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Conserved domains on  [gi|1992493415|ref|XP_039509204|]
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suppressor of cytokine signaling 5b [Pimephales promelas]

Protein Classification

SH2 domain-containing protein; tyrosine-protein kinase( domain architecture ID 10576468)

SH2 (Src homology 2) domain-containing protein may act as an intracellular signal-transducing protein| tyrosine-protein kinase catalyzes the autophosphorylation on a C-terminal tyrosine cluster and also phosphorylates endogenous protein substrates by using ATP as the phosphoryl donor

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
SH2 super family cl15255
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
396-496 1.56e-62

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.


The actual alignment was detected with superfamily member cd10385:

Pssm-ID: 472789  Cd Length: 101  Bit Score: 200.69  E-value: 1.56e-62
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992493415 396 VPDLQAITALPCYWGVMDRYQAEALLDGRPEGTFLLRDSAQEDYLFSVSFRRYNRSLHARIEQWNHNFSFDAHDPCVFHS 475
Cdd:cd10385     1 VPDLLQINNNPCYWGVMDKYAAEALLEGKPEGTFLLRDSAQEDYLFSVSFRRYSRSLHARIEQWNHNFSFDAHDPCVFHS 80
                          90       100
                  ....*....|....*....|.
gi 1992493415 476 STVTGLLEHYKDPSACMFFEP 496
Cdd:cd10385    81 PDITGLLEHYKDPSACMFFEP 101
SOCS_SOCS5 cd03739
SOCS (suppressors of cytokine signaling) box of SOCS5-like proteins. Together with CIS1, the ...
505-561 5.79e-37

SOCS (suppressors of cytokine signaling) box of SOCS5-like proteins. Together with CIS1, the CIS/SOCS family of proteins is characterized by the presence of a C-terminal SOCS box and a central SH2 domain. SOCS5 inhibits Th2 differentiation by inhibiting IL-4 signaling. The general function of the SOCS box is the recruitment of the ubiquitin-transferase system. The SOCS box interacts with Elongins B and C, Cullin-5 or Cullin-2, Rbx-1, and E2. Therefore, SOCS-box-containing proteins probably function as E3 ubiquitin ligases and mediate the degradation of proteins associated through their N-terminal regions.


:

Pssm-ID: 239708  Cd Length: 57  Bit Score: 130.88  E-value: 5.79e-37
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1992493415 505 TFPFSLQHLARAAICRCTTYDGIGALPLPPTMQDFLKEYHYKQKVRVRWLEREPPFK 561
Cdd:cd03739     1 TFPFSLQYICRAVICRCTTYDGIDALPLPSMLQDFLKEYHYKQKVRVRWLEREPIKK 57
SOCS pfam12610
Suppressor of cytokine signalling; This domain family is found in bacteria and eukaryotes, and ...
138-195 9.37e-19

Suppressor of cytokine signalling; This domain family is found in bacteria and eukaryotes, and is approximately 60 amino acids in length. The family is found in association with pfam07525, pfam00017. The suppressors of cytokine signaling (SOCS) family play important roles in regulating a variety of signal transduction pathways that are involved in immunity, growth and development of organizms.


:

Pssm-ID: 432667  Cd Length: 57  Bit Score: 80.21  E-value: 9.37e-19
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1992493415 138 SRGSTARRERRYGVSSIQEINDSVGaGSSGRSLSNRSLRQRLRDTVGLCLPLTTHSRS 195
Cdd:pfam12610   1 TRGPRRRRERRCSCSSIQEMSDSVD-DVSGRALSRRSLRQKLQDTVGLCLPLRSHRRS 57
 
Name Accession Description Interval E-value
SH2_SOCS4 cd10385
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
396-496 1.56e-62

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. 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: 198248  Cd Length: 101  Bit Score: 200.69  E-value: 1.56e-62
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992493415 396 VPDLQAITALPCYWGVMDRYQAEALLDGRPEGTFLLRDSAQEDYLFSVSFRRYNRSLHARIEQWNHNFSFDAHDPCVFHS 475
Cdd:cd10385     1 VPDLLQINNNPCYWGVMDKYAAEALLEGKPEGTFLLRDSAQEDYLFSVSFRRYSRSLHARIEQWNHNFSFDAHDPCVFHS 80
                          90       100
                  ....*....|....*....|.
gi 1992493415 476 STVTGLLEHYKDPSACMFFEP 496
Cdd:cd10385    81 PDITGLLEHYKDPSACMFFEP 101
SOCS_SOCS5 cd03739
SOCS (suppressors of cytokine signaling) box of SOCS5-like proteins. Together with CIS1, the ...
505-561 5.79e-37

SOCS (suppressors of cytokine signaling) box of SOCS5-like proteins. Together with CIS1, the CIS/SOCS family of proteins is characterized by the presence of a C-terminal SOCS box and a central SH2 domain. SOCS5 inhibits Th2 differentiation by inhibiting IL-4 signaling. The general function of the SOCS box is the recruitment of the ubiquitin-transferase system. The SOCS box interacts with Elongins B and C, Cullin-5 or Cullin-2, Rbx-1, and E2. Therefore, SOCS-box-containing proteins probably function as E3 ubiquitin ligases and mediate the degradation of proteins associated through their N-terminal regions.


Pssm-ID: 239708  Cd Length: 57  Bit Score: 130.88  E-value: 5.79e-37
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1992493415 505 TFPFSLQHLARAAICRCTTYDGIGALPLPPTMQDFLKEYHYKQKVRVRWLEREPPFK 561
Cdd:cd03739     1 TFPFSLQYICRAVICRCTTYDGIDALPLPSMLQDFLKEYHYKQKVRVRWLEREPIKK 57
SOCS pfam12610
Suppressor of cytokine signalling; This domain family is found in bacteria and eukaryotes, and ...
138-195 9.37e-19

Suppressor of cytokine signalling; This domain family is found in bacteria and eukaryotes, and is approximately 60 amino acids in length. The family is found in association with pfam07525, pfam00017. The suppressors of cytokine signaling (SOCS) family play important roles in regulating a variety of signal transduction pathways that are involved in immunity, growth and development of organizms.


Pssm-ID: 432667  Cd Length: 57  Bit Score: 80.21  E-value: 9.37e-19
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1992493415 138 SRGSTARRERRYGVSSIQEINDSVGaGSSGRSLSNRSLRQRLRDTVGLCLPLTTHSRS 195
Cdd:pfam12610   1 TRGPRRRRERRCSCSSIQEMSDSVD-DVSGRALSRRSLRQKLQDTVGLCLPLRSHRRS 57
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
406-490 5.23e-17

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 [Multi-domain]  Cd Length: 84  Bit Score: 76.11  E-value: 5.23e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992493415  406 PCYWGVMDRYQAEALLDGRPEGTFLLRDSAQEDYLFSVSFRRYNRSLHARIEQWNHN-FSFDahDPCVFHSstVTGLLEH 484
Cdd:smart00252   2 PWYHGFISREEAEKLLKNEGDGDFLVRDSESSPGDYVLSVRVKGKVKHYRIRRNEDGkFYLE--GGRKFPS--LVELVEH 77

                   ....*.
gi 1992493415  485 YKDPSA 490
Cdd:smart00252  78 YQKNSL 83
SOCS smart00253
suppressors of cytokine signalling; suppressors of cytokine signalling
501-543 4.25e-11

suppressors of cytokine signalling; suppressors of cytokine signalling


Pssm-ID: 128549  Cd Length: 43  Bit Score: 57.69  E-value: 4.25e-11
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1992493415  501 PLHRTFPFSLQHLARAAICRCTTYDGIGALPLPPTMQDFLKEY 543
Cdd:smart00253   1 LPRPSNVPSLQHLCRFTIRRCTRTDQIKTLPLPPKLKDYLSYY 43
SH2 pfam00017
SH2 domain;
408-485 5.77e-08

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 49.91  E-value: 5.77e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992493415 408 YWGVMDRYQAEALL-DGRPEGTFLLRDSAQEDYLFSVSFRRYNRSLHARIEQ---------WNHNFsfdahdpcvfhsST 477
Cdd:pfam00017   2 YHGKISRQEAERLLlNGKPDGTFLVRESESTPGGYTLSVRDDGKVKHYKIQStdnggyyisGGVKF------------SS 69

                  ....*...
gi 1992493415 478 VTGLLEHY 485
Cdd:pfam00017  70 LAELVEHY 77
SOCS_box pfam07525
SOCS box; The SOCS box acts as a bridge between specific substrate- binding domains and more ...
506-541 1.50e-07

SOCS box; The SOCS box acts as a bridge between specific substrate- binding domains and more generic proteins that comprise a large family of E3 ubiquitin protein ligases.


