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 1201920975 201 QYWQHHPEKLIFQSCDYKAFYLGSMLIKELRGTESTQDACAKMRancqKSTEQMKKVPTIILSVSYKGVKFIDATNKNII 280
Cdd:cd01274     1 TQWRHSPEKLITGSVNYEAHYLGSTEIKELRGTESTKKAIQKLK----KSTREMKKIPTIILSISYKGVKFIDATTKNLI 76

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1201920975 281 AEHEIRNISCAAQDPEDLSTFAYITKDLKSNHHYCHVFTAFDVNLAYEIILTLGQAFEVAYQLALQARKG 350
Cdd:cd01274    77 CEHEIRNISCACQDPEDLNTFAYITKDLKTDHHYCHVFCVLTVDLATEIILTLGQAFEVAYQLALRAQKS 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        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1201920975 108 DGYHPTSVAEWLDSIELGDYTKAFLINGYTSMDLLKKIWEVELINqssVCEI 159
Cdd:cd09500     1 DGNSPASVSEWLDSIGLGDYIETFLKHGYTSMERVKRIWEVELTN---VLEI 49

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 1201920975 201 QYWQHHPEKLIFQSCDYKAFYLGSMLIKELRGTESTQDACAKMRancqKSTEQMKKVPTIILSVSYKGVKFIDATNKNII 280
Cdd:cd01274     1 TQWRHSPEKLITGSVNYEAHYLGSTEIKELRGTESTKKAIQKLK----KSTREMKKIPTIILSISYKGVKFIDATTKNLI 76

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1201920975 281 AEHEIRNISCAAQDPEDLSTFAYITKDLKSNHHYCHVFTAFDVNLAYEIILTLGQAFEVAYQLALQARKG 350
Cdd:cd01274    77 CEHEIRNISCACQDPEDLNTFAYITKDLKTDHHYCHVFCVLTVDLATEIILTLGQAFEVAYQLALRAQKS 146

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 1201920975  213 QSCDYKAFYLGSMLIKELRGTESTQDACAKMRAncqKSTEQMKKVPTIILSVSYKGVKFIDATNKNIIAEHEIRNISCAA 292
Cdd:smart00462   2 SGVSFRVKYLGSVEVPEARGLQVVQEAIRKLRA---AQGSEKKEPQKVILSISSRGVKLIDEDTKAVLHEHPLRRISFCA 78

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1201920975  293 QDPEDLSTFAYITKDLKSNHHYCHVFTAFDVnlAYEIILTLGQAFEVAYQLALQARK 349
Cdd:smart00462  79 VGPDDLDVFGYIARDPGSSRFACHVFRCEKA--AEDIALAIGQAFQLAYELKLKARS 133

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 1201920975   34 PRCPVQTVGQWLESIGLPQYENHLMANGFDNVQFMgsNVMEDQDLLEIGILNSGHRQRILQAIQLL 99
Cdd:smart00454   2 SQWSPESVADWLESIGLEQYADNFRKNGIDGALLL--LLTSEEDLKELGITKLGHRKKILKAIQKL 65

Phosphotyrosine interaction domain (PTB/PID);

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1201920975 217 YKAFYLGSMLIKELR------GTESTQDA--CAKMRANCQKSTEQMKKVP--TIILSVSYKGVKFIDATNKNIIAEHEIR 286
Cdd:pfam00640   1 FAVRYLGSVEVPEERapdkntRMQQAREAirRVKAAKINKIRGLSGETGPgtKVDLFISTDGLKLLNPDTQELIHDHPLV 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1201920975 287 NIS-CAAQDPEDLSTFAYITKDLKSNHHYCHVFTAFDvnLAYEIILTLGQAFEVA 340
Cdd:pfam00640  81 SISfCADGDPDLMRYFAYIARDKATNKFACHVFESED--GAQDIAQSIGQAFALA 133

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
                   ....*....|....*....|....*....|....*....|...
gi 1201920975  108 DGYHPTSVAEWLDSIELGDYTKAFLINGYTSMDLLKKIWEVEL 150
Cdd:smart00454   2 SQWSPESVADWLESIGLEQYADNFRKNGIDGALLLLLTSEEDL 44

