Protein tyrosine phosphatase, catalytic domain, undefined specificity; Protein tyrosine phosphatases. Homologues detected by this profile and not by those of "PTPc" or "DSPc" are predicted to be protein phosphatases with a similar fold to DSPs and PTPs, yet with unpredicted specificities.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17507407      4 INLIEAVN------YDTNPVVVHCSAGVGRSGTIVGISLIMDKMIQGINCKDMKKLVEEIRNQRHYAIQTEAQYMYIHRV 77
Cdd:smart00012  23 LELLRAVKknlnqsESSGPVVVHCSAGVGRTGTFVAIDILLQQLEAEAGEVDIFDTVKELRSQRPGMVQTEEQYLFLYRA 102

                   ...
gi 17507407     78 LLE 80
Cdd:smart00012 103 LLE 105

Protein tyrosine phosphatase, catalytic domain, undefined specificity; Protein tyrosine phosphatases. Homologues detected by this profile and not by those of "PTPc" or "DSPc" are predicted to be protein phosphatases with a similar fold to DSPs and PTPs, yet with unpredicted specificities.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17507407      4 INLIEAVN------YDTNPVVVHCSAGVGRSGTIVGISLIMDKMIQGINCKDMKKLVEEIRNQRHYAIQTEAQYMYIHRV 77
Cdd:smart00012  23 LELLRAVKknlnqsESSGPVVVHCSAGVGRTGTFVAIDILLQQLEAEAGEVDIFDTVKELRSQRPGMVQTEEQYLFLYRA 102

                   ...
gi 17507407     78 LLE 80
Cdd:smart00012 103 LLE 105

catalytic domain of protein tyrosine phosphatases; Protein tyrosine phosphatases (PTP, EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. The depth of the active site cleft renders the enzyme specific for phosphorylated Tyr (pTyr) residues, instead of pSer or pThr. This family has a distinctive active site signature motif, HCSAGxGRxG, and are characterized as either transmembrane, receptor-like or non-transmembrane (soluble) PTPs. Receptor-like PTP domains tend to occur in two copies in the cytoplasmic region of the transmembrane proteins, only one copy may be active.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 17507407   4 INLIEAVNY----DTNPVVVHCSAGVGRSGTIVGISLIMDKMIQGiNCKDMKKLVEEIRNQRHYAIQTEAQYMYIHR 76
Cdd:cd00047 125 LALVRRVRKearkPNGPIVVHCSAGVGRTGTFIAIDILLERLEAE-GEVDVFEIVKALRKQRPGMVQTLEQYEFIYE 200

protein tyrosine phosphatase; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 17507407   16 PVVVHCSAGVGRSGTIVGISLIMDKMIQgINCKDMKKLVEEIRNQRHYAIQTEAQYMYIHRV--LLEYFLELHK 87
Cdd:PHA02747 231 PIVVHCSDGVGKTGIFCAVDICLNQLVK-RKAICLAKTAEKIREQRHAGIMNFDDYLFIQPGyeVLHYFLSKIK 303

Protein tyrosine phosphatase, catalytic domain, undefined specificity; Protein tyrosine phosphatases. Homologues detected by this profile and not by those of "PTPc" or "DSPc" are predicted to be protein phosphatases with a similar fold to DSPs and PTPs, yet with unpredicted specificities.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17507407      4 INLIEAVN------YDTNPVVVHCSAGVGRSGTIVGISLIMDKMIQGINCKDMKKLVEEIRNQRHYAIQTEAQYMYIHRV 77
Cdd:smart00012  23 LELLRAVKknlnqsESSGPVVVHCSAGVGRTGTFVAIDILLQQLEAEAGEVDIFDTVKELRSQRPGMVQTEEQYLFLYRA 102

