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 442627014  67 HQWQADEEAVRSATCSFSVKYLGCVEVFESRGMQVCEEALKVLRQSRRRPVRGLLHVSGDGLRVVDDETKGLIVDQTIEK 146
Cdd:cd01268    1 HQWQADEEAVRSGTCSFPVKYLGCVEVGESRGMQVCEEALKKLKASRKKPVRAVLWVSGDGLRVVDEKTKGLIVDQTIEK 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 442627014 147 VSFCAPDRNHERGFSYICRDGTTRRWMCHGFLACKDSGERLSHAVGCAFAVCLER 201
Cdd:cd01268   81 VSFCAPDRNHERAFSYICRDGTTRRWMCHCFLAVKDSGERLSHAVGCAFAACLER 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 442627014  67 HQWQADEEAVRSATCSFSVKYLGCVEVFESRGMQVCEEALKVLRQSRRRPVRGLLHVSGDGLRVVDDETKGLIVDQTIEK 146
Cdd:cd01268    1 HQWQADEEAVRSGTCSFPVKYLGCVEVGESRGMQVCEEALKKLKASRKKPVRAVLWVSGDGLRVVDEKTKGLIVDQTIEK 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 442627014 147 VSFCAPDRNHERGFSYICRDGTTRRWMCHGFLACKDSGERLSHAVGCAFAVCLER 201
Cdd:cd01268   81 VSFCAPDRNHERAFSYICRDGTTRRWMCHCFLAVKDSGERLSHAVGCAFAACLER 135

Phosphotyrosine interaction domain (PTB/PID);

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442627014   83 FSVKYLGCVEVFESR------GMQVCEEALKVLRQ---SRRRPVRGL--------LHVSGDGLRVVDDETKGLIVDQTIE 145
Cdd:pfam00640   1 FAVRYLGSVEVPEERapdkntRMQQAREAIRRVKAakiNKIRGLSGEtgpgtkvdLFISTDGLKLLNPDTQELIHDHPLV 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 442627014  146 KVSFCAP-DRNHERGFSYICRDGTTRRWMCHGFlACKDSGERLSHAVGCAFAVC 198
Cdd:pfam00640  81 SISFCADgDPDLMRYFAYIARDKATNKFACHVF-ESEDGAQDIAQSIGQAFALA 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 442627014  67 HQWQADEEAVRSATCSFSVKYLGCVEVFESRGMQVCEEALKVLRQSRRRPVRGLLHVSGDGLRVVDDETKGLIVDQTIEK 146
Cdd:cd01268    1 HQWQADEEAVRSGTCSFPVKYLGCVEVGESRGMQVCEEALKKLKASRKKPVRAVLWVSGDGLRVVDEKTKGLIVDQTIEK 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 442627014 147 VSFCAPDRNHERGFSYICRDGTTRRWMCHGFLACKDSGERLSHAVGCAFAVCLER 201
Cdd:cd01268   81 VSFCAPDRNHERAFSYICRDGTTRRWMCHCFLAVKDSGERLSHAVGCAFAACLER 135

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 442627014  81 CSFSVKYLGCVEVFESRGMQVCEEALK----VLRQSRRRPVRGLLHVSGDGLRVVDDETKGLIVDQTIEKVSFCAPDRNH 156
Cdd:cd00934    1 ASFQVKYLGSVEVGSSRGVDVVEEALKalaaALKSSKRKPGPVLLEVSSKGVKLLDLDTKELLLRHPLHRISYCGRDPDN 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 442627014 157 ERGFSYICRDGTTRRWMCHGFLaCKDS--GERLSHAVGCAF 195
Cdd:cd00934   81 PNVFAFIAGEEGGSGFRCHVFQ-CEDEeeAEEILQAIGQAF 120

NUMB domain; This presumed domain is found in the Numb family of proteins adjacent to the PTB domain..