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 1201920975 201 QYWQHHPEKLIFQSCDYKAFYLGSMLIKELRGTESTQDACAKMRancqKSTEQMKKVPTIILSVSYKGVKFIDATNKNII 280
Cdd:cd01274     1 TQWRHSPEKLITGSVNYEAHYLGSTEIKELRGTESTKKAIQKLK----KSTREMKKIPTIILSISYKGVKFIDATTKNLI 76

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1201920975 281 AEHEIRNISCAAQDPEDLSTFAYITKDLKSNHHYCHVFTAFDVNLAYEIILTLGQAFEVAYQLALQARKG 350
Cdd:cd01274    77 CEHEIRNISCACQDPEDLNTFAYITKDLKTDHHYCHVFCVLTVDLATEIILTLGQAFEVAYQLALRAQKS 146

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 1201920975  213 QSCDYKAFYLGSMLIKELRGTESTQDACAKMRAncqKSTEQMKKVPTIILSVSYKGVKFIDATNKNIIAEHEIRNISCAA 292
Cdd:smart00462   2 SGVSFRVKYLGSVEVPEARGLQVVQEAIRKLRA---AQGSEKKEPQKVILSISSRGVKLIDEDTKAVLHEHPLRRISFCA 78

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1201920975  293 QDPEDLSTFAYITKDLKSNHHYCHVFTAFDVnlAYEIILTLGQAFEVAYQLALQARK 349
Cdd:smart00462  79 VGPDDLDVFGYIARDPGSSRFACHVFRCEKA--AEDIALAIGQAFQLAYELKLKARS 133

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 1201920975 205 HHPEKLIFQSCDYKAFYLGSMLIKELRGTESTQDACAKMRANCQKSTEQMKKVPTIILSVSYKGVKFIDATNKNIIAEHE 284
Cdd:cd01273     2 HPPEALIKGHVAYLVKFLGCTEVEQPKGTEVVKEAIRKLKFARQLKKSEGAKLPKVELQISIDGVKIQDPKTKVIMHQFP 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1201920975 285 IRNISCAAQDPEDLSTFAYITKDLKSNHHYCHVFTAfdVNLAYEIILTLGQAFEVAYQLALQ 346
Cdd:cd01273    82 LHRISFCADDKTDKRIFSFIAKDSESEKHLCFVFDS--EKLAEEITLTIGQAFDLAYRRFLE 141

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 1201920975   34 PRCPVQTVGQWLESIGLPQYENHLMANGFDNVQFMgsNVMEDQDLLEIGILNSGHRQRILQAIQLL 99
Cdd:smart00454   2 SQWSPESVADWLESIGLEQYADNFRKNGIDGALLL--LLTSEEDLKELGITKLGHRKKILKAIQKL 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 1201920975  37 PVQTVGQWLESIGLPQYENHLMAnGFDNVQFMGSnvMEDQDLLEIGILNSGHRQRILQAIQLL 99
Cdd:pfam00536   4 SVEDVGEWLESIGLGQYIDSFRA-GYIDGDALLQ--LTEDDLLKLGVTLLGHRKKILYAIQRL 63

Low Density Lipoprotein Receptor Adaptor Protein 1 (LDLRAP1) in mammals and similar proteins Phosphotyrosine-binding (PTB) PH-like fold; The null mutations in the LDL receptor adaptor protein 1 (LDLRAP1) gene, which serves as an adaptor for LDLR endocytosis in the liver, causes autosomal recessive hypercholesterolemia (ARH). LDLRAP1 contains a single 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 contains mammals, insects, and sponges.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1201920975 217 YKAFYLGSMLIKELRGTESTQDACAKMRAnCQKSTEqmKKVPTIILSVSYKGVKFIDATNKNIIAEHEIRNIS-CAAqDP 295
Cdd:cd13159     5 FYLKYLGSTLVEKPKGEGATAEAVKTIIA-MAKASG--KKLQKVTLTVSPKGIKVTDSATNETILEVSIYRISyCTA-DA 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1201920975 296 EDLSTFAYITKDLKSNHHYCHVFTAFDVNLAYEIILTLGQAFE 338
Cdd:cd13159    81 NHDKVFAFIATNQDNEKLECHAFLCAKRKMAQAVTLTVAQAFN 123