Pssm-ID: 462192  Cd Length: 39  Bit Score: 47.55  E-value: 1.50e-07
                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1992493415 506 FPFSLQHLARAAICRCTTY---DGIGALPLPPTMQDFLK 541
Cdd:pfam07525   1 TPRSLQHLCRLAIRRALGKrrlGAIDKLPLPPLLKDYLL 39
 
Name Accession Description Interval E-value
SH2_SOCS4 cd10385
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
396-496 1.56e-62

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. 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: 198248  Cd Length: 101  Bit Score: 200.69  E-value: 1.56e-62
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992493415 396 VPDLQAITALPCYWGVMDRYQAEALLDGRPEGTFLLRDSAQEDYLFSVSFRRYNRSLHARIEQWNHNFSFDAHDPCVFHS 475
Cdd:cd10385     1 VPDLLQINNNPCYWGVMDKYAAEALLEGKPEGTFLLRDSAQEDYLFSVSFRRYSRSLHARIEQWNHNFSFDAHDPCVFHS 80
                          90       100
                  ....*....|....*....|.
gi 1992493415 476 STVTGLLEHYKDPSACMFFEP 496
Cdd:cd10385    81 PDITGLLEHYKDPSACMFFEP 101
SH2_SOCS5 cd10386
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) family; SH2 ...
406-486 9.15e-55

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) family; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. 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: 198249  Cd Length: 81  Bit Score: 179.50  E-value: 9.15e-55
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992493415 406 PCYWGVMDRYQAEALLDGRPEGTFLLRDSAQEDYLFSVSFRRYNRSLHARIEQWNHNFSFDAHDPCVFHSSTVTGLLEHY 485
Cdd:cd10386     1 PCYWGVMDRYEAEALLEGKPEGTFLLRDSAQEDYLFSVSFRRYNRSLHARIEQWNHNFSFDAHDPCVFHSSTVTGLLEHY 80

                  .
gi 1992493415 486 K 486
Cdd:cd10386    81 K 81
SH2_SOCS_family cd09923
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) family; SH2 ...
406-486 6.95e-44

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) family; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. 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: 198178  Cd Length: 81  Bit Score: 150.43  E-value: 6.95e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992493415 406 PCYWGVMDRYQAEALLDGRPEGTFLLRDSAQEDYLFSVSFRRYNRSLHARIEQWNHNFSFDAHDPCVFHSSTVTGLLEHY 485
Cdd:cd09923     1 GWYWGGITRYEAEELLAGKPEGTFLVRDSSDSRYLFSVSFRTYGRTLHARIEYSNGRFSFDSSDPSVPRFPCVVELIEHY 80

                  .
gi 1992493415 486 K 486
Cdd:cd09923    81 V 81
SOCS_SOCS5 cd03739
SOCS (suppressors of cytokine signaling) box of SOCS5-like proteins. Together with CIS1, the ...
505-561 5.79e-37

SOCS (suppressors of cytokine signaling) box of SOCS5-like proteins. Together with CIS1, the CIS/SOCS family of proteins is characterized by the presence of a C-terminal SOCS box and a central SH2 domain. SOCS5 inhibits Th2 differentiation by inhibiting IL-4 signaling. The general function of the SOCS box is the recruitment of the ubiquitin-transferase system. The SOCS box interacts with Elongins B and C, Cullin-5 or Cullin-2, Rbx-1, and E2. Therefore, SOCS-box-containing proteins probably function as E3 ubiquitin ligases and mediate the degradation of proteins associated through their N-terminal regions.


Pssm-ID: 239708  Cd Length: 57  Bit Score: 130.88  E-value: 5.79e-37
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1992493415 505 TFPFSLQHLARAAICRCTTYDGIGALPLPPTMQDFLKEYHYKQKVRVRWLEREPPFK 561
Cdd:cd03739     1 TFPFSLQYICRAVICRCTTYDGIDALPLPSMLQDFLKEYHYKQKVRVRWLEREPIKK 57
SOCS_SOCS4 cd03738
SOCS (suppressors of cytokine signaling) box of SOCS4-like proteins. Together with CIS1, the ...
505-552 2.43e-22

SOCS (suppressors of cytokine signaling) box of SOCS4-like proteins. Together with CIS1, the CIS/SOCS family of proteins is characterized by the presence of a C-terminal SOCS box and a central SH2 domain. The general function of the SOCS box is the recruitment of the ubiquitin-transferase system. The SOCS box interacts with Elongins B and C, Cullin-5 or Cullin-2, Rbx-1, and E2. Therefore, SOCS-box-containing proteins probably function as E3 ubiquitin ligases and mediate the degradation of proteins associated through their N-terminal regions.


Pssm-ID: 239707  Cd Length: 56  Bit Score: 90.05  E-value: 2.43e-22
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1992493415 505 TFPFSLQHLARAAICRCTTYDGIGALPLPPTMQDFLKEYHYKQKVRVR 552
Cdd:cd03738     1 TFPFSLQHICRTVICNCTTYDGIDALPIPSSMKLYLKEYHYKSKVRVL 48
SH2_SOCS6 cd10387
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
408-489 4.42e-19

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. 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: 198250  Cd Length: 100  Bit Score: 82.58  E-value: 4.42e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992493415 408 YWGVMDRYQAEALLDGRPEGTFLLRDSAQEDYLFSVSFRRYNRSLHARIEQWNHNFSFDAHDPCVFHSSTVTgLLEHYKD 487
Cdd:cd10387    13 YWGPITRWEAEGKLANVPDGSFLVRDSSDDRYLLSLSFRSHGKTLHTRIEHSNGRFSFYEQPDVEGHTSIVD-LIEHSIR 91

                  ..
gi 1992493415 488 PS 489
Cdd:cd10387    92 DS 93
SOCS pfam12610
Suppressor of cytokine signalling; This domain family is found in bacteria and eukaryotes, and ...
138-195 9.37e-19

Suppressor of cytokine signalling; This domain family is found in bacteria and eukaryotes, and is approximately 60 amino acids in length. The family is found in association with pfam07525, pfam00017. The suppressors of cytokine signaling (SOCS) family play important roles in regulating a variety of signal transduction pathways that are involved in immunity, growth and development of organizms.


