Src Homology 3 domain of Epidermal growth factor receptor kinase substrate 8 and similar proteins; This group is composed of Eps8 and Eps8-like proteins including Eps8-like 1-3, among others. These proteins contain N-terminal Phosphotyrosine-binding (PTB), central SH3, and C-terminal effector domains. Eps8 binds either Abi1 (also called E3b1) or Rab5 GTPase activating protein RN-tre through its SH3 domain. With Abi1 and Sos1, it becomes part of a trimeric complex that is required to activate Rac. Together with RN-tre, it inhibits the internalization of EGFR. The SH3 domains of Eps8 and similar proteins recognize peptides containing a PxxDY motif, instead of the classical PxxP motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 808356802 561 LAVVTYDRGGQNTKELTVHKGEYLEVIFDERNWWECKNMHQRVGYVPHTILSMV 614
Cdd:cd11764    1 YVRVLYDFTARNSKELSVLKGEYLEVLDDSRQWWKVRNSRGQVGYVPHNILEPY 54

Chromatin assembly factor 1 complex p150 subunit, N-terminal; CAF-1_p150 is a polypeptide subunit of CAF-1, which functions in depositing newly synthesized and acetylated histones H3/H4 into chromatin during DNA replication and repair. CAF-1_p150 includes the HP1 interaction site, the PEST, KER and ED interacting sites. CAF-1_p150 interacts directly with newly synthesized and acetylated histones through the acidic KER and ED domains. The PEST domain is associated with proteins that undergo rapid proteolysis.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 808356802  455 RERLEFEKAKIMEResRLRHEEKQIEDEKRRMHAEKDLIT----KETTQPVP 502
Cdd:pfam11600  94 KEKQEALEAKLEEK--RKKEEEKRLKEEEKRIKAEKAEITrflqKPKTQQAP 143

Src Homology 3 domain of Epidermal growth factor receptor kinase substrate 8 and similar proteins; This group is composed of Eps8 and Eps8-like proteins including Eps8-like 1-3, among others. These proteins contain N-terminal Phosphotyrosine-binding (PTB), central SH3, and C-terminal effector domains. Eps8 binds either Abi1 (also called E3b1) or Rab5 GTPase activating protein RN-tre through its SH3 domain. With Abi1 and Sos1, it becomes part of a trimeric complex that is required to activate Rac. Together with RN-tre, it inhibits the internalization of EGFR. The SH3 domains of Eps8 and similar proteins recognize peptides containing a PxxDY motif, instead of the classical PxxP motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 808356802 561 LAVVTYDRGGQNTKELTVHKGEYLEVIFDERNWWECKNMHQRVGYVPHTILSMV 614
Cdd:cd11764    1 YVRVLYDFTARNSKELSVLKGEYLEVLDDSRQWWKVRNSRGQVGYVPHNILEPY 54

SAM domain of EPS8-like subfamily; SAM (sterile alpha motif) domain of EPS8-like subfamily is a putative protein-protein interaction domain. This subfamily includes epidermal growth factor receptor kinase substrate 8 proteins (EPS8) and epidermal growth factor receptor kinase substrate 8-like (EPSL8) 1, 2, 3 proteins with the SAM domain located in the C-terminal effector region. This region is responsible for intracellular protein localization and is involved in small GTPases (such as Rac and Rab5) activation/inhibition. Proteins belonging to this group participate in coordination and integration of multiple signaling pathways; in particular, they play a role in the control of actin dynamics and in receptor endocytosis. They can form complexes with other proteins; for example, in the actin signaling network they interact with SOS1 and E3b1 (Abl1) proteins as well as with CRIB (via SH3 domains) during the actin filament formation, and in the receptor endocytosis their partner is RN-tre protein.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 808356802 764 AINEKSSPEDVTRWLQEKGFSPRVIDLLDGQDGANLFSLSKLHLQQACGrDEGGYLYSQLLVQK 827
Cdd:cd09540    1 PLTYDSSPEEVKAWLQAKGFSKITVRSLGVLTGAQLFSLNKEELKTVCP-EEGARVYSQLTVQK 63

Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain; PTB/PI domain structure similar to those of pleckstrin homology (PH) and IRS-1-like PTB domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808356802    26 DVTPSYYVEHLATFAVGRQFGLTFPADGIRKLKQMEKNSAIWAQP--LILRFRHNAVTVEDDNGELVEqFPLELIeqptA 103
Cdd:smart00462   1 GSGVSFRVKYLGSVEVPEARGLQVVQEAIRKLRAAQGSEKKEPQKviLSISSRGVKLIDEDTKAVLHE-HPLRRI----S 75

