ELRKTWLESMARIHEKNGNFSEAAMCYIHIAALVAEYLK----RKDL--------------------------------- 43
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1725 sgkyftesgLVGLLEQAAASFSMAGMYEAVNEVYKVLIPIHEANRDAKKLSTIHGKLQEAFSKIVHQSTGWERMFGTYFR 1804
Cdd:cd11694    44 ---------LLELLEACVEGLWKAERYELLGELYKLIIPIYEKRRDFEQLADCYRTLHRAYEKVVEVMESGKRLLGTYYR 114
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1805 VGFYGTK-FGDLDEQEFVYKEPAITKLAEISHRLEGFYGERFGEDVVEVIKDSNPVDKCKLDPNKAYIQITYVEPYFDTY 1883
Cdd:cd11694   115 VAFYGQAfFEEEDGKEYIYKEPKVTSLSEISERLLKLYGDKFGSENVKLIQDSGKVNPKDLDPKYAYIQVTHVTPYFDEK 194
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1884 EMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKRKTILTTSHAFPYIKTRVNVTHKEEIILTPIEVAIEDMQKK 1963
Cdd:cd11694   195 ELEDRKTEFERNHNIRRFVFETPFTLSGKARGAVEEQWKRRTILTTSHSFPYVKKRIPVVQREIIELSPIEVAIDEMQSK 274
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1964 TQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQVFLSEIPSdPKLFRHH-NKLRLCFKDFTKRCEDALRKNKSL 2042
Cdd:cd11694   275 VKELEELISTEPVDMKKLQLRLQGSVSVQVNAGPLAYARAFLEPTTV-KNYPDDQvEDLKDVFRDFIKACGQALELNERL 353
                         410       420
                  ....*....|....*....|...
gi 431822377 2043 IGPDQKEYQRELERNYHRLKEAL 2065
Cdd:cd11694   354 IKEDQREYHEVLKENYRKMVKEL 376
DHR2_DOCK11 cd11700
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 11; Dock11, also ...
1644-2065 3.70e-116

Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 11; Dock11, also called Zizimin2 or activated Cdc42-associated GEF (ACG), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPase Cdc42 by exchanging bound GDP for free GTP. Dock11 is predominantly expressed in lymphocytes and is found in high levels in germinal center B lymphocytes after T cell dependent antigen immunization. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock11, which contains the catalytic GEF activity for Cdc42. Class D DOCKs also contain a Pleckstrin homology (PH) domain at the N-terminus.


Pssm-ID: 212573  Cd Length: 413  Bit Score: 375.10  E-value: 3.70e-116
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1644 PDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLsmlEDRKYLPVGCVTFQNISSNVLEESAVSDDVVSPDeegi 1723
Cdd:cd11700     1 PELRKTWLDSMAKIHVKNGDFSEAAMCYVHVAALVAEFL---HRKKLFPSGCAAFKKITPNIDEEGAMKEDIGMMD---- 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1724 csgKYFTESGLVGLLEQAAASFSMAGMYEAVNEVYKVLIPIHEANRDAKKLSTIHGKLQEAFSKIVHQSTGWERMFGTYF 1803
Cdd:cd11700    74 ---VHYSEEVLVELLEQCVDGLWKAERYELISEISKLIIPIYEKRREFEKLTQLYRTLHGAYAKILEVMHTGKRLLGTFF 150
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1804 RVGFYG-TKFGDLDEQEFVYKEPAITKLAEISHRLEGFYGERFGEDVVEVIKDSNPVDKCKLDPNKAYIQITYVEPYFDT 1882
Cdd:cd11700   151 RVAFYGqGFFEEEDGKEYIYKEPKLTGLSEISHRLLKLYGEKFGSENVKIIQDSNKVNQKDLDPKYAHIQVTYVKPYFDD 230
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1883 YEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKRKTILTTSHAFPYIKTRVNVTHKEEIILTPIEVAIEDMQK 1962
Cdd:cd11700   231 KEMAERKTEFERNHNIQRFVFETPYTLSGKKQGGVEEQCKRRTILTTANSFPYVKKRIPVNGEKQTNLKPIDVATDEIKD 310
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1963 KTQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQVFLSEIPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSL 2042
Cdd:cd11700   311 KTAELQKLCSNQDVDMIQLQLKLQGCVSVQVNAGPLAYARAFLDDSQASKYPNKKVKELKEMFRKFIQACSIALELNERL 390
                         410       420
                  ....*....|....*....|...
gi 431822377 2043 IGPDQKEYQRELERNYHRLKEAL 2065
Cdd:cd11700   391 IKEDQVEYHEGLKSNFRDMVKEL 413
C2_Dock-C cd08696
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 ...
560-737 2.14e-115

