Fe65 C-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 C-terminal PTB domain is responsible for APP binding. 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 1039777013 312 PKNELVQKFQVYYLGNVPVAKPVGVDVINGALESVLSSSSREQWTPSHVSVAPATLTILHQQ-TEAVLGECRVRFLSFLA 390
Cdd:cd01271     1 PKEEPVQKLKALYLGSTPVSKPTGMDVLNEAIDTLLSSVPKEQWTPVNVSVAPSTVTILSQKdEEEVLVECRVRFLSFMG 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1039777013 391 VGRDVHTFAFIMAAGPASFCCHMFWCEPNAASLSEAVQAACMLRYQK 437
Cdd:cd01271    81 IGKDVHTFAFIMDTGPQLFQCHVFWCEPNAGALSEAVQAACMLRYQK 127

Fe65 C-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 C-terminal PTB domain is responsible for APP binding. 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 1039777013 312 PKNELVQKFQVYYLGNVPVAKPVGVDVINGALESVLSSSSREQWTPSHVSVAPATLTILHQQ-TEAVLGECRVRFLSFLA 390
Cdd:cd01271     1 PKEEPVQKLKALYLGSTPVSKPTGMDVLNEAIDTLLSSVPKEQWTPVNVSVAPSTVTILSQKdEEEVLVECRVRFLSFMG 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1039777013 391 VGRDVHTFAFIMAAGPASFCCHMFWCEPNAASLSEAVQAACMLRYQK 437
Cdd:cd01271    81 IGKDVHTFAFIMDTGPQLFQCHVFWCEPNAGALSEAVQAACMLRYQK 127

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 1039777013  142 PGIKCFAVRSLGWVEMTEEelapgRSSVAVNNCIRQLSYHknnlhdpMAGGWGEGKDLLLQLEDETLKLVEPQNQTLLHA 221
Cdd:smart00462   1 GSGVSFRVKYLGSVEVPEA-----RGLQVVQEAIRKLRAA-------QGSEKKEPQKVILSISSRGVKLIDEDTKAVLHE 68

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1039777013  222 QPIVSIRVWGVGRDsgRERDFAYVARDKLTQMLKCHVFRCEAPAKNIATSLHEICSKIMSERRNARCL 289
Cdd:smart00462  69 HPLRRISFCAVGPD--DLDVFGYIARDPGSSRFACHVFRCEKAAEDIALAIGQAFQLAYELKLKARSE 134

WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds proline-rich peptide motifs in vitro.

                          10        20        30
                  ....*....|....*....|....*....|
gi 1039777013  32 LPAGWMRVQDTSG-TYYWHIPTGTTQWEPP 60
Cdd:pfam00397   1 LPPGWEERWDPDGrVYYYNHETGETQWEKP 30

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.

                          10        20
                  ....*....|....*....|....*....
gi 1039777013  33 PAGWMRVQDTSG-TYYWHIPTGTTQWEPP 60
Cdd:cd00201     1 PPGWEERWDPDGrVYYYNHNTKETQWEDP 29

Fe65 C-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 C-terminal PTB domain is responsible for APP binding. 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 1039777013 312 PKNELVQKFQVYYLGNVPVAKPVGVDVINGALESVLSSSSREQWTPSHVSVAPATLTILHQQ-TEAVLGECRVRFLSFLA 390
Cdd:cd01271     1 PKEEPVQKLKALYLGSTPVSKPTGMDVLNEAIDTLLSSVPKEQWTPVNVSVAPSTVTILSQKdEEEVLVECRVRFLSFMG 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1039777013 391 VGRDVHTFAFIMAAGPASFCCHMFWCEPNAASLSEAVQAACMLRYQK 437
Cdd:cd01271    81 IGKDVHTFAFIMDTGPQLFQCHVFWCEPNAGALSEAVQAACMLRYQK 127

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 1039777013  142 PGIKCFAVRSLGWVEMTEEelapgRSSVAVNNCIRQLSYHknnlhdpMAGGWGEGKDLLLQLEDETLKLVEPQNQTLLHA 221
Cdd:smart00462   1 GSGVSFRVKYLGSVEVPEA-----RGLQVVQEAIRKLRAA-------QGSEKKEPQKVILSISSRGVKLIDEDTKAVLHE 68

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1039777013  222 QPIVSIRVWGVGRDsgRERDFAYVARDKLTQMLKCHVFRCEAPAKNIATSLHEICSKIMSERRNARCL 289
Cdd:smart00462  69 HPLRRISFCAVGPD--DLDVFGYIARDPGSSRFACHVFRCEKAAEDIALAIGQAFQLAYELKLKARSE 134