Pssm-ID: 432667  Cd Length: 57  Bit Score: 80.21  E-value: 9.37e-19
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1992493415 138 SRGSTARRERRYGVSSIQEINDSVGaGSSGRSLSNRSLRQRLRDTVGLCLPLTTHSRS 195
Cdd:pfam12610   1 TRGPRRRRERRCSCSSIQEMSDSVD-DVSGRALSRRSLRQKLQDTVGLCLPLRSHRRS 57
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
406-490 5.23e-17

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 [Multi-domain]  Cd Length: 84  Bit Score: 76.11  E-value: 5.23e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992493415  406 PCYWGVMDRYQAEALLDGRPEGTFLLRDSAQEDYLFSVSFRRYNRSLHARIEQWNHN-FSFDahDPCVFHSstVTGLLEH 484
Cdd:smart00252   2 PWYHGFISREEAEKLLKNEGDGDFLVRDSESSPGDYVLSVRVKGKVKHYRIRRNEDGkFYLE--GGRKFPS--LVELVEH 77

                   ....*.
gi 1992493415  485 YKDPSA 490
Cdd:smart00252  78 YQKNSL 83
SH2_SOCS7 cd10388
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
408-483 1.53e-16

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. 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: 198251  Cd Length: 101  Bit Score: 75.08  E-value: 1.53e-16
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1992493415 408 YWGVMDRYQAEALLDGRPEGTFLLRDSAQEDYLFSVSFRRYNRSLHARIEQWNHNFSFDAHDPCVFHSSTVTGLLE 483
Cdd:cd10388    13 YWGPMSWEDAEKVLSNKPDGSFLVRDSSDDRYIFSLSFRSQGSVHHTRIEQYQGTFSLGSRNKFVDRSQSLVEFIE 88
SOCS_SOCS_like cd03717
SOCS (suppressors of cytokine signaling) box of SOCS-like proteins. The CIS/SOCS family of ...
505-543 1.13e-14

SOCS (suppressors of cytokine signaling) box of SOCS-like proteins. The CIS/SOCS family of proteins is characterized by the presence of a C-terminal SOCS box and a central SH2 domain. These intracellular proteins regulate the responses of immune cells to cytokines. Identified as negative regulators of the cytokine-JAK-STAT pathway, they seem to play a role in many immunological and pathological processes. The function of the SOCS box is the recruitment of the ubiquitin-transferase system. Related SOCS boxes are also present in Rab40-like proteins and insect proteins of unknown function that also contain a NEUZ (domain in neuralized proteins) domain.


Pssm-ID: 239687  Cd Length: 39  Bit Score: 68.01  E-value: 1.13e-14
                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1992493415 505 TFPFSLQHLARAAICRCTTYDGIGALPLPPTMQDFLKEY 543
Cdd:cd03717     1 TSVRSLQHLCRFVIRQCTRRDLIDQLPLPRRLKDYLKEY 39
SH2_SOCS1 cd10382
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
408-485 2.80e-13

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. 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: 198245  Cd Length: 98  Bit Score: 65.85  E-value: 2.80e-13
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1992493415 408 YWGVMDRYQAEALLDGRPEGTFLLRDSAQEDYLFSVSFRRYNRSLHARIEQWNHNFSFDAHDPCvfhSSTVTGLLEHY 485
Cdd:cd10382    13 YWGPLSVEEAHAKLKREPVGTFLIRDSRQKNCFFALSVKMASGPVSIRILFKAGKFSLDGSKES---FDCLFKLLEHY 87
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
406-485 4.61e-12

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 [Multi-domain]  Cd Length: 79  Bit Score: 61.70  E-value: 4.61e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992493415 406 PCYWGVMDRYQAEALLDGRPEGTFLLRDSAQEDYLFSVSFR-RYNRSLHARIEQWNHNFSFDAHDPCVFhsSTVTGLLEH 484
Cdd:cd00173     1 PWFHGSISREEAERLLRGKPDGTFLVRESSSEPGDYVLSVRsGDGKVKHYLIERNEGGYYLLGGSGRTF--PSLPELVEH 78

                  .
gi 1992493415 485 Y 485
Cdd:cd00173    79 Y 79
SOCS smart00253
suppressors of cytokine signalling; suppressors of cytokine signalling
501-543 4.25e-11

suppressors of cytokine signalling; suppressors of cytokine signalling


Pssm-ID: 128549  Cd Length: 43  Bit Score: 57.69  E-value: 4.25e-11
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1992493415  501 PLHRTFPFSLQHLARAAICRCTTYDGIGALPLPPTMQDFLKEY 543
Cdd:smart00253   1 LPRPSNVPSLQHLCRFTIRRCTRTDQIKTLPLPPKLKDYLSYY 43
SH2_SOCS2 cd10383
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
408-485 1.29e-09

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. 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: 198246  Cd Length: 103  Bit Score: 55.66  E-value: 1.29e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992493415 408 YWGVMDRYQAEALLDGRPEGTFLLRDSAQEDYLFSVSFRRYNRSLHARIEQWNHNFSFDAhDPCV------FHSstVTGL 481
Cdd:cd10383    10 YWGSMTVNEAKEKLQDAPEGTFLVRDSSHSDYLLTISVKTSAGPTNLRIEYQDGKFRLDS-IICVksklkqFDS--VVHL 86

                  ....
gi 1992493415 482 LEHY 485
Cdd:cd10383    87 IEYY 90
SOCS cd03587
SOCS (suppressors of cytokine signaling) box. The SOCS box is found in the C-terminal region ...
507-543 1.92e-09

SOCS (suppressors of cytokine signaling) box. The SOCS box is found in the C-terminal region of CIS/SOCS family proteins (in combination with a SH2 domain), ASBs (ankyrin repeat-containing proteins with a SOCS box), SSBs (SPRY domain-containing proteins with a SOCS box), and WSBs (WD40 repeat-containing proteins with a SOCS box), as well as, other miscellaneous proteins. The function of the SOCS box is the recruitment of the ubiquitin-transferase system. The SOCS box interacts with Elongins B and C, Cullin-5 or Cullin-2, Rbx-1, and E2. Therefore, SOCS-box-containing proteins probably function as E3 ubiquitin ligases and mediate the degradation of proteins associated through their N-terminal regions.


Pssm-ID: 239641  Cd Length: 41  Bit Score: 53.24  E-value: 1.92e-09
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1992493415 507 PFSLQHLARAAICRCT---TYDGIGALPLPPTMQDFLKEY 543
Cdd:cd03587     2 PRSLQHLCRLAIRRCLgkrRLDLIDKLPLPPRLKDYLLYK 41
SH2_Vav_family cd09940
Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several ...
402-489 2.00e-09

Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, Vav2 and Vav3 are more ubiquitously expressed. The members here include insect and amphibian Vavs. 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: 198193  Cd Length: 102  Bit Score: 54.99  E-value: 2.00e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992493415 402 ITALPCYWGVMDRYQAEALLDGRPEGTFLLRDSAQEDYLFSVSFRRYNRSLHARIEQWNHNFSFDAHDpcvFHSSTVTGL 481
Cdd:cd09940     2 LSEFLWFVGEMERDTAENRLENRPDGTYLVRVRPQGETQYALSIKYNGDVKHMKIEQRSDGLYYLSES---RHFKSLVEL 78

                  ....*...
gi 1992493415 482 LEHYKDPS 489
Cdd:cd09940    79 VNYYERNS 86
SH2_CIS cd10718
Src homology 2 (SH2) domain found in cytokine-inducible SH2-containing protein (CIS); CIS ...
408-485 5.76e-09

Src homology 2 (SH2) domain found in cytokine-inducible SH2-containing protein (CIS); CIS family members are known to be cytokine-inducible negative regulators of cytokine signaling. The expression of the CIS gene can be induced by IL2, IL3, GM-CSF and EPO in hematopoietic cells. Proteasome-mediated degradation of this protein has been shown to be involved in the inactivation of the erythropoietin receptor. Suppressor of cytokine signalling (SOCS) was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. 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: 198285  Cd Length: 88  Bit Score: 53.22  E-value: 5.76e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992493415 408 YWGVMDRYQAEALLDGRPEGTFLLRDSAQEDYLFSVSFRRYNRSLHARIEQWNHNFSFDAHDPCVFHSST---VTGLLEH 484
Cdd:cd10718     7 YWGSITASEAHQALQKAPEGTFLVRDSSHPSYMLTLSVKTTRGPTNVRIEYSDGSFRLDSSSLARPRLLSfpdVVSLVQH 86