                   ...
gi 17507407     78 LLE 80
Cdd:smart00012 103 LLE 105

Protein-tyrosine phosphatase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17507407     1 MGAINLIEAVN-----YDTNPVVVHCSAGVGRSGTIVGISLIMDKMIQGiNCKDMKKLVEEIRNQRHYAIQTEAQYMYIH 75
Cdd:pfam00102 151 NSLLDLLRKVRkssldGRSGPIVVHCSAGIGRTGTFIAIDIALQQLEAE-GEVDIFQIVKELRSQRPGMVQTLEQYIFLY 229

                  ....*
gi 17507407    76 RVLLE 80
Cdd:pfam00102 230 DAILE 234

catalytic domain of protein tyrosine phosphatases; Protein tyrosine phosphatases (PTP, EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. The depth of the active site cleft renders the enzyme specific for phosphorylated Tyr (pTyr) residues, instead of pSer or pThr. This family has a distinctive active site signature motif, HCSAGxGRxG, and are characterized as either transmembrane, receptor-like or non-transmembrane (soluble) PTPs. Receptor-like PTP domains tend to occur in two copies in the cytoplasmic region of the transmembrane proteins, only one copy may be active.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 17507407   4 INLIEAVNY----DTNPVVVHCSAGVGRSGTIVGISLIMDKMIQGiNCKDMKKLVEEIRNQRHYAIQTEAQYMYIHR 76
Cdd:cd00047 125 LALVRRVRKearkPNGPIVVHCSAGVGRTGTFIAIDILLERLEAE-GEVDVFEIVKALRKQRPGMVQTLEQYEFIYE 200

catalytic domain of tyrosine-protein phosphatase non-receptor type 11 and type 6; Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) and type 6 (PTPN6) belong to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN11 and PTPN6, are also called SH2 domain-containing tyrosine phosphatase 2 (SHP2) and 1 (SHP1), respectively. They contain two tandem SH2 domains: a catalytic PTP domain, and a C-terminal tail with regulatory properties. Although structurally similar, they have different localization and different roles in signal transduction. PTPN11/SHP2 is expressed ubiquitously and plays a positive role in cell signaling, leading to cell activation, while PTPN6/SHP1 expression is restricted mainly to hematopoietic and epithelial cells and functions as a negative regulator of signaling events.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17507407   2 GAINLIEAVNY------DTNPVVVHCSAGVGRSGTIVGISLIMDKMI-QGINCK-DMKKLVEEIRNQRHYAIQTEAQYMY 73
Cdd:cd14544 161 GVLNFLEDVNQrqeslpHAGPIVVHCSAGIGRTGTFIVIDMLLDQIKrKGLDCDiDIQKTIQMVRSQRSGMVQTEAQYKF 240

                ....*...
gi 17507407  74 IHRVLLEY 81
Cdd:cd14544 241 IYVAVAQY 248

catalytic domain of tyrosine-protein phosphatase non-receptor type 6; Tyrosine-protein phosphatase non-receptor type 6 (PTPN6), also called SH2 domain-containing protein-tyrosine phosphatase 1 (SHP1 or SHP-1), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN6 expression is restricted mainly to hematopoietic and epithelial cells. It is an important regulator of hematopoietic cells, downregulating pathways that promote cell growth, survival, adhesion, and activation. It regulates glucose homeostasis by modulating insulin signalling in the liver and muscle, and it also negatively regulates bone resorption, affecting both the formation and the function of osteoclasts. PTPN6 contains two tandem SH2 domains, a catalytic PTP domain, and a C-terminal tail with regulatory properties.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 17507407  16 PVVVHCSAGVGRSGTIVGISLIMDKM-IQGINCK-DMKKLVEEIRNQRHYAIQTEAQYMYIHRVLLEY 81
Cdd:cd14606 196 PIIVHCSAGIGRTGTIIVIDMLMENIsTKGLDCDiDIQKTIQMVRAQRSGMVQTEAQYKFIYVAIAQF 263

