SAM domain of SASH1 proteins, repeat 2; SAM (sterile alpha motif) repeat 2 of SASH1 proteins is a protein-protein interaction domain. Members of this subfamily are putative adaptor proteins. They appear to mediate signal transduction. SASH1 can bind 14-3-3 proteins in response to IGF1/phosphatidylinositol 3-kinase signaling. SASH1 was found upregulated in different tissues including thymus, placenta, lungs and downregulated in some breast tumors, liver metastases and colon cancers if compare to corresponding normal tissues. SASH1 is a potential candidate for a tumor suppressor gene in breast cancers. At the same time, downregulation of SASH1 in colon cancer is associated with metastasis and a poor prognosis.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958655374 1099 PLSPGCVTSVSDWLISIGLPMYTSTLSDAGFSALSQVPSLSHTCLQEAGITEERHIRKLVTAARLFKLPP 1168
Cdd:cd09492      1 PVSPGHVSSVSDWLVSIGLPMYSPPLLEAGFSTLSRVSSLSETCLREAGITEERHIRKLLSAARLVSAEQ 70

Lymphocyte signaling adaptor protein; This domain family is found in eukaryotes, and is typically between 144 and 156 amino acids in length. The family is found in association with pfam07647, pfam07653. There is a conserved LGKK sequence motif. SLY contains a Src homology 3 domain and a sterile alpha motif, suggesting that it functions as a signaling adaptor protein in lymphocytes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958655374  339 RTCSFGGFDLTNRSLHVGSNNSDPMGKEGD---FVYKEVIKSPSASRISLGKKVKSVKETMRKRMSKKYSSPVTEQDsGL 415
Cdd:pfam12485    4 RSSSFGDFDKSRPSSPVVKPEEFNLEEPEDeagEPGPEEAGKPSTSGGKLGKKMRAISRTMRRKMGKKYVKALSEEM-GE 82

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958655374  416 DGTPGSPTSVKPD----SEHMDKPKLKAGGSVESLRsSLSGQSSMSGHTVSTTDSSTSNRESVKSEDgddeEPPYRGPF 490
Cdd:pfam12485   83 DEEEGSDSPPSPDdpedGPHTEKVSLKASDSEESLY-SPLSGQSSSSSGVTSPSDGTSNRDSLRLEE----EPPYTGPF 156

SAM domain of SASH1 proteins, repeat 2; SAM (sterile alpha motif) repeat 2 of SASH1 proteins is a protein-protein interaction domain. Members of this subfamily are putative adaptor proteins. They appear to mediate signal transduction. SASH1 can bind 14-3-3 proteins in response to IGF1/phosphatidylinositol 3-kinase signaling. SASH1 was found upregulated in different tissues including thymus, placenta, lungs and downregulated in some breast tumors, liver metastases and colon cancers if compare to corresponding normal tissues. SASH1 is a potential candidate for a tumor suppressor gene in breast cancers. At the same time, downregulation of SASH1 in colon cancer is associated with metastasis and a poor prognosis.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958655374 1099 PLSPGCVTSVSDWLISIGLPMYTSTLSDAGFSALSQVPSLSHTCLQEAGITEERHIRKLVTAARLFKLPP 1168
Cdd:cd09492      1 PVSPGHVSSVSDWLVSIGLPMYSPPLLEAGFSTLSRVSSLSETCLREAGITEERHIRKLLSAARLVSAEQ 70

Lymphocyte signaling adaptor protein; This domain family is found in eukaryotes, and is typically between 144 and 156 amino acids in length. The family is found in association with pfam07647, pfam07653. There is a conserved LGKK sequence motif. SLY contains a Src homology 3 domain and a sterile alpha motif, suggesting that it functions as a signaling adaptor protein in lymphocytes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958655374  339 RTCSFGGFDLTNRSLHVGSNNSDPMGKEGD---FVYKEVIKSPSASRISLGKKVKSVKETMRKRMSKKYSSPVTEQDsGL 415
Cdd:pfam12485    4 RSSSFGDFDKSRPSSPVVKPEEFNLEEPEDeagEPGPEEAGKPSTSGGKLGKKMRAISRTMRRKMGKKYVKALSEEM-GE 82

