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 319738661 562 PKTELVQKFRVQYLGMLPVDRPVGMDTLNSAIENLMTSSSKEDWPSVNMNVADATVTVISEKNEEEVLVECRVRFLSFMG 641
Cdd:cd01271    1 PKEEPVQKLKALYLGSTPVSKPTGMDVLNEAIDTLLSSVPKEQWTPVNVSVAPSTVTILSQKDEEEVLVECRVRFLSFMG 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 319738661 642 VGKDVHTFAFIMDTGNQRFECHVFWCEPNAANVSEAVQAACMLRYQK 688
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 319738661 562 PKTELVQKFRVQYLGMLPVDRPVGMDTLNSAIENLMTSSSKEDWPSVNMNVADATVTVISEKNEEEVLVECRVRFLSFMG 641
Cdd:cd01271    1 PKEEPVQKLKALYLGSTPVSKPTGMDVLNEAIDTLLSSVPKEQWTPVNVSVAPSTVTILSQKDEEEVLVECRVRFLSFMG 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 319738661 642 VGKDVHTFAFIMDTGNQRFECHVFWCEPNAANVSEAVQAACMLRYQK 688
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 319738661   394 PEAKCFAVRSLGWVEMAEEDlapgkSSVAVNNCIRQLSYCKndirdtVGIWGEGKDMYLSLENDMLSLVDPMDRSVLHSQ 473
Cdd:smart00462   1 GSGVSFRVKYLGSVEVPEAR-----GLQVVQEAIRKLRAAQ------GSEKKEPQKVILSISSRGVKLIDEDTKAVLHEH 69

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 319738661   474 PIVNIRVWGVGRDNGRDFAYVARDKDTRILKCHVFRCDTPAKAIATSLHEICSKIMAERKNAK 536
Cdd:smart00462  70 PLRRISFCAVGPDDLDVFGYIARDPGSSRFACHVFRCEKAAEDIALAIGQAFQLAYELKLKAR 132

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

                           10        20        30
                   ....*....|....*....|....*....|...
gi 319738661   292 DLPPGWKRVNDIAG-TYYWHIPTGTTQWERPVS 323
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 319738661 294 PPGWKRVNDIAG-TYYWHIPTGTTQWERPV 322
Cdd:cd00201    1 PPGWEERWDPDGrVYYYNHNTKETQWEDPR 30

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 319738661 562 PKTELVQKFRVQYLGMLPVDRPVGMDTLNSAIENLMTSSSKEDWPSVNMNVADATVTVISEKNEEEVLVECRVRFLSFMG 641
Cdd:cd01271    1 PKEEPVQKLKALYLGSTPVSKPTGMDVLNEAIDTLLSSVPKEQWTPVNVSVAPSTVTILSQKDEEEVLVECRVRFLSFMG 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 319738661 642 VGKDVHTFAFIMDTGNQRFECHVFWCEPNAANVSEAVQAACMLRYQK 688
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 319738661   394 PEAKCFAVRSLGWVEMAEEDlapgkSSVAVNNCIRQLSYCKndirdtVGIWGEGKDMYLSLENDMLSLVDPMDRSVLHSQ 473
Cdd:smart00462   1 GSGVSFRVKYLGSVEVPEAR-----GLQVVQEAIRKLRAAQ------GSEKKEPQKVILSISSRGVKLIDEDTKAVLHEH 69

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 319738661   474 PIVNIRVWGVGRDNGRDFAYVARDKDTRILKCHVFRCDTPAKAIATSLHEICSKIMAERKNAK 536
Cdd:smart00462  70 PLRRISFCAVGPDDLDVFGYIARDPGSSRFACHVFRCEKAAEDIALAIGQAFQLAYELKLKAR 132

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 319738661 568 QKFRVQYLGMLPVDRPVGMDTLNSAIENLMT--SSSKEDWPSVNMNVADATVTVIsEKNEEEVLVECRVRFLSFMGVGKD 645
Cdd:cd00934    1 ASFQVKYLGSVEVGSSRGVDVVEEALKALAAalKSSKRKPGPVLLEVSSKGVKLL-DLDTKELLLRHPLHRISYCGRDPD 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 319738661 646 V-HTFAFI-MDTGNQRFECHVFWCEPN--AANVSEAVQAAC 682
Cdd:cd00934   80 NpNVFAFIaGEEGGSGFRCHVFQCEDEeeAEEILQAIGQAF 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 319738661 570 FRVQYLGMLPVDRPVGMDTLNSAIENLmtSSSKEDWPSVNMNVADATVTVIsEKNEEEVLVECRVRFLSFMGV-GKDVHT 648
Cdd:cd13161    4 FEAKYLGSVPVKEPKGNDVVMAAVKRL--KDLKLKPKPVVLVVSSEGIRVV-ERLTGEVLTNVPIKDISFVTVdPKDKKL 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 319738661 649 FAFIM-DTGNQRFECHVFWCEPNAANVSEAVQAA 681
Cdd:cd13161   81 FAFIShDPRLGRITCHVFRCKRGAQEICDTIAEA 114

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

                           10        20        30
                   ....*....|....*....|....*....|...
gi 319738661   292 DLPPGWKRVNDIAG-TYYWHIPTGTTQWERPVS 323
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 319738661 294 PPGWKRVNDIAG-TYYWHIPTGTTQWERPV 322
Cdd:cd00201    1 PPGWEERWDPDGrVYYYNHNTKETQWEDPR 30

GTPase activating protein for Rab 6 Phosphotyrosine-binding (PTB) domain; GAPCenA is a centrosome-associated GTPase activating protein (GAP) for Rab 6. It consists of an N-terminal PTB domain and a C-terminal TBC 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 319738661 461 LVDPMDRSVLHSQPIVNIRVWGVGRDNGRD---FAYVARDKDTRILKCHVFRCDTPakaiatslhEICSKIMAERKNA 535
Cdd:cd01211   54 LYDPTSNTEIASYPIYRILFCARGPDGTSEsdcFAFTWSHGETAIFQCHVFRCEIP---------EAVSKVLYSFAKA 122

Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif (APPL; also called DCC-interacting protein (DIP)-13alpha) Phosphotyrosine-binding (PTB) domain; APPL interacts with oncoprotein serine/threonine kinase AKT2, tumor suppressor protein DCC (deleted in colorectal cancer), Rab5, GIPC (GAIP-interacting protein, C terminus), human follicle-stimulating hormone receptor (FSHR), and the adiponectin receptors AdipoR1 and AdipoR2. There are two isoforms of human APPL: APPL1 and APPL2, which share about 50% sequence identity. APPL has a BAR and a PH domain near its N terminus, and the two domains are thought to function as a unit (BAR-PH domain). C-terminal to this is a PTB domain. Lipid binding assays show that the BAR, PH, and PTB domains can bind phospholipids. 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 319738661 456 NDMLSLVDPMDRSVLHSQPIVNIRVWGVGRDNGRDFAYVARDKDTR----ILKCHVFRCDTPAKaiatslhEICSKI 528
Cdd:cd13158   60 SDCLRLIDPQTQVTRARFPLADVVQFAAHQENKRLFGFVVRTPEGDgeepSFSCYVFESNTEGE-------KICDAI 129