                  .
gi 1992493415 485 Y 485
Cdd:cd10718    87 Y 87
SH2_SOCS3 cd10384
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
408-491 1.48e-08

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. 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: 198247  Cd Length: 101  Bit Score: 52.43  E-value: 1.48e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992493415 408 YWGVMDRYQAEALLDGRPEGTFLLRDSAQEDYLFSVSFRRYNRSLHARIEQWNHNFSFDAhDP----CVFHSSTVTGLLE 483
Cdd:cd10384    13 YWSTVSGKEANLLLSAEPAGTFLIRDSSDQRHFFTLSVKTESGTKNLRIQCEGGSFSLQT-DPrstqPVPRFDCVLKLVH 91

                  ....*...
gi 1992493415 484 HYKDPSAC 491
Cdd:cd10384    92 HYMPPSAA 99
SOCS_box smart00969
The SOCS box acts as a bridge between specific substrate- binding domains and more generic ...
508-543 5.57e-08

The SOCS box acts as a bridge between specific substrate- binding domains and more generic proteins that comprise a large family of E3 ubiquitin protein ligases;


Pssm-ID: 198037  Cd Length: 34  Bit Score: 48.94  E-value: 5.57e-08
                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 1992493415  508 FSLQHLARAAICRCTtyDGIGALPLPPTMQDFLKEY 543
Cdd:smart00969   1 RSLQHLCRLAIRRSL--GGIDKLPLPPRLKDYLLYY 34
SH2 pfam00017
SH2 domain;
408-485 5.77e-08

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 49.91  E-value: 5.77e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992493415 408 YWGVMDRYQAEALL-DGRPEGTFLLRDSAQEDYLFSVSFRRYNRSLHARIEQ---------WNHNFsfdahdpcvfhsST 477
Cdd:pfam00017   2 YHGKISRQEAERLLlNGKPDGTFLVRESESTPGGYTLSVRDDGKVKHYKIQStdnggyyisGGVKF------------SS 69

                  ....*...
gi 1992493415 478 VTGLLEHY 485
Cdd:pfam00017  70 LAELVEHY 77
SOCS_box pfam07525
SOCS box; The SOCS box acts as a bridge between specific substrate- binding domains and more ...
506-541 1.50e-07

SOCS box; The SOCS box acts as a bridge between specific substrate- binding domains and more generic proteins that comprise a large family of E3 ubiquitin protein ligases.


Pssm-ID: 462192  Cd Length: 39  Bit Score: 47.55  E-value: 1.50e-07
                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1992493415 506 FPFSLQHLARAAICRCTTY---DGIGALPLPPTMQDFLK 541
Cdd:pfam07525   1 TPRSLQHLCRLAIRRALGKrrlGAIDKLPLPPLLKDYLL 39
SH2_Nck_family cd09943
Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate ...
406-486 9.16e-07

Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. 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: 198196  Cd Length: 93  Bit Score: 47.12  E-value: 9.16e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992493415 406 PCYWGVMDRYQAEALLDGRP-EGTFLLRDSAQEDYLFSVSFRRYNRSLHARIEQWNHNFsfdahdpCV----FHssTVTG 480
Cdd:cd09943     2 PWYYGRITRHQAETLLNEHGhEGDFLIRDSESNPGDYSVSLKAPGRNKHFKVQVVDNVY-------CIgqrkFH--TMDE 72

                  ....*.
gi 1992493415 481 LLEHYK 486
Cdd:cd09943    73 LVEHYK 78
SH2_Nck2 cd10409
Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin ...
408-486 2.04e-06

Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. 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: 198272  Cd Length: 98  Bit Score: 46.18  E-value: 2.04e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992493415 408 YWGVMDRYQAEALLDGRP-EGTFLLRDSAQEDYLFSVSFRRYNRSLHARIEQWNHNFsfdahdpCV----FHSstVTGLL 482
Cdd:cd10409     4 YYGNVTRHQAECALNERGvEGDFLIRDSESSPSDFSVSLKAVGKNKHFKVQLVDNVY-------CIgqrrFNS--MDELV 74

                  ....
gi 1992493415 483 EHYK 486
Cdd:cd10409    75 EHYK 78
SH2_Nck1 cd10408
Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin ...
406-486 2.90e-06

Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. 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: 198271  Cd Length: 97  Bit Score: 45.79  E-value: 2.90e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992493415 406 PCYWGVMDRYQAEALLDGRP-EGTFLLRDSAQEDYLFSVSFRRYNRSLHARIEQWNHNFsfdahdpCVFHS--STVTGLL 482
Cdd:cd10408     2 PWYYGKVTRHQAEMALNERGnEGDFLIRDSESSPNDFSVSLKAQGKNKHFKVQLKECVY-------CIGQRkfSSMEELV 74

                  ....
gi 1992493415 483 EHYK 486
Cdd:cd10408    75 EHYK 78
SH2_Src_Src42 cd10370
Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the ...
404-485 9.26e-06

Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the Src non-receptor type tyrosine kinase family of proteins. The integration of receptor tyrosine kinase-induced RAS and Src42 signals by Connector eNhancer of KSR (CNK) as a two-component input is essential for RAF activation in Drosophila. Src42 is present in a wide variety of organisms including: California sea hare, pea aphid, yellow fever mosquito, honey bee, Panamanian leafcutter ant, and sea urchin. Src42 has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its C-terminal tail. 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: 198233  Cd Length: 96  Bit Score: 44.42  E-value: 9.26e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992493415 404 ALPCYWGVMDRYQAEA--LLDGRPEGTFLLRDSAQEDYLFSVSFRRYNRSLHARIEQWNHNFSFDAHDpCVFhsSTVTGL 481
Cdd:cd10370     2 AEPWYFGKIKRIEAEKklLLPENEHGAFLIRDSESRHNDYSLSVRDGDTVKHYRIRQLDEGGFFIARR-TTF--RTLQEL 78

                  ....
gi 1992493415 482 LEHY 485
Cdd:cd10370    79 VEHY 82
SH2_nSH2_p85_like cd09942
N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
408-493 1.01e-05

N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. p110, the catalytic subunit, is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. The regulatory unit is called p85 and is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, an internal SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are 2 inhibitory interactions between p110alpha and p85 of P13K: (1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and (2) p85 iSH2 domain with C2 domain of p110alpha. There are 3 inhibitory interactions between p110beta and p85 of P13K: (1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, (2) p85 iSH2 domain with C2 domain of p110alpha, and (3) p85 cSH2 domain with the kinase domain of p110alpha. It is interesting to note that p110beta is oncogenic as a wild type protein while p110alpha lacks this ability. One explanation is the idea that the regulation of p110beta by p85 is unique because of the addition of inhibitory contacts from the cSH2 domain and the loss of contacts in the iSH2 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: 198195  Cd Length: 110  Bit Score: 44.62  E-value: 1.01e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992493415 408 YWGVMDRYQAEALLDGRPEGTFLLRD--SAQEDYLFSVSFRRYNRSLhaRIEQWNHNFSFDahDPCVFHSstVTGLLEHY 485
Cdd:cd09942    10 YWGDISREEVNEKMRDTPDGTFLVRDasTMKGDYTLTLRKGGNNKLI--KIFHRDGKYGFS--DPLTFNS--VVELINYY 83

                  ....*...
gi 1992493415 486 KDPSACMF 493
Cdd:cd09942    84 RNNSLAEY 91
SH2_Nterm_shark_like cd10347
N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
408-485 5.34e-05

