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Conserved domains on  [gi|114326482|ref|NP_033309|]
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signal transducer and activator of transcription 1 isoform 2 [Mus musculus]

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List of domain hits

Name Accession Description Interval E-value
SH2_STAT1 cd10372
Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) 1 ...
557-707 4.20e-104

Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) 1 proteins; STAT1 is a member of the STAT family of transcription factors. STAT1 is involved in upregulating genes due to a signal by interferons. STAT1 forms homodimers or heterodimers with STAT3 that bind to the Interferon-Gamma Activated Sequence (GAS) promoter element in response to IFN-gamma stimulation. STAT1 forms a heterodimer with STAT2 that can bind Interferon Stimulated Response Element (ISRE) promoter element in response to either IFN-alpha or IFN-beta stimulation. Binding in both cases leads to an increased expression of ISG (Interferon Stimulated Genes). STAT1 has been shown to interact with protein kinase R, Src, IRF1, STAT3, MCM5, STAT2, CD117, Fanconi anemia, complementation group C, CREB-binding protein, Interleukin 27 receptor, alpha subunit, PIAS1, BRCA1, Epidermal growth factor receptor, PTK2, Mammalian target of rapamycin, IFNAR2, PRKCD, TRADD, C-jun, Calcitriol receptor, ISGF3G, and GNB2L1. STAT proteins mediate the signaling of cytokines and a number of growth factors from the receptors of these extracellular signaling molecules to the cell nucleus. STATs are specifically phosphorylated by receptor-associated Janus kinases, receptor tyrosine kinases, or cytoplasmic tyrosine kinases. The phosphorylated STAT molecules dimerize by reciprocal binding of their SH2 domains to the phosphotyrosine residues. These dimeric STATs translocate into the nucleus, bind to specific DNA sequences, and regulate the transcription of their target genes. However there are a number of unphosphorylated STATs that travel between the cytoplasm and nucleus and some STATs that exist as dimers in unstimulated cells that can exert biological functions independent of being activated. There are seven mammalian STAT family members which have been identified: STAT1, STAT2, STAT3, STAT4, STAT5 (STAT5A and STAT5B), and STAT6. There are 6 conserved domains in STAT: N-terminal domain (NTD), coiled-coil domain (CCD), DNA-binding domain (DBD), alpha-helical linker domain (LD), SH2 domain, and transactivation domain (TAD). NTD is involved in dimerization of unphosphorylated STATs monomers and for the tetramerization between STAT1, STAT3, STAT4 and STAT5 on promoters with two or more tandem STAT binding sites. It also plays a role in promoting interactions with transcriptional co-activators such as CREB binding protein (CBP)/p300, as well as being important for nuclear import and deactivation of STATs involving tyrosine de-phosphorylation. CCD interacts with other proteins, such as IFN regulatory protein 9 (IRF-9/p48) with STAT1 and c-JUN with STAT3 and is also thought to participate in the negative regulation of these proteins. Distinct genes are bound to STATs via their DBD domain. This domain is also involved in nuclear translocation of activated STAT1 and STAT3 phosphorylated dimers upon cytokine stimulation. LD links the DNA-binding and SH2 domains and is important for the transcriptional activation of STAT1 in response to IFN-gamma. It also plays a role in protein-protein interactions and has also been implicated in the constitutive nucleocytoplasmic shuttling of unphosphorylated STATs in resting cells. The SH2 domain is necessary for receptor association and tyrosine phosphodimer formation. Residues within this domain may be particularly important for some cellular functions mediated by the STATs as well as residues adjacent to this domain. The TAD interacts with several proteins, namely minichromosome maintenance complex component 5 (MCM5), breast cancer 1 (BRCA1) and CBP/p300. TAD also contains a modulatory phosphorylation site that regulates STAT activity and is necessary for maximal transcription of a number of target genes. The conserved tyrosine residue present in the C-terminus is crucial for dimerization via interaction with the SH2 domain upon the interaction of the ligand with the receptor. STAT activation by tyrosine phosphorylation also determines nuclear import and retention, DNA binding to specific DNA elements in the promoters of responsive genes, and transcriptional activation of STAT dimers. In addition to the SH2 domain there is a coiled-coil domain, a DNA binding domain, and a transactivation domain in the STAT proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


:

Pssm-ID: 198235  Cd Length: 151  Bit Score: 318.00  E-value: 4.20e-104
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482 557 WIDTILELIKKHLLCLWNDGCIMGFISKERERALLKDQQPGTFLLRFSESSREGAITFTWVERSQNGGEPDFHAVEPYTK 636
Cdd:cd10372    1 WIESILELIKKHLLSLWNDGCIMGFISKERERALLKDQQPGTFLLRFSESSREGAITFTWVERSQNGGEPDFHAVEPYTK 80
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 114326482 637 KELSAVTFPDIIRNYKVMAAENIPENPLKYLYPNIDKDHAFGKYYSRPKEAPEPMELDDPKRTGYIKTELI 707
Cdd:cd10372   81 KELSAVTFPDIIRNYKVMAAENIPENPLKYLYPNIDKDHAFGKYYSRPKEAPEPMELDGPKGTGYIKTELI 151
STAT_bind pfam02864
STAT protein, DNA binding domain; STAT proteins (Signal Transducers and Activators of ...
317-567 3.82e-144

STAT protein, DNA binding domain; STAT proteins (Signal Transducers and Activators of Transcription) are a family of transcription factors that are specifically activated to regulate gene transcription when cells encounter cytokines and growth factors. This family represents the DNA binding domain of STAT, which has an ig-like fold. STAT proteins also include an SH2 domain pfam00017.


:

Pssm-ID: 145817  Cd Length: 254  Bit Score: 425.74  E-value: 3.82e-144
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482  317 FVVERQPCMPTHPQRPLVLKTGVQFTVKLRLLVKLQELNYNLKVKVSFDKDVNEKNTVKGFRKFNILGTHTKVMNMEEST 396
Cdd:pfam02864   1 FVVERQPCMPTHPQRPLVLKTGTQFTAKVRLLVKLQELNYQLKPKVVIDKIVSEKQAQRGFRKFNILGTNTKILNMEESM 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482  397 NGSLAAEFRHLQLKEQKN-AGNRTN-EGPLIVTEELHSLSFETQLCQPGLVIDLETTSLPVVVISNVSQLPSGWASILWY 474
Cdd:pfam02864  81 NGSLAAEFRHLTLREQRLkKGKRANrKGPLSVTEELHAILFETQFTVQGLKIDLETLSLPVVVISNGNQLPNAWASILWY 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482  475 NMLVTEPRNLSFFLNPPCAWWSQLSEVLSWQFSSVTKRGLNADQLSMLGEKLLGPNA-GPDGLIPWTRFCKENINDKNFS 553
Cdd:pfam02864 161 NALTEDPRNLVFFLVPPRVTWAQLSEVLSWQFSSEVGRGLNIEQLGFLAEKLFGQNSsYSGGSISWSQFCKENLPGKSFT 240
                         250
                  ....*....|....
gi 114326482  554 FWPWIDTILELIKK 567
Cdd:pfam02864 241 FWQWFDAILDLVKK 254
STAT_alpha pfam01017
STAT protein, all-alpha domain; STAT proteins (Signal Transducers and Activators of ...
136-315 7.30e-73

STAT protein, all-alpha domain; STAT proteins (Signal Transducers and Activators of Transcription) are a family of transcription factors that are specifically activated to regulate gene transcription when cells encounter cytokines and growth factors. STAT proteins also include an SH2 domain pfam00017.


:

Pssm-ID: 250297  Cd Length: 182  Bit Score: 236.44  E-value: 7.30e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482  136 LDKQKELDSKVRNVKDQVMCIEQEIKTLEELQDEYDFKCKTSQNR-EGEANGVA-KSDQKQEQLLLHKMFLMLDNKRKEI 213
Cdd:pfam01017   1 SEKQLEIDSKVEDLRNSVQDTEQDIKQLEDLQDEFDFRYKTLQSLiETPANGTSlKEHLKQEKLTLQQMLNKLDQKRKEL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482  214 IHKIRELLNSIELTQNTLINDELVEWKRRQQSACIGGPPNACLDQLQSWFTIVAETLQQIRQQLKKLEELEQKFTYEPDP 293
Cdd:pfam01017  81 ADKHQETLGLLEALQNALLDEELIEWKRRQQLACIGGPPEGCLDQLQNWFTALAESLFQLRQQLKKLEELRQKLTYEGDP 160
                         170       180
                  ....*....|....*....|..
gi 114326482  294 ITKNKQVLSDRTFLLFQQLIQS 315
Cdd:pfam01017 161 ITKGRPQLNERVTELLKNLVTS 182
STAT_int smart00964
STAT protein, protein interaction domain; STAT proteins (Signal Transducers and Activators of ...
2-121 1.68e-56

STAT protein, protein interaction domain; STAT proteins (Signal Transducers and Activators of Transcription) are a family of transcription factors that are specifically activated to regulate gene transcription when cells encounter cytokines and growth factors. STAT proteins also include an SH2 domain.


:

Pssm-ID: 214942  Cd Length: 120  Bit Score: 189.42  E-value: 1.68e-56
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482     2 SQWFELQQLDSKFLEQVHQLYDDSFPMEIRQYLAQWLEKQDWEHAAYDVSFATIRFHDLLSQLDDQYSRFSLENNFLLQH 81
Cdd:smart00964   1 SQWAQLQQLDSKFLEQVQQLYGDNFPMELRHYLADWIESQDWELAANDEAQATRLFHNLLEQLDQQLSRFSQESNFLLKH 80
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 114326482    82 NIRKSKRNLQDNFQEDPVQMSMIIYNCLKEERKILENAQR 121
Cdd:smart00964  81 NLRHIKSNLQSLYQENPLELARIIRNILQEERRILAEASR 120
STAT1_TAZ2bind pfam12162
STAT1 TAZ2 binding domain; This domain family is found in eukaryotes, and is approximately 20 ...
715-739 5.43e-05

STAT1 TAZ2 binding domain; This domain family is found in eukaryotes, and is approximately 20 amino acids in length, and the family is found in association with pfam02865, pfam00017, pfam01017, pfam02864. This domain is the C terminal domain of STAT1. This domain binds selectively to the TAZ2 domain of CRB (CREB-binding protein). In this process it becomes a transcriptional activator and can initiate transcription of certain genes.


