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 2462596961 562 PKTELVQKFHVQYLGMLPVDKPVGMDILNSAIENLMTSSNKEDWLSVNMNVADATVTVISEKNEEEVLVECRVRFLSFMG 641
Cdd:cd01271     1 PKEEPVQKLKALYLGSTPVSKPTGMDVLNEAIDTLLSSVPKEQWTPVNVSVAPSTVTILSQKDEEEVLVECRVRFLSFMG 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 2462596961 642 VGKDVHTFAFIMDTGNQRFECHVFWCEPNAGNVSEAVQAACMLRYQK 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 2462596961 562 PKTELVQKFHVQYLGMLPVDKPVGMDILNSAIENLMTSSNKEDWLSVNMNVADATVTVISEKNEEEVLVECRVRFLSFMG 641
Cdd:cd01271     1 PKEEPVQKLKALYLGSTPVSKPTGMDVLNEAIDTLLSSVPKEQWTPVNVSVAPSTVTILSQKDEEEVLVECRVRFLSFMG 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 2462596961 642 VGKDVHTFAFIMDTGNQRFECHVFWCEPNAGNVSEAVQAACMLRYQK 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 2462596961  394 PEAKCFAVRSLGWVEMAEEDlapgkSSVAVNNCIRQLSYCKndirdtVGIWGEGKDMYLILENDMLSLVDPMDRSVLHSQ 473
Cdd:smart00462   1 GSGVSFRVKYLGSVEVPEAR-----GLQVVQEAIRKLRAAQ------GSEKKEPQKVILSISSRGVKLIDEDTKAVLHEH 69

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462596961  474 PIVSIRVWGVGRDNGRDFAYVARDKDTRILKCHVFRCDTPAKAIATSLHEICSKIMAERKNAK 536
Cdd:smart00462  70 PLRRISFCAVGPDDLDVFGYIARDPGSSRFACHVFRCEKAAEDIALAIGQAFQLAYELKLKAR 132

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 2462596961 293 LPPGWKRVSDIAG-TYYWHIPTGTTQWERP 321
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        30
                  ....*....|....*....|....*....|
gi 2462596961 294 PPGWKRVSDIAG-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 2462596961 562 PKTELVQKFHVQYLGMLPVDKPVGMDILNSAIENLMTSSNKEDWLSVNMNVADATVTVISEKNEEEVLVECRVRFLSFMG 641
Cdd:cd01271     1 PKEEPVQKLKALYLGSTPVSKPTGMDVLNEAIDTLLSSVPKEQWTPVNVSVAPSTVTILSQKDEEEVLVECRVRFLSFMG 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 2462596961 642 VGKDVHTFAFIMDTGNQRFECHVFWCEPNAGNVSEAVQAACMLRYQK 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 2462596961  394 PEAKCFAVRSLGWVEMAEEDlapgkSSVAVNNCIRQLSYCKndirdtVGIWGEGKDMYLILENDMLSLVDPMDRSVLHSQ 473
Cdd:smart00462   1 GSGVSFRVKYLGSVEVPEAR-----GLQVVQEAIRKLRAAQ------GSEKKEPQKVILSISSRGVKLIDEDTKAVLHEH 69

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462596961  474 PIVSIRVWGVGRDNGRDFAYVARDKDTRILKCHVFRCDTPAKAIATSLHEICSKIMAERKNAK 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 2462596961 398 CFAVRSLGWVEMAEEDLAPGkSSVAVNNCIRQLSYCKNdirdtvgiwgEGKDMYLILENDMLSLVDPMDRSVLHSQPIVS 477
Cdd:cd00934     2 SFQVKYLGSVEVGSSRGVDV-VEEALKALAAALKSSKR----------KPGPVLLEVSSKGVKLLDLDTKELLLRHPLHR 70

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 2462596961 478 IRVWGVGRDNGRDFAYVARDKDTRILKCHVFRCDTP--AKAIATSLHEIC 525
Cdd:cd00934    71 ISYCGRDPDNPNVFAFIAGEEGGSGFRCHVFQCEDEeeAEEILQAIGQAF 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 2462596961 570 FHVQYLGMLPVDKPVGMDILNSAIENLMTSSNKEDwlSVNMNVADATVTVIsEKNEEEVLVECRVRFLSFMGV-GKDVHT 648
Cdd:cd13161     4 FEAKYLGSVPVKEPKGNDVVMAAVKRLKDLKLKPK--PVVLVVSSEGIRVV-ERLTGEVLTNVPIKDISFVTVdPKDKKL 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 2462596961 649 FAFIM-DTGNQRFECHVFWCEPNAGNVSEAVQAA 681
Cdd:cd13161    81 FAFIShDPRLGRITCHVFRCKRGAQEICDTIAEA 114

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 2462596961 293 LPPGWKRVSDIAG-TYYWHIPTGTTQWERP 321
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        30
                  ....*....|....*....|....*....|
gi 2462596961 294 PPGWKRVSDIAG-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 2462596961 461 LVDPMDRSVLHSQPIVSIRVWGVGRDNGRD---FAYVARDKDTRILKCHVFRCDTPakaiatslhEICSKIMAERKNA 535
Cdd:cd01211    54 LYDPTSNTEIASYPIYRILFCARGPDGTSEsdcFAFTWSHGETAIFQCHVFRCEIP---------EAVSKVLYSFAKA 122

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 2462596961 565 ELVQKFHVQY----LGMLPVDKPVGMDILNSAIENL-----MTSSNKEDWLSVNMNVADATVTVISEKNeEEVLVECRVR 635
Cdd:cd01273     5 EALIKGHVAYlvkfLGCTEVEQPKGTEVVKEAIRKLkfarqLKKSEGAKLPKVELQISIDGVKIQDPKT-KVIMHQFPLH 83

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 2462596961 636 FLSFMGVGKDV-HTFAFIM-DTGNQRFECHVFWCEPNAGNVSEAVQAACMLRYQKCL 690
Cdd:cd01273    84 RISFCADDKTDkRIFSFIAkDSESEKHLCFVFDSEKLAEEITLTIGQAFDLAYRRFL 140