N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) proteins; These non-receptor protein-tyrosine kinases contain two SH2 domains, five ankyrin (ANK)-like repeats, and a potential tyrosine phosphorylation site in the carboxyl-terminal tail which resembles the phosphorylation site in members of the src family. Like, mammalian non-receptor protein-tyrosine kinases, ZAP-70 and syk proteins, they do not have SH3 domains. However, the presence of ANK makes these unique among protein-tyrosine kinases. Both tyrosine kinases and ANK repeats have been shown to transduce developmental signals, and SH2 domains are known to participate intimately in tyrosine kinase signaling. These tyrosine kinases are believed to be involved in epithelial cell polarity. The members of this family include the shark (SH2 domains, ANK, and kinase domain) gene in Drosophila and yellow fever mosquitos, as well as the hydra protein HTK16. Drosophila Shark is proposed to transduce intracellularly the Crumbs, a protein necessary for proper organization of ectodermal epithelia, intercellular signal. 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: 198210  Cd Length: 81  Bit Score: 41.59  E-value: 5.34e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992493415 408 YWGVMDRYQAEALL--DGRPEGTFLLRDS--AQEDYLFSVSFRryNRSLHARIEQWNHNFSFDAHDPCVFHSstVTGLLE 483
Cdd:cd10347     4 YHGKISREVAEALLlrEGGRDGLFLVREStsAPGDYVLSLLAQ--GEVLHYQIRRHGEDAFFSDDGPLIFHG--LDTLIE 79

                  ..
gi 1992493415 484 HY 485
Cdd:cd10347    80 HY 81
SOCS_SOCS7 cd03741
SOCS (suppressors of cytokine signaling) box of SOCS7-like proteins. Together with CIS1, the ...
509-545 6.09e-05

SOCS (suppressors of cytokine signaling) box of SOCS7-like proteins. Together with CIS1, the CIS/SOCS family of proteins is characterized by the presence of a C-terminal SOCS box and a central SH2 domain. SOCS7 is important in the functioning of neuronal cells. The general function of the SOCS box is the recruitment of the ubiquitin-transferase system. The SOCS box interacts with Elongins B and C, Cullin-5 or Cullin-2, Rbx-1, and E2. Therefore, SOCS-box-containing proteins probably function as E3 ubiquitin ligases and mediate the degradation of proteins associated through their N-terminal regions.


Pssm-ID: 239710  Cd Length: 49  Bit Score: 40.47  E-value: 6.09e-05
                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 1992493415 509 SLQHLARAAICRCTTYDGIGALPLPPTMQDFLKEYHY 545
Cdd:cd03741     5 SLQHLCRFVIRKLVRRDHIPALPLPRRLIDYLREKHY 41
SOCS_SOCS2 cd03736
SOCS (suppressors of cytokine signaling) box of SOCS2-like proteins. Together with CIS1, the ...
509-545 6.43e-05

SOCS (suppressors of cytokine signaling) box of SOCS2-like proteins. Together with CIS1, the CIS/SOCS family of proteins is characterized by the presence of a C-terminal SOCS box and a central SH2 domain. SOCS2 has recently been shown to regulate neuronal differentiation by controlling expression of a neurogenic transcription factor, Neurogenin-1. SOCS2 binds to GH receptors and inhibits the activation of STAT5b induced by GH. The general function of the SOCS box is the recruitment of the ubiquitin-transferase system. The SOCS box interacts with Elongins B and C, Cullin-5 or Cullin-2, Rbx-1, and E2. Therefore, SOCS-box-containing proteins probably function as E3 ubiquitin ligases and mediate the degradation of proteins associated through their N-terminal regions.


Pssm-ID: 239705  Cd Length: 41  Bit Score: 40.22  E-value: 6.43e-05
                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 1992493415 509 SLQHLARAAICRCTtyDGIGALPLPPTMQDFLKEYHY 545
Cdd:cd03736     5 SLQHLCRITINKCT--RQIQELPLPTRLKDYLTEYTY 39
SH2_a2chimerin_b2chimerin cd10352
Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins ...
408-456 8.16e-05

Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins are a family of phorbol ester- and diacylglycerol-responsive GTPase-activating proteins. Alpha1-chimerin (formerly known as n-chimerin) and alpha2-chimerin are alternatively spliced products of a single gene, as are beta1- and beta2-chimerin. alpha1- and beta1-chimerin have a relatively short N-terminal region that does not encode any recognizable domains, whereas alpha2- and beta2-chimerin both include a functional SH2 domain that can bind to phosphotyrosine motifs within receptors. All of the isoforms contain a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. Other C1 domain-containing diacylglycerol receptors including: PKC, Munc-13 proteins, phorbol ester binding scaffolding proteins involved in Ca2+-stimulated exocytosis, and RasGRPs, diacylglycerol-activated guanine-nucleotide exchange factors (GEFs) for Ras and Rap1. 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: 198215  Cd Length: 91  Bit Score: 41.58  E-value: 8.16e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1992493415 408 YWGVMDRYQAEALLDGRPEGTFLLRDSAQEDYLFSVSFRRYNRSLHARI 456
Cdd:cd10352     9 YHGLISREEAEQLLSGASDGSYLIRESSRDDGYYTLSLRFNGKVKNYKL 57
SH2_csk_like cd09937
Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal ...
405-486 8.72e-05

Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal Src kinase (CSK) and CSK-homologous kinase (CHK) are members of the CSK-family of protein tyrosine kinases. These proteins suppress activity of Src-family kinases (SFK) by selectively phosphorylating the conserved C-terminal tail regulatory tyrosine by a similar mechanism. CHK is also capable of inhibiting SFKs by a non-catalytic mechanism that involves binding of CHK to SFKs to form stable protein complexes. The unphosphorylated form of SFKs is inhibited by CSK and CHK by a two-step mechanism. The first step involves the formation of a complex of SFKs with CSK/CHK with the SFKs in the complex are inactive. The second step, involves the phosphorylation of the C-terminal tail tyrosine of SFKs, which then dissociates and adopt an inactive conformation. The structural basis of how the phosphorylated SFKs dissociate from CSK/CHK to adopt the inactive conformation is not known. The inactive conformation of SFKs is stabilized by two intramolecular inhibitory interactions: (a) the pYT:SH2 interaction in which the phosphorylated C-terminal tail tyrosine (YT) binds to the SH2 domain, and (b) the linker:SH3 interaction of which the SH2-kinase domain linker binds to the SH3 domain. SFKs are activated by multiple mechanisms including binding of the ligands to the SH2 and SH3 domains to displace the two inhibitory intramolecular interactions, autophosphorylation, and dephosphorylation of YT. By selective phosphorylation and the non-catalytic inhibitory mechanism CSK and CHK are able to inhibit the active forms of SFKs. CSK and CHK are regulated by phosphorylation and inter-domain interactions. They both contain SH3, SH2, and kinase domains separated by the SH3-SH2 connector and SH2 kinase linker, intervening segments separating the three domains. They lack a conserved tyrosine phosphorylation site in the kinase domain and the C-terminal tail regulatory tyrosine phosphorylation site. The CSK SH2 domain is crucial for stabilizing the kinase domain in the active conformation. A disulfide bond here regulates CSK kinase activity. The subcellular localization and activity of CSK are regulated by its 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: 198190  Cd Length: 98  Bit Score: 41.51  E-value: 8.72e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992493415 405 LPCYWGVMDRYQAEALLDGRPEGTFLLRDSAQE--DYLFSVSFRRynRSLHARIEQWNHNFSFDahDPCVFhsSTVTGLL 482
Cdd:cd09937     3 MPWFHGKISREEAERLLQPPEDGLFLVRESTNYpgDYTLCVSFEG--KVEHYRVIYRNGKLTID--EEEYF--ENLIQLV 76

                  ....
gi 1992493415 483 EHYK 486
Cdd:cd09937    77 EHYT 80
SOCS_CIS1 cd03734
SOCS (suppressors of cytokine signaling) box of CIS (cytokine-inducible SH2 protein) 1-like ...
509-546 1.20e-04

SOCS (suppressors of cytokine signaling) box of CIS (cytokine-inducible SH2 protein) 1-like proteins. Together with the SOCS proteins, the CIS/SOCS family of proteins is characterized by the presence of a C-terminal SOCS box and a central SH2 domain. CIS1, like SOCS1 and SOCS3, is involved in the down-regulation of the JAK/STAT pathway. CIS1 binds to cytokine receptors at STAT5-docking sites, which prohibits recruitment of STAT5 to the receptor signaling complex and results in the down-regulation of activation by STAT5.