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958655374  416 DGTPGSPTSVKPD----SEHMDKPKLKAGGSVESLRsSLSGQSSMSGHTVSTTDSSTSNRESVKSEDgddeEPPYRGPF 490
Cdd:pfam12485   83 DEEEGSDSPPSPDdpedGPHTEKVSLKASDSEESLY-SPLSGQSSSSSGVTSPSDGTSNRDSLRLEE----EPPYTGPF 156

SAM domain (Sterile alpha motif);

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1958655374 1107 SVSDWLISIGLPMYTSTLSDAGFSALSQVPSLSHTCLQEAGITEERHIRKLVTAARLFK 1165
Cdd:pfam07647    8 SVADWLRSIGLEQYTDNFRDQGITGAELLLRLTLEDLKRLGITSVGHRRKILKKIQELK 66

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 1958655374   491 CGRARVHTDFTPSpyDTDSLKLKKGDIIDIISKPPMGTWMG-LLNNKVGTFKFIYV 545
Cdd:smart00326    2 GPQVRALYDYTAQ--DPDELSFKKGDIITVLEKSDDGWWKGrLGRGKEGLFPSNYV 55

Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. In many cases mediates homodimerisation.

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958655374   570 PKSVEDLLDRINLKEHMPTFLFNGYEDLDTFKLLEEEDLDELNIRDPEHRAVLLTAVELLQEY 632
Cdd:smart00454    6 PESVADWLESIGLEQYADNFRKNGIDGALLLLLTSEEDLKELGITKLGHRKKILKAIQKLKEQ 68

SAM domain of SASH1 proteins, repeat 2; SAM (sterile alpha motif) repeat 2 of SASH1 proteins is a protein-protein interaction domain. Members of this subfamily are putative adaptor proteins. They appear to mediate signal transduction. SASH1 can bind 14-3-3 proteins in response to IGF1/phosphatidylinositol 3-kinase signaling. SASH1 was found upregulated in different tissues including thymus, placenta, lungs and downregulated in some breast tumors, liver metastases and colon cancers if compare to corresponding normal tissues. SASH1 is a potential candidate for a tumor suppressor gene in breast cancers. At the same time, downregulation of SASH1 in colon cancer is associated with metastasis and a poor prognosis.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958655374 1099 PLSPGCVTSVSDWLISIGLPMYTSTLSDAGFSALSQVPSLSHTCLQEAGITEERHIRKLVTAARLFKLPP 1168
Cdd:cd09492      1 PVSPGHVSSVSDWLVSIGLPMYSPPLLEAGFSTLSRVSSLSETCLREAGITEERHIRKLLSAARLVSAEQ 70

Lymphocyte signaling adaptor protein; This domain family is found in eukaryotes, and is typically between 144 and 156 amino acids in length. The family is found in association with pfam07647, pfam07653. There is a conserved LGKK sequence motif. SLY contains a Src homology 3 domain and a sterile alpha motif, suggesting that it functions as a signaling adaptor protein in lymphocytes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958655374  339 RTCSFGGFDLTNRSLHVGSNNSDPMGKEGD---FVYKEVIKSPSASRISLGKKVKSVKETMRKRMSKKYSSPVTEQDsGL 415
Cdd:pfam12485    4 RSSSFGDFDKSRPSSPVVKPEEFNLEEPEDeagEPGPEEAGKPSTSGGKLGKKMRAISRTMRRKMGKKYVKALSEEM-GE 82

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958655374  416 DGTPGSPTSVKPD----SEHMDKPKLKAGGSVESLRsSLSGQSSMSGHTVSTTDSSTSNRESVKSEDgddeEPPYRGPF 490
Cdd:pfam12485   83 DEEEGSDSPPSPDdpedGPHTEKVSLKASDSEESLY-SPLSGQSSSSSGVTSPSDGTSNRDSLRLEE----EPPYTGPF 156

