Ankyrin repeat and sterile alpha motif (SAM) domain-containing (Anks) protein family Phosphotyrosine-binding (PTB) domain; Both AIDA-1b (AbetaPP intracellular domain-associated protein 1b) and Odin (also known as ankyrin repeat and sterile alpha motif domain-containing 1A; ANKS1A) belong to the Anks protein family. Both of these family members interacts with the EphA8 receptor. Ank members consists of ankyrin repeats, a SAM domain and a C-terminal PTB domain which is crucial for interaction with the juxtamembrane (JM) region of EphA8. PTB domains are classified into three groups, namely, phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains of which the Anks PTB is a member. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720389706 194 QSWQHQPEKLIFESCGYEANYLGSMLIKDLRGTESTQDACAKMRKSTEHMKKIPTIILSITYKGVKFIDASNKNVIAEHE 273
Cdd:cd01274     1 TQWRHSPEKLITGSVNYEAHYLGSTEIKELRGTESTKKAIQKLKKSTREMKKIPTIILSISYKGVKFIDATTKNLICEHE 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720389706 274 IRNISCAAQDPEDLCTFAYITKDLQTSHHYCHVFSTVDVNLTYEIILTLGQAFEVAYQLALQAQKS 339
Cdd:cd01274    81 IRNISCACQDPEDLNTFAYITKDLKTDHHYCHVFCVLTVDLATEIILTLGQAFEVAYQLALRAQKS 146

SAM (Sterile alpha motif ); SAM (Sterile Alpha Motif) domain is a module consisting of approximately 70 amino acids. This domain is found in the Fungi/Metazoa group and in a restricted number of bacteria. Proteins with SAM domains are represented by a wide variety of domain architectures and have different intracellular localization, including nucleus, cytoplasm and membranes. SAM domains have diverse functions. They can interact with proteins, RNAs and membrane lipids, contain site of phosphorylation and/or kinase docking site, and play a role in protein homo and hetero dimerization/oligomerization in processes ranging from signal transduction to regulation of transcription. Mutations in SAM domains have been linked to several diseases.

                          10        20        30
                  ....*....|....*....|....*....|.
gi 1720389706   1 MEEQDLREIGISDPQHRRKLLQAARSLPKVK 31
Cdd:cd09499    37 MEDQDLKEIGITDEQHRQIILQAARSLPKKK 67

Ankyrin repeat and sterile alpha motif (SAM) domain-containing (Anks) protein family Phosphotyrosine-binding (PTB) domain; Both AIDA-1b (AbetaPP intracellular domain-associated protein 1b) and Odin (also known as ankyrin repeat and sterile alpha motif domain-containing 1A; ANKS1A) belong to the Anks protein family. Both of these family members interacts with the EphA8 receptor. Ank members consists of ankyrin repeats, a SAM domain and a C-terminal PTB domain which is crucial for interaction with the juxtamembrane (JM) region of EphA8. PTB domains are classified into three groups, namely, phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains of which the Anks PTB is a member. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720389706 194 QSWQHQPEKLIFESCGYEANYLGSMLIKDLRGTESTQDACAKMRKSTEHMKKIPTIILSITYKGVKFIDASNKNVIAEHE 273
Cdd:cd01274     1 TQWRHSPEKLITGSVNYEAHYLGSTEIKELRGTESTKKAIQKLKKSTREMKKIPTIILSISYKGVKFIDATTKNLICEHE 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720389706 274 IRNISCAAQDPEDLCTFAYITKDLQTSHHYCHVFSTVDVNLTYEIILTLGQAFEVAYQLALQAQKS 339
Cdd:cd01274    81 IRNISCACQDPEDLNTFAYITKDLKTDHHYCHVFCVLTVDLATEIILTLGQAFEVAYQLALRAQKS 146