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442627014  269 PFAIERPHATPNMLERQSSFR-LSTIGSQ-SPFKRQMSLRINDLPSNADRQRAFLTAAAGNPMQTPLRsvSPIAEVSPAk 346
Cdd:pfam06311   1 PFAIERPHAPLSMLQRQGSFRgFPQLSQKnSPFKRQLSLRLNELPSNLQRKRSFSLEPSDPPLKTPVS--NPIPEISPS- 77

                          90       100
                  ....*....|....*....|....*...
gi 442627014  347 SAGADPLSAaavaadsvsqLCQELSQGL 374
Cdd:pfam06311  78 SEQADSISA----------MCQQISSGL 95

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 442627014  82 SFSVKYLGCVEVFESRGMQVCEEALK----VLRQSRRRPVRGLLHVSGDGLRVVDDETKGLIVDQTIEKVSFCAPDRNHE 157
Cdd:cd13159    4 TFYLKYLGSTLVEKPKGEGATAEAVKtiiaMAKASGKKLQKVTLTVSPKGIKVTDSATNETILEVSIYRISYCTADANHD 83

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 442627014 158 RGFSYICRDGTTRRWMCHGFLACKDS-GERLSHAVGCAF 195
Cdd:cd13159   84 KVFAFIATNQDNEKLECHAFLCAKRKmAQAVTLTVAQAF 122

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 442627014  68 QWQADEEAVRSATCSFSVKYLGCVEVFESRGMQVCEEALKVLRQSRRRPVRG---LLHVSGDGLRVVDDETKGLIVDQTI 144
Cdd:cd01274    2 QWRHSPEKLITGSVNYEAHYLGSTEIKELRGTESTKKAIQKLKKSTREMKKIptiILSISYKGVKFIDATTKNLICEHEI 81

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 442627014 145 EKVSFCAPDRNHERGFSYICRDGTTRRWMCHGFLA 179
Cdd:cd01274   82 RNISCACQDPEDLNTFAYITKDLKTDHHYCHVFCV 116

Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442627014 107 KVLRQSRRRPVRGLLHVSGDGLRVVDDETKGLIVDQTIEKVSFCAPDRNHE--RGFSYICRDgttrRWMCHGFLACKdsg 184
Cdd:cd00900    6 VRVYREPTKRVEGTLYITSDRLILRDKNDGGLELSIPISDIVNVNVSPQGPssRYLVLVLKD----RGEFVGFSFPK--- 78

                         90
                 ....*....|.
gi 442627014 185 ERLSHAVGCAF 195
Cdd:cd00900   79 EEDAIEISDAL 89

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 442627014  82 SFSVKYLGCVEVFE--------SRGMQVCEEALKvLRQSRRRPVRG--------LLHVSGDGLRVVDDETKGLIVDQTIE 145
Cdd:cd01272    3 RFAVRSLGWVEMAEedltpgksSVAVNNCIRQLS-YGRNDIRDTVGrwgegkdmLMVLDDDTLKLVDPDDRSVLHSQPIH 81

                         90       100       110
                 ....*....|....*....|....*....|..
gi 442627014 146 KVSFCAPDRNHERGFSYICRDGTTRRWMCHGF 177
Cdd:cd01272   82 SIRVWGVGRDNGRDFAYVARDKDTRVLKCHVF 113

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 442627014  82 SFSVKYLGCVEVFESRGMQVCEE---ALKVLRQSRRRPVRGLLHVSGDGLRVVDDETKGLIVDQT---IEKVSFCAPDRN 155
Cdd:cd13160    2 VFTVKYLGRMPARGLWGIKHTRKplvDALKNLPKGKTLPKTKLEVSSDGVKLEELRGGFGSSKTVffpIHTISYGVQDLV 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 442627014 156 HERGFSYICR-DGTTRR--WMCHGFLaC--KDSGERLSHAVGCAF 195
Cdd:cd13160   82 HTRVFSMIVVgEQDSSNhpFECHAFV-CdsRADARNLTYWLAKAF 125

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 442627014  69 WQADEEAVRSATCSFSVKYLGCVEV--------FESRGM-------QVCEEALKVLRQSRRRPVRGL------------- 120
Cdd:cd01209    3 WLHPDQLGMGPGVSYPVRYVGCIEVlqsmrsldFNTRTQvtreainRVCEAVGGAKGAKRKRKSKALssilgksnlqfag 82

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 442627014 121 ----LHVSGDGLRVVDDETKGLIVDQTIEKVSFCA---PDRNHErgFSYICRDGTTRRwMCH 175
Cdd:cd01209   83 mnisLTISTDGLNLVTPDTGQIIANHHMQSISFASggdPDTYDY--VAYVAKDPVNQR-ACH 141