Shc-like phosphotyrosine-binding (PTB) domain; Shc is a substrate for receptor tyrosine kinases, which can interact with phosphoproteins at NPXY motifs. Shc contains an PTB domain followed by an 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. This cd is part of the Shc-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1201920975 259 TIILSVSYKGVKFIDATNKNIIAEHEIRNISCAA-QDPEDLSTFAYITKDlKSNHHYCHVFTAFDvNLAYEIILTLGQAF 337
Cdd:cd01209    84 NISLTISTDGLNLVTPDTGQIIANHHMQSISFASgGDPDTYDYVAYVAKD-PVNQRACHVLECGD-GLAQDVIATIGQAF 161

                  ....*....
gi 1201920975 338 EVAYQLALQ 346
Cdd:cd01209   162 ELRFKQYLK 170

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 1201920975 201 QYWQHHPEKLIFQSCDYKAFYLGSMLIKELRGTESTQDACAKMRANcqksteqMKKVPTIILSVSYKGVKFIDATNKNII 280
Cdd:cd01268     1 HQWQADEEAVRSGTCSFPVKYLGCVEVGESRGMQVCEEALKKLKAS-------RKKPVRAVLWVSGDGLRVVDEKTKGLI 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1201920975 281 AEHEIRNISCAAQDPEDLSTFAYITKDLKSNHHYCHVFTA 320
Cdd:cd01268    74 VDQTIEKVSFCAPDRNHERAFSYICRDGTTRRWMCHCFLA 113

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 1201920975 216 DYKAFYLGSMLIKELRGTESTQDACAKMRaNCQKSTEQMKKvpTIILSVSYKGVKFIDATNKNIIAEHEIRNISCAAQDP 295
Cdd:cd01215    17 RFKAKLIGIDEVPAARGDKMCQDAMMKLK-GAVKAAGEHKQ--RIWLNISLEGIKILDEKTGALLHHHPVHKISFIARDT 93

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1201920975 296 EDLSTFAYITKdLKSNHHYCHVFTAfdvNLAYEIILTLGQAFEVAYQL 343
Cdd:cd01215    94 TDNRAFGYVCG-LDGGHRFFAIKTA---KAAEPVVLDLRDLFQVVFEL 137

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1201920975  37 PVQTVGQWLESIGLPQYENHLMANGFDNvqfMGSNV-MEDQDLLEIGILNSGHRQRILQAIQLL 99
Cdd:cd09488     1 AFRSVGEWLESIKMGRYKENFTAAGYTS---LDAVAqMTAEDLTRLGVTLVGHQKKILNSIQAL 61

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1201920975  40 TVGQWLESIGLPQYENHLMANGFDNVQFMGSnvMEDQDLLEIGILNSGHRQRILQAIQLL 99
Cdd:cd09547     5 TVSDWLDSIKMGQYKNNFMAAGFTTLDMVSR--MTIDDIRRIGVTLIGHQRRIVSSIQTL 62

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 1201920975  40 TVGQWLESIGLPQYENHLMANGFDNVQFMGSnvMEDQDLLEIGILNSGHRQRILQAIQ 97
Cdd:cd09551     8 SVEDWLSAIKMSQYRDNFLSSGFTSLQLVAQ--MTSEDLLRIGVTLAGHQKKILNSIQ 63

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 1201920975  40 TVGQWLESIGLPQYENHLMANGFDNVQFMGSNVMEdqDLLEIGILNSGHRQRILQAI 96
Cdd:cd09498     9 DLLEWLSLLGLPQYHKVLVENGYDSIDFVTDLTWE--DLQDIGITKLGHQKKLMLAI 63