catalytic domain of receptor-type tyrosine-protein phosphatase G, repeat 1; Receptor-type tyrosine-protein phosphatase G (PTPRG), also called protein-tyrosine phosphatase gamma (R-PTP-gamma), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRG is an important tumor suppressor gene in multiple human cancers such as lung, ovarian, and breast cancers. It is widely expressed in many tissues, including the central nervous system, where it plays a role during neuroinflammation processes. It can dephosphorylate platelet-derived growth factor receptor beta (PDGFRB) and may play a role in PDGFRB-related infantile myofibromatosis. PTPRG has four splicing isoforms: three transmembrane isoforms, PTPRG-A, B, and C, and one secretory isoform, PTPRG-S, which are expressed in many tissues including the brain. PTPRG is a type 1 integral membrane protein consisting of an extracellular region with a carbonic anhydrase-like (CAH) and a fibronectin type III (FN3) domains, and an intracellular region with a catalytic PTP domain (repeat 1) proximal to the membrane, and a catalytically inactive PTP-fold domain (repeat 2) distal to the membrane. This model represents the catalytic PTP domain (repeat 1).

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 17507407  13 DTNPVVVHCSAGVGRSGTIVgislIMDKMIQGINCK---DMKKLVEEIRNQRHYAIQTEAQYMYIHRVLLEYFL 83
Cdd:cd17667 205 EMGPVLVHCSAGVGRTGTYI----VIDSMLQQIKDKstvNVLGFLKHIRTQRNYLVQTEEQYIFIHDALLEAIL 274

catalytic domain of receptor-type tyrosine-protein phosphatase E, repeat 1; Receptor-type tyrosine-protein phosphatase E (PTPRE), also known as receptor-type tyrosine-protein phosphatase epsilon (R-PTP-epsilon), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. The PTPRE gene contains two distinct promoters that generate the two major isoforms: transmembrane (receptor type RPTPe or PTPeM) and cytoplasmic (cyt-PTPe or PTPeC). Receptor type RPTPe plays a critical role in signaling transduction pathways and phosphoprotein network topology in red blood cells, and may also play a role in osteoclast formation and function. It also negatively regulates PDGFRbeta-mediated signaling pathways that are crucial for the pathogenesis of atherosclerosis. cyt-PTPe acts as a negative regulator of insulin receptor signaling in skeletal muscle. It regulates insulin-induced phosphorylation of proteins downstream of the insulin receptor. Receptor type RPTPe contains a small extracellular region, a single transmembrane segment, and an intracellular region two tandem catalytic PTP domains. This model represents the first PTP domain (repeat 1).

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 17507407  16 PVVVHCSAGVGRSGTIVGISLIMDkMIQGINCKDMKKLVEEIRNQRHYAIQTEAQYMYIHRVLLE 80
Cdd:cd14620 166 PIVVHCSAGVGRTGTFIVIDAMID-MMHAEQKVDVFEFVSRIRNQRPQMVQTDMQYSFIYQALLE 229

catalytic domain of receptor-type tyrosine-protein phosphatase Z, repeat 1; Receptor-type tyrosine-protein phosphatase Z (PTPRZ), also called receptor-type tyrosine-protein phosphatase zeta (R-PTP-zeta), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. Three isoforms are generated by alternative splicing from a single PTPRZ gene: two transmembrane isoforms, PTPRZ-A and PTPRZ-B, and one secretory isoform, PTPRZ-S (also known as phosphacan); all are preferentially expressed in the central nervous system (CNS) as chondroitin sulfate (CS) proteoglycans. PTPRZ isoforms play important roles in maintaining oligodendrocyte precursor cells in an undifferentiated state. PTPRZ is a type 1 integral membrane protein consisting of an extracellular region with a carbonic anhydrase-like (CAH) and a fibronectin type III (FN3) domains, and an intracellular region with a catalytic PTP domain (repeat 1) proximal to the membrane, and a catalytically inactive PTP-fold domain (repeat 2) distal to the membrane. This model represents the catalytic PTP domain (repeat 1).

