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 33468877 533 PKNELVQKFQVYYLGNVPVAKPVGVDVINGALESVLSSSSREQWTPSHVSVAPATLTILHQQ-TEAVLGECRVRFLSFLA 611
Cdd:cd01271   1 PKEEPVQKLKALYLGSTPVSKPTGMDVLNEAIDTLLSSVPKEQWTPVNVSVAPSTVTILSQKdEEEVLVECRVRFLSFMG 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 33468877 612 VGRDVHTFAFIMAAGPASFCCHMFWCEPNAASLSEAVQAACMLRYQK 658
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 33468877 533 PKNELVQKFQVYYLGNVPVAKPVGVDVINGALESVLSSSSREQWTPSHVSVAPATLTILHQQ-TEAVLGECRVRFLSFLA 611
Cdd:cd01271   1 PKEEPVQKLKALYLGSTPVSKPTGMDVLNEAIDTLLSSVPKEQWTPVNVSVAPSTVTILSQKdEEEVLVECRVRFLSFMG 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 33468877 612 VGRDVHTFAFIMAAGPASFCCHMFWCEPNAASLSEAVQAACMLRYQK 658
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 33468877    365 PGIKCFAVRSLGWVEMTEEelapgRSSVAVNNCIRQLSYHknnlhdpMAGGWGEGKDLLLQLEDETLKLVEPQNQTLLHA 444
Cdd:smart00462   1 GSGVSFRVKYLGSVEVPEA-----RGLQVVQEAIRKLRAA-------QGSEKKEPQKVILSISSRGVKLIDEDTKAVLHE 68

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 33468877    445 QPIVSIRVWGVGRDSGRDFAYVARDKLTQMLKCHVFRCEAPAKNIATSLHEICSKIMSERRNARCL 510
Cdd:smart00462  69 HPLRRISFCAVGPDDLDVFGYIARDPGSSRFACHVFRCEKAAEDIALAIGQAFQLAYELKLKARSE 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 33468877   255 LPAGWMRVQDTSG-TYYWHIPTGTTQWEPP 283
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 33468877 256 PAGWMRVQDTSG-TYYWHIPTGTTQWEPP 283
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 33468877 533 PKNELVQKFQVYYLGNVPVAKPVGVDVINGALESVLSSSSREQWTPSHVSVAPATLTILHQQ-TEAVLGECRVRFLSFLA 611
Cdd:cd01271   1 PKEEPVQKLKALYLGSTPVSKPTGMDVLNEAIDTLLSSVPKEQWTPVNVSVAPSTVTILSQKdEEEVLVECRVRFLSFMG 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 33468877 612 VGRDVHTFAFIMAAGPASFCCHMFWCEPNAASLSEAVQAACMLRYQK 658
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 33468877    365 PGIKCFAVRSLGWVEMTEEelapgRSSVAVNNCIRQLSYHknnlhdpMAGGWGEGKDLLLQLEDETLKLVEPQNQTLLHA 444
Cdd:smart00462   1 GSGVSFRVKYLGSVEVPEA-----RGLQVVQEAIRKLRAA-------QGSEKKEPQKVILSISSRGVKLIDEDTKAVLHE 68

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 33468877    445 QPIVSIRVWGVGRDSGRDFAYVARDKLTQMLKCHVFRCEAPAKNIATSLHEICSKIMSERRNARCL 510
Cdd:smart00462  69 HPLRRISFCAVGPDDLDVFGYIARDPGSSRFACHVFRCEKAAEDIALAIGQAFQLAYELKLKARSE 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 33468877 539 QKFQVYYLGNVPVAKPVGVDVINGALESVL--SSSSREQWTPSHVSVAPATLTILHQQTEAVLGECRVRFLSFLAVGRDV 616
Cdd:cd00934   1 ASFQVKYLGSVEVGSSRGVDVVEEALKALAaaLKSSKRKPGPVLLEVSSKGVKLLDLDTKELLLRHPLHRISYCGRDPDN 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 33468877 617 -HTFAFIMAAGPAS-FCCHMFWCEPN--AASLSEAVQAAC 652
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 33468877 541 FQVYYLGNVPVAKPVGVDVINGALESVLSSSSREqwTPSHVSVAPATLTILHQQTEAVLGECRVRFLSFLAV-GRDVHTF 619
Cdd:cd13161   4 FEAKYLGSVPVKEPKGNDVVMAAVKRLKDLKLKP--KPVVLVVSSEGIRVVERLTGEVLTNVPIKDISFVTVdPKDKKLF 81

                        90       100       110
                ....*....|....*....|....*....|...
gi 33468877 620 AFIMAAGPASFC-CHMFWCEPNAASLSEAVQAA 651
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 33468877    254 DLPAGWMRVQDTSG-TYYWHIPTGTTQWEPP 283
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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 33468877 424 LQLEDETLKLVEPQNQTLLHAQPIVSIRVWGVGRDSGRDFAYVARDKLTQMLKCHVFRCEAPAKNIAT 491
Cdd:cd13161  42 LVVSSEGIRVVERLTGEVLTNVPIKDISFVTVDPKDKKLFAFISHDPRLGRITCHVFRCKRGAQEICD 109

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 33468877 541 FQVYYLGNVPVAKPVGVDVINGALESV-----LSSSSREQWTPSHVSVAPATLTILHQQTEAVLGECRVRFLSFLAVGRD 615
Cdd:cd01273  14 YLVKFLGCTEVEQPKGTEVVKEAIRKLkfarqLKKSEGAKLPKVELQISIDGVKIQDPKTKVIMHQFPLHRISFCADDKT 93

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 33468877 616 V-HTFAFImAAGPAS--FCCHMFWCEPNAASLSEAVQAACMLRYQKCLD 661
Cdd:cd01273  94 DkRIFSFI-AKDSESekHLCFVFDSEKLAEEITLTIGQAFDLAYRRFLE 141