C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 classes of Dock family proteins. The members here include: Dock6/Zir1, Dock7/Zir2, and Dock8/Zir3. Dock-C members are GEFs for both Rac and Cdc42. In addition to the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker), which all Dock180-related proteins have, Dock-C members contain a functionally uncharacterized domain upstream of the C2 domain. DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176078  Cd Length: 179  Bit Score: 362.83  E-value: 2.14e-115
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377  560 YRNLLYIYPQSLNFANRQGSARNITVKVQFMYGEDPSNAMPVIFGKSSCSEFSKEAYTAVVYHNRSPDFHEEIKVKLPAT 639
Cdd:cd08696     1 YRNLLYVYPQSLNFSNRLGSARNIAVKVQLMSGEDESQALPVIFKGSSPEEFLTEAYTAVTYHNKSPDFYDEIKIKLPAD 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377  640 LTDHHHLLFTFYHVSCQQKQ-NTPLETPVGYTWIPMLQNGRLKTGQFCLPVSLEKPPQAYSVLSPEVPLPGMKWVDNHKG 718
Cdd:cd08696    81 LTDNHHLLFTFYHISCQKKQeGGSVETPIGYTWLPLLRNGRLQSGEFNLPVSLEKPPSNYSPDSPEVKLPGTKWVDNHKG 160
                         170
                  ....*....|....*....
gi 431822377  719 VFNVEVVAVSSIHTQDPYL 737
Cdd:cd08696   161 VFSVSVEAVSSVHTQDSYL 179
DHR2_DOCK cd11684
Dock Homology Region 2, a GEF domain, of Dedicator of Cytokinesis proteins; DOCK proteins ...
1645-2065 4.02e-114

Dock Homology Region 2, a GEF domain, of Dedicator of Cytokinesis proteins; DOCK proteins comprise a family of atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. As GEFs, they activate the small GTPases Rac and Cdc42 by exchanging bound GDP for free GTP. They are also called the CZH (CED-5, Dock180, and MBC-zizimin homology) family, after the first family members identified. Dock180 was first isolated as a binding partner for the adaptor protein Crk. The Caenorhabditis elegans protein, Ced-5, is essential for cell migration and phagocytosis, while the Drosophila ortholog, Myoblast city (MBC), is necessary for myoblast fusion and dorsal closure. DOCKs are divided into four classes (A-D) based on sequence similarity and domain architecture: class A includes Dock1 (or Dock180), 2 and 5; class B includes Dock3 and 4; class C includes Dock6, 7, and 8; and class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1, and DHR-2 (also called CZH2 or Docker). This alignment model represents the DHR-2 domain of DOCK proteins, which contains the catalytic GEF activity for Rac and/or Cdc42.


Pssm-ID: 212566  Cd Length: 392  Bit Score: 368.16  E-value: 4.02e-114
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1645 DLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLsmledrkylpvgcvtfqnissnvleesavsDDVVSPDEEGIC 1724
Cdd:cd11684     1 ELYIRYLHKLADLHEERGNYVEAALCLLLHADLYAWDL------------------------------KALVPALAESLS 50
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1725 SGKYFTESGLVGLLEQAAASFSMAGMYEAVNEVYKVLIPIHEANRDAKKLSTIHGKLQEAFSKIVHQstgwERMFGTYFR 1804
Cdd:cd11684    51 FPEQTSFERKEALYKKAIDLFDKGKAWEFAIALYKELIPQYENNFDYAKLSEVHRKIAKLYEKIAEK----DRLFPTYFR 126
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1805 VGFYGTKF-GDLDEQEFVYKEPAITKLAEISHRLEGFYGERfgedvvEVIKDSNPVDKCKLDPNKAYIQITYVEPYFDTY 1883
Cdd:cd11684   127 VGFYGKGFpESLRGKEFIYRGPEFERLGDFCERLKSLYPGA------EIIQSSEEPDDEILDSEGQYIQITSVEPYFDDE 200
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1884 EMK----DRITYFDKNYNLRRFMYCTPFTLDGRA-HGELHEQFKRKTILTTSHAFPYIKTRVNVTHKEEIILTPIEVAIE 1958
Cdd:cd11684   201 DLVsraaPGVRQFYRNNNINTFVYERPFTKGGKKsQNEITDQWKERTILTTEESFPTILRRSEVVSIEEIELSPIENAIE 280
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1959 DMQKKTQELAFATHQ----DPADPKMLQMVLQGSVGTTVNQGPLEVAQVFLS-EIPSDPKLFRHHNKLRLCFKDFTKRCE 2033
Cdd:cd11684   281 DIEKKTEELRSLINKyrsgDSPNVNPLQMLLQGTVDAAVNGGPVAYAEAFLSeEYLSNYPEAEKVKKLKEAFEEFLEILK 360
                         410       420       430
                  ....*....|....*....|....*....|..
gi 431822377 2034 DALRKNKSLIGPDQKEYQRELERNYHRLKEAL 2065
Cdd:cd11684   361 RGLALHAKLCPPEMAPLHEELEEGFEKLFKEL 392
DHR2_DOCK9 cd11698
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 9; Dock9, also ...
1645-2065 9.72e-108

Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 9; Dock9, also called Zizimin1, is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPase Cdc42 by exchanging bound GDP for free GTP. It plays important roles in spine formation and dendritic growth. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock9, which contains the catalytic GEF activity for Cdc42. Class D DOCKs also contain a Pleckstrin homology (PH) domain at the N-terminus.