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 17507407   9 AVNYDTNPVVVHCSAGVGRSGTIVgislIMDKMIQGI---NCKDMKKLVEEIRNQRHYAIQTEAQYMYIHRVLL 79
Cdd:cd17668 140 AKRHAVGPVVVHCSAGVGRTGTYI----VLDSMLQQIqheGTVNIFGFLKHIRSQRNYLVQTEEQYVFIHDALV 209

catalytic domain of receptor-type tyrosine-protein phosphatase F, repeat 1; Receptor-type tyrosine-protein phosphatase F (PTPRF), also known as leukocyte common antigen related (LAR), is the prototypical member of the LAR family of receptor-type tyrosine-protein phosphatases (RPTPs), which belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRF/LAR plays a role for LAR in cadherin complexes where it associates with and dephosphorylates beta-catenin, a pathway which may be critical for cadherin complex stability and cell-cell association. It also regulates focal adhesions through cyclin-dependent kinase-1 and is involved in axon guidance in the developing nervous system. It also functions in regulating insulin signaling. PTPRF contains an extracellular region with three immunoglobulin-like (Ig) domains and four to eight fibronectin type III (FN3) repeats (determined by alternative splicing), a single transmembrane domain, followed by an intracellular region with a membrane-proximal catalytic PTP domain (repeat 1, also called D1) and a membrane-distal non-catalytic PTP-like domain (repeat 2, also called D2). This model represents the catalytic PTP domain (repeat 1).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17507407   1 MGAINLIEAVN-YDTNPVVVHCSAGVGRSGTIVGISLIMDKMiQGINCKDMKKLVEEIRNQRHYAIQTEAQYMYIHRVLL 79
Cdd:cd14626 193 LAFLRRVKACNpPDAGPMVVHCSAGVGRTGCFIVIDAMLERM-KHEKTVDIYGHVTCMRSQRNYMVQTEDQYIFIHEALL 271

                .
gi 17507407  80 E 80
Cdd:cd14626 272 E 272

catalytic domain of tyrosine-protein phosphatase non-receptor type 20; Tyrosine-protein phosphatase non-receptor type 20 (PTPN20) belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. Human PTPN20 is a widely expressed phosphatase with a dynamic subcellular distribution that is targeted to sites of actin polymerization.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 17507407  12 YDTNPVVVHCSAGVGRSGTIVGISLIMDKMIQGInCKDMKKLVEEIRNQRHYAIQTEAQYMYIHRVLLE 80
Cdd:cd14596 137 HNTGPIVVHCSAGIGRAGVLICVDVLLSLIEKDL-SFNIKDIVREMRQQRYGMIQTKDQYLFCYKVVLE 204

catalytic domain of tyrosine-protein phosphatase non-receptor type 13; Tyrosine-protein phosphatase non-receptor type 13 (PTPN13, also known as PTPL1) belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. Human PTPN13 is an important regulator of tumor aggressiveness. It regulates breast cancer cell aggressiveness through direct inactivation of Src kinase. In hepatocellular carcinoma, PTPN13 is a tumor suppressor. PTPN13 contains a FERM domain, five PDZ domains, and a C-terminal catalytic PTP domain. With its PDZ domains, PTPN13 has numerous interacting partners that can actively participate in the regulation of its phosphatase activity or can permit direct or indirect recruitment of tyrosine phosphorylated substrates. Its FERM domain is necessary for localization to the membrane.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 17507407  12 YDTNPVVVHCSAGVGRSGTIVGISLIMDKMIQGINCkDMKKLVEEIRNQRHYAIQTEAQYMYIHRVLL 79
Cdd:cd14597 165 HKSGPIITHCSAGIGRSGTLICIDVVLGLISKDLDF-DISDIVRTMRLQRHGMVQTEDQYIFCYQVIL 231