Src homology 3 domain of SAM And SH3 Domain Containing Proteins; This subfamily, also called the SLY family, is composed of SAM And SH3 Domain Containing Protein 1 (SASH1), SASH2, SASH3, and similar proteins. These are adaptor proteins containing a central conserved region with a bipartite nuclear localization signal (NLS) as wells as SAM (sterile alpha motif) and SH3 domains. SASH1 is a potential tumor suppressor in breast and colon cancer. It is widely expressed in normal tissues (except lymphocytes and dendritic cells) and is localized in the nucleus and the cytoplasm. SASH1 interacts with the oncoprotein cortactin and is important in cell migration and adhesion. SASH2 (also called SAMSN-1, SLY2, HACS1 or NASH1) and SASH3 (also called SLY/SLY1) are expressed mainly in hematopoietic cells, although SASH2 is also found in endothelial cells as well as myeloid leukemias and myeloma. SASH2 was found to be differentially expressed in malignant haematopoietic cells and in colorectal tumors, and is a potential tumor suppressor in lung cancer. SASH3 is essential in the full activation of adaptive immunity and is involved in the signaling of T cell receptors. 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 1958655374  493 RARVHTDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIY 544
Cdd:cd11822      1 RAKVHTDFTPSPYDTDSLKLKKGDIIDIINKPPMGIWTGMLNNKVGNFKFIY 52

SAM domain of SASH3 subfamily; SAM (sterile alpha motif) domain of SAHS3 (also known as SLY) proteins is a predicted protein-protein interaction domain. Members of this subfamily are putative signaling/adaptor proteins. In addition to SAM, they contain SLY and SH3 domains. They appear to mediate signal transduction in lymphoid tissues. Murine SASH3 is involved in preventing DN thymocytes from premature initiation of programmed cell death and in mTOR (mammalian target of rapamycin) activation via signal integration of the Notch receptor and preTCR (T cell receptor) pathways.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958655374  569 QPKSVEDLLDRINLKEHMPTFLFNGYEDLDTFKLLEEEDLDELNIRDPEHRAVLLTAVELLQEYD 633
Cdd:cd09560      4 KPKTLHELLERIGLEEHTSTLLLNGYQTLEDFKELRETHLNELNIMDPQHRAKLLTAAELLLDYD 68

C-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 C-terminal SH3 domain of CRK has not been shown to bind any target protein; it acts as a negative regulator of CRK function by stabilizing a structure that inhibits the access by target proteins to the N-terminal SH3 domain. 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 by intramolecular interactions, changing the subcellular localization of signal pathway components, and mediating the formation of multiprotein complex assemblies.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1958655374  493 RARVHTDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVDV 547
Cdd:cd11759      3 YARVIQKRVPNAYDKTALALEVGDLVKVTKINVSGQWEGELNGKVGHFPFTHVEL 57

SAM domain (Sterile alpha motif);

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1958655374 1107 SVSDWLISIGLPMYTSTLSDAGFSALSQVPSLSHTCLQEAGITEERHIRKLVTAARLFK 1165
Cdd:pfam07647    8 SVADWLRSIGLEQYTDNFRDQGITGAELLLRLTLEDLKRLGITSVGHRRKILKKIQELK 66

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. 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 1958655374  493 RARVhtDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTF 540
Cdd:cd11874      1 RCKV--LFSYTPQNEDELELKVGDTIEVLGEVEEGWWEGKLNGKVGVF 46

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). 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 1958655374  504 PYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVD 546
Cdd:cd11827     10 AQDTDELSFNEGDIIEILKEDPSGWWTGRLRGKEGLFPGNYVE 52

SAM domain of Ship2 lipid phosphatase proteins; SAM (sterile alpha motif) domain of Ship2 subfamily is a protein-protein interaction domain. Ship2 proteins are lipid phosphatases (Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 2) containing an N-terminal SH2 domain, a central phosphatase domain and a C-terminal SAM domain. Ship2 is involved in a number of PI3K signaling pathways. For example, it plays a role in regulation of the actin cytoskeleton remodeling, in insulin signaling pathways, and in EphA2 receptor endocytosis. SAM domain of Ship2 can interact with SAM domain of other proteins in these pathways, thus participating in signal transduction. In particular, SAM of Ship2 is known to form heterodimers with SAM domain of Eph-A2 receptor tyrosine kinase during receptor endocytosis as well as with SAM domain of PI3K effector protein Arap3 in the actin cytoskeleton signaling network. Since Ship2 plays a role in negatively regulating insulin signaling, it has been suggested that inhibition of its expression or function may contribute in treating type 2 diabetes and obesity-induced insulin resistance.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1958655374 1100 LSPGCvtSVSDWLISIGLPMYTSTLSDAGFSALSQVPSLSHTCLQEAGITEERHIRKLV 1158
Cdd:cd09491      2 LSWPK--TVSEWLMNLGLQQYEEGLMHNGWDSLEFLSDITEEDLEEAGVTNPAHKRRLL 58

Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CIN85. SH3B has been shown to bind Cbl proline-rich peptides and ubiquitin. 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 1958655374  495 RVHTDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTF 540
Cdd:cd12055      1 RCQVAFSYLPQNEDELELKVGDIIEVVGEVEEGWWEGVLNGKTGMF 46

SAM domain of EPH-A4 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A4 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A4 receptors and appears to mediate cell-cell initiated signal transduction. SAM domains of EPH-A4 receptors can form homodimers. EPH-A4 receptors bind ligands such as erphirin A1, A4, A5. They are known to interact with a number of different proteins, including meltrin beta metalloprotease, Cdk5, and EFS2alpha, however SAM domain doesn't participate in these interactions. EPH-A4 receptors are involved in regulation of corticospinal tract formation, in pathway controlling voluntary movements, in formation of motor neurons, and in axon guidance (SAM domain is not required for axon guidance or for EPH-A4 kinase signaling). In Xenopus embryos EPH-A4 induces loss of cell adhesion, ventro-lateral protrusions, and severely expanded posterior structures. Mutations in SAM domain conserved tyrosine (Y928F) enhance the ability of EPH-A4 to induce these phenotypes, thus supporting the idea that the SAM domain may negatively regulate some aspects of EPH-A4 activity. EphA4 gene was found overexpressed in a number of different cancers including human gastric cancer, colorectal cancer, and pancreatic ductal adenocarcinoma. It is likely to be a promising molecular target for the cancer therapy.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1958655374 1105 VTSVSDWLISIGLPMYTSTLSDAGFSALSQVPSLSHTCLQEAGITEERHIRKLVTAAR 1162
Cdd:cd09545      3 VASVDDWLQAIKMERYKDNFTAAGYTTLEAVVHMNQDDLARIGISAIAHQNKILSSVQ 60

Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CD2AP. SH3B binds to c-Cbl in a site (TPSSRPLR is the core binding motif) distinct from the c-Cbl/SH3A binding site. 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 1958655374  504 PYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVDVL 548
Cdd:cd12054     11 PQNEDELELKVGDIIDINEEVEEGWWSGTLNGKSGLFPSNFVKEL 55

SAM domain of caskin protein repeat 2; SAM (sterile alpha motif) domain repeat 2 of caskin1,2 proteins is a protein-protein interaction domain. Caskin has two tandem SAM domains. Caskin protein is known to interact with membrane-associated guanylate kinase CASK, and may play a role in neural development, synaptic protein targeting, and regulation of gene expression.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1958655374 1106 TSVSDWLISIGLPMYTSTLSDAGFSALSQVPSLSHTCLQEAGITEERHIRKLVTA 1160
Cdd:cd09498      8 NDLLEWLSLLGLPQYHKVLVENGYDSIDFVTDLTWEDLQDIGITKLGHQKKLMLA 62

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The C-terminal SH3 domains (SH3c) of GRB2 and GRAP2 have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically 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 1958655374  493 RARVHTDFTPSpyDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYV 545
Cdd:cd11805      1 RVQALYDFNPQ--EPGELEFRRGDIITVLDSSDPDWWKGELRGRVGIFPANYV 51

SAM domain of EPH family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH (erythropoietin-producing hepatocyte) family of receptor tyrosine kinases is a C-terminal signal transduction module located in the cytoplasmic region of these receptors. SAM appears to mediate cell-cell initiated signal transduction via binding proteins to a conserved tyrosine that is phosphorylated. In some cases the SAM domain mediates homodimerization/oligomerization and plays a role in the clustering process necessary for signaling. EPH kinases are the largest family of receptor tyrosine kinases. They are classified into two groups based on their abilities to bind ephrin-A and ephrin-B ligands. The EPH receptors are involved in regulation of cell movement, shape, and attachment during embryonic development; they control cell-cell interactions in the vascular, nervous, epithelial, and immune systems, and in many tumors. They are potential molecular markers for cancer diagnostics and potential targets for cancer therapy.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1958655374 1104 CVTSVSDWLISIGLPMYTSTLSDAGFSALSQVPSLSHTCLQEAGITEERHIRKLV 1158
Cdd:cd09488      1 AFRSVGEWLESIKMGRYKENFTAAGYTSLDAVAQMTAEDLTRLGVTLVGHQKKIL 55

Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the Saccharomyces cerevisiae proteins, Ysc84p (also called LAS17-binding protein 4, Lsb4p) and Lsb3p, and similar fungal proteins. They contain an N-terminal SYLF domain (also called DUF500) and a C-terminal SH3 domain. Ysc84p localizes to actin patches and plays an important in actin polymerization during endocytosis. The N-terminal domain of both Ysc84p and Lsb3p can bind and bundle actin filaments. A study of the yeast SH3 domain interactome predicts that the SH3 domains of Lsb3p and Lsb4p may function as molecular hubs for the assembly of endocytic complexes. 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 1958655374  493 RARVHTDFTPSpyDTDSLKLKKGDIIDIISKPPMGT--WMGLLNNKVGTFKFIYVDV 547
Cdd:cd11842      1 KAVALYDFAGE--QPGDLAFQKGDIITILKKSDSQNdwWTGRIGGREGIFPANYVEL 55

SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily conserved protein binding domain that is involved in the regulation of numerous developmental processes in diverse eukaryotes. The SAM domain can potentially function as a protein interaction module through its ability to homo- and heterooligomerise with other SAM domains.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958655374 1105 VTSVSDWLISIGLPMYTSTLSdAGFSALSQVPSLSHTCLQEAGITEERHIRKLVTAARLFK 1165
Cdd:pfam00536    5 VEDVGEWLESIGLGQYIDSFR-AGYIDGDALLQLTEDDLLKLGVTLLGHRKKILYAIQRLK 64

large tegument protein UL36; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958655374  762 PEPVESWPRSHSLDDlqgDADVGKDVPTEKPETCPENVPEVPQKASACTSKALPRGRDPTAedvmfLTQSKRFSDPPKTM 841
Cdd:PHA03247  2612 APPSPLPPDTHAPDP---PPPSPSPAANEPDPHPPPTVPPPERPRDDPAPGRVSRPRRARR-----LGRAAQASSPPQRP 2683

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958655374  842 AKKLEGSAVASNLGIAPPQCIPRNFEAQPPVKPGLTRTSLEGLRKGHDHHSLGTKEGVDGEQSTPETRTQSRHPSQPPpV 921
Cdd:PHA03247  2684 RRRAARPTVGSLTSLADPPPPPPTPEPAPHALVSATPLPPGPAAARQASPALPAAPAPPAVPAGPATPGGPARPARPP-T 2762

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958655374  922 PAKKSRERLANGLHLVPSPEAPILPLKKASPA-----SPVSPSDCPSPREPRSSSGTEPGSPVCTRPPP 985
Cdd:PHA03247  2763 TAGPPAPAPPAAPAAGPPRRLTRPAVASLSESreslpSPWDPADPPAAVLAPAAALPPAASPAGPLPPP 2831

104 kDa microneme/rhoptry antigen; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958655374  906 PETRTQSRHPSQP--------PPVPAKKSRERLANGLHLVPSPEAPILPLKKASPASPVSPSDCPSPREPRSS-SGTEPG 976
Cdd:PTZ00449   579 PEFPKDPKHPKDPeepkkpkrPRSAQRPTRPKSPKLPELLDIPKSPKRPESPKSPKRPPPPQRPSSPERPEGPkIIKSPK 658

                   ....*...
gi 1958655374  977 SPVCTRPP 984
Cdd:PTZ00449   659 PPKSPKPP 666

transcriptional regulator ICP4; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958655374  635 NSDQSGSQEKLLADSQGLSGRSPRDSGCYESSENLENGKTQKPSALSTKSSTESNLKSFNRSQPGNYPTLPLTKSGEvrk 714
Cdd:PHA03307    39 SQGQLVSDSAELAAVTVVAGAAACDRFEPPTGPPPGPGTEAPANESRSTPTWSLSTLAPASPAREGSPTPPGPSSPD--- 115