Pssm-ID: 212571  Cd Length: 415  Bit Score: 350.87  E-value: 9.72e-108
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1645 DLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLSmledRK-YLPVGCVTFQNISSNVLEESAVSDDVVSPDeegi 1723
Cdd:cd11698     1 ELRKTWLDSMARIHVKNGDLSEAAMCYVHVAALVAEYLT----RKgMFRQGCTAFRVITPNIDEEASMMEDVGMQD---- 72
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1724 csgKYFTESGLVGLLEQAAASFSMAGMYEAVNEVYKVLIPIHEANRDAKKLSTIHGKLQEAFSKIVHQSTGWERMFGTYF 1803
Cdd:cd11698    73 ---VHFNEDVLMELLEQCADGLWKAERYELIADIYKLIIPIYEKRRDFERLAHLYDTLHRAYSKVTEVMHSGKRLLGTYF 149
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1804 RVGFYGTKF-GDLDEQEFVYKEPAITKLAEISHRLEGFYGERFGEDVVEVIKDSNPVDKCKLDPNKAYIQITYVEPYFDT 1882
Cdd:cd11698   150 RVAFFGQGFfEDEDGKEYIYKEPKLTPLSEISQRLLKLYSDKFGSENVKMIQDSGKVNPKDLDSKYAYIQVTHVTPYFDE 229
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1883 YEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKRKTILTTSHAFPYIKTRVNVTHKEEIILTPIEVAIEDMQK 1962
Cdd:cd11698   230 KELQERKTDFERSHNIRRFMFEMPFTQSGKRQGGVEEQCKRRTILTAIHCFPYVKKRIPVMYQHHTDLNPIEVAIDEMSK 309
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1963 KTQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQVFLSEIPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSL 2042
Cdd:cd11698   310 KVAELRQLCSSAEVDMIKLQLKLQGSVSVQVNAGPLAYARAFLDDTNTKRYPDNKVKLLKEVFRQFVEACGQALAVNERL 389
                         410       420
                  ....*....|....*....|...
gi 431822377 2043 IGPDQKEYQRELERNYHRLKEAL 2065
Cdd:cd11698   390 IKEDQLEYQEEMKANYREMAKEL 412
DHR2_DOCK10 cd11699
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 10; Dock10, also ...
1644-2058 3.01e-102

Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 10; Dock10, also called Zizimin3, is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPase Cdc42 by exchanging bound GDP for free GTP. Dock10 is preferentially expressed in lymphocytes and may play a role in interleukin-4 induced activation of B cells. It may also play a role in the invasion of tumor cells. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock10, which contains the catalytic GEF activity for Cdc42. Class D DOCKs also contain a Pleckstrin homology (PH) domain at the N-terminus.


Pssm-ID: 212572  Cd Length: 446  Bit Score: 336.25  E-value: 3.01e-102
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1644 PDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYL--------------SMLEDRKYLP----------------V 1693
Cdd:cd11699     1 PELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLkrkgywkmekictsSMLPEDSQVYdsnlllttstggsmfsM 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1694 GCVTFQNISSNVLEESAVSDDVVSPDEEgicsgkyFTESGLVGLLEQAAASFSMAGMYEAVNEVYKVLIPIHEANRDAKK 1773
Cdd:cd11699    81 GWPAFLSITPNIKEEGAMKEDSGMQDTP-------YNENTLVEQLELCVDYLWKSERYELIADVNKPVIAVFEKQRDFKR 153
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1774 LSTIHGKLQEAFSKIVHQSTGWERMFGTYFRVGFYGTKFGDLDE-QEFVYKEPAITKLAEISHRLEGFYGERFGEDVVEV 1852
Cdd:cd11699   154 LSELYYDIHRSYLKVAEVVNSEKRLFGRYYRVAFYGQGFFEEEEgKEYIYKEPKLTGLSEISQRLLKLYADKFGADNVKI 233
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1853 IKDSNPVDKCKLDPNKAYIQITYVEPYFDTYEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKRKTILTTSHA 1932
Cdd:cd11699   234 IQDSNKVNPKELDPKFAYIQVTYVTPYFDEKEQEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVEEQCKRRTILTTSHS 313
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1933 FPYIKTRVNVTHKEEIILTPIEVAIEDMQKKTQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQVFLSEIPSDP 2012
Cdd:cd11699   314 FPYVKKRIQVVSQTSTELNPIEVAIDEMSKKVSELNQLCTMEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKK 393
                         410       420       430       440
                  ....*....|....*....|....*....|....*....|....*.
gi 431822377 2013 KLFRHHNKLRLCFKDFTKRCEDALRKNKSLIGPDQKEYQRELERNY 2058
Cdd:cd11699   394 YPDNQVKLLKEIFRQFAEACGQALDVNERLIKEDQLEYQEEMRSHY 439
DOCK-C2 pfam14429
C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical ...
557-736 1.69e-66

C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical GTP/GDP exchange factors for the small GTPases Rac and Cdc42 and are implicated cell-migration and phagocytosis. Across all Dock180 proteins, two regions are conserved: C-terminus termed CZH2 or DHR2 (or the Dedicator of cytokinesis) whereas CZH1/DHR1 contain a new family of the C2 domain.