Pssm-ID: 239703  Cd Length: 41  Bit Score: 39.56  E-value: 1.20e-04
                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1992493415 509 SLQHLARAAICRCTTydGIGALPLPPTMQDFLKEYHYK 546
Cdd:cd03734     5 SLQHLCRLVINRLVT--DVDCLPLPRRMADYLRQYPFQ 40
SH2_Vav2 cd10406
Src homology 2 (SH2) domain found in the Vav2 proteins; Proto-oncogene vav is a member of the ...
403-461 2.97e-04

Src homology 2 (SH2) domain found in the Vav2 proteins; Proto-oncogene vav is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. All vavs are activated by tyrosine phosphorylation leading to their activation. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, and Vav2 and Vav3 are more ubiquitously expressed. Vav2 is a GEF for RhoA, RhoB and RhoG and may activate Rac1 and Cdc42. Vav2 has been shown to interact with CD19 and Grb2. Alternatively spliced transcript variants encoding different isoforms have been found for Vav2. Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated 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: 198269  Cd Length: 103  Bit Score: 40.44  E-value: 2.97e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1992493415 403 TALPCYWGVMDRYQAEALLDGRPEGTFLLRDSAQEDYLFSVSFRRYNRSLHARI---EQWNH 461
Cdd:cd10406     3 TAYPWFAGNMERQQTDNLLKSHASGTYLIRERPAEAERFAISIKFNDEVKHIKVvekDNWIH 64
SOCS_Rab40 cd03742
SOCS (suppressors of cytokine signaling) box of Rab40-like proteins. Rab40 is part of the Rab ...
508-543 3.26e-04

SOCS (suppressors of cytokine signaling) box of Rab40-like proteins. Rab40 is part of the Rab family of small GTP-binding proteins that form the largest family within the Ras superfamily. Rab proteins regulate vesicular trafficking pathways, behaving as membrane-associated molecular switches. Rab40 is characterized by a SOCS box c-terminal to the GTPase domain. The SOCS boxes interact with Elongins B and C, Cullin-5 or Cullin-2, Rbx-1, and E2. Therefore, SOCS-box-containing proteins probably function as E3 ubiquitin ligases and mediate the degradation of proteins associated through their N-terminal regions.


Pssm-ID: 239711  Cd Length: 43  Bit Score: 38.31  E-value: 3.26e-04
                          10        20        30
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gi 1992493415 508 FSLQHLARAAICRCTTYDGIGALPLPPTMQDFLKEY 543
Cdd:cd03742     4 LSLQDLCCRAIVSCTPVYLIDKLPLPVSIKSHLKSF 39
SH2_DAPP1_BAM32_like cd10355
Src homology 2 domain found in dual adaptor for phosphotyrosine and 3-phosphoinositides ( ...
402-488 3.28e-04

Src homology 2 domain found in dual adaptor for phosphotyrosine and 3-phosphoinositides ( DAPP1)/B lymphocyte adaptor molecule of 32 kDa (Bam32)-like proteins; DAPP1/Bam32 contains a putative myristoylation site at its N-terminus, followed by a SH2 domain, and a pleckstrin homology (PH) domain at its C-terminus. DAPP1 could potentially be recruited to the cell membrane by any of these domains. Its putative myristoylation site could facilitate the interaction of DAPP1 with the lipid bilayer. Its SH2 domain may also interact with phosphotyrosine residues on membrane-associated proteins such as activated tyrosine kinase receptors. And finally its PH domain exhibits a high-affinity interaction with the PtdIns(3,4,5)P(3) PtdIns(3,4)P(2) second messengers produced at the cell membrane following the activation of PI 3-kinases. DAPP1 is thought to interact with both tyrosine phosphorylated proteins and 3-phosphoinositides and therefore may play a role in regulating the location and/or activity of such proteins(s) in response to agonists that elevate PtdIns(3,4,5)P(3) and PtdIns(3,4)P(2). This protein is likely to play an important role in triggering signal transduction pathways that lie downstream from receptor tyrosine kinases and PI 3-kinase. It is likely that DAPP1 functions as an adaptor to recruit other proteins to the plasma membrane in response to extracellular signals. 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: 198218  Cd Length: 92  Bit Score: 39.77  E-value: 3.28e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992493415 402 ITALPCYWGVMDRYQAEA-LLDGRPEGTFLLRDSAQEDYLFSVSFRRYNRSLHARIEQWNHNFSFdahDPCVFhsSTVTG 480
Cdd:cd10355     3 LQSLGWYHGNLTRHAAEAlLLSNGVDGSYLLRNSNEGTGLFSLSVRAKDSVKHFHVEYTGYSFKF---GFNEF--SSLQD 77

                  ....*...
gi 1992493415 481 LLEHYKDP 488
Cdd:cd10355    78 FVKHFANQ 85
SH2_ShkD_ShkE cd10357
Src homology 2 (SH2) domain found in SH2 domain-bearing protein kinases D and E (ShkD and ShkE) ...
408-464 3.28e-04

Src homology 2 (SH2) domain found in SH2 domain-bearing protein kinases D and E (ShkD and ShkE); SH2-bearing genes cloned from Dictyostelium include two transcription factors, STATa and STATc, and a signaling factor, SHK1 (shkA). A database search of the Dictyostelium discoideum genome revealed two additional putative STAT sequences, dd-STATb and dd-STATd, and four additional putative SHK genes, dd-SHK2 (shkB), dd-SHK3 (shkC), dd-SHK4 (shkD), and dd-SHK5 (shkE). This model contains members of shkD and shkE. All of the SHK members are most closely related to the protein kinases found in plants. However these kinases in plants are not conjugated to any SH2 or SH2-like sequences. Alignment data indicates that the SHK SH2 domains carry some features of the STAT SH2 domains in Dictyostelium. When STATc's linker domain was used for a BLAST search, the sequence between the protein kinase domain and the SH2 domain (the linker) of SHK was recovered, suggesting a close relationship among these molecules within this region. SHK's linker domain is predicted to contain an alpha-helix which is indeed homologous to that of STAT. Based on the phylogenetic alignment, SH2 domains can be grouped into two categories, STAT-type and Src-type. SHK family members are in between, but are closer to the STAT-type which indicates a close relationship between SHK and STAT families in their SH2 domains and further supports the notion that SHKs linker-SH2 domain evolved from STAT or STATL (STAT-like Linker-SH2) domain found in plants. In SHK, STAT, and SPT6, the linker-SH2 domains all reside exclusively in the C-terminal regions. 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: 198220  Cd Length: 87  Bit Score: 39.80  E-value: 3.28e-04
                          10        20        30        40        50
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gi 1992493415 408 YWGVMDRYQAEALLDGRPEGTFLLRDSAQE--DYLFSVSFRRYNRSLHARIEQWNHNFS 464
Cdd:cd10357    13 FHGDISRDEAEKRLRGRPEGTFLIRLSSTDpkKTPFTISKKKKSKPVHKRISRIDVNNY 71
SH2_Vav3 cd10407
Src homology 2 (SH2) domain found in the Vav3 proteins; Proto-oncogene vav is a member of the ...
406-456 8.20e-04