:

Pssm-ID: 152597  Cd Length: 23  Bit Score: 41.61  E-value: 5.43e-05
                          10        20
                  ....*....|....*....|....*
gi 114326482  715 SRLQttDNLLPMSPEEFDEMSRIVG 739
Cdd:pfam12162   1 SRLQ--DNMLPMSPDDFDELHRMVG 23
 
Name Accession Description Interval E-value
SH2_STAT1 cd10372
Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) 1 ...
557-707 4.20e-104

Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) 1 proteins; STAT1 is a member of the STAT family of transcription factors. STAT1 is involved in upregulating genes due to a signal by interferons. STAT1 forms homodimers or heterodimers with STAT3 that bind to the Interferon-Gamma Activated Sequence (GAS) promoter element in response to IFN-gamma stimulation. STAT1 forms a heterodimer with STAT2 that can bind Interferon Stimulated Response Element (ISRE) promoter element in response to either IFN-alpha or IFN-beta stimulation. Binding in both cases leads to an increased expression of ISG (Interferon Stimulated Genes). STAT1 has been shown to interact with protein kinase R, Src, IRF1, STAT3, MCM5, STAT2, CD117, Fanconi anemia, complementation group C, CREB-binding protein, Interleukin 27 receptor, alpha subunit, PIAS1, BRCA1, Epidermal growth factor receptor, PTK2, Mammalian target of rapamycin, IFNAR2, PRKCD, TRADD, C-jun, Calcitriol receptor, ISGF3G, and GNB2L1. STAT proteins mediate the signaling of cytokines and a number of growth factors from the receptors of these extracellular signaling molecules to the cell nucleus. STATs are specifically phosphorylated by receptor-associated Janus kinases, receptor tyrosine kinases, or cytoplasmic tyrosine kinases. The phosphorylated STAT molecules dimerize by reciprocal binding of their SH2 domains to the phosphotyrosine residues. These dimeric STATs translocate into the nucleus, bind to specific DNA sequences, and regulate the transcription of their target genes. However there are a number of unphosphorylated STATs that travel between the cytoplasm and nucleus and some STATs that exist as dimers in unstimulated cells that can exert biological functions independent of being activated. There are seven mammalian STAT family members which have been identified: STAT1, STAT2, STAT3, STAT4, STAT5 (STAT5A and STAT5B), and STAT6. There are 6 conserved domains in STAT: N-terminal domain (NTD), coiled-coil domain (CCD), DNA-binding domain (DBD), alpha-helical linker domain (LD), SH2 domain, and transactivation domain (TAD). NTD is involved in dimerization of unphosphorylated STATs monomers and for the tetramerization between STAT1, STAT3, STAT4 and STAT5 on promoters with two or more tandem STAT binding sites. It also plays a role in promoting interactions with transcriptional co-activators such as CREB binding protein (CBP)/p300, as well as being important for nuclear import and deactivation of STATs involving tyrosine de-phosphorylation. CCD interacts with other proteins, such as IFN regulatory protein 9 (IRF-9/p48) with STAT1 and c-JUN with STAT3 and is also thought to participate in the negative regulation of these proteins. Distinct genes are bound to STATs via their DBD domain. This domain is also involved in nuclear translocation of activated STAT1 and STAT3 phosphorylated dimers upon cytokine stimulation. LD links the DNA-binding and SH2 domains and is important for the transcriptional activation of STAT1 in response to IFN-gamma. It also plays a role in protein-protein interactions and has also been implicated in the constitutive nucleocytoplasmic shuttling of unphosphorylated STATs in resting cells. The SH2 domain is necessary for receptor association and tyrosine phosphodimer formation. Residues within this domain may be particularly important for some cellular functions mediated by the STATs as well as residues adjacent to this domain. The TAD interacts with several proteins, namely minichromosome maintenance complex component 5 (MCM5), breast cancer 1 (BRCA1) and CBP/p300. TAD also contains a modulatory phosphorylation site that regulates STAT activity and is necessary for maximal transcription of a number of target genes. The conserved tyrosine residue present in the C-terminus is crucial for dimerization via interaction with the SH2 domain upon the interaction of the ligand with the receptor. STAT activation by tyrosine phosphorylation also determines nuclear import and retention, DNA binding to specific DNA elements in the promoters of responsive genes, and transcriptional activation of STAT dimers. In addition to the SH2 domain there is a coiled-coil domain, a DNA binding domain, and a transactivation domain in the STAT proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198235  Cd Length: 151  Bit Score: 318.00  E-value: 4.20e-104
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482 557 WIDTILELIKKHLLCLWNDGCIMGFISKERERALLKDQQPGTFLLRFSESSREGAITFTWVERSQNGGEPDFHAVEPYTK 636
Cdd:cd10372    1 WIESILELIKKHLLSLWNDGCIMGFISKERERALLKDQQPGTFLLRFSESSREGAITFTWVERSQNGGEPDFHAVEPYTK 80
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 114326482 637 KELSAVTFPDIIRNYKVMAAENIPENPLKYLYPNIDKDHAFGKYYSRPKEAPEPMELDDPKRTGYIKTELI 707
Cdd:cd10372   81 KELSAVTFPDIIRNYKVMAAENIPENPLKYLYPNIDKDHAFGKYYSRPKEAPEPMELDGPKGTGYIKTELI 151
STAT_bind pfam02864
STAT protein, DNA binding domain; STAT proteins (Signal Transducers and Activators of ...
317-567 3.82e-144

STAT protein, DNA binding domain; STAT proteins (Signal Transducers and Activators of Transcription) are a family of transcription factors that are specifically activated to regulate gene transcription when cells encounter cytokines and growth factors. This family represents the DNA binding domain of STAT, which has an ig-like fold. STAT proteins also include an SH2 domain pfam00017.


Pssm-ID: 145817  Cd Length: 254  Bit Score: 425.74  E-value: 3.82e-144
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482  317 FVVERQPCMPTHPQRPLVLKTGVQFTVKLRLLVKLQELNYNLKVKVSFDKDVNEKNTVKGFRKFNILGTHTKVMNMEEST 396
Cdd:pfam02864   1 FVVERQPCMPTHPQRPLVLKTGTQFTAKVRLLVKLQELNYQLKPKVVIDKIVSEKQAQRGFRKFNILGTNTKILNMEESM 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482  397 NGSLAAEFRHLQLKEQKN-AGNRTN-EGPLIVTEELHSLSFETQLCQPGLVIDLETTSLPVVVISNVSQLPSGWASILWY 474
Cdd:pfam02864  81 NGSLAAEFRHLTLREQRLkKGKRANrKGPLSVTEELHAILFETQFTVQGLKIDLETLSLPVVVISNGNQLPNAWASILWY 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482  475 NMLVTEPRNLSFFLNPPCAWWSQLSEVLSWQFSSVTKRGLNADQLSMLGEKLLGPNA-GPDGLIPWTRFCKENINDKNFS 553
Cdd:pfam02864 161 NALTEDPRNLVFFLVPPRVTWAQLSEVLSWQFSSEVGRGLNIEQLGFLAEKLFGQNSsYSGGSISWSQFCKENLPGKSFT 240
                         250
                  ....*....|....
gi 114326482  554 FWPWIDTILELIKK 567
Cdd:pfam02864 241 FWQWFDAILDLVKK 254
STAT_alpha pfam01017
STAT protein, all-alpha domain; STAT proteins (Signal Transducers and Activators of ...
136-315 7.30e-73

STAT protein, all-alpha domain; STAT proteins (Signal Transducers and Activators of Transcription) are a family of transcription factors that are specifically activated to regulate gene transcription when cells encounter cytokines and growth factors. STAT proteins also include an SH2 domain pfam00017.


Pssm-ID: 250297  Cd Length: 182  Bit Score: 236.44  E-value: 7.30e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482  136 LDKQKELDSKVRNVKDQVMCIEQEIKTLEELQDEYDFKCKTSQNR-EGEANGVA-KSDQKQEQLLLHKMFLMLDNKRKEI 213
Cdd:pfam01017   1 SEKQLEIDSKVEDLRNSVQDTEQDIKQLEDLQDEFDFRYKTLQSLiETPANGTSlKEHLKQEKLTLQQMLNKLDQKRKEL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482  214 IHKIRELLNSIELTQNTLINDELVEWKRRQQSACIGGPPNACLDQLQSWFTIVAETLQQIRQQLKKLEELEQKFTYEPDP 293
Cdd:pfam01017  81 ADKHQETLGLLEALQNALLDEELIEWKRRQQLACIGGPPEGCLDQLQNWFTALAESLFQLRQQLKKLEELRQKLTYEGDP 160
                         170       180
                  ....*....|....*....|..
gi 114326482  294 ITKNKQVLSDRTFLLFQQLIQS 315
Cdd:pfam01017 161 ITKGRPQLNERVTELLKNLVTS 182
STAT_int smart00964
STAT protein, protein interaction domain; STAT proteins (Signal Transducers and Activators of ...
2-121 1.68e-56

STAT protein, protein interaction domain; STAT proteins (Signal Transducers and Activators of Transcription) are a family of transcription factors that are specifically activated to regulate gene transcription when cells encounter cytokines and growth factors. STAT proteins also include an SH2 domain.


Pssm-ID: 214942  Cd Length: 120  Bit Score: 189.42  E-value: 1.68e-56
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482     2 SQWFELQQLDSKFLEQVHQLYDDSFPMEIRQYLAQWLEKQDWEHAAYDVSFATIRFHDLLSQLDDQYSRFSLENNFLLQH 81
Cdd:smart00964   1 SQWAQLQQLDSKFLEQVQQLYGDNFPMELRHYLADWIESQDWELAANDEAQATRLFHNLLEQLDQQLSRFSQESNFLLKH 80
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 114326482    82 NIRKSKRNLQDNFQEDPVQMSMIIYNCLKEERKILENAQR 121
Cdd:smart00964  81 NLRHIKSNLQSLYQENPLELARIIRNILQEERRILAEASR 120
STAT_int pfam02865
STAT protein, protein interaction domain; STAT proteins (Signal Transducers and Activators of ...
2-121 5.29e-54

STAT protein, protein interaction domain; STAT proteins (Signal Transducers and Activators of Transcription) are a family of transcription factors that are specifically activated to regulate gene transcription when cells encounter cytokines and growth factors. STAT proteins also include an SH2 domain pfam00017.