Pssm-ID: 433949  Cd Length: 185  Bit Score: 222.84  E-value: 1.69e-66
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377   557 NTTYRNLLYIYPQSLNFANR-QGSARNITVKVQFMYGEdpSNAMP-VIFGKSSCsEFSKEAYTAVVYHNRSPDFHEEIKV 634
Cdd:pfam14429    1 PGDYRNDLYVTPKSGNFSKGkKSSARNIEVTVEVRDSD--GEPLPnCIYGGSGG-PLVTEFKSTVYYHNKSPTWYEEIKI 77
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377   635 KLPATLTDHHHLLFTFYHVSCQQKqNTPLETPVGYTWIPMLQNGR--LKTGQFCLPVSL-EKPPQAYSVLS-------PE 704
Cdd:pfam14429   78 ALPIELTPKHHLLFTFYHVSCQKK-KDKVEKPFGYAFLPLLDDDGafLRDGEHTLPVYKyDELPPGYLSLPwskggekES 156
                          170       180       190
                   ....*....|....*....|....*....|..
gi 431822377   705 VPLPGMKwvdNHKGVFNVEVVAVSSIHTQDPY 736
Cdd:pfam14429  157 SALPGLK---GHKDVFKVRTLLCSTKLTQDPH 185
C2_Dock-D cd08697
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 ...
560-737 7.23e-53

C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 classes of Dock family proteins. The members here include: Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2/ACG (activated Cdc42-associated GEF). Dock-D are Cdc42-specific GEFs. In addition to the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker), which all Dock180-related proteins have, Dock-D members contain a functionally uncharacterized domain and a PH domain upstream of the C2 domain. DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The PH domain broadly binds to phospholipids and is thought to be involved in targeting the plasma membrane. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176079  Cd Length: 185  Bit Score: 184.06  E-value: 7.23e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377  560 YRNLLYIYPQSLNFANRQGS--ARNITVKVQFMYGeDPSNAMPV--IFGKSSCSeFSKEAYTAVVYHNRSPDFHEEIKVK 635
Cdd:cd08697     1 YKNHLYVYPLHLKYDSQKTFakARNIAVCIEFRDS-DEEDAKPLkcIYYGPGGG-FTTSAYAAVLHHNQNPEFYDEIKIE 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377  636 LPATLTDHHHLLFTFYHVSCQQ----KQNTPLETPVGYTWIPMLQ-NGRLKTGQFCLPVSLEKPPQAYSVLSPEVPLPGM 710
Cdd:cd08697    79 LPTQLHEKHHLLFTFYHVSCDInkkgKKKDGVETPVGYAWLPLLKdKGRLNSEEQTPPVANLLPNYPDGYLSIQPHGPEV 158
                         170       180
                  ....*....|....*....|....*..
gi 431822377  711 KWVDNHKGVFNVEVVAVSSIHTQDPYL 737
Cdd:cd08697   159 KWVDGGKPLFKVSTHLVSTVYTQDQHL 185
C2_DOCK180_related cd08679
C2 domains found in Dedicator Of CytoKinesis 1 (DOCK 180) and related proteins; Dock180 was ...
560-737 9.76e-52

C2 domains found in Dedicator Of CytoKinesis 1 (DOCK 180) and related proteins; Dock180 was first identified as an 180kd proto-oncogene product c-Crk-interacting protein involved in actin cytoskeletal changes. It is now known that it has Rac-specific GEF activity, but lacks the conventional Dbl homology (DH) domain. There are 10 additional related proteins that can be divided into four classes based on sequence similarity and domain organization: Dock-A which includes Dock180/Dock1, Dock2, and Dock5; Dock-B which includes Dock3/MOCA (modifier of cell adhesion) and Dock4; Dock-C which includes Dock6/Zir1, Dock7/Zir2, and Dock8/Zir3; and Dock-D, which includes Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2/ACG (activated Cdc42-associated GEF). Most of members of classes Dock-A and Dock-B are the GEFs specific for Rac. Those of Dock-D are Cdc42-specific GEFs while those of Dock-C are the GEFs for both. All Dock180-related proteins have two common homology domains: the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker). DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176061  Cd Length: 178  Bit Score: 180.60  E-value: 9.76e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377  560 YRNLLYIYPQSLNFANRQGSARNITVKVQFMYGEDPSNAMPVIFgkSSCSEFSKEAYTAVVYHNRSPDFHEEIKVKLPAT 639
Cdd:cd08679     1 LRNDLYVYPQSGELSKAKSKGRNIEITVEVRDDDGDIIEPCISA--PGSGSELRSEYTSVVYYHKNPVFNDEIKIQLPAD 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377  640 LTDHHHLLFTFYHVSCQQKQNTPLETPVGYTWIPML--QNGRLKTGQFCLPVSLEkPPQAYSVLSPEVPLPGMKWVDNHK 717
Cdd:cd08679    79 LTPQHHLLFTFYHVSSKKKQGDKEETPFGYAFLPLMdkDGAFIKDGDHTLPVYKY-DKRPDVGPSGYLSLPSTLANGKSS 157
                         170       180
                  ....*....|....*....|.
gi 431822377  718 G-VFNVEVVAVSSIHTQDPYL 737
Cdd:cd08679   158 KdTFKIKTRLCSTILTQDKSL 178
DUF3398 pfam11878
Domain of unknown function (DUF3398); This domain is functionally uncharacterized. This domain ...
52-161 2.20e-50

Domain of unknown function (DUF3398); This domain is functionally uncharacterized. This domain is found in eukaryotes. This presumed domain is about 100 amino acids in length.