SAM domain of EPH-B4 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B4 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B4 receptors and appears to mediate cell-cell initiated signal transduction. EPH-B4 protein kinase performs kinase-dependent and kinase-independent functions. These receptors play a role in the regular vascular system development during embryogenesis. They were found overexpressed in a variety of cancers, including carcinoma of the head and neck, ovarian cancer, bladder cancer, and downregulated in bone myeloma. Thus, EphB4 is a potential biomarker and a target for drug design.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1201920975  40 TVGQWLESIGLPQYENHLMANGFDNVQFMgSNVmEDQDLLEIGILNSGHRQRILQAIQ 97
Cdd:cd09554     5 SVGEWLRAIKMERYEDSFLQAGFTTFQLV-SQI-STEDLLRMGVTLAGHQKKILSSIQ 60

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1201920975  43 QWLESIGLPQYENHLMANGFDnvqfMGS-NVMEDQDLLEIGILNSGHRQRILQAIQLLPK 101
Cdd:cd09497     9 DWLREFGLEEYTPNFIKAGYD----LPTiSRMTPEDLTAIGITKPGHRKKLKSEIAQLQI 64

SAM domain of EPH-A10 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A10 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A10 receptors and appears to mediate cell-cell initiated signal transduction. It was found preferentially expressed in the testis. EphA10 may be involved in the pathogenesis and development of prostate carcinoma and lymphocytic leukemia. It is a potential molecular marker and/or therapy target for these types of cancers.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1201920975  40 TVGQWLESIGLPQYENHLMANGFDNVQFMGSnvMEDQDLLEIGILNSGHRQRILQAIQLL 99
Cdd:cd09549     9 SVGEWLEALDLCRYKDNFAAAGYGSLEAVAR--MTAQDVLSLGITSLEHQELLLAGIQAL 66

SAM domain of EPH-B2 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B2 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B2 receptors and appears to mediate cell-cell initiated signal transduction. SAM domains of this subfamily form homodimers/oligomers (in head-to-head/tail-to-tail orientation); apparently such clustering is necessary for signaling. EPH-B2 receptor is involved in regulation of synaptic function; it is needed for normal vestibular function, proper formation of anterior commissure, control of cell positioning, and ordered migration in the intestinal epithelium. EPH-B2 plays a tumor suppressor role in colorectal cancer. It was found to be downregulated in gastric cancer and thus may be a negative biomarker for it.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1201920975  40 TVGQWLESIGLPQYENHLMANGFDNVQFMGSNVMEdqDLLEIGILNSGHRQRILQAIQLL 99
Cdd:cd09552     8 TVDEWLDAIKMGQYKESFANAGFTSFDVVSQMTME--DILRVGVTLAGHQKKILNSIQVM 65

SAM domain of Ste50_like (ubc2) subfamily; SAM (sterile alpha motif) domain of Ste50-like (or Ubc2 for Ustilago bypass of cyclase) subfamily is a putative protein-protein interaction domain. This group includes only fungal proteins. Basidiomycetes have an N-terminal SAM domain, central UBQ domain, and C-terminal SH3 domain, while Ascomycetes lack the SH3 domain. Ubc2 of Ustilago maydis is a major virulence and maize pathogenicity factor. It is required for filamentous growth (the budding haploid form of Ustilago maydis is a saprophyte, while filamentous dikaryotic form is a pathogen). Also the Ubc2 protein is involved in the pheromone-responsive morphogenesis via the MAP kinase cascade. The SAM domain is necessary for ubc2 function; deletion of SAM eliminates this function. A Lys-to-Glu mutation in the SAM domain of ubc2 gene induces temperature sensitivity.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1201920975  41 VGQWLESIGLPQYENHLMANGFDNVQFMgsnVMEDQDLLEIGILNSGHRQRILQAI 96
Cdd:cd09533     2 VADWLSSLGLPQYEDQFIENGITGDVLV---ALDHEDLKEMGITSVGHRLTILKAV 54