Pssm-ID: 251576  Cd Length: 125  Bit Score: 182.49  E-value: 5.29e-54
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482    2 SQWFELQQLDSKFLEQVHQLYDDSFPMEIRQYLAQWLEKQDWEHAAY----DVSFATIRFHDLLSQLDDQYSRFSLENNF 77
Cdd:pfam02865   1 SLWKQLQQLDPEFLEQVQQLYGDNFPIEVRHYLAQWIESQDWEEAALdnpqDESQATVLFHNLLQELQRQASRLSQEDNF 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 114326482   78 LLQHNIRKSKRNLQDNFQEDPVQMSMIIYNCLKEERKILENAQR 121
Cdd:pfam02865  81 LLRHNLREIARNLQNRYQHNPLELARIIRNCLQEERRIVQEASR 124
SH2 pfam00017
SH2 domain;
578-622 3.54e-08

SH2 domain;


Pssm-ID: 249511  Cd Length: 77  Bit Score: 51.42  E-value: 3.54e-08
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 114326482  578 IMGFISK-ERERALLKDQQPGTFLLRFSESSrEGAITFTWVERSQN 622
Cdd:pfam00017   2 YHGKISReEAERLLLNGKPDGTFLVRESESK-PGDYTLSVRDDGRV 46
STAT1_TAZ2bind pfam12162
STAT1 TAZ2 binding domain; This domain family is found in eukaryotes, and is approximately 20 ...
715-739 5.43e-05

STAT1 TAZ2 binding domain; This domain family is found in eukaryotes, and is approximately 20 amino acids in length, and the family is found in association with pfam02865, pfam00017, pfam01017, pfam02864. This domain is the C terminal domain of STAT1. This domain binds selectively to the TAZ2 domain of CRB (CREB-binding protein). In this process it becomes a transcriptional activator and can initiate transcription of certain genes.


Pssm-ID: 152597  Cd Length: 23  Bit Score: 41.61  E-value: 5.43e-05
                          10        20
                  ....*....|....*....|....*
gi 114326482  715 SRLQttDNLLPMSPEEFDEMSRIVG 739
Cdd:pfam12162   1 SRLQ--DNMLPMSPDDFDELHRMVG 23
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
579-622 2.52e-04

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.


Pssm-ID: 214585  Cd Length: 84  Bit Score: 39.90  E-value: 2.52e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 114326482   579 MGFISKERERALLKDQQPGTFLLRFSESSREG-AITFTWVERSQN 622
Cdd:smart00252   5 HGFISREEAEKLLKNEGDGDFLVRDSESSPGDyVLSVRVKGKVKH 49
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
6-290 3.42e-03

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins].


Pssm-ID: 233757 [Multi-domain]  Cd Length: 1179  Bit Score: 39.65  E-value: 3.42e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482     6 ELQQLDSKFLEQVHQLydDSFPMEIRQYLAQWLEKQDwEHAAYDVSFATI--RFHDLLSQLDDqysrfsLENNflLQHnI 83
Cdd:TIGR02168  240 ELEELQEELKEAEEEL--EELTAELQELEEKLEELRL-EVSELEEEIEELqkELYALANEISR------LEQQ--KQI-L 307
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482    84 RKSKRNLQDNFQEDPVQMsmiiyncLKEERKILENAQRFNQAQEgniqntvmldKQKELDSKVRNVKDQVMCIEQEIKTL 163
Cdd:TIGR02168  308 RERLANLERQLEELEAQL-------EELESKLDELAEELAELEE----------KLEELKEELESLEAELEELEAELEEL 370
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482   164 EELQDEYDfkcktsQNREGEANGVAKSDQKQEQLllhkmflmldnkRKEIIhKIRELLNSIELTQNTLI------NDELV 237
Cdd:TIGR02168  371 ESRLEELE------EQLETLRSKVAQLELQIASL------------NNEIE-RLEARLERLEDRRERLQqeieelLKKLE 431
                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|...
gi 114326482   238 EWKRRQQSACIGGPpNACLDQLQSWFTIVAETLQQIRQQLKKLEELEQKFTYE 290
Cdd:TIGR02168  432 EAELKELQAELEEL-EEELEELQEELERLEEALEELREELEEAEQALDAAERE 483
SbcC COG0419
ATPase involved in DNA repair [DNA replication, recombination, and repair]
82-287 8.49e-03

ATPase involved in DNA repair [DNA replication, recombination, and repair]


Pssm-ID: 223496 [Multi-domain]  Cd Length: 908  Bit Score: 38.20  E-value: 8.49e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482  82 NIRKSKRNLQDNFQEDPVQMsmiiyncLKEERKILE-NAQRFNQAQEGNIQNTVMLDKQKELDSKVRNVKDQVMCIEQEI 160
Cdd:COG0419  537 KLENLLEELEELKEKLQLQQ-------LKEELRQLEdRLQELKELLEELRLLRTRKEELEELRERLKELKKKLKELEERL 609
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482 161 KTLEELQDEYDFKCKTSQNREGEANGVAKSDQKQEQL----LLHKMFLMLDNKRKEIIHKIRELLNSIELTQNTLINDEL 236
Cdd:COG0419  610 SQLEELLQSLELSEAENELEEAEEELESELEKLNLQAeleeLLQAALEELEEKVEELEAEIRRELQRIENEEQLEEKLEE 689
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 114326482 237 VEWKRRQqsaciggppnacLDQLQSWFTIVAETLQQIRQQLKKLEELEQKF 287
Cdd:COG0419  690 LEQLEEE------------LEQLREELEELLKKLGEIEQLIEELESRKAEL 728
 
Name Accession Description Interval E-value
SH2_STAT1 cd10372
Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) 1 ...
557-707 4.20e-104

Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) 1 proteins; STAT1 is a member of the STAT family of transcription factors. STAT1 is involved in upregulating genes due to a signal by interferons. STAT1 forms homodimers or heterodimers with STAT3 that bind to the Interferon-Gamma Activated Sequence (GAS) promoter element in response to IFN-gamma stimulation. STAT1 forms a heterodimer with STAT2 that can bind Interferon Stimulated Response Element (ISRE) promoter element in response to either IFN-alpha or IFN-beta stimulation. Binding in both cases leads to an increased expression of ISG (Interferon Stimulated Genes). STAT1 has been shown to interact with protein kinase R, Src, IRF1, STAT3, MCM5, STAT2, CD117, Fanconi anemia, complementation group C, CREB-binding protein, Interleukin 27 receptor, alpha subunit, PIAS1, BRCA1, Epidermal growth factor receptor, PTK2, Mammalian target of rapamycin, IFNAR2, PRKCD, TRADD, C-jun, Calcitriol receptor, ISGF3G, and GNB2L1. STAT proteins mediate the signaling of cytokines and a number of growth factors from the receptors of these extracellular signaling molecules to the cell nucleus. STATs are specifically phosphorylated by receptor-associated Janus kinases, receptor tyrosine kinases, or cytoplasmic tyrosine kinases. The phosphorylated STAT molecules dimerize by reciprocal binding of their SH2 domains to the phosphotyrosine residues. These dimeric STATs translocate into the nucleus, bind to specific DNA sequences, and regulate the transcription of their target genes. However there are a number of unphosphorylated STATs that travel between the cytoplasm and nucleus and some STATs that exist as dimers in unstimulated cells that can exert biological functions independent of being activated. There are seven mammalian STAT family members which have been identified: STAT1, STAT2, STAT3, STAT4, STAT5 (STAT5A and STAT5B), and STAT6. There are 6 conserved domains in STAT: N-terminal domain (NTD), coiled-coil domain (CCD), DNA-binding domain (DBD), alpha-helical linker domain (LD), SH2 domain, and transactivation domain (TAD). NTD is involved in dimerization of unphosphorylated STATs monomers and for the tetramerization between STAT1, STAT3, STAT4 and STAT5 on promoters with two or more tandem STAT binding sites. It also plays a role in promoting interactions with transcriptional co-activators such as CREB binding protein (CBP)/p300, as well as being important for nuclear import and deactivation of STATs involving tyrosine de-phosphorylation. CCD interacts with other proteins, such as IFN regulatory protein 9 (IRF-9/p48) with STAT1 and c-JUN with STAT3 and is also thought to participate in the negative regulation of these proteins. Distinct genes are bound to STATs via their DBD domain. This domain is also involved in nuclear translocation of activated STAT1 and STAT3 phosphorylated dimers upon cytokine stimulation. LD links the DNA-binding and SH2 domains and is important for the transcriptional activation of STAT1 in response to IFN-gamma. It also plays a role in protein-protein interactions and has also been implicated in the constitutive nucleocytoplasmic shuttling of unphosphorylated STATs in resting cells. The SH2 domain is necessary for receptor association and tyrosine phosphodimer formation. Residues within this domain may be particularly important for some cellular functions mediated by the STATs as well as residues adjacent to this domain. The TAD interacts with several proteins, namely minichromosome maintenance complex component 5 (MCM5), breast cancer 1 (BRCA1) and CBP/p300. TAD also contains a modulatory phosphorylation site that regulates STAT activity and is necessary for maximal transcription of a number of target genes. The conserved tyrosine residue present in the C-terminus is crucial for dimerization via interaction with the SH2 domain upon the interaction of the ligand with the receptor. STAT activation by tyrosine phosphorylation also determines nuclear import and retention, DNA binding to specific DNA elements in the promoters of responsive genes, and transcriptional activation of STAT dimers. In addition to the SH2 domain there is a coiled-coil domain, a DNA binding domain, and a transactivation domain in the STAT proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198235  Cd Length: 151  Bit Score: 318.00  E-value: 4.20e-104
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482 557 WIDTILELIKKHLLCLWNDGCIMGFISKERERALLKDQQPGTFLLRFSESSREGAITFTWVERSQNGGEPDFHAVEPYTK 636
Cdd:cd10372    1 WIESILELIKKHLLSLWNDGCIMGFISKERERALLKDQQPGTFLLRFSESSREGAITFTWVERSQNGGEPDFHAVEPYTK 80
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 114326482 637 KELSAVTFPDIIRNYKVMAAENIPENPLKYLYPNIDKDHAFGKYYSRPKEAPEPMELDDPKRTGYIKTELI 707
Cdd:cd10372   81 KELSAVTFPDIIRNYKVMAAENIPENPLKYLYPNIDKDHAFGKYYSRPKEAPEPMELDGPKGTGYIKTELI 151
STAT_bind pfam02864
STAT protein, DNA binding domain; STAT proteins (Signal Transducers and Activators of ...
317-567 3.82e-144

STAT protein, DNA binding domain; STAT proteins (Signal Transducers and Activators of Transcription) are a family of transcription factors that are specifically activated to regulate gene transcription when cells encounter cytokines and growth factors. This family represents the DNA binding domain of STAT, which has an ig-like fold. STAT proteins also include an SH2 domain pfam00017.


