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 1227962993 637 TQWRHSPQDLVSGSVNYVANYLGSTVVKELRGTESTKKSIQKLKKSstcTKDAKATPDIILAISYRGVKFLNTITKELVC 716
Cdd:cd01274     1 TQWRHSPEKLITGSVNYEAHYLGSTEIKELRGTESTKKAIQKLKKS---TREMKKIPTIILSISYKGVKFIDATTKNLIC 77

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1227962993 717 GHEIRNIHCACQDADDLTHFAYITKDHASKGHYCHVFCVQTMDQATEVILTLGQAFEVAYQMALRDQVT 785
Cdd:cd01274    78 EHEIRNISCACQDPEDLNTFAYITKDLKTDHHYCHVFCVLTVDLATEIILTLGQAFEVAYQLALRAQKS 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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1227962993 389 SVGQWLGGLGLADYESLLRNNGYDDLDFI-CGVLEDQDLKELGIDNEQDRKVILESAGSLPCKV 451
Cdd:cd09499     4 SVGQWLESIGLPQYESKLLLNGFDDVDFLgSGVMEDQDLKEIGITDEQHRQIILQAARSLPKKK 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 1227962993 637 TQWRHSPQDLVSGSVNYVANYLGSTVVKELRGTESTKKSIQKLKKSstcTKDAKATPDIILAISYRGVKFLNTITKELVC 716
Cdd:cd01274     1 TQWRHSPEKLITGSVNYEAHYLGSTEIKELRGTESTKKAIQKLKKS---TREMKKIPTIILSISYKGVKFIDATTKNLIC 77

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1227962993 717 GHEIRNIHCACQDADDLTHFAYITKDHASKGHYCHVFCVQTMDQATEVILTLGQAFEVAYQMALRDQVT 785
Cdd:cd01274    78 EHEIRNISCACQDPEDLNTFAYITKDLKTDHHYCHVFCVLTVDLATEIILTLGQAFEVAYQLALRAQKS 146

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 1227962993 389 SVGQWLGGLGLADYESLLRNNGYDDLDFI-CGVLEDQDLKELGIDNEQDRKVILESAGSLPCKV 451
Cdd:cd09499     4 SVGQWLESIGLPQYESKLLLNGFDDVDFLgSGVMEDQDLKEIGITDEQHRQIILQAARSLPKKK 67

Phosphotyrosine interaction domain (PTB/PID);

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1227962993 653 YVANYLGST-VVKELRGTESTKKSI----------QKLKKSSTCTKDAKATPDIILAISYRGVKFLNTITKELVCGHEIR 721
Cdd:pfam00640   1 FAVRYLGSVeVPEERAPDKNTRMQQareairrvkaAKINKIRGLSGETGPGTKVDLFISTDGLKLLNPDTQELIHDHPLV 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1227962993 722 NI-HCACQDADDLTHFAYITKDHASKGHYCHVF-CVqtmDQATEVILTLGQAFEVA 775
Cdd:pfam00640  81 SIsFCADGDPDLMRYFAYIARDKATNKFACHVFeSE---DGAQDIAQSIGQAFALA 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
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1227962993  388 SSVGQWLGGLGLADYESLLRNNGYDDLDFIcGVLEDQDLKELGIDNEQDRKVILES 443
Cdd:smart00454   7 ESVADWLESIGLEQYADNFRKNGIDGALLL-LLTSEEDLKELGITKLGHRKKILKA 61

SAM domain (Sterile alpha motif);

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1227962993 387 TSSVGQWLGGLGLADYESLLRNNGYDDLDFICGvLEDQDLKELGIDNEQDRKVILESAGSL 447
Cdd:pfam07647   6 LESVADWLRSIGLEQYTDNFRDQGITGAELLLR-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 1227962993 637 TQWRHSPQDLVSGSVNYVANYLGSTVVKELRGTESTKKSIQKLKKSstcTKDAKATPDIILAISYRGVKFLNTITKELVC 716
Cdd:cd01274     1 TQWRHSPEKLITGSVNYEAHYLGSTEIKELRGTESTKKAIQKLKKS---TREMKKIPTIILSISYKGVKFIDATTKNLIC 77

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1227962993 717 GHEIRNIHCACQDADDLTHFAYITKDHASKGHYCHVFCVQTMDQATEVILTLGQAFEVAYQMALRDQVT 785
Cdd:cd01274    78 EHEIRNISCACQDPEDLNTFAYITKDLKTDHHYCHVFCVLTVDLATEIILTLGQAFEVAYQLALRAQKS 146

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 1227962993 389 SVGQWLGGLGLADYESLLRNNGYDDLDFI-CGVLEDQDLKELGIDNEQDRKVILESAGSLPCKV 451
Cdd:cd09499     4 SVGQWLESIGLPQYESKLLLNGFDDVDFLgSGVMEDQDLKEIGITDEQHRQIILQAARSLPKKK 67