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1201920975  37 PVQTVGQWLESIGLPQYENHLMANGFDNVQ-FMGSNvmeDQDLLEIGILNSGHRQRILQAIQ 97
Cdd:cd09490     2 ADLDIAEWLASIHLEQYLDLFREHGYVTATdCQGIN---DSRLKQIGISPTGHRRRILKQLP 60

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1201920975  38 VQTVGQWLESIGLPQYENHLMANGFDNVQFMGSnvMEDQDLLEIGILNSGHRQRILQAIQLL 99
Cdd:cd09492     7 VSSVSDWLVSIGLPMYSPPLLEAGFSTLSRVSS--LSETCLREAGITEERHIRKLLSAARLV 66

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1201920975  40 TVGQWLESIGLPQYENHLMANGFDNVQFMGSnvMEDQDLLEIGILNSGHRQRILQAIQLL 99
Cdd:cd09550     4 SVDDWLDSIKMGRYKDHFAAGGYSSLGMVMR--MNIEDIRRLGITLMGHQKKILTSIQVM 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
                  ....*....|....*....|....*....|....
gi 1201920975 112 PTSVAEWLDSIELGDYTKAFLINGYTSMDLLKKI 145
Cdd:cd09488     2 FRSVGEWLESIKMGRYKENFTAAGYTSLDAVAQM 35

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1201920975 221 YLGSMLIKELRGTESTQDACAKMRANCQKSTEqmkkvptIILSV--SYKG-VKFIDATNKNIIAEHEIRNIS-CA--AQD 294
Cdd:cd01211     8 YLGCAKVNAPRSETEALRIMAILREQSAQPIK-------VTLSVpnSSEGsVRLYDPTSNTEIASYPIYRILfCArgPDG 80

                          90       100
                  ....*....|....*....|....
gi 1201920975 295 PEDLSTFAYITKDLKSNHHYCHVF 318
Cdd:cd01211    81 TSESDCFAFTWSHGETAIFQCHVF 104

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
                  ....*....|....*....|....*....|...
gi 1201920975 108 DGYHPTSVAEWLDSIELGDYTKAFLINGYTSMD 140
Cdd:cd09543     1 EGVPFRTVAEWLESIKMQQYTEHFMAAGYNSID 33

SAM domain of Shank1,2,3 family proteins; SAM (sterile alpha motif) domain of Shank1,2,3 family proteins is a protein-protein interaction domain. Shank1,2,3 proteins are scaffold proteins that are known to interact with a variety of cytoplasmic and membrane proteins. SAM domains of the Shank1,2,3 family are prone to homooligomerization. They are highly enriched in the postsynaptic density, acting as scaffolds to organize assembly of postsynaptic proteins. SAM domains of Shank3 proteins can form large sheets of helical fibers. Shank genes show distinct patterns of expression, in rat Shank1 mRNA is found almost exclusively in brain, Shank2 in brain, kidney and liver, and Shank3 in heart, brain and spleen.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1201920975  38 VQTVGQWLESIGLPQYENHLMANGFDnvqfmGSNV--MEDQDLLEIGILNSGHRQRILQAIQLL 99
Cdd:cd09506     7 VDDVGDWLESLNLGEHRERFMDNEID-----GSHLpnLDKEDLTELGVTRVGHRMNIERALKKL 65

X11-like Phosphotyrosine-binding (PTB) domain; The function of the neuronal protein X11 is unknown to date. X11 has a PTB domain followed by two PDZ 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 1201920975 219 AFYLGSMLIKELRGTEST------QDACAKMRA---NCQKSTEqmkkvptIILSVSYKGVKFIDATNKNIIAEHEIRNIS 289
Cdd:cd01208    12 ANYLGSTQLLSERNPSKNvrmaqaQEAVSRVKApegESQPSTE-------VDLFISTERIKVLNADTQETMMDHALRTIS 84

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1201920975 290 CAA-----------------QDPEDLSTFAYITKDLKSNHHYCHVFTAFDVNLayeIILTLGQAFEVAYQLALQA 347
Cdd:cd01208    85 YIAdignivvlmarrrmprsSSQECVETTPPSQEGKRQYKMICHVFESEDAQL---IAQSIGQAFSVAYQEFLRA 156