Pssm-ID: 145817  Cd Length: 254  Bit Score: 425.74  E-value: 3.82e-144
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482  317 FVVERQPCMPTHPQRPLVLKTGVQFTVKLRLLVKLQELNYNLKVKVSFDKDVNEKNTVKGFRKFNILGTHTKVMNMEEST 396
Cdd:pfam02864   1 FVVERQPCMPTHPQRPLVLKTGTQFTAKVRLLVKLQELNYQLKPKVVIDKIVSEKQAQRGFRKFNILGTNTKILNMEESM 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482  397 NGSLAAEFRHLQLKEQKN-AGNRTN-EGPLIVTEELHSLSFETQLCQPGLVIDLETTSLPVVVISNVSQLPSGWASILWY 474
Cdd:pfam02864  81 NGSLAAEFRHLTLREQRLkKGKRANrKGPLSVTEELHAILFETQFTVQGLKIDLETLSLPVVVISNGNQLPNAWASILWY 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482  475 NMLVTEPRNLSFFLNPPCAWWSQLSEVLSWQFSSVTKRGLNADQLSMLGEKLLGPNA-GPDGLIPWTRFCKENINDKNFS 553
Cdd:pfam02864 161 NALTEDPRNLVFFLVPPRVTWAQLSEVLSWQFSSEVGRGLNIEQLGFLAEKLFGQNSsYSGGSISWSQFCKENLPGKSFT 240
                         250
                  ....*....|....
gi 114326482  554 FWPWIDTILELIKK 567
Cdd:pfam02864 241 FWQWFDAILDLVKK 254
STAT_alpha pfam01017
STAT protein, all-alpha domain; STAT proteins (Signal Transducers and Activators of ...
136-315 7.30e-73

STAT protein, all-alpha domain; STAT proteins (Signal Transducers and Activators of Transcription) are a family of transcription factors that are specifically activated to regulate gene transcription when cells encounter cytokines and growth factors. STAT proteins also include an SH2 domain pfam00017.


Pssm-ID: 250297  Cd Length: 182  Bit Score: 236.44  E-value: 7.30e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482  136 LDKQKELDSKVRNVKDQVMCIEQEIKTLEELQDEYDFKCKTSQNR-EGEANGVA-KSDQKQEQLLLHKMFLMLDNKRKEI 213
Cdd:pfam01017   1 SEKQLEIDSKVEDLRNSVQDTEQDIKQLEDLQDEFDFRYKTLQSLiETPANGTSlKEHLKQEKLTLQQMLNKLDQKRKEL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482  214 IHKIRELLNSIELTQNTLINDELVEWKRRQQSACIGGPPNACLDQLQSWFTIVAETLQQIRQQLKKLEELEQKFTYEPDP 293
Cdd:pfam01017  81 ADKHQETLGLLEALQNALLDEELIEWKRRQQLACIGGPPEGCLDQLQNWFTALAESLFQLRQQLKKLEELRQKLTYEGDP 160
                         170       180
                  ....*....|....*....|..
gi 114326482  294 ITKNKQVLSDRTFLLFQQLIQS 315
Cdd:pfam01017 161 ITKGRPQLNERVTELLKNLVTS 182
SH2_STAT4 cd10375
Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) ...
557-692 1.57e-64

Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) 4proteins; STAT4 mediate signals from the IL-12 receptors. STAT4 is mainly phosphorylated by IL-12-mediated signaling pathway in T cells. STAT4 expression is restricted in myeloid cells, thymus and testis. L-12 is the major cytokine that can activate STAT4, resulting in its tyrosine phosphorylation. The IL-12 receptor has two chains, termed IL-12R 1 and IL-12R 2, and ligand binding results in heterodimer formation and activation of the receptor associated JAK kinases, Jak2 and Tyk2. Phosphorylated STAT4 homo-dimerizes via its SH2 domain, and translocates into nucleus where it can recognize traditional N3 STAT target sequences in IL-12 responsive genes. STAT4 can also be phosphorylated in response to IFN-gamma stimulation through activation of Jak1 and Tyk2 in human. IL-17 can also activate STAT4 in human monocytic leukemia cell lines and IL-2 can induce Jak2 and Stat4 activation in NK cells but not in T cells. T helper 1 (Th1) cells produce IL-2 and IFNgamma, whereas Th2 cells secrete IL-4, IL-5, IL-6 and IL-13. Th1 cells are responsible for cell-mediated/inflammatory immunity and can enhance defenses against infectious agents and cancer, while Th2 cells are essential for humoral immunity and the clearance of parasitic antigens. The most potent factors that can promote Th1 and Th2 differentiation are the cytokines IL-12 and IL-4 respectively Although STAT4 is expressed both in Th1 and Th2 cells, STAT4 can only be phosphorylated by IL-12 which suggests that STAT4 plays an important role in Th1 cell function or development. STAT4 activation leads to Th1 differentiation, including the target genes of STAT4 such as ERM, a transcription factor that belongs to the Ets family of transcription factors. The expression of ERM is specifically induced by IL-12 in wild-type Th1 cells, but not in STAT4-deficient T cells. STAT proteins mediate the signaling of cytokines and a number of growth factors from the receptors of these extracellular signaling molecules to the cell nucleus. STATs are specifically phosphorylated by receptor-associated Janus kinases, receptor tyrosine kinases, or cytoplasmic tyrosine kinases. The phosphorylated STAT molecules dimerize by reciprocal binding of their SH2 domains to the phosphotyrosine residues. These dimeric STATs translocate into the nucleus, bind to specific DNA sequences, and regulate the transcription of their target genes. However there are a number of unphosphorylated STATs that travel between the cytoplasm and nucleus and some STATs that exist as dimers in unstimulated cells that can exert biological functions independent of being activated. There are seven mammalian STAT family members which have been identified: STAT1, STAT2, STAT3, STAT4, STAT5 (STAT5A and STAT5B), and STAT6. There are 6 conserved domains in STAT: N-terminal domain (NTD), coiled-coil domain (CCD), DNA-binding domain (DBD), alpha-helical linker domain (LD), SH2 domain, and transactivation domain (TAD). NTD is involved in dimerization of unphosphorylated STATs monomers and for the tetramerization between STAT1, STAT3, STAT4 and STAT5 on promoters with two or more tandem STAT binding sites. It also plays a role in promoting interactions with transcriptional co-activators such as CREB binding protein (CBP)/p300, as well as being important for nuclear import and deactivation of STATs involving tyrosine de-phosphorylation. CCD interacts with other proteins, such as IFN regulatory protein 9 (IRF-9/p48) with STAT1 and c-JUN with STAT3 and is also thought to participate in the negative regulation of these proteins. Distinct genes are bound to STATs via their DBD domain. This domain is also involved in nuclear translocation of activated STAT1 and STAT3 phosphorylated dimers upon cytokine stimulation. LD links the DNA-binding and SH2 domains and is important for the transcriptional activation of STAT1 in response to IFN-gamma. It also plays a role in protein-protein interactions and has also been implicated in the constitutive nucleocytoplasmic shuttling of unphosphorylated STATs in resting cells. The SH2 domain is necessary for receptor association and tyrosine phosphodimer formation. Residues within this domain may be particularly important for some cellular functions mediated by the STATs as well as residues adjacent to this domain. The TAD interacts with several proteins, namely minichromosome maintenance complex component 5 (MCM5), breast cancer 1 (BRCA1) and CBP/p300. TAD also contains a modulatory phosphorylation site that regulates STAT activity and is necessary for maximal transcription of a number of target genes. The conserved tyrosine residue present in the C-terminus is crucial for dimerization via interaction with the SH2 domain upon the interaction of the ligand with the receptor. STAT activation by tyrosine phosphorylation also determines nuclear import and retention, DNA binding to specific DNA elements in the promoters of responsive genes, and transcriptional activation of STAT dimers. In addition to the SH2 domain there is a coiled-coil domain, a DNA binding domain, and a transactivation domain in the STAT proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198238  Cd Length: 148  Bit Score: 212.82  E-value: 1.57e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482 557 WIDTILELIKKHLLCLWNDGCIMGFISKERERALLKDQQPGTFLLRFSESSReGAITFTWVERSQNgGEPDFHAVEPYTK 636
Cdd:cd10375    1 WLEAILDLIKKHILPLWIDGYIMGFVSKEKERLLLKDKMPGTFLLRFSESHL-GGITFTWVDQSEN-GEVRFHSVEPYNK 78
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 114326482 637 KELSAVTFPDIIRNYKVMAAENIPENPLKYLYPNIDKDHAFGKYY-SRPKEAPEPME 692
Cdd:cd10375   79 GRLSALPFADILRDYKVIMAENIPENPLKYLYPDIPKDKAFGKHYsSQPCEVSRPTE 135
SH2_STAT3 cd10374
Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) 3 ...
550-710 6.05e-62

Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) 3 proteins; STAT3 encoded by this gene is a member of the STAT protein family. STAT3 mediates the expression of a variety of genes in response to cell stimuli, and plays a key role in many cellular processes such as cell growth and apoptosis. The small GTPase Rac1 regulates the activity of STAT3 and PIAS3 inhibits it. Three alternatively spliced transcript variants encoding distinct isoforms have been described. STAT 3 activation is required for self-renewal of embryonic stem cells (ESCs) and is essential for the differentiation of the TH17 helper T cells. Mutations in the STAT3 gene result in Hyperimmunoglobulin E syndrome and human cancers. STAT3 has been shown to interact with Androgen receptor, C-jun, ELP2, EP300, Epidermal growth factor receptor, Glucocorticoid receptor, HIF1A, Janus kinase 1, KHDRBS1, Mammalian target of rapamycin, MyoD, NDUFA13, NFKB1, Nuclear receptor coactivator 1, Promyelocytic leukemia protein, RAC1, RELA, RET proto-oncogene, RPA2, Src, STAT1, and TRIP10. STAT proteins mediate the signaling of cytokines and a number of growth factors from the receptors of these extracellular signaling molecules to the cell nucleus. STATs are specifically phosphorylated by receptor-associated Janus kinases, receptor tyrosine kinases, or cytoplasmic tyrosine kinases. The phosphorylated STAT molecules dimerize by reciprocal binding of their SH2 domains to the phosphotyrosine residues. These dimeric STATs translocate into the nucleus, bind to specific DNA sequences, and regulate the transcription of their target genes. However there are a number of unphosphorylated STATs that travel between the cytoplasm and nucleus and some STATs that exist as dimers in unstimulated cells that can exert biological functions independent of being activated. There are seven mammalian STAT family members which have been identified: STAT1, STAT2, STAT3, STAT4, STAT5 (STAT5A and STAT5B), and STAT6. There are 6 conserved domains in STAT: N-terminal domain (NTD), coiled-coil domain (CCD), DNA-binding domain (DBD), alpha-helical linker domain (LD), SH2 domain, and transactivation domain (TAD). NTD is involved in dimerization of unphosphorylated STATs monomers and for the tetramerization between STAT1, STAT3, STAT4 and STAT5 on promoters with two or more tandem STAT binding sites. It also plays a role in promoting interactions with transcriptional co-activators such as CREB binding protein (CBP)/p300, as well as being important for nuclear import and deactivation of STATs involving tyrosine de-phosphorylation. CCD interacts with other proteins, such as IFN regulatory protein 9 (IRF-9/p48) with STAT1 and c-JUN with STAT3 and is also thought to participate in the negative regulation of these proteins. Distinct genes are bound to STATs via their DBD domain. This domain is also involved in nuclear translocation of activated STAT1 and STAT3 phosphorylated dimers upon cytokine stimulation. LD links the DNA-binding and SH2 domains and is important for the transcriptional activation of STAT1 in response to IFN-gamma. It also plays a role in protein-protein interactions and has also been implicated in the constitutive nucleocytoplasmic shuttling of unphosphorylated STATs in resting cells. The SH2 domain is necessary for receptor association and tyrosine phosphodimer formation. Residues within this domain may be particularly important for some cellular functions mediated by the STATs as well as residues adjacent to this domain. The TAD interacts with several proteins, namely minichromosome maintenance complex component 5 (MCM5), breast cancer 1 (BRCA1) and CBP/p300. TAD also contains a modulatory phosphorylation site that regulates STAT activity and is necessary for maximal transcription of a number of target genes. The conserved tyrosine residue present in the C-terminus is crucial for dimerization via interaction with the SH2 domain upon the interaction of the ligand with the receptor. STAT activation by tyrosine phosphorylation also determines nuclear import and retention, DNA binding to specific DNA elements in the promoters of responsive genes, and transcriptional activation of STAT dimers. In addition to the SH2 domain there is a coiled-coil domain, a DNA binding domain, and a transactivation domain in the STAT proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198237  Cd Length: 162  Bit Score: 206.03  E-value: 6.05e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482 550 KNFSFWPWIDTILELIKKHLLCLWNDGCIMGFISKERERALLKDQQPGTFLLRFSESSREGAITFTWVERSQNgGEPDFH 629
Cdd:cd10374    4 KGFSFWVWLDNIIDLVKKYILALWNEGYIMGFISKERERAILSTKPPGTFLLRFSESSKEGGVTFTWVEKDIS-GKTQIQ 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482 630 AVEPYTKKELSAVTFPDIIRNYKVMAAENIPENPLKYLYPNIDKDHAFGKyYSRPKEAPEPmELDDPKRTGYIKTELISV 709
Cdd:cd10374   83 SVEPYTKQQLNNMSFAEIIMGYKIMDATNILVSPLVYLYPDIPKEEAFGK-YCRPESQEHP-EADPGSAAPYLKTKFICV 160

                 .
gi 114326482 710 S 710
Cdd:cd10374  161 T 161
STAT_int smart00964
STAT protein, protein interaction domain; STAT proteins (Signal Transducers and Activators of ...
2-121 1.68e-56

STAT protein, protein interaction domain; STAT proteins (Signal Transducers and Activators of Transcription) are a family of transcription factors that are specifically activated to regulate gene transcription when cells encounter cytokines and growth factors. STAT proteins also include an SH2 domain.


Pssm-ID: 214942  Cd Length: 120  Bit Score: 189.42  E-value: 1.68e-56
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482     2 SQWFELQQLDSKFLEQVHQLYDDSFPMEIRQYLAQWLEKQDWEHAAYDVSFATIRFHDLLSQLDDQYSRFSLENNFLLQH 81
Cdd:smart00964   1 SQWAQLQQLDSKFLEQVQQLYGDNFPMELRHYLADWIESQDWELAANDEAQATRLFHNLLEQLDQQLSRFSQESNFLLKH 80
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 114326482    82 NIRKSKRNLQDNFQEDPVQMSMIIYNCLKEERKILENAQR 121
Cdd:smart00964  81 NLRHIKSNLQSLYQENPLELARIIRNILQEERRILAEASR 120
STAT_int pfam02865
STAT protein, protein interaction domain; STAT proteins (Signal Transducers and Activators of ...
2-121 5.29e-54

STAT protein, protein interaction domain; STAT proteins (Signal Transducers and Activators of Transcription) are a family of transcription factors that are specifically activated to regulate gene transcription when cells encounter cytokines and growth factors. STAT proteins also include an SH2 domain pfam00017.


Pssm-ID: 251576  Cd Length: 125  Bit Score: 182.49  E-value: 5.29e-54
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482    2 SQWFELQQLDSKFLEQVHQLYDDSFPMEIRQYLAQWLEKQDWEHAAY----DVSFATIRFHDLLSQLDDQYSRFSLENNF 77
Cdd:pfam02865   1 SLWKQLQQLDPEFLEQVQQLYGDNFPIEVRHYLAQWIESQDWEEAALdnpqDESQATVLFHNLLQELQRQASRLSQEDNF 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 114326482   78 LLQHNIRKSKRNLQDNFQEDPVQMSMIIYNCLKEERKILENAQR 121
Cdd:pfam02865  81 LLRHNLREIARNLQNRYQHNPLELARIIRNCLQEERRIVQEASR 124
SH2_STAT2 cd10373
Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) 2 ...
557-710 1.36e-47

Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) 2 proteins; STAT2 is a member of the STAT protein family. In response to interferon, STAT2 forms a complex with STAT1 and IFN regulatory factor family protein p48 (ISGF3G), in which this protein acts as a transactivator, but lacks the ability to bind DNA directly. Transcription adaptor P300/CBP (EP300/CREBBP) has been shown to interact specifically with STAT2, which is thought to be involved in the process of blocking IFN-alpha response by adenovirus. STAT2 has been shown to interact with MED14, CREB-binding protein, SMARCA4, STAT1, IFNAR2, IFNAR1, and ISGF3G. STAT proteins mediate the signaling of cytokines and a number of growth factors from the receptors of these extracellular signaling molecules to the cell nucleus. STATs are specifically phosphorylated by receptor-associated Janus kinases, receptor tyrosine kinases, or cytoplasmic tyrosine kinases. The phosphorylated STAT molecules dimerize by reciprocal binding of their SH2 domains to the phosphotyrosine residues. These dimeric STATs translocate into the nucleus, bind to specific DNA sequences, and regulate the transcription of their target genes. However there are a number of unphosphorylated STATs that travel between the cytoplasm and nucleus and some STATs that exist as dimers in unstimulated cells that can exert biological functions independent of being activated. There are seven mammalian STAT family members which have been identified: STAT1, STAT2, STAT3, STAT4, STAT5 (STAT5A and STAT5B), and STAT6. There are 6 conserved domains in STAT: N-terminal domain (NTD), coiled-coil domain (CCD), DNA-binding domain (DBD), alpha-helical linker domain (LD), SH2 domain, and transactivation domain (TAD). NTD is involved in dimerization of unphosphorylated STATs monomers and for the tetramerization between STAT1, STAT3, STAT4 and STAT5 on promoters with two or more tandem STAT binding sites. It also plays a role in promoting interactions with transcriptional co-activators such as CREB binding protein (CBP)/p300, as well as being important for nuclear import and deactivation of STATs involving tyrosine de-phosphorylation. CCD interacts with other proteins, such as IFN regulatory protein 9 (IRF-9/p48) with STAT1 and c-JUN with STAT3 and is also thought to participate in the negative regulation of these proteins. Distinct genes are bound to STATs via their DBD domain. This domain is also involved in nuclear translocation of activated STAT1 and STAT3 phosphorylated dimers upon cytokine stimulation. LD links the DNA-binding and SH2 domains and is important for the transcriptional activation of STAT1 in response to IFN-gamma. It also plays a role in protein-protein interactions and has also been implicated in the constitutive nucleocytoplasmic shuttling of unphosphorylated STATs in resting cells. The SH2 domain is necessary for receptor association and tyrosine phosphodimer formation. Residues within this domain may be particularly important for some cellular functions mediated by the STATs as well as residues adjacent to this domain. The TAD interacts with several proteins, namely minichromosome maintenance complex component 5 (MCM5), breast cancer 1 (BRCA1) and CBP/p300. TAD also contains a modulatory phosphorylation site that regulates STAT activity and is necessary for maximal transcription of a number of target genes. The conserved tyrosine residue present in the C-terminus is crucial for dimerization via interaction with the SH2 domain upon the interaction of the ligand with the receptor. STAT activation by tyrosine phosphorylation also determines nuclear import and retention, DNA binding to specific DNA elements in the promoters of responsive genes, and transcriptional activation of STAT dimers. In addition to the SH2 domain there is a coiled-coil domain, a DNA binding domain, and a transactivation domain in the STAT proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198236  Cd Length: 151  Bit Score: 165.45  E-value: 1.36e-47
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482 557 WIDTILELIKKHLLCLWNDGCIMGFISKERERALLKDQQPGTFLLRFSESSrEGAITFTWVERsQNGGEPDFHAVEPYTK 636
Cdd:cd10373    1 WLDKILELVHDHLKDLWKDGRIMGFVSRNQERRLLKKTISGTFLLRFSETS-EGGITCSWVEH-QDDDKVLIYSVQPYTK 78
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 114326482 637 KELSAVTFPDIIRNYKVMAAENIPENPLKYLYPNIDKDHAFGKYYsrpKEAPEPMElddpkRTGYIKTELISVS 710
Cdd:cd10373   79 EVLQSLPLTEIIRHYQLLTEENIPENPLRFLYPRIPRDEAFGCYY---QEKVNLEE-----REKYLKHKLIVVS 144
SH2_STAT_family cd09919
Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) ...
557-682 2.51e-47

Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) family; STAT proteins mediate the signaling of cytokines and a number of growth factors from the receptors of these extracellular signaling molecules to the cell nucleus. STATs are specifically phosphorylated by receptor-associated Janus kinases, receptor tyrosine kinases, or cytoplasmic tyrosine kinases. The phosphorylated STAT molecules dimerize by reciprocal binding of their SH2 domains to the phosphotyrosine residues. These dimeric STATs translocate into the nucleus, bind to specific DNA sequences, and regulate the transcription of their target genes. However there are a number of unphosphorylated STATs that travel between the cytoplasm and nucleus and some STATs that exist as dimers in unstimulated cells that can exert biological functions independent of being activated by a receptor. There are seven mammalian STAT family members which have been identified: STAT1, STAT2, STAT3, STAT4, STAT5 (STAT5A and STAT5B), and STAT6. There are 6 conserved domains in STAT: N-terminal domain (NTD), coiled-coil domain (CCD), DNA-binding domain (DBD), alpha-helical linker domain (LD), SH2 domain, and transactivation domain (TAD). NTD is involved in dimerization of unphosphorylated STATs monomers and for the tetramerization between STAT1, STAT3, STAT4 and STAT5 on promoters with two or more tandem STAT binding sites. It also plays a role in promoting interactions with transcriptional co-activators such as CREB binding protein (CBP)/p300, as well as being important for nuclear import and deactivation of STATs involving tyrosine de-phosphorylation. The CCD interacts with other proteins, such as IFN regulatory protein 9 (IRF-9/p48) with STAT1 and c-JUN with STAT3 and is also thought to participate in the negative regulation of these proteins. Distinct genes are bound to STATs via their DBD domain. This domain is also involved in nuclear translocation of activated STAT1 and STAT3 phosphorylated dimers upon cytokine stimulation. LD links the DNA-binding and SH2 domains and is important for the transcriptional activation of STAT1 in response to IFN-gamma. It also plays a role in protein-protein interactions and has also been implicated in the constitutive nucleocytoplasmic shuttling of unphosphorylated STATs in resting cells. The SH2 domain is necessary for receptor association and tyrosine phosphodimer formation. Residues within this domain may be particularly important for some cellular functions mediated by the STATs as well as residues adjacent to this domain. The TAD interacts with several proteins, namely minichromosome maintenance complex component 5 (MCM5), breast cancer 1 (BRCA1) and CBP/p300. TAD also contains a modulatory phosphorylation site that regulates STAT activity and is necessary for maximal transcription of a number of target genes. The conserved tyrosine residue present in the C-terminus is crucial for dimerization via interaction with the SH2 domain upon the interaction of the ligand with the receptor. STAT activation by tyrosine phosphorylation also determines nuclear import and retention, DNA binding to specific DNA elements in the promoters of responsive genes, and transcriptional activation of STAT dimers. In addition to the SH2 domain there is a coiled-coil domain, a DNA binding domain, and a transactivation domain in the STAT proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198175  Cd Length: 115  Bit Score: 163.52  E-value: 2.51e-47
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482 557 WIDTILELIKKHLLCLWNDGCIMGFISKERERALLKDQQPGTFLLRFSESSrEGAITFTWVERSQNgGEPDFHAVEPYTK 636
Cdd:cd09919    1 WFFAIMLLTKRHLLKLWQDGLIMGFISKEEAEDLLKKKPPGTFLLRFSDSE-LGGITIAWVNEDPD-GQSQVIHLQPYTK 78
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 114326482 637 KELSAVTFPDIIRNYKvmaaenipenPLKYLYPNIDKDHAFGKYYS 682
Cdd:cd09919   79 KDLDIRSLADRIRDLP----------QLVYLYPDIPKDEAFGKYYS 114
SH2_STAT6 cd10377
Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) 6 ...
557-706 2.99e-29

Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) 6 proteins; STAT6 mediate signals from the IL-4 receptor. Unlike the other STAT proteins which bind an IFNgamma Activating Sequence (GAS), STAT6 stands out as having a unique binding site preference. This site consists of a palindromic sequence separated by a 3 bp spacer (TTCNNNG-AA)(N3 site). STAT6 is able to bind the GAS site but only at a low affinity. STAT6 may be an important regulator of mitogenesis when cells respond normally to IL-4. There is speculation that the inappropriate activation of STAT6 is involved in uncontrolled cell growth in an oncogenic state. IFNgamma is a negative regulator of STAT6 dependent transcription of target genes. Bcl-6 is another negative regulator of STAT6 activity. Bcl-6 is a transcriptional repressor normally expressed in germinal center B cells and some T cells. IL-4 signaling via STAT6 initially occurs unopposed, but is then dampened by a negative feedback mechanism through the IL-4/Stat6 dependent induction of SOCS1 expression. The IL-4 dependent aspect of Th2 differentiation requires the activation of STAT6. IL-4 signaling and STAT6 appear to play an important role in the immune response. Recently, it was shown that large scale chromatin remodeling of the IL-4 gene occurs as cells differentiate into Th2 effectors is STAT6 dependent. STAT proteins mediate the signaling of cytokines and a number of growth factors from the receptors of these extracellular signaling molecules to the cell nucleus. STATs are specifically phosphorylated by receptor-associated Janus kinases, receptor tyrosine kinases, or cytoplasmic tyrosine kinases. The phosphorylated STAT molecules dimerize by reciprocal binding of their SH2 domains to the phosphotyrosine residues. These dimeric STATs translocate into the nucleus, bind to specific DNA sequences, and regulate the transcription of their target genes. However there are a number of unphosphorylated STATs that travel between the cytoplasm and nucleus and some STATs that exist as dimers in unstimulated cells that can exert biological functions independent of being activated. There are seven mammalian STAT family members which have been identified: STAT1, STAT2, STAT3, STAT4, STAT5 (STAT5A and STAT5B), and STAT6. There are 6 conserved domains in STAT: N-terminal domain (NTD), coiled-coil domain (CCD), DNA-binding domain (DBD), alpha-helical linker domain (LD), SH2 domain, and transactivation domain (TAD). NTD is involved in dimerization of unphosphorylated STATs monomers and for the tetramerization between STAT1, STAT3, STAT4 and STAT5 on promoters with two or more tandem STAT binding sites. It also plays a role in promoting interactions with transcriptional co-activators such as CREB binding protein (CBP)/p300, as well as being important for nuclear import and deactivation of STATs involving tyrosine de-phosphorylation. CCD interacts with other proteins, such as IFN regulatory protein 9 (IRF-9/p48) with STAT1 and c-JUN with STAT3 and is also thought to participate in the negative regulation of these proteins. Distinct genes are bound to STATs via their DBD domain. This domain is also involved in nuclear translocation of activated STAT1 and STAT3 phosphorylated dimers upon cytokine stimulation. LD links the DNA-binding and SH2 domains and is important for the transcriptional activation of STAT1 in response to IFN-gamma. It also plays a role in protein-protein interactions and has also been implicated in the constitutive nucleocytoplasmic shuttling of unphosphorylated STATs in resting cells. The SH2 domain is necessary for receptor association and tyrosine phosphodimer formation. Residues within this domain may be particularly important for some cellular functions mediated by the STATs as well as residues adjacent to this domain. The TAD interacts with several proteins, namely minichromosome maintenance complex component 5 (MCM5), breast cancer 1 (BRCA1) and CBP/p300. TAD also contains a modulatory phosphorylation site that regulates STAT activity and is necessary for maximal transcription of a number of target genes. The conserved tyrosine residue present in the C-terminus is crucial for dimerization via interaction with the SH2 domain upon the interaction of the ligand with the receptor. STAT activation by tyrosine phosphorylation also determines nuclear import and retention, DNA binding to specific DNA elements in the promoters of responsive genes, and transcriptional activation of STAT dimers. In addition to the SH2 domain there is a coiled-coil domain, a DNA binding domain, and a transactivation domain in the STAT proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198240  Cd Length: 129  Bit Score: 113.73  E-value: 2.99e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482 557 WIDTILELIKKHLLCLWNDGCIMGFISKERERALLKDQQPGTFLLRFSESSReGAITFTWVERSQNGGEpDFHAVEPYTK 636
Cdd:cd10377    1 WFDGVLDLTKRCLRSYWSDRLIIGFISKQYVTSLLLNEPDGTFLLRFSDSEI-GGITIAHVIRGQDGSP-QIENIQPFSA 78
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482 637 KELSAVTFPDIIRNYKvmaaenipenPLKYLYPNIDKDHAFGKYYSrPKEAPEPmelddpkrTGYIKTEL 706
Cdd:cd10377   79 KDLSIRSLGDRIRDLA----------QLKNLYPKKPKDEAFRSHYK-PEQMKDG--------RGYVPATI 129
SH2_STAT5 cd10376
Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) 5 ...
557-709 6.04e-20

Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) 5 proteins; STAT5 is a member of the STAT family of transcription factors. Two highly related proteins, STAT5a and STAT5b are encoded by separate genes, but are 90% identical at the amino acid level. Both STAT5a and STAT5b are ubiquitously expressed and functionally interchangeable. Mice lacking either STAT5a or STAT5b have mild defects in prolactin dependent mammary differentiation or sexually dimorphic growth hormone-dependent effects, respectively. Mice lacking both STAT5a and STAT5b exhibit a perinatal lethal phenotype and have multiple defects, including anemia and a virtual absence of B and T lymphocytes. STAT proteins mediate the signaling of cytokines and a number of growth factors from the receptors of these extracellular signaling molecules to the cell nucleus. STATs are specifically phosphorylated by receptor-associated Janus kinases, receptor tyrosine kinases, or cytoplasmic tyrosine kinases. The phosphorylated STAT molecules dimerize by reciprocal binding of their SH2 domains to the phosphotyrosine residues. These dimeric STATs translocate into the nucleus, bind to specific DNA sequences, and regulate the transcription of their target genes. However there are a number of unphosphorylated STATs that travel between the cytoplasm and nucleus and some STATs that exist as dimers in unstimulated cells that can exert biological functions independent of being activated. There are seven mammalian STAT family members which have been identified: STAT1, STAT2, STAT3, STAT4, STAT5 (STAT5A and STAT5B), and STAT6. There are 6 conserved domains in STAT: N-terminal domain (NTD), coiled-coil domain (CCD), DNA-binding domain (DBD), alpha-helical linker domain (LD), SH2 domain, and transactivation domain (TAD). NTD is involved in dimerization of unphosphorylated STATs monomers and for the tetramerization between STAT1, STAT3, STAT4 and STAT5 on promoters with two or more tandem STAT binding sites. It also plays a role in promoting interactions with transcriptional co-activators such as CREB binding protein (CBP)/p300, as well as being important for nuclear import and deactivation of STATs involving tyrosine de-phosphorylation. CCD interacts with other proteins, such as IFN regulatory protein 9 (IRF-9/p48) with STAT1 and c-JUN with STAT3 and is also thought to participate in the negative regulation of these proteins. Distinct genes are bound to STATs via their DBD domain. This domain is also involved in nuclear translocation of activated STAT1 and STAT3 phosphorylated dimers upon cytokine stimulation. LD links the DNA-binding and SH2 domains and is important for the transcriptional activation of STAT1 in response to IFN-gamma. It also plays a role in protein-protein interactions and has also been implicated in the constitutive nucleocytoplasmic shuttling of unphosphorylated STATs in resting cells. The SH2 domain is necessary for receptor association and tyrosine phosphodimer formation. Residues within this domain may be particularly important for some cellular functions mediated by the STATs as well as residues adjacent to this domain. The TAD interacts with several proteins, namely minichromosome maintenance complex component 5 (MCM5), breast cancer 1 (BRCA1) and CBP/p300. TAD also contains a modulatory phosphorylation site that regulates STAT activity and is necessary for maximal transcription of a number of target genes. The conserved tyrosine residue present in the C-terminus is crucial for dimerization via interaction with the SH2 domain upon the interaction of the ligand with the receptor. STAT activation by tyrosine phosphorylation also determines nuclear import and retention, DNA binding to specific DNA elements in the promoters of responsive genes, and transcriptional activation of STAT dimers. In addition to the SH2 domain there is a coiled-coil domain, a DNA binding domain, and a transactivation domain in the STAT proteins.


Pssm-ID: 198239  Cd Length: 137  Bit Score: 87.34  E-value: 6.04e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482 557 WIDTILELIKKHLLCLWNDGCIMGFISKERERALLKDQQPGTFLLRFSESSReGAITFTWVERSQnggEPDFHAVEPYTK 636
Cdd:cd10376    1 WFDGVMEVLKKHLKPHWNDGAILGFVNKQQAHDLLINKPDGTFLLRFSDSEI-GGITIAWKFDSP---DRALWNLMPFTT 76
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 114326482 637 KELSAVTFPDIIRNYkvmaaenipeNPLKYLYPNIDKDHAFGKYYSrpkeapePMELDDPKRTGYIKTELISV 709
Cdd:cd10376   77 RDFSIRSLADRLGDL----------NYLIYVFPDRPKDEVFSKYYT-------PVLCNPSAVDGYVKPQIKQV 132
SH2_STAT5b cd10420
Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) ...
557-709 1.99e-19

Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) 5b proteins; STAT5 is a member of the STAT family of transcription factors. Two highly related proteins, STAT5a and STAT5b are encoded by separate genes, but are 90% identical at the amino acid level. Both STAT5a and STAT5b are ubiquitously expressed and functionally interchangeable. Mice lacking either STAT5a or STAT5b have mild defects in prolactin dependent mammary differentiation or sexually dimorphic growth hormone-dependent effects, respectively. Mice lacking both STAT5a and STAT5b exhibit a perinatal lethal phenotype and have multiple defects, including anemia and a virtual absence of B and T lymphocytes. STAT proteins mediate the signaling of cytokines and a number of growth factors from the receptors of these extracellular signaling molecules to the cell nucleus. STATs are specifically phosphorylated by receptor-associated Janus kinases, receptor tyrosine kinases, or cytoplasmic tyrosine kinases. The phosphorylated STAT molecules dimerize by reciprocal binding of their SH2 domains to the phosphotyrosine residues. These dimeric STATs translocate into the nucleus, bind to specific DNA sequences, and regulate the transcription of their target genes. However there are a number of unphosphorylated STATs that travel between the cytoplasm and nucleus and some STATs that exist as dimers in unstimulated cells that can exert biological functions independent of being activated. There are seven mammalian STAT family members which have been identified: STAT1, STAT2, STAT3, STAT4, STAT5 (STAT5A and STAT5B), and STAT6. There are 6 conserved domains in STAT: N-terminal domain (NTD), coiled-coil domain (CCD), DNA-binding domain (DBD), alpha-helical linker domain (LD), SH2 domain, and transactivation domain (TAD). NTD is involved in dimerization of unphosphorylated STATs monomers and for the tetramerization between STAT1, STAT3, STAT4 and STAT5 on promoters with two or more tandem STAT binding sites. It also plays a role in promoting interactions with transcriptional co-activators such as CREB binding protein (CBP)/p300, as well as being important for nuclear import and deactivation of STATs involving tyrosine de-phosphorylation. CCD interacts with other proteins, such as IFN regulatory protein 9 (IRF-9/p48) with STAT1 and c-JUN with STAT3 and is also thought to participate in the negative regulation of these proteins. Distinct genes are bound to STATs via their DBD domain. This domain is also involved in nuclear translocation of activated STAT1 and STAT3 phosphorylated dimers upon cytokine stimulation. LD links the DNA-binding and SH2 domains and is important for the transcriptional activation of STAT1 in response to IFN-gamma. It also plays a role in protein-protein interactions and has also been implicated in the constitutive nucleocytoplasmic shuttling of unphosphorylated STATs in resting cells. The SH2 domain is necessary for receptor association and tyrosine phosphodimer formation. Residues within this domain may be particularly important for some cellular functions mediated by the STATs as well as residues adjacent to this domain. The TAD interacts with several proteins, namely minichromosome maintenance complex component 5 (MCM5), breast cancer 1 (BRCA1) and CBP/p300. TAD also contains a modulatory phosphorylation site that regulates STAT activity and is necessary for maximal transcription of a number of target genes. The conserved tyrosine residue present in the C-terminus is crucial for dimerization via interaction with the SH2 domain upon the interaction of the ligand with the receptor. STAT activation by tyrosine phosphorylation also determines nuclear import and retention, DNA binding to specific DNA elements in the promoters of responsive genes, and transcriptional activation of STAT dimers. In addition to the SH2 domain there is a coiled-coil domain, a DNA binding domain, and a transactivation domain in the STAT proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198283  Cd Length: 145  Bit Score: 86.28  E-value: 1.99e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482 557 WIDTILELIKKHLLCLWNDGCIMGFISKERERALLKDQQPGTFLLRFSESSReGAITFTWVERSQnggEPDFHAVEPYTK 636
Cdd:cd10420    1 WFDGVMEVLKKHLKPHWNDGAILGFVNKQQAHDLLINKPDGTFLLRFSDSEI-GGITIAWKFDSQ---ERMFWNLMPFTT 76
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 114326482 637 KELSAVTFPDIIRNYKVmaaenipenpLKYLYPNIDKDHAFGKYYSrpkeaPEPMELDDPKRT-GYIKTELISV 709
Cdd:cd10420   77 RDFSIRSLADRLGDLNY----------LIYVFPDRPKDEVYSKYYT-----PVPCEPATAKAVdGYVKPQIKQV 135
SH2_STAT5a cd10421
Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) ...
557-682 6.53e-17

Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) 5a proteins; STAT5 is a member of the STAT family of transcription factors. Two highly related proteins, STAT5a and STAT5b are encoded by separate genes, but are 90% identical at the amino acid level. Both STAT5a and STAT5b are ubiquitously expressed and functionally interchangeable. Mice lacking either STAT5a or STAT5b have mild defects in prolactin dependent mammary differentiation or sexually dimorphic growth hormone-dependent effects, respectively. Mice lacking both STAT5a and STAT5b exhibit a perinatal lethal phenotype and have multiple defects, including anemia and a virtual absence of B and T lymphocytes. STAT proteins mediate the signaling of cytokines and a number of growth factors from the receptors of these extracellular signaling molecules to the cell nucleus. STATs are specifically phosphorylated by receptor-associated Janus kinases, receptor tyrosine kinases, or cytoplasmic tyrosine kinases. The phosphorylated STAT molecules dimerize by reciprocal binding of their SH2 domains to the phosphotyrosine residues. These dimeric STATs translocate into the nucleus, bind to specific DNA sequences, and regulate the transcription of their target genes. However there are a number of unphosphorylated STATs that travel between the cytoplasm and nucleus and some STATs that exist as dimers in unstimulated cells that can exert biological functions independent of being activated. There are seven mammalian STAT family members which have been identified: STAT1, STAT2, STAT3, STAT4, STAT5 (STAT5A and STAT5B), and STAT6. There are 6 conserved domains in STAT: N-terminal domain (NTD), coiled-coil domain (CCD), DNA-binding domain (DBD), alpha-helical linker domain (LD), SH2 domain, and transactivation domain (TAD). NTD is involved in dimerization of unphosphorylated STATs monomers and for the tetramerization between STAT1, STAT3, STAT4 and STAT5 on promoters with two or more tandem STAT binding sites. It also plays a role in promoting interactions with transcriptional co-activators such as CREB binding protein (CBP)/p300, as well as being important for nuclear import and deactivation of STATs involving tyrosine de-phosphorylation. CCD interacts with other proteins, such as IFN regulatory protein 9 (IRF-9/p48) with STAT1 and c-JUN with STAT3 and is also thought to participate in the negative regulation of these proteins. Distinct genes are bound to STATs via their DBD domain. This domain is also involved in nuclear translocation of activated STAT1 and STAT3 phosphorylated dimers upon cytokine stimulation. LD links the DNA-binding and SH2 domains and is important for the transcriptional activation of STAT1 in response to IFN-gamma. It also plays a role in protein-protein interactions and has also been implicated in the constitutive nucleocytoplasmic shuttling of unphosphorylated STATs in resting cells. The SH2 domain is necessary for receptor association and tyrosine phosphodimer formation. Residues within this domain may be particularly important for some cellular functions mediated by the STATs as well as residues adjacent to this domain. The TAD interacts with several proteins, namely minichromosome maintenance complex component 5 (MCM5), breast cancer 1 (BRCA1) and CBP/p300. TAD also contains a modulatory phosphorylation site that regulates STAT activity and is necessary for maximal transcription of a number of target genes. The conserved tyrosine residue present in the C-terminus is crucial for dimerization via interaction with the SH2 domain upon the interaction of the ligand with the receptor. STAT activation by tyrosine phosphorylation also determines nuclear import and retention, DNA binding to specific DNA elements in the promoters of responsive genes, and transcriptional activation of STAT dimers. In addition to the SH2 domain there is a coiled-coil domain, a DNA binding domain, and a transactivation domain in the STAT proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198284  Cd Length: 140  Bit Score: 78.55  E-value: 6.53e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482 557 WIDTILELIKKHLLCLWNDGCIMGFISKERERALLKDQQPGTFLLRFSESSReGAITFTWVERSqnggePD--FHAVEPY 634
Cdd:cd10421    1 WFDGVMEVLKKHHKPHWNDGAILGFVNKQQAHDLLINKPDGTFLLRFSDSEI-GGITIAWKFDS-----PDrnLWNLKPF 74
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 114326482 635 TKKELSAVTFPDIIRNYkvmaaenipeNPLKYLYPNIDKDHAFGKYYS 682
Cdd:cd10421   75 TTRDFSIRSLADRLGDL----------NYLIYVFPDRPKDEVFSKYYT 112
SH2 pfam00017
SH2 domain;
578-622 3.54e-08