Pssm-ID: 432155  Cd Length: 112  Bit Score: 174.00  E-value: 2.20e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377    52 TEAVDPVDLEDYLITHPLAVDSGPLRDLIEFPPDDIEVVYSPRDCRTLVSAVPEE--SEMDPHVRDCIRSYTEDWAIVIR 129
Cdd:pfam11878    1 PKLVEPLDYEEFISQHLTQLDNDPLRDLLLFPDDDVEVATLPRECRTLQPTVPEEaeKEADSLVRECIKTYTSDWHVVNY 80
                           90       100       110
                   ....*....|....*....|....*....|..
gi 431822377   130 KYHKLGTGFNPNTLDKQKERQKGLPKQVFESD 161
Cdd:pfam11878   81 KYEDYSGDFRQLPRNKRRERPEKLPKQVFEID 112
DHR2_DOCK_B cd11696
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis proteins; DOCK ...
1759-2065 2.02e-17

Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. As GEFs, they activate small GTPases by exchanging bound GDP for free GTP. They are divided into four classes (A-D) based on sequence similarity and domain architecture; class B includes Dock3 and 4. Dock3 is a specific GEF for Rac and it regulates N-cadherin dependent cell-cell adhesion, cell polarity, and neuronal morphology. It promotes axonal growth by stimulating actin polymerization and microtubule assembly. Dock4 activates the Ras family GTPase Rap1, probably indirectly through interaction with Rap regulatory proteins. It plays a role in regulating dendritic growth and branching in hippocampal neurons, where it is highly expressed. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of class B DOCKs, which contains the catalytic GEF activity for Rac and/or Cdc42. Class B DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212569  Cd Length: 391  Bit Score: 86.73  E-value: 2.02e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1759 KVLIPIHEANRDAKKLSTIHGKLQEAFSKIVHQstgwERMFGTYFRVGFYGTKFGD-LDEQEFVYKEPAITKLAEISHRL 1837
Cdd:cd11696    81 RELAELYESLYDYAKLSHILRMEASFYDNILTQ----LRPEPEYFRVGFYGKGFPLfLRNKQFVYRGLDYERIGAFTQRL 156
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1838 EGFYGErfgedvVEVIKDSNPVDKCKLDPNKAYIQITYVEP------YFDTYEMKDRITYFDKNYNLRRFMYCTPF---T 1908
Cdd:cd11696   157 QSEFPQ------AHILTKNTPPDDAILQADGQYIQICNVKPvperrpVLQMVGVPDKVRSFYRVNDVRKFQYDRPIhkgP 230
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1909 LDgrAHGELHEQFKRKTILTTSHAFPYIKTRVNVTHKEEIILTPIEVAIEDMQKKTQELAFATHQDPADPK----MLQMV 1984
Cdd:cd11696   231 ID--KDNEFKSLWIERTTLVTEHSLPGILRWFEVVSREVEEIPPVENACETVENKNQELRSLISQYQADPTrninPFSMR 308
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1985 LQGSVGTTVNQGPLEVAQVFLSE--IPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSLIGPDQKEYQRELERNYHRLK 2062
Cdd:cd11696   309 LQGVIDAAVNGGIAKYQEAFFTPefILSHPEDAEHIARLRELILEQVQILEAGLALHGKLAPPEVRPLHKRLVERFTQMK 388

                  ...
gi 431822377 2063 EAL 2065
Cdd:cd11696   389 QSL 391
DHR2_DOCK3 cd11704
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3; Dock3, also ...
1765-2065 5.40e-14

Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3; Dock3, also called modifier of cell adhesion (MOCA), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates small GTPases by exchanging bound GDP for free GTP. Dock3 is a specific GEF for Rac. It regulates N-cadherin dependent cell-cell adhesion, cell polarity, and neuronal morphology. It promotes axonal growth by stimulating actin polymerization and microtubule assembly. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class B includes Dock3 and 4. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock3, which contains the catalytic GEF activity for Rac and/or Cdc42. Class B DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212577  Cd Length: 392  Bit Score: 76.20  E-value: 5.40e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1765 HEANRDAKKLSTIHGKLQEAFSKIVHQstgwERMFGTYFRVGFYGTKFGD-LDEQEFVYKepaitklAEISHRLEGFYGE 1843
Cdd:cd11704    87 YESLYDYQSLSWIRKMEAAYYDNIMEQ----QRLEPEFFRVGFYGRKFPFfLRNKEYVCR-------GHDYERLEAFQQR 155
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1844 RFGEDVVEV-IKDSNPVDKCKLDPNKAYIQITYVEP---YFDTYEMK---DRITYFDKNYNLRRFMYCTPFTLDGR-AHG 1915
Cdd:cd11704   156 MLSEFPQAIaMQHPNHPDDGILQCDAQYLQIYAVTPipdNMDVLQMDrvpDRIKSFYRVNNVRKFRYDRPFHKGPKdKEN 235
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1916 ELHEQFKRKTILTTSHAFPYIKTRVNVTHKEEIILTPIEVAIEDMQKKTQEL-----AFATHQDPADPKMLQMVLQGSVG 1990
Cdd:cd11704   236 EFKSLWIERTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVENKNQELrtlisQYQHKQLHGNINLLSMCLNGVID 315
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 431822377 1991 TTVNQGPLEVAQVFLSE--IPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSLIGPDQKEYQRELERNYHRLKEAL 2065
Cdd:cd11704   316 AAVNGGIARYQEAFFDKdyISKHPGDAEKITQLKELMQEQVHVLGVGLAVHEKFVHPEMRPLHKKLIDQFQMMRSSL 392
DHR2_DOCK_A cd11697
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis proteins; DOCK ...
1770-2007 1.30e-13

Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. As GEFs, they activate small GTPases by exchanging bound GDP for free GTP. They are divided into four classes (A-D) based on sequence similarity and domain architecture; class A includes Dock1, 2 and 5. Class A DOCKs are specific GEFs for Rac. Dock1 interacts with the scaffold protein Elmo and the resulting complex functions upstream of Rac in many biological events including phagocytosis of apoptotic cells, cell migration and invasion. Dock2 plays an important role in lymphocyte migration and activation, T-cell differentiation, neutrophil chemotaxis, and type I interferon induction. Dock5 functions upstream of Rac1 to regulate osteoclast function. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of class A DOCKs, which contains the catalytic GEF activity for Rac and/or Cdc42. Class A DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212570  Cd Length: 400  Bit Score: 75.06  E-value: 1.30e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1770 DAKKLSTIHGKLQEAFSKIVHQStgweRMFGTYFRVGFYGTKFGD-LDEQEFVYKEPAITKLAEISHRLEGFYGErfged 1848
Cdd:cd11697    97 DYLQLSELLKRMATFYDNIMKTL----RPEPEYFRVGYYGQGFPSfLRNKVFIYRGKEYERLSDFSARLLNQFPN----- 167
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1849 vVEVIKDSNPVDKCKLDPNKAYIQITYVEPYFDTYE------MKDRITYFDKNYNLRRFMYCTPF---TLDGRahGELHE 1919
Cdd:cd11697   168 -AELMNTLTPPGDEIKESPGQYLQINKVDPVMDERPrfkgkpVSDQILNYYKVNEVQRFTFSRPFrrgTKDPD--NEFAN 244
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1920 QFKRKTILTTSHAFPYIKTRVNVTHKEEIILTPIEVAIEDMQKKTQELAFATHQDPADPKM----LQMVLQGSVGTTVNQ 1995
Cdd:cd11697   245 MWLERTTLTTAYKLPGILRWFEVVSTSTVEISPLENAIETMEDTNKKIRDLILQHQSDPTLpinpLSMLLNGIVDAAVMG 324
                         250
                  ....*....|..
gi 431822377 1996 GPLEVAQVFLSE 2007
Cdd:cd11697   325 GIANYEKAFFTE 336
DHR2_DOCK2 cd11706
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 2; Dock2 is a ...
1676-2007 9.99e-12

Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 2; Dock2 is a hematopoietic cell-specific, class A DOCK and is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates small GTPases by exchanging bound GDP for free GTP. It plays an important role in lymphocyte migration and activation, T-cell differentiation, neutrophil chemotaxis, and type I interferon induction. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class A includes Dock1, 2 and 5. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock2, which contains the catalytic GEF activity for Rac and/or Cdc42. Class A DOCKs, like Dock2, are specific GEFs for Rac and they contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212579  Cd Length: 421  Bit Score: 69.25  E-value: 9.99e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1676 ALVAEYLSMLEDrkyLPVGCVTFQNISSNVLEESAV---SDDVVSPDEEGICSGKYFTESGLV-GLLEQAAASFSMAGMY 1751
Cdd:cd11706    19 AMYIRYLYKLRD---LHLDCENYTEAAYTLLLHTRLlkwSDEQCASQVMQTGQQHPQTQRQLKeTLYETIIGYFDKGKMW 95
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1752 EAVNEVYKVLIPIHEAN-RDAKKLSTI---HGKLQEAFSKIVHQSTgwermfgTYFRVGFYGTKFGD-LDEQEFVYKEPA 1826
Cdd:cd11706    96 EEAISLCKELAEQYEMEiFDYELLSQNliqQAKFYESIMKILRPKP-------DYFAVGYYGQGFPSfLRNKVFIYRGKE 168
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1827 ITKLAEISHRLEGFYgerfgEDVVEVIKDSNPVDKCKLDPNKaYIQITYVEPYFDTY------EMKDRITYFDKNYNLRR 1900
Cdd:cd11706   169 YERREDFQMQLMSQF-----PNAEKLNTTSAPGDDIKNSPGQ-YIQCFTVQPVLEEHprlknkPVPDQIINFYKSNYVQR 242
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1901 FMYCTPF---TLDgrAHGELHEQFKRKTILTTSHAFPYIKTRVNVTHKEEIILTPIEVAIEDMQKKTQELAFATHQDPAD 1977
Cdd:cd11706   243 FHYSRPVrkgPVD--PENEFASMWIERTTFVTAYKLPGILRWFEVTHMSQTTISPLENAIETMSTTNEKILMMINQYQSD 320
                         330       340       350
                  ....*....|....*....|....*....|....
gi 431822377 1978 PKM----LQMVLQGSVGTTVNQGPLEVAQVFLSE 2007
Cdd:cd11706   321 ESLpinpLSMLLNGIVDPAVMGGFAKYEKAFFTE 354
DHR2_DOCK4 cd11705
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 4; Dock4 is an ...
1765-2065 1.11e-10

Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 4; Dock4 is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates small GTPases by exchanging bound GDP for free GTP. It plays a role in regulating dendritic growth and branching in hippocampal neurons, where it is highly expressed. It may also regulate spine morphology and synapse formation. Dock4 activates the Ras family GTPase Rap1, probably indirectly through interaction with Rap regulatory proteins. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class B includes Dock3 and 4. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock4, which contains the catalytic GEF activity for Rac and/or Cdc42. Class B DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212578  Cd Length: 391  Bit Score: 65.82  E-value: 1.11e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1765 HEANRDAKKLSTIHGKLQEAFSKIVHQstgwERMFGTYFRVGFYGTKFGD-LDEQEFVYKEPAITKLAEISHRLEGFYGE 1843
Cdd:cd11705    87 YESYYDYRNLSKMRMMEASLYDKIMDQ----QRLEPEFFRVGFYGKKFPFfLRNKEFVCRGHDYERLEAFQQRMLNEFPH 162
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1844 RFGedvvevIKDSNPVDKCKLDPNKAYIQITYVEPYFDTYEM------KDRITYFDKNYNLRRFMYCTPFTLDGR-AHGE 1916
Cdd:cd11705   163 AIA------MQHANQPDETIFQAEAQYLQIYAVTPIPESQEVlqrdgvPDNIKSFYKVNHIWRFRYDRPFHKGTKdKENE 236
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1917 LHEQFKRKTILTTSHAFPYIKTRVNVTHKEEIILTPIEVAIEDMQKKTQELAFATHQ----DPADPKMLQMVLQGSVGTT 1992
Cdd:cd11705   237 FKSLWVERTTLTLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLRTLISQcqtrQMQNINPLTMCLNGVIDAA 316
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 431822377 1993 VNQGPLEVAQVFLSE--IPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSLIGPDQKEYQRELERNYHRLKEAL 2065
Cdd:cd11705   317 VNGGVSRYQEAFFVKeyILNHPEDGDKITRLRELMLEQAQILEFGLAVHEKFVPQDMRPLHKKLVDQFFVMKSSL 391
DHR2_DOCK5 cd11708
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 5; Dock5 is an ...
1737-2033 6.50e-10

Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 5; Dock5 is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates small GTPases by exchanging bound GDP for free GTP. It functions upstream of Rac1 to regulate osteoclast function. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class A includes Dock1, 2 and 5. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock5, which contains the catalytic GEF activity for Rac and/or Cdc42. Class A DOCKs, like Dock5, are specific GEFs for Rac and they contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212581  Cd Length: 400  Bit Score: 63.43  E-value: 6.50e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1737 LLEQAAASFSMAGMYEAVNEVYKVLIPIHEANR-DAKKLSTIHGKLQEAFSKIVHQStgweRMFGTYFRVGFYGTKFGD- 1814
Cdd:cd11708    63 LYQEIISFFDKGKMWEKAIELSKELADMYENQVfDYEGLGNLLKKQAQFYENIMKAM----RPQPEYFAVGYYGQGFPSf 138
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1815 LDEQEFVYKEPAITKLAEISHRLEGFYgerfgEDVVEVIKDSNPVDKCKLDPnKAYIQITYVEPYFD-TYEMKDR----- 1888
Cdd:cd11708   139 LRNKIFIYRGKEYERLEDFSLKLLTQF-----PNAEKMTSTSPPGDEIKSST-KQYVQCFTVKPVMNlPSHYKDKpvpeq 212
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1889 -ITYFDKNyNLRRFMYCTPFTLDGR-AHGELHEQFKRKTILTTSHAFPYIKTRVNVTH--KEEIilTPIEVAIEDMQKKT 1964
Cdd:cd11708   213 iLNYYRAN-EVQQFQYSRPFRKGEKdPDNEFATMWIERTTFTTAYRFPGILKWFEVKQisTEEI--SPLENAIETMELTN 289
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1965 QELAFATHQDPADPKM----LQMVLQGSVGTTVNQGPLEVAQVF-----LSEIPSDP---KLFRH--------------- 2017
Cdd:cd11708   290 EKISNLVQQHAWDRSLpvhpLSMLLNGIVDPAVMGGFSNYEKAFftekyLQEHPEDQekiELLKQlialqmpllaegiri 369
                         330       340
                  ....*....|....*....|....*...
gi 431822377 2018 ------------HNKLRLCFKDFTKRCE 2033
Cdd:cd11708   370 hgeklteqlkplHERLVSCFKDLRAKVE 397
DHR2_DOCK1 cd11707
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 1; Dock1, also ...
1645-2007 1.99e-08

Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 1; Dock1, also called Dock180, is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates small GTPases by exchanging bound GDP for free GTP. Dock1 interacts with the scaffold protein Elmo and the resulting complex functions upstream of Rac in many biological events including phagocytosis of apoptotic cells, cell migration and invasion. In the nervous system, it mediates attractive responses to netrin-1 and thus, plays a role in axon outgrowth and pathfinding. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class A includes Dock1, 2 and 5. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock1, which contains the catalytic GEF activity for Rac and/or Cdc42. Class A DOCKs, like Dock1, are specific GEFs for Rac and they contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212580  Cd Length: 400  Bit Score: 58.90  E-value: 1.99e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1645 DLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVaeylsmledrKYLPVGCVT-------FQNISSNVLEESAVSDDVVS 1717
Cdd:cd11707     1 EMYIRYLYKLCDLHKECDNYTEAAYTLLLHAKLL----------KWSEEACAAhltqrdgYQATTQGQLKDQLYQEIIHY 70
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1718 PDEegicsGKYFTESGLVGLleqaaasfSMAGMYEavNEVYkvlipiheanrDAKKLSTIHGKLQEAFSKIVHQStgweR 1797
Cdd:cd11707    71 FDK-----GKMWEEAIALGK--------ELAEQYE--NEMF-----------DYEQLSELLKKQAQFYENIVKVI----R 120
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1798 MFGTYFRVGFYGTKFGD-LDEQEFVYKEPAITKLAEISHRLEGFYGErfgedvVEVIKDSNPV-DKCKLDPNKaYIQITY 1875
Cdd:cd11707   121 PKPDYFAVGYYGQGFPTfLRNKMFIYRGKEYERREDFEARLLTQFPN------AEKMKTTSPPgDDIKNSSGQ-YIQCFT 193
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377 1876 VEPYFDTYEMK------DRITYFDKNYNLRRFMYCTPFTL-DGRAHGELHEQFKRKTILTTSHAFPYIKTRVNVTHKEEI 1948
Cdd:cd11707   194 VKPLLELPPKFqnkpvsEQIVSFYRVNEVQRFQYSRPVRKgEKDPDNEFANMWIERTTYVTAYKLPGILRWFEVKSVFMV 273
                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 431822377 1949 ILTPIEVAIEDMQKKTQELAFATHQDPADPKM----LQMVLQGSVGTTVNQGPLEVAQVFLSE 2007
Cdd:cd11707   274 EISPLENAIETMQLTNEKINNMVQQHLNDPNLpinpLSMLLNGIVDPAVMGGFANYEKAFFTE 336
C2_Dock-A cd08694
C2 domains found in Dedicator Of CytoKinesis (Dock) class A proteins; Dock-A is one of 4 ...
561-678 3.13e-05

C2 domains found in Dedicator Of CytoKinesis (Dock) class A proteins; Dock-A is one of 4 classes of Dock family proteins. The members here include: Dock180/Dock1, Dock2, and Dock5. Most of these members have been shown to be GEFs specific for Rac. Dock5 has not been well characterized to date, but most likely also is a GEF specific for Rac. In addition to the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker), which all Dock180-related proteins have, Dock-A members contain a proline-rich region and a SH3 domain upstream of the C2 domain. DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176076  Cd Length: 196  Bit Score: 47.01  E-value: 3.13e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377  561 RNLLYIYPQSLNFAN-RQGSARNITVKVQfMYGEDpSNAMPVIFGKSSCSEFSKEAYTAVVYHNRSPDFHEEIKVKLPAT 639
Cdd:cd08694     2 RNDLYLTLVQGDFDKgSKTSDKNVEVTVS-VCNED-GKIIPGVISLGAGEEPIDEYKSVIYYQVDKPKWFETFKVAIPIE 79
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 431822377  640 LTDHHHLLFTFYHVSCQQKQNTPlETPVGYTWIPMLQ-NG 678
Cdd:cd08694    80 DFKSSHLRFTFKHRSSNEAKDKS-EKPFALSFVKLMQeNG 118
C2_Dock-B cd08695
C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins; Dock-B is one of 4 ...
561-678 8.93e-05

C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins; Dock-B is one of 4 classes of Dock family proteins. The members here include: Dock3/MOCA (modifier of cell adhesion) and Dock4. Most of these members have been shown to be GEFs specific for Rac, although Dock4 has also been shown to interact indirectly with the Ras family GTPase Rap1, probably through Rap regulatory proteins. In addition to the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker), which all Dock180-related proteins have, Dock-B members contain a SH3 domain upstream of the C2 domain and a proline-rich region downstream. DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176077  Cd Length: 189  Bit Score: 45.45  E-value: 8.93e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 431822377  561 RNLLYIYPQSLNFaNRQG--SARNITVKVQFMY--GEDPSNAMPVIFGKSSCSEFskeaYTAVVYHNRSPDFHEEIKVKL 636
Cdd:cd08695     2 RNDLYLTLERGEF-EKGGksTAKNIEVTMVVLDadGQVLKDCISLGSGEPPCSEY----RSFVLYHNNSPRWNETIKLPI 76
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 431822377  637 PATLTDHHHLLFTFYHVSCQQKQNTPLetpVGYTWIPMLQNG 678
Cdd:cd08695    77 PIDKFRGSHLRFEFRHCSTKDKGEKKL---FGFSFVPLMRED 115
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.20
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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