Conserved Protein Domain Family
HkD_HkRP

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cd22223: HkD_HkRP 
Hook domain found in the Hook-related protein (HkRP) family
The HkRP family includes Daple, Girdin and Gipie. Daple, also called Dvl-associating protein with a high frequency of leucine residues, or coiled-coil domain-containing protein 88C (CCDC88C), or Hook-related protein 2 (HkRP2), is a novel non-receptor nucleotide exchange factor (GEF) required for activation of guanine nucleotide-binding proteins (G-proteins) during non-canonical Wnt signaling. Girdin, also called Akt phosphorylation enhancer (APE), or coiled-coil domain-containing protein 88A (CCDC88A), or G alpha-interacting vesicle-associated protein (GIV), or Girders of actin filament, or Hook-related protein 1 (HkRP1), is a bifunctional modulator of guanine nucleotide-binding proteins (G proteins). It acts as a non-receptor guanine nucleotide exchange factor which binds to and activates guanine nucleotide-binding protein G(i) alpha subunits. It also acts as a guanine nucleotide dissociation inhibitor for guanine nucleotide-binding protein G(s) subunit alpha GNAS. In addition, Girdin plays an essential role in cell migration. Gipie, also called GRP78-interacting protein induced by ER stress, or coiled-coil domain-containing protein 88B (CCDC88B), or brain leucine zipper domain-containing protein, or Hook-related protein 3 (HkRP3), is a novel actin cytoskeleton-binding protein and Akt substrate that regulates cell migratory responses in various biological contexts. It acts as a positive regulator of T-cell maturation and inflammatory function. As a microtubule-binding protein, Gipie regulates lytic granule clustering and NK cell killing. All family members contain a conserved globular Hook domain which folds as a variant of the helical calponin homology (CH) domain.
Statistics
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PSSM-Id: 411794
Aligned: 31 rows
Threshold Bit Score: 133.1
Created: 21-Jul-2020
Updated: 25-Oct-2021
Structure
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Aligned Rows:
 
putative
Feature 1:putative LIC-binding interface [polypeptide binding site]
Evidence:
  • Comment:the conserved Hook domain interacts directly with the dynein light intermediate chain 1 (LIC1)
  • Comment:based on the structure evidence that Homo sapiens Hook 3 (6B9H) interacts with a dynein light intermediate.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                                                         
Q9P219         12 FLQSPLVTWVKTFGPfgsgs-------------qdnlTMYMDLVDGIFLNQIMLQIDprptnqrin-------------- 64   human
EFX72875       24 LMQGPLVAWVRTFKDddes---------------rteLDYSQLIDGAFLDNVLSRIDprtngrah--------------- 73   common water ...
NP_647780      15 FVNSSIISWLESCLPrae-----------------llAGYTSLLDGHIIHSVWLQIDpepqnnpsel------------- 64   fruit fly
OQV24144       18 FLQSPLVHWALSLSGngdgqeeneessstgerirrspGSGLDLCNSRFLKDLLEQMEpqliseesv-------------- 83   Hypsibius duj...
XP_009013903    4 QTSASLLKWAQLFGDatg-----------------reMTWTDLVDGIFLNDIMKKINskyeyldkf-------------- 52   Helobdella ro...
TKR87956        6 FWSGPLGRWVVDVAAsgvgsllpehe-wrraervnanVLYSDLCDGFVLNLLYFFIDpasanlilvke------------ 72   Steinernema c...
CDJ90365        6 FWEHPLGSWLNDVALgispvvdekn--wrspsrfdlpLQYGELCDGVLLSVLFHQIDpssvdvvspr------------- 70   barber pole worm
TRY78921        9 FLNGPLLQWLRTLPEap------------------aeITFAELTSGQFLHNVLQSLRssrrvdndddddddddddddsda 70   Tigriopus cal...
XP_023337878   10 FLSSPLVRWTSSLLPgg------------------ddLSWQLLAKGVTLATLLEGLDasfqiavd--------------- 56   Eurytemora af...
F3Y5P4          7 NWSHPLAFWLCDCAAiipnp-------------atqnFAKNDFLDGLLMLNLMKFINphfs------------------- 54   Caenorhabditi...
Feature 1                                                                                      #  
Q9P219         65 --------khvnndvnLRIQNLTILVRNIKTYYQEVLQQLIVmNLPNVLMIGRDPls--gKSMEEIKKVLLLVLGCAVQC 134  human
EFX72875       74 --------iqpaedvyTRIRNFDALVRAVKGFYEDVLGQFVLvRLPDPVTLGRDPds--eTGLAGMQTLLLLVLGCAVQG 143  common water ...
NP_647780      65 ------ndlngkslsiARAKNFECVVRNLKSFFEEELGQTIL-VLPDAFTLGHHPes--kNGLEQMKTLLTLLLGAAVQC 135  fruit fly
OQV24144       84 --------awqddpvlHRLSVLESLVTNLRAYFTDHLGQIMVmRPPDILFMCQFPga--dHTVSEMRKLLCEILSFAVQS 153  Hypsibius duj...
XP_009013903   53 --------erksseqnIQVELWKSLINAIFSYYQDTLEIVIFmEPPDIFLICNQPftaenTTVKQLSKTLLLLLGCAVQC 124  Helobdella ro...
TKR87956       73 -----vstsnfqvdhpTRFRLFTLLLHNLHRFYRLRLNRIVVmTLPDVFSIVRNPta--eGSGHELNKVLLLLLGCAVQS 145  Steinernema c...
CDJ90365       71 ------evrfddqdlrARQRLFIALIDAIRRLYKRRLRQLIVlSPPDIFSIVRNPrp--dVSGEELNKFVLLLLGCAVQG 142  barber pole worm
TRY78921       71 nipttspkfdsnpdlrARVMNINLLIEKLKLYYENILSQTIViALPNTIKICQSPpt--dQSLQEMDTLLLLLLGAAVQS 148  Tigriopus cal...
XP_023337878   57 ---------sdpidtaARARNILLILKSIKYFYKEILGQLLLiSLPAPRDLSQIPps--tNSLASMETLLLLVLGVAVQS 125  Eurytemora af...
F3Y5P4         55 ------------enekNGQSLYEELLNQISQFYEKNLDQVIVcKMPEISILESSGei-deITFEELKKLLLLLLGCAIQS 121  Caenorhabditi...
Feature 1            #  ## #    #  ## ##  ##  # 
Q9P219        135 ErKEEFIERIKqLDIETQAGIVAHIQEVTH 164  human
EFX72875      144 PsKESVIEDIKrLPLATQHDIVNCIQQVAD 173  common water flea
NP_647780     136 PnKELFIARIKeLDLETQHAIVGLIKQVTD 165  fruit fly
OQV24144      154 GrKEEIIERIQgMDEDVQKGIVECIKEVTD 183  Hypsibius dujardini
XP_009013903  125 NnRRKVLEQIKsMDLGTQQHLLGCIAEVTD 154  Helobdella robusta
TKR87956      146 DqKEIFINRIKsMNLELQTALVAEIKKVGS 175  Steinernema carpocapsae
CDJ90365      143 DkKKTFVSRITkLEKRLQQGIAKEIQKITE 172  barber pole worm
TRY78921      149 SqKEHAVNSIQnLPVELQHAFVDKIKDVTD 178  Tigriopus californicus
XP_023337878  126 EqKQEVIITIKnLPLETQHEIVDRIRAITD 155  Eurytemora affinis
F3Y5P4        122 DhKKVFVDRITgFDQTIQAELAACIQKLTE 151  Caenorhabditis elegans

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