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 808356802   104 HVSNDSRetYNNVLLFVVREDRKRMstpTEMHIFQCIRVsATDVAEDLKNYVQGQFRRVRNGRRT 168
Cdd:smart00462  76 FCAVGPD--DLDVFGYIARDPGSSR---FACHVFRCEKA-AEDIALAIGQAFQLAYELKLKARSE 134

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 808356802  563 VVTYDRGGQNTKELTVHKGEYLEVI-FDERNWWECKNMHQRVGYVPH 608
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIVLeKSEDGWWKGRNKGGKEGLIPS 47

Src Homology 3 domain of Epidermal growth factor receptor kinase substrate 8 and similar proteins; This group is composed of Eps8 and Eps8-like proteins including Eps8-like 1-3, among others. These proteins contain N-terminal Phosphotyrosine-binding (PTB), central SH3, and C-terminal effector domains. Eps8 binds either Abi1 (also called E3b1) or Rab5 GTPase activating protein RN-tre through its SH3 domain. With Abi1 and Sos1, it becomes part of a trimeric complex that is required to activate Rac. Together with RN-tre, it inhibits the internalization of EGFR. The SH3 domains of Eps8 and similar proteins recognize peptides containing a PxxDY motif, instead of the classical PxxP motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 808356802 561 LAVVTYDRGGQNTKELTVHKGEYLEVIFDERNWWECKNMHQRVGYVPHTILSMV 614
Cdd:cd11764    1 YVRVLYDFTARNSKELSVLKGEYLEVLDDSRQWWKVRNSRGQVGYVPHNILEPY 54

SAM domain of EPS8-like subfamily; SAM (sterile alpha motif) domain of EPS8-like subfamily is a putative protein-protein interaction domain. This subfamily includes epidermal growth factor receptor kinase substrate 8 proteins (EPS8) and epidermal growth factor receptor kinase substrate 8-like (EPSL8) 1, 2, 3 proteins with the SAM domain located in the C-terminal effector region. This region is responsible for intracellular protein localization and is involved in small GTPases (such as Rac and Rab5) activation/inhibition. Proteins belonging to this group participate in coordination and integration of multiple signaling pathways; in particular, they play a role in the control of actin dynamics and in receptor endocytosis. They can form complexes with other proteins; for example, in the actin signaling network they interact with SOS1 and E3b1 (Abl1) proteins as well as with CRIB (via SH3 domains) during the actin filament formation, and in the receptor endocytosis their partner is RN-tre protein.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 808356802 764 AINEKSSPEDVTRWLQEKGFSPRVIDLLDGQDGANLFSLSKLHLQQACGrDEGGYLYSQLLVQK 827
Cdd:cd09540    1 PLTYDSSPEEVKAWLQAKGFSKITVRSLGVLTGAQLFSLNKEELKTVCP-EEGARVYSQLTVQK 63

Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain; PTB/PI domain structure similar to those of pleckstrin homology (PH) and IRS-1-like PTB domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808356802    26 DVTPSYYVEHLATFAVGRQFGLTFPADGIRKLKQMEKNSAIWAQP--LILRFRHNAVTVEDDNGELVEqFPLELIeqptA 103
Cdd:smart00462   1 GSGVSFRVKYLGSVEVPEARGLQVVQEAIRKLRAAQGSEKKEPQKviLSISSRGVKLIDEDTKAVLHE-HPLRRI----S 75

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 808356802   104 HVSNDSRetYNNVLLFVVREDRKRMstpTEMHIFQCIRVsATDVAEDLKNYVQGQFRRVRNGRRT 168
Cdd:smart00462  76 FCAVGPD--DLDVFGYIARDPGSSR---FACHVFRCEKA-AEDIALAIGQAFQLAYELKLKARSE 134

First Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The first SH3 domain of Nck proteins preferentially binds the PxxDY sequence, which is present in the CD3e cytoplasmic tail. This binding inhibits phosphorylation by Src kinases, resulting in the downregulation of TCR surface expression. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 808356802 561 LAVVTYDRGGQNTKELTVHKGEYLEVIFDERNWWECKNMHQRVGYVP 607
Cdd:cd11765    1 YVVAKYDYTAQGDQELSIKKNEKLTLLDDSKHWWKVQNSSNQTGYVP 47

First Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 808356802 561 LAVVTYDRGGQNTKELTVHKGEYLEVI--FDERNWWECKNMHQRVGYVP 607
Cdd:cd11761    3 TCKVLYSYEAQRPDELTITEGEELEVIedGDGDGWVKARNKSGEVGYVP 51

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 808356802  563 VVTYDRGGQNTKELTVHKGEYLEVI-FDERNWWECKNMHQRVGYVPH 608
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIVLeKSEDGWWKGRNKGGKEGLIPS 47

Third Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 808356802 574 KELTVHKGEYLEVIFDERN---WWECKNMHQRVGYVP 607
Cdd:cd11903   15 EELNFEKGETMEVIEKPENdpeWWKCKNSRGQVGLVP 51

N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor proteins consists of SH2 and SH3 domains, which bind tyrosine-phosphorylated peptides and proline-rich motifs, respectively. They function downstream of protein tyrosine kinases in many signaling pathways started by various extracellular signals, including growth and differentiation factors. Cellular CRK (c-CRK) contains a single SH2 domain, followed by N-terminal and C-terminal SH3 domains. It is involved in the regulation of many cellular processes including cell growth, motility, adhesion, and apoptosis. CRK has been implicated in the malignancy of various human cancers. The N-terminal SH3 domain of CRK binds a number of target proteins including DOCK180, C3G, SOS, and cABL. The CRK family includes two alternatively spliced protein forms, CRKI and CRKII, that are expressed by the CRK gene, and the CRK-like (CRKL) protein, which is expressed by a distinct gene (CRKL). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 808356802 565 TYDRGGQNTKELTVHKGEYLEVIF-DERNWWECKNMHQRVGYVP 607
Cdd:cd11758    6 LFDFPGNDDEDLPFKKGEILTVIRkPEEQWWNARNSEGKTGMIP 49

Src homology 3 domain of Apoptosis Stimulating of p53 proteins (ASPP); The ASPP family of proteins bind to important regulators of apoptosis (p53, Bcl-2, and RelA) and cell growth (APCL, PP1). They share similarity at their C-termini, where they harbor a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain. Vertebrates contain three members of the family: ASPP1, ASPP2, and iASPP. ASPP1 and ASPP2 activate the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73), while iASPP is an oncoprotein that specifically inhibits p53-induced apoptosis. The expression of ASPP proteins is altered in tumors; ASPP1 and ASPP2 are downregulated whereas iASPP is upregulated is some cancer types. ASPP proteins also bind and regulate protein phosphatase 1 (PP1), and this binding is competitive with p53 binding. The SH3 domain and the ANK repeats of ASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 808356802 562 AVVTYDrgGQNTKELTVHKGEYLEVIF----DERNWWECKNmHQRVGYVPHTILSM 613
Cdd:cd11807    5 ALFDYE--AENGDELSFREGDELTVLRkgddDETEWWWARL-NDKEGYVPRNLLGL 57

Third Src Homology 3 domain of Nck adaptor proteins; This group contains the third SH3 domain of Nck, the first SH3 domain of Caenorhabditis elegans Ced-2 (Cell death abnormality protein 2), and similar domains. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. Ced-2 is a cell corpse engulfment protein that interacts with Ced-5 in a pathway that regulates the activation of Ced-10, a Rac small GTPase.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 808356802 562 AVVTYDRGGQNTKELTVHKGEYLEVI---FDERNWWECKNMHQRVGYVP 607
Cdd:cd11767    2 VVALYPFTGENDEELSFEKGERLEIIekpEDDPDWWKARNALGTTGLVP 50

First Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The first SH3 domain of Nck1 binds the PxxDY sequence in the CD3e cytoplasmic tail; this binding inhibits phosphorylation by Src kinases, resulting in the downregulation of TCR surface expression. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 808356802 561 LAVVTYDRGGQNTKELTVHKGEYLEVIFDERNWWECKNMHQRVGYVP 607
Cdd:cd11900    4 VVVAKFDYVAQQDQELDIKKNERLWLLDDSKSWWRVRNAMNKTGFVP 50

Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Saccharomyces cerevisiae has two myosins-I, Myo3 and Myo5, which are involved in endocytosis and the polarization of the actin cytoskeleton. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 808356802 564 VTYDRGGQNTKELTVHKGEYLEVIFDERN-WWECKNMHQRV-GYVP 607
Cdd:cd11858    4 ALYDFAGSVANELSLKKDDIVYIVQKEDNgWWLAKKLDESKeGWVP 49