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 1227962993 641 HSPQDLVSGSVNYVANYLGSTVVKELRGTESTKKSIQKLK-----KSSTCTKdakaTPDIILAISYRGVKFLNTITKELV 715
Cdd:cd01273     2 HPPEALIKGHVAYLVKFLGCTEVEQPKGTEVVKEAIRKLKfarqlKKSEGAK----LPKVELQISIDGVKIQDPKTKVIM 77

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1227962993 716 CGHEIRNI-HCAcQDADDLTHFAYITKDHASKGHYCHVFCVQTMdqATEVILTLGQAFEVAYQMAL 780
Cdd:cd01273    78 HQFPLHRIsFCA-DDKTDKRIFSFIAKDSESEKHLCFVFDSEKL--AEEITLTIGQAFDLAYRRFL 140

Phosphotyrosine interaction domain (PTB/PID);

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1227962993 653 YVANYLGST-VVKELRGTESTKKSI----------QKLKKSSTCTKDAKATPDIILAISYRGVKFLNTITKELVCGHEIR 721
Cdd:pfam00640   1 FAVRYLGSVeVPEERAPDKNTRMQQareairrvkaAKINKIRGLSGETGPGTKVDLFISTDGLKLLNPDTQELIHDHPLV 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1227962993 722 NI-HCACQDADDLTHFAYITKDHASKGHYCHVF-CVqtmDQATEVILTLGQAFEVA 775
Cdd:pfam00640  81 SIsFCADGDPDLMRYFAYIARDKATNKFACHVFeSE---DGAQDIAQSIGQAFALA 133

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 1227962993 657 YLGSTVVKELRGTESTK---KSIQKLKKSStctkdAKATPDIILAISYRGVKFLNTITKELVCGHEIRNI-HCACQDADD 732
Cdd:cd13159     9 YLGSTLVEKPKGEGATAeavKTIIAMAKAS-----GKKLQKVTLTVSPKGIKVTDSATNETILEVSIYRIsYCTADANHD 83

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1227962993 733 LThFAYITKDHASKGHYCHVFCVQTMDQATEVILTLGQAFE 773
Cdd:cd13159    84 KV-FAFIATNQDNEKLECHAFLCAKRKMAQAVTLTVAQAFN 123

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
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1227962993 492 VDRWLRSIRLDIYRDTFRKHlYTDMDRVRRIWEVELTAvLEIHRVGHRKRILASV 546
Cdd:pfam00536   8 VGEWLESIGLGQYIDSFRAG-YIDGDALLQLTEDDLLK-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
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1227962993  388 SSVGQWLGGLGLADYESLLRNNGYDDLDFIcGVLEDQDLKELGIDNEQDRKVILES 443
Cdd:smart00454   7 ESVADWLESIGLEQYADNFRKNGIDGALLL-LLTSEEDLKELGITKLGHRKKILKA 61

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 1227962993 389 SVGQWLGGLGLADYESLLRNNGYDDLDFICgvLEDQDLKELGIDNEQDRKVIL 441
Cdd:cd09487     1 DVAEWLESLGLEQYADLFRKNEIDGDALLL--LTDEDLKELGITSPGHRKKIL 51

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        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1227962993 386 GTSSVGQWLGGLGLADYESLLRNNGYDDLDfICGVLEDQDLKELGIDNEQDRKVILE 442
Cdd:cd09527     1 CSNIVYDWLRTLQLEQYAEKFVDNGYDDLE-VCKQIGDPDLDAIGVMNPAHRKRILE 56

SAM domain (Sterile alpha motif);

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1227962993 387 TSSVGQWLGGLGLADYESLLRNNGYDDLDFICGvLEDQDLKELGIDNEQDRKVILESAGSL 447
Cdd:pfam07647   6 LESVADWLRSIGLEQYTDNFRDQGITGAELLLR-LTLEDLKRLGITSVGHRRKILKKIQEL 65

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 1227962993 647 VSGSVNYVANYLGSTVVKELRGtESTKKSIQKLKKSSTCTKDakatpdIILAISYRGVKFLNTITKELVCGHEIRNI-HC 725
Cdd:cd13157     2 VSRNAQYIGSFPVSGLDVADRA-DSVRKQLESLKESGSRGRP------VILSVSLSGIKICSEDGKVVLMAHALRRVsYS 74

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1227962993 726 ACQDADDLthFAYITKD---HASKgHYCHVFCVQTMDQATEVILTLGQAFEVAY 776
Cdd:cd13157    75 TCRPAHAQ--FAFVARNpggPTNR-QYCHVFVTRSPREAQELNLLLCRAFQLAY 125

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 1227962993 490 SAVDRWLRSIRLDIYRDTFRKHLYTDMDRVRRIWEVELTAvLEIHRVGHRKRILASVSS 548
Cdd:cd09554     4 GSVGEWLRAIKMERYEDSFLQAGFTTFQLVSQISTEDLLR-MGVTLAGHQKKILSSIQA 61