SAM domain of AIDA1AB-like proteins, repeat 2; SAM (sterile alpha motif) domain repeat 2 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 the SAM2 (motif HKRK). This signal plays a role in decoupling of SAM2 from SAM1, thus facilitating translocation of this type proteins into the nucleus. SAM domains of the AIDA1AB-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 1720389706  36 DGVSPTSVPSWLDSLGLQDYVHSFLSSGYSSIDTVKNLWELELVNVLKVHLLGHRKRIIASLADR 100
Cdd:cd09500     1 DGNSPASVSEWLDSIGLGDYIETFLKHGYTSMERVKRIWEVELTNVLEINKLGHRKRILASLADR 65

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 1720389706  36 DGVSPTSVPSWLDSLGLQDYVHSFlSSGYSSIDTVKNLWELELVNvLKVHLLGHRKRIIASL 97
Cdd:pfam00536   1 DGWSVEDVGEWLESIGLGQYIDSF-RAGYIDGDALLQLTEDDLLK-LGVTLLGHRKKILYAI 60

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 1720389706   35 YDGVSPTSVPSWLDSLGLQDYVHSFLSSGYSSIDTVkNLWELELVNVLKVHLLGHRKRIIASL 97
Cdd:smart00454   1 VSQWSPESVADWLESIGLEQYADNFRKNGIDGALLL-LLTSEEDLKELGITKLGHRKKILKAI 62

SAM domain (Sterile alpha motif);

                          10        20
                  ....*....|....*....|....*..
gi 1720389706   1 MEEQDLREIGISDPQHRRKLLQAARSL 27
Cdd:pfam07647  39 LTLEDLKRLGITSVGHRRKILKKIQEL 65

Ankyrin repeat and sterile alpha motif (SAM) domain-containing (Anks) protein family Phosphotyrosine-binding (PTB) domain; Both AIDA-1b (AbetaPP intracellular domain-associated protein 1b) and Odin (also known as ankyrin repeat and sterile alpha motif domain-containing 1A; ANKS1A) belong to the Anks protein family. Both of these family members interacts with the EphA8 receptor. Ank members consists of ankyrin repeats, a SAM domain and a C-terminal PTB domain which is crucial for interaction with the juxtamembrane (JM) region of EphA8. PTB domains are classified into three groups, namely, phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains of which the Anks PTB is a member. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720389706 194 QSWQHQPEKLIFESCGYEANYLGSMLIKDLRGTESTQDACAKMRKSTEHMKKIPTIILSITYKGVKFIDASNKNVIAEHE 273
Cdd:cd01274     1 TQWRHSPEKLITGSVNYEAHYLGSTEIKELRGTESTKKAIQKLKKSTREMKKIPTIILSISYKGVKFIDATTKNLICEHE 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720389706 274 IRNISCAAQDPEDLCTFAYITKDLQTSHHYCHVFSTVDVNLTYEIILTLGQAFEVAYQLALQAQKS 339
Cdd:cd01274    81 IRNISCACQDPEDLNTFAYITKDLKTDHHYCHVFCVLTVDLATEIILTLGQAFEVAYQLALRAQKS 146

SAM domain of AIDA1AB-like proteins, repeat 2; SAM (sterile alpha motif) domain repeat 2 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 the SAM2 (motif HKRK). This signal plays a role in decoupling of SAM2 from SAM1, thus facilitating translocation of this type proteins into the nucleus. SAM domains of the AIDA1AB-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 1720389706  36 DGVSPTSVPSWLDSLGLQDYVHSFLSSGYSSIDTVKNLWELELVNVLKVHLLGHRKRIIASLADR 100
Cdd:cd09500     1 DGNSPASVSEWLDSIGLGDYIETFLKHGYTSMERVKRIWEVELTNVLEINKLGHRKRILASLADR 65

