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 209862959  23 HQWQTDEEGVRTGKCSFPVKYLGHVEVDESRGMHICEDAVKRLKAERKffkgffgktgkKAVKAVLWVSADGLRVVDEKT 102
Cdd:cd01268    1 HQWQADEEAVRSGTCSFPVKYLGCVEVGESRGMQVCEEALKKLKASRK-----------KPVRAVLWVSGDGLRVVDEKT 69

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 209862959 103 KDLIVDQTIEKVSFCAPDRNFDRAFSYICRDGTTRRWICHCFMAVKDTGERLSHAVGCAFAACLER 168
Cdd:cd01268   70 KGLIVDQTIEKVSFCAPDRNHERAFSYICRDGTTRRWMCHCFLAVKDSGERLSHAVGCAFAACLER 135

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 209862959  23 HQWQTDEEGVRTGKCSFPVKYLGHVEVDESRGMHICEDAVKRLKAERKffkgffgktgkKAVKAVLWVSADGLRVVDEKT 102
Cdd:cd01268    1 HQWQADEEAVRSGTCSFPVKYLGCVEVGESRGMQVCEEALKKLKASRK-----------KPVRAVLWVSGDGLRVVDEKT 69

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 209862959 103 KDLIVDQTIEKVSFCAPDRNFDRAFSYICRDGTTRRWICHCFMAVKDTGERLSHAVGCAFAACLER 168
Cdd:cd01268   70 KGLIVDQTIEKVSFCAPDRNHERAFSYICRDGTTRRWMCHCFLAVKDSGERLSHAVGCAFAACLER 135

Phosphotyrosine interaction domain (PTB/PID);

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209862959   39 FPVKYLGHVEVDESR------GMHICEDAVKRLKAE-RKFFKGFFGKTGKKaVKAVLWVSADGLRVVDEKTKDLIVDQTI 111
Cdd:pfam00640   1 FAVRYLGSVEVPEERapdkntRMQQAREAIRRVKAAkINKIRGLSGETGPG-TKVDLFISTDGLKLLNPDTQELIHDHPL 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 209862959  112 EKVSFCAP-DRNFDRAFSYICRDGTTRRWICHCFMAVKDtGERLSHAVGCAFAAC 165
Cdd:pfam00640  80 VSISFCADgDPDLMRYFAYIARDKATNKFACHVFESEDG-AQDIAQSIGQAFALA 133

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 209862959  23 HQWQTDEEGVRTGKCSFPVKYLGHVEVDESRGMHICEDAVKRLKAERKffkgffgktgkKAVKAVLWVSADGLRVVDEKT 102
Cdd:cd01268    1 HQWQADEEAVRSGTCSFPVKYLGCVEVGESRGMQVCEEALKKLKASRK-----------KPVRAVLWVSGDGLRVVDEKT 69

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 209862959 103 KDLIVDQTIEKVSFCAPDRNFDRAFSYICRDGTTRRWICHCFMAVKDTGERLSHAVGCAFAACLER 168
Cdd:cd01268   70 KGLIVDQTIEKVSFCAPDRNHERAFSYICRDGTTRRWMCHCFLAVKDSGERLSHAVGCAFAACLER 135

Phosphotyrosine interaction domain (PTB/PID);

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209862959   39 FPVKYLGHVEVDESR------GMHICEDAVKRLKAE-RKFFKGFFGKTGKKaVKAVLWVSADGLRVVDEKTKDLIVDQTI 111
Cdd:pfam00640   1 FAVRYLGSVEVPEERapdkntRMQQAREAIRRVKAAkINKIRGLSGETGPG-TKVDLFISTDGLKLLNPDTQELIHDHPL 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 209862959  112 EKVSFCAP-DRNFDRAFSYICRDGTTRRWICHCFMAVKDtGERLSHAVGCAFAAC 165
Cdd:pfam00640  80 VSISFCADgDPDLMRYFAYIARDKATNKFACHVFESEDG-AQDIAQSIGQAFALA 133

Phosphotyrosine-binding (PTB) PH-like fold; PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to bind 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 209862959  37 CSFPVKYLGHVEVDESRGMHICEDAVKRLKAERKFFKgffgktgKKAVKAVLWVSADGLRVVDEKTKDLIVDQTIEKVSF 116
Cdd:cd00934    1 ASFQVKYLGSVEVGSSRGVDVVEEALKALAAALKSSK-------RKPGPVLLEVSSKGVKLLDLDTKELLLRHPLHRISY 73

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 209862959 117 CAPDRNFDRAFSYICRDGTTRRWICHCFMAV-KDTGERLSHAVGCAF 162
Cdd:cd00934   74 CGRDPDNPNVFAFIAGEEGGSGFRCHVFQCEdEEEAEEILQAIGQAF 120

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 209862959  35 GKCSFPVKYLGHVEVDESRGMHICEDAVKRLKAERKFFKGffgkTGKKAVKAVLWVSADGLRVVDEKTKDLIVDQTIEKV 114
Cdd:cd01273   10 GHVAYLVKFLGCTEVEQPKGTEVVKEAIRKLKFARQLKKS----EGAKLPKVELQISIDGVKIQDPKTKVIMHQFPLHRI 85

