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 966948682 281 AVSQAAQKYEALYMGTLPVTKAMGMDVLNEAIGTLTTRGDRNAWVPTMLSVSDSLMTAHPIQAEasteEEPLWQCPVRLV 360
Cdd:cd01271    1 PKEEPVQKLKALYLGSTPVSKPTGMDVLNEAIDTLLSSVPKEQWTPVNVSVAPSTVTILSQKDE----EEVLVECRVRFL 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 966948682 361 TFIGVGRDPHTFGLIADLGRQSFQCAAFWCQPHAGGLSEAVQAACMVQYQK 411
Cdd:cd01271   77 SFMGIGKDVHTFAFIMDTGPQLFQCHVFWCEPNAGALSEAVQAACMLRYQK 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 966948682 281 AVSQAAQKYEALYMGTLPVTKAMGMDVLNEAIGTLTTRGDRNAWVPTMLSVSDSLMTAHPIQAEasteEEPLWQCPVRLV 360
Cdd:cd01271    1 PKEEPVQKLKALYLGSTPVSKPTGMDVLNEAIDTLLSSVPKEQWTPVNVSVAPSTVTILSQKDE----EEVLVECRVRFL 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 966948682 361 TFIGVGRDPHTFGLIADLGRQSFQCAAFWCQPHAGGLSEAVQAACMVQYQK 411
Cdd:cd01271   77 SFMGIGKDVHTFAFIMDTGPQLFQCHVFWCEPNAGALSEAVQAACMLRYQK 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 966948682   114 PGAKCFAVRSLGWVEVPEEDlapgkSSIAVNNCIQQLAQTRSrsqpldGAWGEGQNMLMILKKDAMSLVNPLDHSLIHCQ 193
Cdd:smart00462   1 GSGVSFRVKYLGSVEVPEAR-----GLQVVQEAIRKLRAAQG------SEKKEPQKVILSISSRGVKLIDEDTKAVLHEH 69

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 966948682   194 PLVHIRVWGVGSSKGRDFAFVASDKDSCMLKCHVFRCDVPAKVIASALHGLCAQILSER 252
Cdd:smart00462  70 PLRRISFCAVGPDDLDVFGYIARDPGSSRFACHVFRCEKAAEDIALAIGQAFQLAYELK 128

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

                           10        20        30
                   ....*....|....*....|....*....|...
gi 966948682    30 GLPPGWRKIHDAAG-TYYWHVPSGSTQWQRPAW 61
Cdd:smart00456   1 PLPPGWEERKDPDGrPYYYNHETKETQWEKPRE 33

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        30
                 ....*....|....*....|....*....|.
gi 966948682  32 PPGWRKIHDAAG-TYYWHVPSGSTQWQRPAW 61
Cdd:cd00201    1 PPGWEERWDPDGrVYYYNHNTKETQWEDPRE 31

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 966948682 281 AVSQAAQKYEALYMGTLPVTKAMGMDVLNEAIGTLTTRGDRNAWVPTMLSVSDSLMTAHPIQAEasteEEPLWQCPVRLV 360
Cdd:cd01271    1 PKEEPVQKLKALYLGSTPVSKPTGMDVLNEAIDTLLSSVPKEQWTPVNVSVAPSTVTILSQKDE----EEVLVECRVRFL 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 966948682 361 TFIGVGRDPHTFGLIADLGRQSFQCAAFWCQPHAGGLSEAVQAACMVQYQK 411
Cdd:cd01271   77 SFMGIGKDVHTFAFIMDTGPQLFQCHVFWCEPNAGALSEAVQAACMLRYQK 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 966948682   114 PGAKCFAVRSLGWVEVPEEDlapgkSSIAVNNCIQQLAQTRSrsqpldGAWGEGQNMLMILKKDAMSLVNPLDHSLIHCQ 193
Cdd:smart00462   1 GSGVSFRVKYLGSVEVPEAR-----GLQVVQEAIRKLRAAQG------SEKKEPQKVILSISSRGVKLIDEDTKAVLHEH 69

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 966948682   194 PLVHIRVWGVGSSKGRDFAFVASDKDSCMLKCHVFRCDVPAKVIASALHGLCAQILSER 252
Cdd:smart00462  70 PLRRISFCAVGPDDLDVFGYIARDPGSSRFACHVFRCEKAAEDIALAIGQAFQLAYELK 128

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 966948682 118 CFAVRSLGWVEVPEEDlapGKSSIAVNNCIQQLAQTRSRSQPldgawgegQNMLMILKKDAMSLVNPLDHSLIHCQPLVH 197
Cdd:cd00934    2 SFQVKYLGSVEVGSSR---GVDVVEEALKALAAALKSSKRKP--------GPVLLEVSSKGVKLLDLDTKELLLRHPLHR 70

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 966948682 198 IRVWGVGSSKGRDFAFVASDKDSCMLKCHVFRCD--VPAKVIASALH 242
Cdd:cd00934   71 ISYCGRDPDNPNVFAFIAGEEGGSGFRCHVFQCEdeEEAEEILQAIG 117

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 966948682   31 LPPGWRKIHDAAG-TYYWHVPSGSTQWQRP 59
Cdd:pfam00397   1 LPPGWEERWDPDGrVYYYNHETGETQWEKP 30

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 966948682 118 CFAVRSLGWVEVPEedlapGKSSIAVNNCIQQLaqtrsRSQPLDGawgegQNMLMILKKDAMSLVNPLDHSLIHCQPLVH 197
Cdd:cd13161    3 VFEAKYLGSVPVKE-----PKGNDVVMAAVKRL-----KDLKLKP-----KPVVLVVSSEGIRVVERLTGEVLTNVPIKD 67

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 966948682 198 IRVWGVGSSKGRDFAFVASDKDSCMLKCHVFRCDVPAKVIASA 240
Cdd:cd13161   68 ISFVTVDPKDKKLFAFISHDPRLGRITCHVFRCKRGAQEICDT 110

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 966948682 289 YEALYMGTLPVTKAMGMDVLNEAIGTLTTRGdrNAWVPTMLSVSDSLMTAhpiqAEASTeEEPLWQCPVRLVTFIGV-GR 367
Cdd:cd13161    4 FEAKYLGSVPVKEPKGNDVVMAAVKRLKDLK--LKPKPVVLVVSSEGIRV----VERLT-GEVLTNVPIKDISFVTVdPK 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 966948682 368 DPHTFGLIA---DLGRQSfqCAAFWCQPHAGGLSEAVQAA 404
Cdd:cd13161   77 DKKLFAFIShdpRLGRIT--CHVFRCKRGAQEICDTIAEA 114