Cell death protein 6 homolog (CED-6/GULP1) Phosphotyrosine-binding (PTB) domain; CED6 (also known as GULP1: engulfment adaptor PTB domain containing 1) is an adaptor protein involved in the specific recognition and engulfment of apoptotic cells. CED6 has been shown to interact with the cytoplasmic tail of another protein involved in the engulfment of apoptotic cells, CED1. CED6 has a C-terminal PTB domain, which can bind to NPXY motifs. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720389706 198 HQPEKLIFESCGYEANYLGSMLIKDLRGTESTQDACAKMrKSTEHMK-----KIPTIILSITYKGVKFIDASNKNVIAEH 272
Cdd:cd01273     2 HPPEALIKGHVAYLVKFLGCTEVEQPKGTEVVKEAIRKL-KFARQLKksegaKLPKVELQISIDGVKIQDPKTKVIMHQF 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1720389706 273 EIRNISCAAQDPEDLCTFAYITKDLQTSHHYCHVFstVDVNLTYEIILTLGQAFEVAYQLALQ 335
Cdd:cd01273    81 PLHRISFCADDKTDKRIFSFIAKDSESEKHLCFVF--DSEKLAEEITLTIGQAFDLAYRRFLE 141

Phosphotyrosine interaction domain (PTB/PID);

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720389706 210 YEANYLGSM-------LIKDLRgTESTQDA--CAKM------RKSTEHMKKIPTIILSITYKGVKFIDASNKNVIAEHEI 274
Cdd:pfam00640   1 FAVRYLGSVevpeeraPDKNTR-MQQAREAirRVKAakinkiRGLSGETGPGTKVDLFISTDGLKLLNPDTQELIHDHPL 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1720389706 275 RNIS-CAAQDPEDLCTFAYITKDLQTSHHYCHVFSTVDvnLTYEIILTLGQAFEVA 329
Cdd:pfam00640  80 VSISfCADGDPDLMRYFAYIARDKATNKFACHVFESED--GAQDIAQSIGQAFALA 133

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 1720389706  36 DGVSPTSVPSWLDSLGLQDYVHSFlSSGYSSIDTVKNLWELELVNvLKVHLLGHRKRIIASL 97
Cdd:pfam00536   1 DGWSVEDVGEWLESIGLGQYIDSF-RAGYIDGDALLQLTEDDLLK-LGVTLLGHRKKILYAI 60

Numb Phosphotyrosine-binding (PTB) domain; Numb is a membrane associated adaptor protein which plays critical roles in cell fate determination. Numb proteins are involved in control of asymmetric cell division and cell fate choice, endocytosis, cell adhesion, cell migration, ubiquitination of specific substrates and a number of signaling pathways (Notch, Hedgehog, p53). Mutations in Numb plays a critical role in disease (cancer). Numb has an N-terminal PTB domain and a C-terminal NumbF domain. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720389706 194 QSWQHQPEKLIFESCGYEANYLGSMLIKDLRGTESTQDACAKMRKSTehmKKIPTIILSITYKGVKFIDASNKNVIAEHE 273
Cdd:cd01268     1 HQWQADEEAVRSGTCSFPVKYLGCVEVGESRGMQVCEEALKKLKASR---KKPVRAVLWVSGDGLRVVDEKTKGLIVDQT 77

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1720389706 274 IRNISCAAQDPEDLCTFAYITKDLQTSHHYCHVFSTVD 311
Cdd:cd01268    78 IEKVSFCAPDRNHERAFSYICRDGTTRRWMCHCFLAVK 115

Tensin-related Phosphotyrosine-binding (PTB) domain; Tensin plays critical roles in renal function, muscle regeneration, and cell migration. It binds to actin filaments and interacts with the cytoplasmic tails of beta-integrin via its PTB domain, allowing tensin to link actin filaments to integrin receptors. Tensin functions as a platform for assembly and disassembly of signaling complexes at focal adhesions by recruiting tyrosine-phosphorylated signaling molecules, and also by providing interaction sites for other proteins. In addition to its PTB domain, it contains a C-terminal SH2 domain. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720389706 212 ANYLGSMLIKDLrgteSTQDACAKMRKSTEHMKKIPT----IILSITYKGVKFIDASNKNVIAEHEIRNISCAAQDPEDl 287
Cdd:cd13157     6 AQYIGSFPVSGL----DVADRADSVRKQLESLKESGSrgrpVILSVSLSGIKICSEDGKVVLMAHALRRVSYSTCRPAH- 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1720389706 288 CTFAYITKDLQ--TSHHYCHVFSTVDVNLTYEIILTLGQAFEVAY 330
Cdd:cd13157    81 AQFAFVARNPGgpTNRQYCHVFVTRSPREAQELNLLLCRAFQLAY 125