Src homology 2 (SH2) domain found in the Vav3 proteins; Proto-oncogene vav is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. All vavs are activated by tyrosine phosphorylation leading to their activation. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, and Vav2 and Vav3 are more ubiquitously expressed. Vav3 preferentially activates RhoA, RhoG and, to a lesser extent, Rac1. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. VAV3 has been shown to interact with Grb2. Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated 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: 198270  Cd Length: 103  Bit Score: 39.22  E-value: 8.20e-04
                          10        20        30        40        50
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gi 1992493415 406 PCYWGVMDRYQAEALLDGRPEGTFLLRDSAQEDYLFSVSFRRYNRSLHARI 456
Cdd:cd10407     6 PWYAGAMERLQAETELINRVNSTYLVRHRTKESGEYAISIKYNNEVKHIKI 56
SH2_C-SH2_PLC_gamma_like cd09932
C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
406-458 9.87e-04

C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. 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: 198186  Cd Length: 104  Bit Score: 38.79  E-value: 9.87e-04
                          10        20        30        40        50
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gi 1992493415 406 PCYWGVMDRYQAEALLDGRPE-GTFLLRDSAQEDYLFSVSFRRYNRSLHARIEQ 458
Cdd:cd09932     5 EWFHANLTREQAEEMLMRVPRdGAFLVRPSETDPNSFAISFRAEGKIKHCRIKQ 58
SOCS_SOCS6 cd03740
SOCS (suppressors of cytokine signaling) box of SOCS6-like proteins. Together with CIS1, the ...
509-545 1.10e-03

SOCS (suppressors of cytokine signaling) box of SOCS6-like proteins. Together with CIS1, the CIS/SOCS family of proteins is characterized by the presence of a C-terminal SOCS box and a central SH2 domain. The general function of the SOCS box is the recruitment of the ubiquitin-transferase system. The SOCS box interacts with Elongins B and C, Cullin-5 or Cullin-2, Rbx-1, and E2. Therefore, SOCS-box-containing proteins probably function as E3 ubiquitin ligases and mediate the degradation of proteins associated through their N-terminal regions.


Pssm-ID: 239709  Cd Length: 41  Bit Score: 37.01  E-value: 1.10e-03
                          10        20        30
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gi 1992493415 509 SLQHLARAAICRCTTYDGIGALPLPPTMQDFLKEYHY 545
Cdd:cd03740     5 SLQYLCRFVIRQYTRIDLIQKLPLPNKMKGYLLEKHY 41
SH2_SH2D4B cd10351
Src homology 2 domain found in the SH2 domain containing protein 4B (SH2D4B); SH2D4B contains ...
406-487 1.12e-03

Src homology 2 domain found in the SH2 domain containing protein 4B (SH2D4B); SH2D4B 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: 198214  Cd Length: 103  Bit Score: 38.72  E-value: 1.12e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992493415 406 PCYWGVMDRYQAEALLDGRPEGTFLLRDSaQEDYLFSVSFRRYNRSLHARIEQWNHNFSFDAHDPCvfHSSTVTGLLEHY 485
Cdd:cd10351     8 PWFHGIISREEAEALLMNATEGSFLVRVS-EKIWGYTLSYRLQSGFKHFLVDASGDFYSFLGVDPN--RHATLTDLIDFH 84

                  ..
gi 1992493415 486 KD 487
Cdd:cd10351    85 KE 86
SH2_CRK_like cd09926
Src homology 2 domain found in cancer-related signaling adaptor protein CRK; SH2 domain in the ...
408-444 1.19e-03

Src homology 2 domain found in cancer-related signaling adaptor protein CRK; SH2 domain in the CRK proteins. CRKI (SH2-SH3) and CRKII (SH2-SH3-SH3) are splicing isoforms of the oncoprotein CRK. CRKs regulate transcription and cytoskeletal reorganization for cell growth and motility by linking tyrosine kinases to small G proteins. The SH2 domain of CRK associates with tyrosine-phosphorylated receptors or components of focal adhesions, such as p130Cas and paxillin. CRK transmits signals to small G proteins through effectors that bind its SH3 domain, such as C3G, the guanine-nucleotide exchange factor (GEF) for Rap1 and R-Ras, and DOCK180, the GEF for Rac6. The binding of p130Cas to the CRK-C3G complex activates Rap1, leading to regulation of cell adhesion, and activates R-Ras, leading to JNK-mediated activation of cell proliferation, whereas the binding of CRK DOCK180 induces Rac1-mediated activation of cellular migration. The activity of the different splicing isoforms varies greatly with CRKI displaying substantial transforming activity, CRKII less so, and phosphorylated CRKII with no biological activity whatsoever. CRKII has a linker region with a phosphorylated Tyr and an additional C-terminal SH3 domain. The phosphorylated Tyr creates a binding site for its SH2 domain which disrupts the association between CRK and its SH2 target 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: 198180 [Multi-domain]  Cd Length: 106  Bit Score: 38.61  E-value: 1.19e-03
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gi 1992493415 408 YWGVMDRYQAEALLDGRPEGTFLLRDSAQ--EDYLFSVS 444
Cdd:cd09926    10 YFGPMSRQEAQELLQGQRHGVFLVRDSSTipGDYVLSVS 48
SH2_cSH2_p85_like cd09930
C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
407-489 1.66e-03

C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. p110, the catalytic subunit, is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. The regulatory unit is called p85 and is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, a inter SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are 2 inhibitory interactions between p110alpha and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and 2) p85 iSH2 domain with C2 domain of p110alpha. There are 3 inhibitory interactions between p110beta and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, 2) p85 iSH2 domain with C2 domain of p110alpha, and 3) p85 cSH2 domain with the kinase domain of p110alpha. It is interesting to note that p110beta is oncogenic as a wild type protein while p110alpha lacks this ability. One explanation is the idea that the regulation of p110beta by p85 is unique because of the addition of inhibitory contacts from the cSH2 domain and the loss of contacts in the iSH2 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: 198184  Cd Length: 104  Bit Score: 38.16  E-value: 1.66e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992493415 407 CYWGVMD--RYQAEALLDGRPEGTFLLRDSAQEDYlFSVSFRRYNRSLHARIEQWNHNFSFDAhdPCVFHSStVTGLLEH 484
Cdd:cd09930     6 RTWLVGDinRTQAEELLRGKPDGTFLIRESSTQGC-YACSVVCNGEVKHCVIYKTETGYGFAE--PYNLYES-LKELVLH 81

                  ....*
gi 1992493415 485 YKDPS 489
Cdd:cd09930    82 YAHNS 86
SOCS_ASB_like cd03716
SOCS (suppressors of cytokine signaling) box of ASB (ankyrin repeat and SOCS box) and SSB ...
507-540 1.68e-03

SOCS (suppressors of cytokine signaling) box of ASB (ankyrin repeat and SOCS box) and SSB (SPRY domain-containing SOCS box proteins) protein families. ASB family members have a C-terminal SOCS box and an N-terminal ankyrin-related sequence of a variable number of repeats. SSB proteins contain a central SPRY domain and a C-terminal SOCS. Recently, it has been shown that all four SSB proteins interact with the MET, the receptor protein-tyrosine kinase for hepatocyte growth factor (HGF), and that SSB-1, SSB-2, and SSB-4 interact with prostate apoptosis response protein-4. Both types of interactions are mediated through the SPRY domain.