catalytic domain of receptor-type tyrosine-protein phosphatase S, repeat 1; Receptor-type tyrosine-protein phosphatase S (PTPRS), also known as receptor-type tyrosine-protein phosphatase sigma (R-PTP-sigma), belongs to the LAR (leukocyte common antigen-related) family of receptor-type tyrosine-protein phosphatases (RPTPs), which belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRS is a receptor for glycosaminoglycans, including heparan sulfate proteoglycan and neural chondroitin sulfate proteoglycans (CSPGs), which present a barrier to axon regeneration. It also plays a role in stimulating neurite outgrowth in response to the heparan sulfate proteoglycan GPC2. PTPRS contains an extracellular region with three immunoglobulin-like (Ig) domains and four to eight fibronectin type III (FN3) repeats (determined by alternative splicing), a single transmembrane domain, followed by an intracellular region with a membrane-proximal catalytic PTP domain (repeat 1, also called D1) and a membrane-distal non-catalytic PTP-like domain (repeat 2, also called D2). This model represents the catalytic PTP domain (repeat 1).

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 17507407  13 DTNPVVVHCSAGVGRSGTIVGISLIMDKmIQGINCKDMKKLVEEIRNQRHYAIQTEAQYMYIHRVLLE 80
Cdd:cd14625 212 DAGPIVVHCSAGVGRTGCFIVIDAMLER-IKHEKTVDIYGHVTLMRSQRNYMVQTEDQYSFIHDALLE 278

fungal protein tyrosine phosphatases; This subfamily contains Saccharomyces cerevisiae protein-tyrosine phosphatases 1 (PTP1) and 2 (PTP2), Schizosaccharomyces pombe PTP1, PTP2, and PTP3, and similar fungal proteins. PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. PTP2, together with PTP3, is the major phosphatase that dephosphorylates and inactivates the MAP kinase HOG1 and also modulates its subcellular localization.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17507407   4 INLIEAVNYD---TNPVVVHCSAGVGRSGTIVGISLIMDKMIQGIN----CKDMKKLVEEI----RNQRHYAIQTEAQYM 72
Cdd:cd18533 129 IKLKRELNDSaslDPPIIVHCSAGVGRTGTFIALDSLLDELKRGLSdsqdLEDSEDPVYEIvnqlRKQRMSMVQTLRQYI 208

                ...
gi 17507407  73 YIH 75
Cdd:cd18533 209 FLY 211

catalytic domain of receptor-type tyrosine-protein phosphatase E, repeat 2; Receptor-type tyrosine-protein phosphatase E (PTPRE), also known as receptor-type tyrosine-protein phosphatase epsilon (R-PTP-epsilon), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. The PTPRE gene contains two distinct promoters that generate the two major isoforms: transmembrane (receptor type RPTPe or PTPeM) and cytoplasmic (cyt-PTPe or PTPeC). Receptor type RPTPe plays a critical role in signaling transduction pathways and phosphoprotein network topology in red blood cells, and may also play a role in osteoclast formation and function. It also negatively regulates PDGFRbeta-mediated signaling pathways that are crucial for the pathogenesis of atherosclerosis. cyt-PTPe acts as a negative regulator of insulin receptor signaling in skeletal muscle. It regulates insulin-induced phosphorylation of proteins downstream of the insulin receptor. Receptor type RPTPe contains a small extracellular region, a single transmembrane segment, and an intracellular region two tandem catalytic PTP domains. This model represents the second PTP domain (repeat 2).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17507407   2 GAINLIEAVNYD-----TNPVVVHCSAGVGRSGTIVGISLIMDKmIQGINCKDMKKLVEEIRNQRHYAIQTEAQYMYIHR 76
Cdd:cd14622 122 GMIDLIAAVQKQqqqtgNHPIVVHCSAGAGRTGTFIALSNILER-VKAEGLLDVFQTVKSLRLQRPHMVQTLEQYEFCYR 200