SAM domain of EPH-A2 family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A2 subfamily of receptor tyrosine kinases is a C-terminal protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A2 receptors and appears to mediate cell-cell initiated signal transduction. For example, SAM domain of EPH-A2 receptors interacts with SAM domain of Ship2 proteins (SH2 containing phosphoinositide 5-phosphotase-2) forming heterodimers; such recruitment of Ship2 by EPH-A2 attenuates the positive signal for receptor endocytosis. Eph-A2 is found overexpressed in many types of human cancer, including breast, prostate, lung and colon cancer. High level of expression could induce cancer progression by a variety of mechanisms and could be used as a novel tag for cancer immunotherapy. EPH-A2 receptors are attractive targets for drag design.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1720389706  36 DGVSPTSVPSWLDSLGLQDYVHSFLSSGYSSIDTVKNLwELELVNVLKVHLLGHRKRIIASL 97
Cdd:cd09543     1 EGVPFRTVAEWLESIKMQQYTEHFMAAGYNSIDKVLQM-TQEDIKHIGVRLPGHQKRIAYSI 61

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 1720389706  39 SPTSVPSWLDSLGLQDYVHSFLSSGYSSIDTVKNLWELELVNvLKVHLLGHRKRIIASL 97
Cdd:cd09488     1 AFRSVGEWLESIKMGRYKENFTAAGYTSLDAVAQMTAEDLTR-LGVTLVGHQKKILNSI 58

Disabled (Dab) Phosphotyrosine-binding domain; Dab is a cystosolic adaptor protein, which binds to the cytoplasmic tails of lipoprotein receptors, such as ApoER2 and VLDLR, via its PTB domain. The dab PTB domain has a preference for unphosphorylated tyrosine within an NPxY motif. Additionally, the Dab PTB domain, which is structurally similar to PH domains, binds to phosphatidlyinositol phosphate 4,5 bisphosphate in a manner characteristic of phosphoinositide binding PH domains. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720389706 210 YEANYLGSMLIKDLRGTESTQDACAKM----RKSTEHMKKIptiILSITYKGVKFIDASNKNVIAEHEIRNISCAAQDPE 285
Cdd:cd01215    18 FKAKLIGIDEVPAARGDKMCQDAMMKLkgavKAAGEHKQRI---WLNISLEGIKILDEKTGALLHHHPVHKISFIARDTT 94

                          90
                  ....*....|....*...
gi 1720389706 286 DLCTFAYITKdLQTSHHY 303
Cdd:cd01215    95 DNRAFGYVCG-LDGGHRF 111

SAM domain of EPH-A6 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A6 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A6 receptors and appears to mediate cell-cell initiated signal transduction. Eph-A6 gene is preferentially expressed in the nervous system. EPH-A6 receptors are involved in primate retina vascular and axon guidance, and in neural circuits responsible for learning and memory. EphA6 gene was significantly down regulated in colorectal cancer and in malignant melanomas. It is a potential molecular marker for these cancers.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1720389706  42 SVPSWLDSLGLQDYVHSFLSSGYSSIDTVKNLwELELVNVLKVHLLGHRKRIIASL 97
Cdd:cd09547     5 TVSDWLDSIKMGQYKNNFMAAGFTTLDMVSRM-TIDDIRRIGVTLIGHQRRIVSSI 59

JNK-interacting protein-like (JIP) Phosphotyrosine-binding (PTB) domain; JIP is a mitogen-activated protein kinase scaffold protein. JIP consists of a C-terminal SH3 domain, followed by a PTB domain. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720389706 234 AKMRKSTEHMKKIPTIILSITYKGVKFIDASNKNVIA-------EHEIRNIS-CAAQdPEDLCTFAYITK--DLQTSHhy 303
Cdd:cd01212    32 ATARRLTVHLRPPQSCILEISDRGLKMVDRSKPNKKDgkpcihyFYSLKNISfCGFH-PRNSRYFGFITKhpLLQRFA-- 108