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 1227962993 638 QWRHSPQDLVSGSVNYVANYLGSTVVKELRGTESTKKSIQKLKKSStctkdaKATPDIILAISYRGVKFLNTITKELVCG 717
Cdd:cd01268     2 QWQADEEAVRSGTCSFPVKYLGCVEVGESRGMQVCEEALKKLKASR------KKPVRAVLWVSGDGLRVVDEKTKGLIVD 75

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1227962993 718 HEIRNIH-CAcQDADDLTHFAYITKDHASKGHYCHVF 753
Cdd:cd01268    76 QTIEKVSfCA-PDRNHERAFSYICRDGTTRRWMCHCF 111

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 1227962993 492 VDRWLRSIRLDIYRDTFRKHlYTDMDRVRRIWEVELTAvLEIHRVGHRKRILASV 546
Cdd:cd09487     2 VAEWLESLGLEQYADLFRKN-EIDGDALLLLTDEDLKE-LGITSPGHRKKILRAI 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
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1227962993 489 ESAVDRWLRSIRLDIYRDTFRKHLYTDMDRVRRIWEVELTAvLEIHRVGHRKRILA 544
Cdd:cd09490     3 DLDIAEWLASIHLEQYLDLFREHGYVTATDCQGINDSRLKQ-IGISPTGHRRRILK 57

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        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1227962993 490 SAVDRWLRSIRLDIYRDTFRKHLYTDMDRVRRIWEVELTAvLEIHRVGHRKRILASV 546
Cdd:cd09527     3 NIVYDWLRTLQLEQYAEKFVDNGYDDLEVCKQIGDPDLDA-IGVMNPAHRKRILEAV 58

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
                  ....*....|....*....|....*....|....*....|....*
gi 1227962993 388 SSVGQWLGGLGLADYESLLRNNGYDDLDFICGvLEDQDLKELGID 432
Cdd:cd09498     8 NDLLEWLSLLGLPQYHKVLVENGYDSIDFVTD-LTWEDLQDIGIT 51

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 1227962993 387 TSSVGQWLGGLGLADYESLLRNNGYDDLDFIcgVLEDQDLKELGIDNEQDRKVI 440
Cdd:cd09512     9 VQQVCQWLMGLGLEQYIPEFTANNIDGQQLL--QLDSSKLKALGITSSSDRSLL 60

SAM domain of EPH-A5 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A5 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A5 receptors and appears to mediate cell-cell initiated signal transduction. Eph-A5 gene is almost exclusively expressed in the nervous system. Murine EPH-A5 receptors participate in axon guidance during embryogenesis and play a role in the adult synaptic plasticity, particularly in neuron-target interactions in multiple neural circuits. Additionally EPH-A5 receptors and its ligand ephrin A5 regulate dopaminergic axon outgrowth and influence the formation of the midbrain dopaminergic pathways. EphA5 gene expression was found decreased in a few different breast cancer cell lines, thus it might be a potential molecular marker for breast cancer carcinogenesis and progression.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1227962993 487 GDESAVDRWLRSIRLDIYRDTFRKHLYTDMDRVRRIwEVELTAVLEIHRVGHRKRILASVSSQHPH 552
Cdd:cd09546     1 GAYRSVGEWLEAIKMGRYTEIFMENGYSSMDAVAQV-TLEDLRRLGVTLVGHQKKIMNSIQEMRVQ 65

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 1227962993 389 SVGQWLGGLGLADYESLLRNNGYDDLDFICGvLEDQDLKELGIDNEQDRKVILESA 444
Cdd:cd09493     4 TVEELLERINLQEHTSTLLLNGYETLEDFKD-LKESHLNELNITDPEHRAKLLTAA 58

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1227962993 388 SSVGQWLGGLGLADYESLLRNNGYDDLDFIcGVLEDQDLKELGIDNEQDRKVILESAGSLPCKV 451
Cdd:cd09549     8 GSVGEWLEALDLCRYKDNFAAAGYGSLEAV-ARMTAQDVLSLGITSLEHQELLLAGIQALRAQV 70

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1227962993 385 GGTSSVGQWLGGLGLADYESLLRNNGYDDLDFICGvLEDQDLKELGIDNEQDRKVILESAGSL 447
Cdd:cd09492     5 GHVSSVSDWLVSIGLPMYSPPLLEAGFSTLSRVSS-LSETCLREAGITEERHIRKLLSAARLV 66

Low Density Lipoprotein Receptor Adaptor Protein 1 (LDLRAP1) in insects 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 insects, ticks, sea urchins, and nematodes.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1227962993 657 YLGSTVVKELRGTESTKKSIQKLKKSStctKDAKATPDIILAISYRGVKFLNTITKELVCGHEIRNIHCACQDADDLTH- 735
Cdd:cd13160     7 YLGRMPARGLWGIKHTRKPLVDALKNL---PKGKTLPKTKLEVSSDGVKLEELRGGFGSSKTVFFPIHTISYGVQDLVHt 83

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1227962993 736 --FAYITK-DHASKGHY--CHVFCVQTMDQATEVILTLGQAF 772
Cdd:cd13160    84 rvFSMIVVgEQDSSNHPfeCHAFVCDSRADARNLTYWLAKAF 125