Pssm-ID: 239686  Cd Length: 42  Bit Score: 36.32  E-value: 1.68e-03
                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 1992493415 507 PFSLQHLARAAICRC---TTYDGIGALPLPPTMQDFL 540
Cdd:cd03716     3 PRSLQHLCRLAIRRClgrRRLELIKKLPLPPRLKDYL 39
SOCS_WSB_SWIP cd03733
SOCS (suppressors of cytokine signaling) box of WSB/SWiP-like proteins. This subfamily ...
509-540 1.75e-03

SOCS (suppressors of cytokine signaling) box of WSB/SWiP-like proteins. This subfamily contains WSB-1 (SOCS-box-containing WD-40 protein), part of an E3 ubiquitin ligase for the thyroid-hormone-activating type 2 iodothyronine deiodinase (D2), and SWiP-1 (SOCS box and WD-repeats in Protein), a WD40-containing protein that is expressed in embryonic structures of chickens and regulated by Sonic Hedgehog (Shh), as well as, their isoforms WSB-2 and SWiP-2. The general function of the SOCS box is the recruitment of the ubiquitin-transferase system. The SOCS box interacts with Elongins B and C, Cullin-5 or Cullin-2, Rbx-1, and E2. Therefore, SOCS-box-containing proteins probably function as E3 ubiquitin ligases and mediate the degradation of proteins associated through their N-terminal regions.


Pssm-ID: 239702  Cd Length: 39  Bit Score: 36.25  E-value: 1.75e-03
                          10        20        30
                  ....*....|....*....|....*....|..
gi 1992493415 509 SLQHLARAAICRCTTYDGIGALPLPPTMQDFL 540
Cdd:cd03733     5 SLQHLCRMALRRVMTTQQVLALPIPKKMKEFL 36
SH2_SHF cd10392
Src homology 2 domain found in SH2 domain-containing adapter protein F (SHF); SHF is thought ...
408-485 1.89e-03

Src homology 2 domain found in SH2 domain-containing adapter protein F (SHF); SHF is thought to play a role in PDGF-receptor signaling and regulation of apoptosis. SHF is mainly expressed in skeletal muscle, brain, liver, prostate, testis, ovary, small intestine, and colon. SHF contains four putative tyrosine phosphorylation sites and an 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: 198255  Cd Length: 98  Bit Score: 37.74  E-value: 1.89e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1992493415 408 YWGVMDRYQAEALLDGRPEGTFLLRDSAQEDYLFSVSFRRYNRSLHARIEQWNHNFSFDAHDPCVFHSstVTGLLEHY 485
Cdd:cd10392     4 YHGAISRTDAENLLRLCKEASYLVRNSETSKNDFSLSLKSSQGFMHMKLSRTKEHKYVLGQNSPPFSS--VPEIIHHY 79
SOCS_WSB1_SWIP1 cd03746
SOCS (suppressors of cytokine signaling) box of WSB1/SWiP1-like proteins. This subfamily ...
509-540 4.49e-03

SOCS (suppressors of cytokine signaling) box of WSB1/SWiP1-like proteins. This subfamily contains WSB-1 (SOCS-box-containing WD-40 protein), part of an E3 ubiquitin ligase for the thyroid-hormone-activating type 2 iodothyronine deiodinase (D2) and SWiP-1 (SOCS box and WD-repeats in Protein), a WD40-containing protein that is expressed in embryonic structures of chickens and regulated by Sonic Hedgehog (Shh). The general function of the SOCS box is the recruitment of the ubiquitin-transferase system. The SOCS box interacts with Elongins B and C, Cullin-5 or Cullin-2, Rbx-1, and E2. Therefore, SOCS-box-containing proteins probably function as E3 ubiquitin ligases and mediate the degradation of proteins associated through their N-terminal regions.


Pssm-ID: 239715  Cd Length: 40  Bit Score: 35.17  E-value: 4.49e-03
                          10        20        30
                  ....*....|....*....|....*....|..
gi 1992493415 509 SLQHLARAAICRCTTYDGIGALPLPPTMQDFL 540
Cdd:cd03746     5 SLQHLCRMAIRRVMPTQQVKELPIPSKLLEFL 36
SH2_ShkA_ShkC cd10356
Src homology 2 (SH2) domain found in SH2 domain-bearing protein kinases A and C (ShkA and ShkC) ...
405-466 6.42e-03

Src homology 2 (SH2) domain found in SH2 domain-bearing protein kinases A and C (ShkA and ShkC); SH2-bearing genes cloned from Dictyostelium include two transcription factors, STATa and STATc, and a signaling factor, SHK1 (shkA). A database search of the Dictyostelium discoideum genome revealed two additional putative STAT sequences, dd-STATb and dd-STATd, and four additional putative SHK genes, dd-SHK2 (shkB), dd-SHK3 (shkC), dd-SHK4 (shkD), and dd-SHK5 (shkE). This model contains members of shkA and shkC. All of the SHK members are most closely related to the protein kinases found in plants. However these kinases in plants are not conjugated to any SH2 or SH2-like sequences. Alignment data indicates that the SHK SH2 domains carry some features of the STAT SH2 domains in Dictyostelium. When STATc's linker domain was used for a BLAST search, the sequence between the protein kinase domain and the SH2 domain (the linker) of SHK was recovered, suggesting a close relationship among these molecules within this region. SHK's linker domain is predicted to contain an alpha-helix which is indeed homologous to that of STAT. Based on the phylogenetic alignment, SH2 domains can be grouped into two categories, STAT-type and Src-type. SHK family members are in between, but are closer to the STAT-type which indicates a close relationship between SHK and STAT families in their SH2 domains and further supports the notion that SHKs linker-SH2 domain evolved from STAT or STATL (STAT-like Linker-SH2) domain found in plants. In SHK, STAT, and SPT6, the linker-SH2 domains all reside exclusively in the C-terminal regions. 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: 198219  Cd Length: 113  Bit Score: 36.82  E-value: 6.42e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1992493415 405 LPCYW--GVMDRYQAEALLDGRPEGTFLLRDSAQEDYLFSVSFRRYNRSL-HARIEQWNHNFSFD 466
Cdd:cd10356     8 MECAWfhGDISTSESENRLNGKPEGTFLVRFSTSEPGAYTISKVSKNGGIsHQRIHRPGGKFQVN 72
SH2_N-SH2_PLC_gamma_like cd10341
N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
413-487 8.82e-03

N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. 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: 199829  Cd Length: 99  Bit Score: 36.17  E-value: 8.82e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992493415 413 DRYQAEALLD---GRPEGTFLLRDSAQ--EDYlfSVSFRRYNRSLHARIEQWNHNFS--FDAHDPCVFhsSTVTGLLEHY 485
Cdd:cd10341    14 GRDEAEKLLLeycEGGDGTFLVRESETfvGDY--TLSFWRNGKVQHCRIRSRQENGEkkYYLTDNLVF--DSLYELIDYY 89

                  ..
gi 1992493415 486 KD 487
Cdd:cd10341    90 RQ 91
SH2_Grb2_like cd09941
Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar ...
406-456 9.94e-03

Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar proteins; The adaptor proteins here include homologs Grb2 in humans, Sex muscle abnormal protein 5 (Sem-5) in Caenorhabditis elegans, and Downstream of receptor kinase (drk) in Drosophila melanogaster. They are composed of one SH2 and two SH3 domains. Grb2/Sem-5/drk regulates the Ras pathway by linking the tyrosine kinases to the Ras guanine nucleotide releasing protein Sos, which converts Ras to the active GTP-bound state. The SH2 domain of Grb2/Sem-5/drk binds class II phosphotyrosyl peptides while its SH3 domain binds to Sos and Sos-derived, proline-rich peptides. Besides it function in Ras signaling, Grb2 is also thought to play a role in apoptosis. Unlike most SH2 structures in which the peptide binds in an extended conformation (such that the +3 peptide residue occupies a hydrophobic pocket in the protein, conferring a modest degree of selectivity), Grb2 forms several hydrogen bonds via main chain atoms with the side chain of +2 Asn. 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: 199828  Cd Length: 95  Bit Score: 35.71  E-value: 9.94e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1992493415 406 PCYWGVMDRYQAEALLDG-RPEGTFLLRDSAQEDYLFSVSFRRYNRSLHARI 456
Cdd:cd09941     4 PWFHGKISRAEAEEILMNqRPDGAFLIRESESSPGDFSLSVKFGNDVQHFKV 55
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

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