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958655374  715 qgeesrlGRGLAPDTAKCCDVPcVTGLSKNRRSLPVSICRSCETLEGPEPVESWPRSHSldDLQGDADVGKDVPtEKPET 794
Cdd:PHA03307   116 -------PPPPTPPPASPPPSP-APDLSEMLRPVGSPGPPPAASPPAAGASPAAVASDA--ASSRQAALPLSSP-EETAR 184

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958655374  795 CPENV-PEVPQKASACTSKALPRGRDPTAedvmfltqSKRFSDPPKTMAKKLEGSAVASNLGIAPPQCI-----PRNFEA 868
Cdd:PHA03307   185 APSSPpAEPPPSTPPAAASPRPPRRSSPI--------SASASSPAPAPGRSAADDAGASSSDSSSSESSgcgwgPENECP 256

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958655374  869 QPP----VKPGLTRTSLEGLRKGHDHhSLGTKEGVDGEQSTPETRTQSRHPSQPPPVPAKKSRERLANGLHLVPSPEAPi 944
Cdd:PHA03307   257 LPRpapiTLPTRIWEASGWNGPSSRP-GPASSSSSPRERSPSPSPSSPGSGPAPSSPRASSSSSSSRESSSSSTSSSSE- 334

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1958655374  945 lplKKASPASPVSPSDCPSPREPRSSSGTEPGSPVcTRPPPWLAELPESTS 995
Cdd:PHA03307   335 ---SSRGAAVSPGPSPSRSPSPSRPPPPADPSSPR-KRPRPSRAPSSPAAS 381

First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This subfamily is composed of the first SH3 domain (SH3A) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3A of both proteins bind to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic domain of the cell adhesion protein CD2. CIN85 SH3A binds to internal proline-rich motifs within the proline-rich region; this intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. CIN85 SH3A has also been shown to bind ubiquitin. 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 1958655374  504 PYDT---DSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTF 540
Cdd:cd11873      7 DYDAeepDELTLKVGDIITNVKKMEEGWWEGTLNGKRGMF 46

Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has been shown to bind ubiquitin. 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 1958655374  504 PYDT---DSLKLKKGDIIDIISKP--PMGTWMGLLNNKVGTFKFIYVDVL 548
Cdd:cd12057      7 PYEAqneDELTIKEGDIVTLISKDciDAGWWEGELNGRRGVFPDNFVKLL 56

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. 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 1958655374  494 ARVHTDFtpSPYDTDSLKLKKGDIIDIISKP-PMGTWMGLLNNKVGTFKFIYVD 546
Cdd:cd11976      2 AKARYDF--CARDRSELSLKEGDIIKILNKKgQQGWWRGEIYGRVGWFPANYVE 53

SAM domain of Arap1,2,3 (angiotensin receptor-associated protein); SAM (sterile alpha motif) domain of Arap1,2,3 subfamily proteins (angiotensin receptor-associated) is a protein-protein interaction domain. Arap1,2,3 proteins are phosphatidylinositol-3,4,5-trisphosphate-dependent GTPase-activating proteins. They are involved in phosphatidylinositol-3 kinase (PI3K) signaling pathways. In addition to SAM domain, Arap1,2,3 proteins contain ArfGap, PH-like, RhoGAP and UBQ domains. SAM domain of Arap3 protein was shown to interact with SAM domain of Ship2 phosphatidylinositol-trisphosphate phosphatase proteins. Such interaction apparently plays a role in inhibition of PI3K regulated pathways since Ship2 converts PI(3,4,5)P3 into PI(3,4)P2. Proteins of this subfamily participate in regulation of signaling and trafficking associated with a number of different receptors (including EGFR, TRAIL-R1/DR4, TRAIL-R2/DR5) in normal and cancer cells; they are involved in regulation of actin cytoskeleton remodeling, cell spreading and formation of lamellipodia.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1958655374 1105 VTSVSDWLISIGLPMYTSTLSDAGFSALSQVPSLSHTCLQEAGITEERHIRKL 1157
Cdd:cd09490      3 DLDIAEWLASIHLEQYLDLFREHGYVTATDCQGINDSRLKQIGISPTGHRRRI 55