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1720389706 304 CHVF----STVDVNltyEIIltlGQAFEVAYQ 331
Cdd:cd01212   109 CHVFvsqeSTRPVA---ESV---GRAFQRFYQ 134

uncharacterized protein LOC417372 Phosphotyrosine-binding (PTB) PH-like fold; The function of LOC417372 and its related proteins are unknown to date. Members here contain a N-terminal RUN domain, followed by a PDZ domain, and a C-terminal PTB domain. The RUN domain is involved in Ras-like GTPase signaling. The PDZ domain (also called DHR/Dlg homologous region or GLGF after its conserved sequence motif) binds C-terminal polypeptides, internal (non-C-terminal) polypeptides, and lipids. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720389706 209 GYEANYLGSMLIKDLRGTESTQDACAKMRKStEHMKKIP-TIILSITykGVKFIDASNKNVIAEHEIRNISCAAQDPEDL 287
Cdd:cd13168     2 LYKALYLGQVEVGEDGGVEQIESAAIIVVLE-SDLTPKEvLLELGEI--GVTVWDKSTSEVLFKHSFPEISSCGRRVDDP 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1720389706 288 CTFAYITKDLQTS---HHYCHVFSTVDVNLTYEIILTLGQAF 326
Cdd:cd13168    79 NYFAYIAGDTPCSlakHFVCYVFEAADEEEAETILQGIAQGF 120

SAM domain of EPH-A8 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A8 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A8 receptors and appears to mediate cell-cell initiated signal transduction. EPH-A8 receptors are involved in ligand dependent (ephirin A2, A3, A5) regulation of cell adhesion and migration, and in ligand independent regulation of neurite outgrowth in neuronal cells. They perform signaling in kinase dependent and kinase independent manner. EPH-A8 receptors are known to interact with a number of different proteins including PI 3-kinase and AIDA1-like subfamily SAM repeat domain containing proteins. However other domains (not SAM) of EPH-A8 receptors are involved in these interactions.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1720389706  39 SPTSVPSWLDSLGLQDYVHSFLSSGYSSIDTVKNLwELELVNVLKVHLLGHRKRIIASL 97
Cdd:cd09550     1 SCLSVDDWLDSIKMGRYKDHFAAGGYSSLGMVMRM-NIEDIRRLGITLMGHQKKILTSI 58

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1720389706  41 TSVPSWLDSLGLQDYVHSFLSSGYSSIDTVKNLWELELVNVlKVHLLGHRKRIIASL 97
Cdd:cd09551     7 TSVEDWLSAIKMSQYRDNFLSSGFTSLQLVAQMTSEDLLRI-GVTLAGHQKKILNSI 62

SAM domain of Samd5 subfamily; SAM (sterile alpha motif) domain of Samd5 subfamily is a putative protein-protein interaction domain. Proteins of this subfamily have a SAM domain at the N-terminus. SAM is a widespread domain in signaling and regulatory proteins. In many cases SAM mediates dimerization/oligomerization. The exact function of proteins belonging to this subfamily is unknown.

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                  ....*....|....*....|....*....|....*....|....*....|....
gi 1720389706  40 PTSVPSWLDSLGLQDYVHSFLSSGYSSIDTVKNLWELELvNVLKVHLLGHRKRI 93
Cdd:cd09527     2 SNIVYDWLRTLQLEQYAEKFVDNGYDDLEVCKQIGDPDL-DAIGVMNPAHRKRI 54

SAM domain of EPH-A7 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A7 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A7 receptors and appears to mediate cell-cell initiated signal transduction. EphA7 was found expressed in human embryonic stem (ES) cells, neural tissues, kidney vasculature. EphA7 knockout mice show decrease in cortical progenitor cell death at mid-neurogenesis and significant increase in cortical size. EphA7 may be involved in the pathogenesis and development of different cancers; in particular, EphA7 was found upregulated in glioblastoma and downregulated in colorectal cancer and gastric cancer. Thus, it is a potential molecular marker and/or therapy target for these types of cancers.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1720389706  36 DGVSPTSVPSWLDSLGLQDYVHSFLSSGYSSIDTVKNLwELELVNVLKVHLLGHRKRIIASL 97
Cdd:cd09548     3 DFTSFCSVGEWLEAIKMERYKDNFTAAGYNSLESVARM-TIEDVMSLGITLVGHQKKIMSSI 63