                ....*
gi 17507407  77 VLLEY 81
Cdd:cd14622 201 VVQDF 205

protein tyrosine phosphatase 1 from Arabidopsis thaliana and similar plant PTPs; Arabidopsis thaliana protein tyrosine phosphatase 1 (AtPTP1) belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. AtPTP1 dephosphorylates and inhibits MAP kinase 6 (MPK6) in non-oxidative stress conditions. Together with MAP kinase phosphatase 1 (MKP1) it expresses salicylic acid (SA) and camalexin biosynthesis, and therefore, modulating defense response.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 17507407  13 DTNPVVVHCSAGVGRSGTIVGISLIMDKMIQG-INCKDMKKLVEEIRNQRHYAIQTEAQYMYIH 75
Cdd:cd17658 142 SAGPIVVHCSAGIGRTGAYCTIHNTIRRILEGdMSAVDLSKTVRKFRSQRIGMVQTQDQYIFCY 205

catalytic domain of receptor-type tyrosine-protein phosphatase T, repeat 1; Receptor-type tyrosine-protein phosphatase T (PTPRT), also known as receptor-type tyrosine-protein phosphatase rho (RPTP-rho or PTPrho), belongs to the type IIb subfamily of receptor protein tyrosine phosphatases (RPTPs), which belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRT is highly expressed in the nervous system and it plays a critical role in regulation of synaptic formation and neuronal development. It dephosphorylates a specific tyrosine residue in syntaxin-binding protein 1, a key component of synaptic vesicle fusion machinery, and regulates its binding to syntaxin 1. PTPRT has been identified as a potential candidate gene for autism spectrum disorder (ASD) susceptibility. It contains an extracellular region with an Meprin-A5 (neuropilin)-mu (MAM) domain, an immunoglobulin (Ig) domain, and four fibronectin type III (FN3) repeats, a transmembrane domain, and an intracellular segment with a juxtamembrane domain similar to the cytoplasmic domain of classical cadherins and two tandem PTP domains. This model represents the first (repeat 1) PTP domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17507407   2 GAINLIEAVNY----DTNPVVVHCSAGVGRSGTIVGISLIMDkMIQGINCKDMKKLVEEIRNQRHYAIQTEAQYMYIHRV 77
Cdd:cd14630 152 GLLGFVRQVKFlnppDAGPIVVHCSAGAGRTGCFIAIDIMLD-MAENEGVVDIFNCVRELRAQRVNMVQTEEQYVFVHDA 230

                ...
gi 17507407  78 LLE 80
Cdd:cd14630 231 ILE 233

catalytic domain of tyrosine-protein phosphatase non-receptor type 21; Tyrosine-protein phosphatase non-receptor type 21 (PTPN21), also called protein-tyrosine phosphatase D1, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN21 is a component of a multivalent scaffold complex nucleated by focal adhesion kinase (FAK) at specific intracellular sites. It promotes cytoskeleton events that induce cell adhesion and migration by modulating Src-FAK signaling. It can also selectively associate with and stimulate Tec family kinases and modulate Stat3 activation. Human PTPN21 may also play a pathologic role in gastrointestinal tract tumorigenesis. PTPN21 contains an N-terminal FERM domain and a C-terminal catalytic PTP domain, separated by a long intervening sequence.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17507407   7 IEAVNYDTN----------PVVVHCSAGVGRSGTIVgISLIMDKMIQGINCKDMKKLVEEIRNQRHYAIQTEAQYMYIHR 76
Cdd:cd14598 135 IQSVRRHTNstidpkspnpPVLVHCSAGVGRTGVVI-LSEIMIACLEHNEMLDIPRVLDMLRQQRMMMVQTLSQYTFVYK 213