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 1039777013 318 QKFQVYYLGNVPVAKPVGVDVINGALESVL--SSSSREQWTPSHVSVAPATLTILHQQTEAVLGECRVRFLSFLAVGRDV 395
Cdd:cd00934     1 ASFQVKYLGSVEVGSSRGVDVVEEALKALAaaLKSSKRKPGPVLLEVSSKGVKLLDLDTKELLLRHPLHRISYCGRDPDN 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1039777013 396 -HTFAFIMAAGPAS-FCCHMFWCEPN--AASLSEAVQAAC 431
Cdd:cd00934    81 pNVFAFIAGEEGGSgFRCHVFQCEDEeeAEEILQAIGQAF 120

Tyrosine-specific kinase/HM-motif TK (TM/HMTK) Phosphotyrosine-binding (PTB) PH-like fold; TK kinases catalyzes the transfer of the terminal phosphate of ATP to a specific tyrosine residue on its target protein. TK kinases play significant roles in development and cell division. Tyrosine-protein kinases can be divided into two subfamilies: receptor tyrosine kinases, which have an intracellular tyrosine kinase domain, a transmembrane domain and an extracellular ligand-binding domain; and non-receptor (cytoplasmic) tyrosine kinases, which are soluble, cytoplasmic kinases. In HMTK the conserved His-Arg-Asp sequence within the catalytic loop is replaced by a His-Met sequence. TM/HMTK have are 2-3 N-terminal PTB domains. PTB domains in TKs are thought to function analogously to the membrane targeting (PH, myristoylation) and pTyr binding (SH2) domains of Src subgroup kinases. 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 1039777013 320 FQVYYLGNVPVAKPVGVDVINGALESVLSSSSREqwTPSHVSVAPATLTILHQQTEAVLGECRVRFLSFLAV-GRDVHTF 398
Cdd:cd13161     4 FEAKYLGSVPVKEPKGNDVVMAAVKRLKDLKLKP--KPVVLVVSSEGIRVVERLTGEVLTNVPIKDISFVTVdPKDKKLF 81

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1039777013 399 AFIMAAGPASFC-CHMFWCEPNAASLSEAVQAA 430
Cdd:cd13161    82 AFISHDPRLGRItCHVFRCKRGAQEICDTIAEA 114

Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds proline-rich polypeptides.

                           10        20        30
                   ....*....|....*....|....*....|.
gi 1039777013   31 DLPAGWMRVQDTSG-TYYWHIPTGTTQWEPP 60
Cdd:smart00456   1 PLPPGWEERKDPDGrPYYYNHETKETQWEKP 31

Tyrosine-specific kinase/HM-motif TK (TM/HMTK) Phosphotyrosine-binding (PTB) PH-like fold; TK kinases catalyzes the transfer of the terminal phosphate of ATP to a specific tyrosine residue on its target protein. TK kinases play significant roles in development and cell division. Tyrosine-protein kinases can be divided into two subfamilies: receptor tyrosine kinases, which have an intracellular tyrosine kinase domain, a transmembrane domain and an extracellular ligand-binding domain; and non-receptor (cytoplasmic) tyrosine kinases, which are soluble, cytoplasmic kinases. In HMTK the conserved His-Arg-Asp sequence within the catalytic loop is replaced by a His-Met sequence. TM/HMTK have are 2-3 N-terminal PTB domains. PTB domains in TKs are thought to function analogously to the membrane targeting (PH, myristoylation) and pTyr binding (SH2) domains of Src subgroup kinases. 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039777013 201 LQLEDETLKLVEPQNQTLLHAQPIVSIrVWgVGRDSGRERDFAYVARDKLTQMLKCHVFRCEAPAKNIAT 270
Cdd:cd13161    42 LVVSSEGIRVVERLTGEVLTNVPIKDI-SF-VTVDPKDKKLFAFISHDPRLGRITCHVFRCKRGAQEICD 109

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 1039777013 143 GIKCFAVRSLGWVEMTEeelapgrsSVAVNNCIRQLSYHKNNLHDPMAGgwgegkdlLLQLEDETLKLVEPQNQTLLHAQ 222
Cdd:cd01268    13 GTCSFPVKYLGCVEVGE--------SRGMQVCEEALKKLKASRKKPVRA--------VLWVSGDGLRVVDEKTKGLIVDQ 76

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1039777013 223 PI--VSIrvwgVGRDSGRERDFAYVARDKLTQMLKCHVF 259
Cdd:cd01268    77 TIekVSF----CAPDRNHERAFSYICRDGTTRRWMCHCF 111

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 1039777013 320 FQVYYLGNVPVAKPVGVDVINGALESV-----LSSSSREQWTPSHVSVAPATLTILHQQTEAVLGECRVRFLSFLAVGRD 394
Cdd:cd01273    14 YLVKFLGCTEVEQPKGTEVVKEAIRKLkfarqLKKSEGAKLPKVELQISIDGVKIQDPKTKVIMHQFPLHRISFCADDKT 93

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1039777013 395 V-HTFAFImAAGPAS--FCCHMFWCEPNAASLSEAVQAACMLRYQKCLD 440
Cdd:cd01273    94 DkRIFSFI-AKDSESekHLCFVFDSEKLAEEITLTIGQAFDLAYRRFLE 141