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
                  ....*....|....*....|....*....|..
gi 1201920975 114 SVAEWLDSIELGDYTKAFLINGYTSMDLLKKI 145
Cdd:cd09547     5 TVSDWLDSIKMGQYKNNFMAAGFTTLDMVSRM 36

SAM domain of EPH-B4 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B4 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B4 receptors and appears to mediate cell-cell initiated signal transduction. EPH-B4 protein kinase performs kinase-dependent and kinase-independent functions. These receptors play a role in the regular vascular system development during embryogenesis. They were found overexpressed in a variety of cancers, including carcinoma of the head and neck, ovarian cancer, bladder cancer, and downregulated in bone myeloma. Thus, EphB4 is a potential biomarker and a target for drug design.

                          10        20        30
                  ....*....|....*....|....*....|..
gi 1201920975 114 SVAEWLDSIELGDYTKAFLINGYTSMDLLKKI 145
Cdd:cd09554     5 SVGEWLRAIKMERYEDSFLQAGFTTFQLVSQI 36

SAM domain of SAM_Neurabin-like subfamily; SAM (sterile alpha motif) domain of Neurabin-like (Neural actin-binding) subfamily is a putative protein-protein interaction domain. This group currently includes the SAM domains of neurobin-I, SAMD14 and neurobin-I/SAMD14-like proteins. Most are multidomain proteins and in addition to SAM domain they contain other protein-binding domains such as PDZ and actin-binding domains. Members of this subfamily participate in signal transduction. Neurabin-I is involved in the regulation of Ca signaling intensity in alpha-adrenergic receptors; it forms a functional pair of opposing regulators with neurabin-II. Neurabins are expressed almost exclusively in neuronal cells. They are known to interact with protein phosphatase 1 and inhibit its activity; they also can bind actin filaments; however, the exact role of the SAM domain is unclear, since SAM doesn't participate in these interactions.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1201920975  38 VQTVGQWLESIGLPQYENHLMANGFDNVQFMGsnvMEDQDLLEIGILNSGHRQRI 92
Cdd:cd09512     9 VQQVCQWLMGLGLEQYIPEFTANNIDGQQLLQ---LDSSKLKALGITSSSDRSLL 60

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1201920975 112 PTSVAEWLDSIELGDYTKAFLINGYTSMDLLKKIWEVELI 151
Cdd:cd09527     2 SNIVYDWLRTLQLEQYAEKFVDNGYDDLEVCKQIGDPDLD 41

SAM domain of liprin-beta1,2 proteins repeat 1; SAM (sterile alpha motif) domain repeat 1 of liprin-beta1,2 proteins is a protein-protein interaction domain. Liprin-beta protein contain three copies (repeats) of SAM domain. They may form heterodimers with liprins-alpha through their SAM domains. It was suggested based on bioinformatic approaches that the second SAM domain of liprin-beta is potentially able to form polymers. Liprins were originally identified as LAR (leukocyte common antigen-related) transmembrane protein-tyrosine phosphatase-interacting proteins. They participate in mammary gland development, in axon guidance, and in the maintenance of lymphatic vessel integrity.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1201920975  37 PVQTVGQWLESIGLPQYENHLMANGFDNVQFMGsnvMEDQDL-LEIGILNSGHRQRILQAIQ 97
Cdd:cd09563     5 STEQVCDWLAELGLGQYVDECRRWVKSGQTLLK---ASPQELeKELGIKHPLHRKKLQLALQ 63

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1201920975 112 PTSVAEWLDSIELGDYTKAFLINGYTSMDLLKKIWEVELI 151
Cdd:cd09493     2 PKTVEELLERINLQEHTSTLLLNGYETLEDFKDLKESHLN 41

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
                  ....*....|....*....|....*....|....*....
gi 1201920975 113 TSVAEWLDSIELGDYTKAFLINGYTSMDLLKKIWEVELI 151
Cdd:cd09553     7 TTVGDWLDAIKMGRYKENFVSAGFASFDLVAQMTAEDLL 45