SH2 domain;


Pssm-ID: 249511  Cd Length: 77  Bit Score: 51.42  E-value: 3.54e-08
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 114326482  578 IMGFISK-ERERALLKDQQPGTFLLRFSESSrEGAITFTWVERSQN 622
Cdd:pfam00017   2 YHGKISReEAERLLLNGKPDGTFLVRESESK-PGDYTLSVRDDGRV 46
STAT1_TAZ2bind pfam12162
STAT1 TAZ2 binding domain; This domain family is found in eukaryotes, and is approximately 20 ...
715-739 5.43e-05

STAT1 TAZ2 binding domain; This domain family is found in eukaryotes, and is approximately 20 amino acids in length, and the family is found in association with pfam02865, pfam00017, pfam01017, pfam02864. This domain is the C terminal domain of STAT1. This domain binds selectively to the TAZ2 domain of CRB (CREB-binding protein). In this process it becomes a transcriptional activator and can initiate transcription of certain genes.


Pssm-ID: 152597  Cd Length: 23  Bit Score: 41.61  E-value: 5.43e-05
                          10        20
                  ....*....|....*....|....*
gi 114326482  715 SRLQttDNLLPMSPEEFDEMSRIVG 739
Cdd:pfam12162   1 SRLQ--DNMLPMSPDDFDELHRMVG 23
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
580-608 1.59e-04

Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they bind pTyr-containing polypeptide ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. They are present in a wide array of proteins including: adaptor proteins (Nck1, Crk, Grb2), scaffolds (Slp76, Shc, Dapp1), kinases (Src, Syk, Fps, Tec), phosphatases (Shp-1, Shp-2), transcription factors (STAT1), Ras signaling molecules (Ras-Gap), ubiquitination factors (c-Cbl), cytoskeleton regulators (Tensin), signal regulators (SAP), and phospholipid second messengers (PLCgamma), amongst others.


Pssm-ID: 198173  Cd Length: 79  Bit Score: 40.52  E-value: 1.59e-04
                         10        20
                 ....*....|....*....|....*....
gi 114326482 580 GFISKERERALLKDQQPGTFLLRFSESSR 608
Cdd:cd00173    5 GSISREEAERLLRGKPDGTFLVRESSSEP 33
SH2_SH2D2A_SH2D7 cd10349
Src homology 2 domain found in the SH2 domain containing protein 2A and 7 (SH2D2A and SH2D7); ...
580-622 2.35e-04

Src homology 2 domain found in the SH2 domain containing protein 2A and 7 (SH2D2A and SH2D7); SH2D2A and SH7 both contain a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199830  Cd Length: 77  Bit Score: 40.20  E-value: 2.35e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 114326482 580 GFISKERERALLKDQQPGTFLLRFSESsregAITFTWVERSQN 622
Cdd:cd10349    5 GFITRREAERLLEPKPQGCYLVRFSES----AVTFVLSYRSRT 43
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
579-622 2.52e-04

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.


Pssm-ID: 214585  Cd Length: 84  Bit Score: 39.90  E-value: 2.52e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 114326482   579 MGFISKERERALLKDQQPGTFLLRFSESSREG-AITFTWVERSQN 622
Cdd:smart00252   5 HGFISREEAEKLLKNEGDGDFLVRDSESSPGDyVLSVRVKGKVKH 49
SH2_SHA cd10338
Src homology 2 (SH2) domain found in SH2 adaptor proteins A (SHA) Signal transducers; Signal ...
578-606 2.54e-03

Src homology 2 (SH2) domain found in SH2 adaptor proteins A (SHA) Signal transducers; Signal transducing adaptor proteins are accessory to main proteins in a signal transduction pathway. These proteins lack intrinsic enzymatic activity, but mediate specific protein-protein interactions that drive the formation of protein complexes. Adaptor proteins usually contain several domains within their structure (e.g. SH2 and SH3 domains) which allow specific interactions with several other specific proteins. Not much is known about the SHA protein except that it is predicted to act as a transcription factor. Arabidopsis SHA pulled down a 120-kD tyrosine-phosphorylated protein in vitro. In addition to the SH2 domain there is a coiled-coil domain, a DNA binding domain, and a transactivation domain in the STAT proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198201  Cd Length: 106  Bit Score: 37.20  E-value: 2.54e-03
                         10        20
                 ....*....|....*....|....*....
gi 114326482 578 IMGFISKERERALLKDQQPGTFLLRFSES 606
Cdd:cd10338   13 IEGFITKEEAERSLQGQVPGTFILRFPTS 41
SH2_SH2D2A cd10416
Src homology 2 domain found in the SH2 domain containing protein 2A (SH2D2A); SH2D2A contains ...
580-621 5.42e-03

Src homology 2 domain found in the SH2 domain containing protein 2A (SH2D2A); SH2D2A contains a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198279  Cd Length: 102  Bit Score: 36.17  E-value: 5.42e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 114326482 580 GFISKERERALLKDQQPGTFLLRFSESsregAITFTWVERSQ 621
Cdd:cd10416   12 GFITRREAERLLEPKPQGCYLVRFSES----AVTFVLTYRSR 49
SH2_SH2D7 cd10417
Src homology 2 domain found in the SH2 domain containing protein 7 (SH2D7); SH2D7 contains a ...
580-607 9.89e-03

Src homology 2 domain found in the SH2 domain containing protein 7 (SH2D7); SH2D7 contains a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199832  Cd Length: 102  Bit Score: 35.25  E-value: 9.89e-03
                         10        20
                 ....*....|....*....|....*...
gi 114326482 580 GFISKERERALLKDQQPGTFLLRFSESS 607
Cdd:cd10417   12 GFITRKQTEQLLRDKALGSFLIRLSDRA 39
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
6-290 3.42e-03

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins].


Pssm-ID: 233757 [Multi-domain]  Cd Length: 1179  Bit Score: 39.65  E-value: 3.42e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482     6 ELQQLDSKFLEQVHQLydDSFPMEIRQYLAQWLEKQDwEHAAYDVSFATI--RFHDLLSQLDDqysrfsLENNflLQHnI 83
Cdd:TIGR02168  240 ELEELQEELKEAEEEL--EELTAELQELEEKLEELRL-EVSELEEEIEELqkELYALANEISR------LEQQ--KQI-L 307
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482    84 RKSKRNLQDNFQEDPVQMsmiiyncLKEERKILENAQRFNQAQEgniqntvmldKQKELDSKVRNVKDQVMCIEQEIKTL 163
Cdd:TIGR02168  308 RERLANLERQLEELEAQL-------EELESKLDELAEELAELEE----------KLEELKEELESLEAELEELEAELEEL 370
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482   164 EELQDEYDfkcktsQNREGEANGVAKSDQKQEQLllhkmflmldnkRKEIIhKIRELLNSIELTQNTLI------NDELV 237
Cdd:TIGR02168  371 ESRLEELE------EQLETLRSKVAQLELQIASL------------NNEIE-RLEARLERLEDRRERLQqeieelLKKLE 431
                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|...
gi 114326482   238 EWKRRQQSACIGGPpNACLDQLQSWFTIVAETLQQIRQQLKKLEELEQKFTYE 290
Cdd:TIGR02168  432 EAELKELQAELEEL-EEELEELQEELERLEEALEELREELEEAEQALDAAERE 483
SbcC COG0419
ATPase involved in DNA repair [DNA replication, recombination, and repair]
82-287 8.49e-03

ATPase involved in DNA repair [DNA replication, recombination, and repair]


Pssm-ID: 223496 [Multi-domain]  Cd Length: 908  Bit Score: 38.20  E-value: 8.49e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482  82 NIRKSKRNLQDNFQEDPVQMsmiiyncLKEERKILE-NAQRFNQAQEGNIQNTVMLDKQKELDSKVRNVKDQVMCIEQEI 160
Cdd:COG0419  537 KLENLLEELEELKEKLQLQQ-------LKEELRQLEdRLQELKELLEELRLLRTRKEELEELRERLKELKKKLKELEERL 609
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114326482 161 KTLEELQDEYDFKCKTSQNREGEANGVAKSDQKQEQL----LLHKMFLMLDNKRKEIIHKIRELLNSIELTQNTLINDEL 236
Cdd:COG0419  610 SQLEELLQSLELSEAENELEEAEEELESELEKLNLQAeleeLLQAALEELEEKVEELEAEIRRELQRIENEEQLEEKLEE 689
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 114326482 237 VEWKRRQqsaciggppnacLDQLQSWFTIVAETLQQIRQQLKKLEELEQKF 287
Cdd:COG0419  690 LEQLEEE------------LEQLREELEELLKKLGEIEQLIEELESRKAEL 728
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.11
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Marchler-Bauer A et al. (2011), "CDD: a Conserved Domain Database for the functional annotation of proteins.", Nucleic Acids Res.39(D)225-9.
  • Marchler-Bauer A et al. (2009), "CDD: specific functional annotation with the Conserved Domain Database.", Nucleic Acids Res.37(D)205-10.
  • Marchler-Bauer A, Bryant SH (2004), "CD-Search: protein domain annotations on the fly.", Nucleic Acids Res.32(W)327-331.
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