GTPase activating protein for Rab 6 Phosphotyrosine-binding (PTB) domain; GAPCenA is a centrosome-associated GTPase activating protein (GAP) for Rab 6. It consists of an N-terminal PTB domain and a C-terminal TBC domain. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720389706 214 YLGSMLIKDLRGTESTQDACAKMRKSTEhmKKIPtIILSI--TYKG-VKFIDASNKNVIAEHEIRNIS-CA---AQDPED 286
Cdd:cd01211     8 YLGCAKVNAPRSETEALRIMAILREQSA--QPIK-VTLSVpnSSEGsVRLYDPTSNTEIASYPIYRILfCArgpDGTSES 84

                          90       100
                  ....*....|....*....|...
gi 1720389706 287 LCtFAYITKDLQTSHHYCHVFST 309
Cdd:cd01211    85 DC-FAFTWSHGETAIFQCHVFRC 106

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1720389706  41 TSVPSWLDSLGLQDYVHSFLSSGYSSIDTVKNLWELELvNVLKVHLLGHRKRIIASL 97
Cdd:cd09490     4 LDIAEWLASIHLEQYLDLFREHGYVTATDCQGINDSRL-KQIGISPTGHRRRILKQL 59

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720389706  40 PTSVPSWLDSLGLQDYVHSFLSSGYSSIDTVKNLWELELVNVlKVHLLGHRKRIIASLAD 99
Cdd:cd09491     5 PKTVSEWLMNLGLQQYEEGLMHNGWDSLEFLSDITEEDLEEA-GVTNPAHKRRLLDSLQD 63

SAM domain of caskin protein repeat 1; SAM (sterile alpha motif) domain repeat 1 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 apparently may play a role in neural development, synaptic protein targeting, and regulation of gene expression.

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                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1720389706  45 SWLDSLGLQDYVHSFLSSGYssidtvkNLWEL-----ELVNVLKVHLLGHRKRIIASLA 98
Cdd:cd09497     9 DWLREFGLEEYTPNFIKAGY-------DLPTIsrmtpEDLTAIGITKPGHRKKLKSEIA 60

SAM (Sterile alpha motif ), SASH1-like; SAM (sterile alpha motif) domain of SASH1-like proteins is a protein-protein interaction domain. Members of this subfamily are putative adaptor proteins. They appear to mediate signal transduction. Proteins of this subfamily are known to be involved in preventing DN thymocytes from premature initiation of programmed cell death and in B cells activation and differentiation. They have been found downregulated in some breast tumors, liver metastases and colon cancers if compare to corresponding normal tissues.

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                  ....*....|....*....|....*.
gi 1720389706   1 MEEQDLREIGISDPQHRRKLLQAARS 26
Cdd:cd09493    35 LKESHLNELNITDPEHRAKLLTAAEL 60

SAM (Sterile alpha motif ); SAM (Sterile Alpha Motif) domain is a module consisting of approximately 70 amino acids. This domain is found in the Fungi/Metazoa group and in a restricted number of bacteria. Proteins with SAM domains are represented by a wide variety of domain architectures and have different intracellular localization, including nucleus, cytoplasm and membranes. SAM domains have diverse functions. They can interact with proteins, RNAs and membrane lipids, contain site of phosphorylation and/or kinase docking site, and play a role in protein homo and hetero dimerization/oligomerization in processes ranging from signal transduction to regulation of transcription. Mutations in SAM domains have been linked to several diseases.

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                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1720389706  42 SVPSWLDSLGLQDYVhSFLSSGYSSIDTVKNLWELELVNvLKVHLLGHRKRIIASL 97
Cdd:cd09487     1 DVAEWLESLGLEQYA-DLFRKNEIDGDALLLLTDEDLKE-LGITSPGHRKKILRAI 54