                ....*.
gi 17507407  77 VLLEYF 82
Cdd:cd14598 214 VLIQFL 219

PTP-like domain of receptor-type tyrosine-protein phosphatase D, repeat 2; Receptor-type tyrosine-protein phosphatase-like D (PTPRD), also known as receptor-type tyrosine-protein phosphatase delta (R-PTP-delta), belongs to the LAR (leukocyte common antigen-related) family of receptor-type tyrosine-protein phosphatases (RPTPs), which belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. LAR-RPTPs are synaptic adhesion molecules that play roles in various aspects of neuronal development, including axon guidance, neurite extension, and synapse formation and function. PTPRD is involved in pre-synaptic differentiation through interaction with SLITRK2. It contains an extracellular region with three immunoglobulin-like (Ig) domains and four to eight fibronectin type III (FN3) repeats (determined by alternative splicing), a single transmembrane domain, followed by an intracellular region with a membrane-proximal catalytic PTP domain (repeat 1, also called D1) and a membrane-distal non-catalytic PTP-like domain (repeat 2, also called D2). This model represents the non-catalytic PTP-like domain (repeat 2). Although described as non-catalytic, this domain contains the catalytic cysteine and the active site signature motif, HCSAGxGRxG.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 17507407  16 PVVVHCSAGVGRSGTIVGISLIMDKM-IQGIncKDMKKLVEEIRNQRHYAIQTEAQYMYIHRVLLEYF 82
Cdd:cd14628 222 PISVHCSAGVGRTGVFITLSIVLERMrYEGV--VDIFQTVKMLRTQRPAMVQTEDQYQFCYRAALEYL 287

PTP-like domain of the LAR family receptor-type tyrosine-protein phosphatases, repeat 2; The LAR (leukocyte common antigen-related) family of receptor-type tyrosine-protein phosphatases (RPTPs) include three vertebrate members: LAR (or PTPRF), R-PTP-delta (or PTPRD), and R-PTP-sigma (or PTPRS). They belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. LAR-RPTPs are synaptic adhesion molecules; they bind to distinct synaptic membrane proteins and are physiologically responsible for mediating presynaptic development by shaping various synaptic adhesion pathways. They play roles in various aspects of neuronal development, including axon guidance, neurite extension, and synapse formation and function. LAR-RPTPs contain an extracellular region with three immunoglobulin-like (Ig) domains and four to eight fibronectin type III (FN3) repeats (determined by alternative splicing), a single transmembrane domain, followed by an intracellular region with a membrane-proximal catalytic PTP domain (repeat 1, also called D1) and a membrane-distal non-catalytic PTP-like domain (repeat 2, also called D2). This model represents the non-catalytic PTP-like domain (repeat 2).

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 17507407  14 TNPVVVHCSAGVGRSGTIVGISLIMDKMiQGINCKDMKKLVEEIRNQRHYAIQTEAQYMYIHRVLL 79
Cdd:cd14554 174 EGPITVHCSAGVGRTGVFITLSIVLERM-RYEGVVDVFQTVKLLRTQRPAMVQTEDQYQFCYRAAL 238

catalytic domain of tyrosine-protein phosphatase non-receptor type 14; Tyrosine-protein phosphatase non-receptor type 14 (PTPN14), also called protein-tyrosine phosphatase pez, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN14 is a potential tumor suppressor and plays a regulatory role in the Hippo and Wnt/beta-catenin signaling pathways. It contains an N-terminal FERM domain and a C-terminal catalytic PTP domain, separated by a long intervening sequence.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 17507407   6 LIEAVNYDTNPVVVHCSAGVGRSGTIVgISLIMDKMIQGINCKDMKKLVEEIRNQRHYAIQTEAQYMYIHRVLLEYF 82
Cdd:cd14599 211 MLDSTKNCNPPIVVHCSAGVGRTGVVI-LTELMIGCLEHNEKVEVPVMLRHLREQRMFMIQTIAQYKFVYQVLIQFL 286