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 209862959 115 SFCAPDRNFDRAFSYICRDGTTRRWICHCFMAVKdTGERLSHAVGCAF 162
Cdd:cd01273   86 SFCADDKTDKRIFSFIAKDSESEKHLCFVFDSEK-LAEEITLTIGQAF 132

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 209862959  30 EGVRtgkcsFPVKYLGHVEVDESRGMHICEDAVKRLKaerkffkGFFGKTGKKAVKAVLWVSADGLRVVDEKTKDLIVDQ 109
Cdd:cd01215   14 DGVR-----FKAKLIGIDEVPAARGDKMCQDAMMKLK-------GAVKAAGEHKQRIWLNISLEGIKILDEKTGALLHHH 81

                         90       100
                 ....*....|....*....|..
gi 209862959 110 TIEKVSFCAPDRNFDRAFSYIC 131
Cdd:cd01215   82 PVHKISFIARDTTDNRAFGYVC 103

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209862959  38 SFPVKYLGHVEVDESRGM-HICEDAVKRLKAERKffkgffgktGKKAVKAVLWVSADGLRVVDEKTKDLIVDQT---IEK 113
Cdd:cd13160    2 VFTVKYLGRMPARGLWGIkHTRKPLVDALKNLPK---------GKTLPKTKLEVSSDGVKLEELRGGFGSSKTVffpIHT 72

                         90       100       110
                 ....*....|....*....|....*....|....
gi 209862959 114 VSFCAPDRNFDRAFSYICR-DGTTRR--WICHCF 144
Cdd:cd13160   73 ISYGVQDLVHTRVFSMIVVgEQDSSNhpFECHAF 106

Fe65 N-terminal Phosphotyrosine-binding (PTB) domain; The neuronal adaptor protein Fe65 is involved in brain development, Alzheimer disease amyloid precursor protein (APP) signaling, and proteolytic processing of APP. It contains three protein-protein interaction domains, one WW domain, and a unique tandem array of phosphotyrosine-binding (PTB) domains. The N-terminal PTB domain was shown to interact with a variety of proteins, including the low density lipoprotein receptor-related protein (LRP-1), the ApoEr2 receptor, and the histone acetyltransferase Tip60. 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 209862959  38 SFPVKYLGHVEVDE--------SRGMHICedaVKRLKAERKFFKGFFGKTGKKavKAVLWVSADG-LRVVDEKTKDLIVD 108
Cdd:cd01272    3 RFAVRSLGWVEMAEedltpgksSVAVNNC---IRQLSYGRNDIRDTVGRWGEG--KDMLMVLDDDtLKLVDPDDRSVLHS 77

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 209862959 109 QTIEKVSFCAPDRNFDRAFSYICRDGTTRRWICHCF 144
Cdd:cd01272   78 QPIHSIRVWGVGRDNGRDFAYVARDKDTRVLKCHVF 113

Carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase protein (CAPON) Phosphotyrosine-binding (PTB) domain; CAPON (also known as Nitric oxide synthase 1 adaptor protein, NOS1AP, encodes a cytosolic protein that binds to the signaling molecule, neuronal NOS (nNOS). It contains a N-terminal PTB domain that binds to the small monomeric G protein, Dexras1 and a C-terminal PDZ-binding domain that mediates interactions with nNOS. Included in this cd are C. elegan proteins dystrobrevin, DYB-1, which controls neurotransmitter release and muscle Ca(2+) transients by localizing BK channels and DYstrophin-like phenotype and CAPON related,DYC-1, which is functionally related to dystrophin homolog, DYS-1. Mutations in the dystrophin gene causes Duchenne muscular dystrophy. DYS-1 shares sequence similarity, including key motifs, with their mammalian counterparts. These CAPON-like proteins all have 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 is part of the Dab-like subgroup.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209862959  38 SFPVKYLGHVEVDE--SRgMHICEdAVKRLKAErkfFKGffgKTGKKAvKAVLWVSADGLRVVDEKTKD----------- 104
Cdd:cd01270   30 TFQAKYIGSLEVPRpsSR-VEIVA-AMRRIRYE---FKA---KNIKKK-KVTITVSVDGVKVVLRKKKKkkgwtwdeskl 100

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 209862959 105 LIVDQTIEKVSFCAPDRNFDRAFSYICRDGTTRRWICHCFMA-VKDTGERLSHAVGCAFAACLERKQKREKE 175
Cdd:cd01270  101 LLMQHPIYRIFYVSHDSQDLKIFSYIARDGSSNVFKCNVFKSkKKSQAMRIVRTIGQAFEVCHKLSLQHMQG 172

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 209862959  38 SFPVKYLGHVEVDESRGMHICEDAVKRLKAERKFfkgffgKTGKKAVkaVLWVSADGLRVVDEKTKDLIVDQTIEKVSFC 117
Cdd:cd13157    3 SRNAQYIGSFPVSGLDVADRADSVRKQLESLKES------GSRGRPV--ILSVSLSGIKICSEDGKVVLMAHALRRVSYS 74

                         90       100
                 ....*....|....*....|....*....
gi 209862959 118 APDRNfDRAFSYICRD--GTTRRWICHCF 144
Cdd:cd13157   75 TCRPA-HAQFAFVARNpgGPTNRQYCHVF 102