SAM domain of EPH-B1 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B1 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH- B1 receptors. In human vascular endothelial cells it appears to mediate cell-cell initiated signal transduction via the binding of the adaptor protein GRB10 (growth factor) through its SH2 domain to a conserved tyrosine that is phosphorylated. EPH-B1 receptors play a role in neurogenesis, in particular in regulation of proliferation and migration of neural progenitors in the hippocampus and in corneal neovascularization; they are involved in converting the crossed retinal projection to ipsilateral retinal projection. They may be potential targets in angiogenesis-related disorders.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1958655374 1106 TSVSDWLISIGLPMYTSTLSDAGFSALSQVPSLSHTCLQEAGITEERHIRKLVTA 1160
Cdd:cd09551      7 TSVEDWLSAIKMSQYRDNFLSSGFTSLQLVAQMTSEDLLRIGVTLAGHQKKILNS 61

large tegument protein UL36; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958655374  906 PETRTQSRHPSQP---PPVPAKKSRERlanglhlvpSPEAPILPlkkASPASPVSPSDcpSPREPRSSSGTEPGSPVCTR 982
Cdd:PHA03247  2561 PAAPDRSVPPPRPaprPSEPAVTSRAR---------RPDAPPQS---ARPRAPVDDRG--DPRGPAPPSPLPPDTHAPDP 2626

                           90       100
                   ....*....|....*....|....*..
gi 1958655374  983 PPPwlAELPESTSLQEHGVKLGPVLSR 1009
Cdd:PHA03247  2627 PPP--SPSPAANEPDPHPPPTVPPPER 2651

SAM domain of AIDA1AB-like proteins, repeat 1; SAM (sterile alpha motif) domain repeat 1 of AIDA1AB-like proteins is a protein-protein interaction domain. AIDA1AB-like proteins have two tandem SAM domains. They may form an intramolecular head-to-tail homodimer. One of two basic motifs of the nuclear localization signal (NLS) is located within helix 5 of SAM2 (motif HKRK). This signal plays a role in decoupling of SAM2 from SAM1, thus facilitating translocation of this type proteins into the nucleus. SAM1 domain has a potential phosphorylation site for CMGC group of serine/threonine kinases. SAM domains of the AIDA1-like subfamily can directly bind ubiquitin and participate in regulating the degradation of ubiquitinated EphA receptors, particularly EPH-A8 receptor. Additionally AIDA1AB-like proteins may participate in the regulation of nucleoplasmic coilin protein interactions.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958655374  570 PKSVEDLLDRINLKEHMPTFLFNGYEDLDTFKLLEEEDLDELNI--RDPEHRAVLLTAVELL 629
Cdd:cd09499      2 VQSVGQWLESIGLPQYESKLLLNGFDDVDFLGSGVMEDQDLKEIgiTDEQHRQIILQAARSL 63

SAM domain of EPH-B3 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B3 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B3 receptors and appears to mediate cell-cell initiated signal transduction. EPH-B3 receptor protein kinase performs kinase-dependent and kinase-independent functions. It is known to be involved in thymus morphogenesis, in regulation of cell adhesion and migration. Also EphB3 controls cell positioning and ordered migration in the intestinal epithelium and plays a role in the regulation of adult retinal ganglion cell axon plasticity after optic nerve injury. In some experimental models overexpression of EphB3 enhances cell/cell contacts and suppresses colon tumor growth.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958655374 1106 TSVSDWLISIGLPMYTSTLSDAGFSALSQVPSLSHTCLQEAGITEERHIRKLVTAARLFKL 1166
Cdd:cd09553      7 TTVGDWLDAIKMGRYKENFVSAGFASFDLVAQMTAEDLLRIGVTLAGHQKKILSSIQDMRL 67

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 1958655374  499 DFTPSpyDTDSLKLKKGDIIDIISKPPMGTWMG-LLNNKVGTF 540
Cdd:pfam00018    5 DYTAQ--EPDELSFKKGDIIIVLEKSEDGWWKGrNKGGKEGLI 45