catalytic domain of tyrosine-protein phosphatase non-receptor type 9; Tyrosine-protein phosphatase non-receptor type 9 (PTPN9), also called protein-tyrosine phosphatase MEG2, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN9 plays an important role in promoting intracellular secretary vesicle fusion in hematopoietic cells and promotes the dephosphorylation of ErbB2 and EGFR in breast cancer cells, leading to impaired activation of STAT5 and STAT3. It also directly dephosphorylates STAT3 at the Tyr705 residue, resulting in its inactivation. PTPN9 has been found to be dysregulated in various human cancers, including breast, colorectal, and gastric cancer.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 17507407  16 PVVVHCSAGVGRSGTIVGISLIMDKMiQGINCKDMKKLVEEIRNQRHYAIQTEAQYMYIH 75
Cdd:cd14543 212 PIVVHCSAGIGRTGTFCTLDICLSQL-EDVGTLNVMQTVRRMRTQRAFSIQTPDQYYFCY 270

catalytic domain of receptor-type tyrosine-protein phosphatase J; Receptor-type tyrosine-protein phosphatase J (PTPRJ or R-PTP-J), also known as receptor-type tyrosine-protein phosphatase eta (R-PTP-eta) or density-enhanced phosphatase 1 (DEP-1) OR CD148, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRJ is a member of the R3 subfamily of receptor-type phosphotyrosine phosphatases (RPTP), characterized by a unique modular composition consisting of multiple extracellular fibronectin type III (FN3) repeats (eight in PTPRJ) and a single (most RPTP subtypes have two) cytoplasmic catalytic PTP domain. It is expressed in various cell types including epithelial, hematopoietic, and endothelial cells. It plays a role in cell adhesion, migration, proliferation and differentiation. It dephosphorylates or contributes to the dephosphorylation of various substrates including protein kinases such as FLT3, PDGFRB, MET, RET (variant MEN2A), VEGFR-2, LYN, SRC, MAPK1, MAPK3, and EGFR, as well as PIK3R1 and PIK3R2.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 17507407  16 PVVVHCSAGVGRSGTIVGISLIMdKMIQGINCKDMKKLVEEIRNQRHYAIQTEAQYMYIHRVLLE 80
Cdd:cd14615 166 PILVHCSAGVGRTGTFIAIDRLI-YQIENENVVDVYGIVYDLRMHRPLMVQTEDQYVFLNQCALD 229

PTP-like domain of receptor-type tyrosine-protein phosphatase S, repeat 2; Receptor-type tyrosine-protein phosphatase S (PTPRS), also known as receptor-type tyrosine-protein phosphatase sigma (R-PTP-sigma), belongs to the LAR (leukocyte common antigen-related) family of receptor-type tyrosine-protein phosphatases (RPTPs), which belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRS is a receptor for glycosaminoglycans, including heparan sulfate proteoglycan and neural chondroitin sulfate proteoglycans (CSPGs), which present a barrier to axon regeneration. It also plays a role in stimulating neurite outgrowth in response to the heparan sulfate proteoglycan GPC2. PTPRS contains an extracellular region with three immunoglobulin-like (Ig) domains and four to eight fibronectin type III (FN3) repeats (determined by alternative splicing), a single transmembrane domain, followed by an intracellular region with a membrane-proximal catalytic PTP domain (repeat 1, also called D1) and a membrane-distal non-catalytic PTP-like domain (repeat 2, also called D2). This model represents the non-catalytic PTP-like domain (repeat 2). Although described as non-catalytic, this domain contains the catalytic cysteine and the active site signature motif, HCSAGxGRxG.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 17507407  16 PVVVHCSAGVGRSGTIVGISLIMDKM-IQGIncKDMKKLVEEIRNQRHYAIQTEAQYMYIHRVLLEYF 82
Cdd:cd14627 223 PISVHCSAGVGRTGVFITLSIVLERMrYEGV--VDIFQTVKMLRTQRPAMVQTEDEYQFCYQAALEYL 288

catalytic domain of receptor-type tyrosine-protein phosphatase K, repeat 1; Receptor-type tyrosine-protein phosphatase K (PTPRK), also known as receptor-type tyrosine-protein phosphatase kappa (RPTP-kappa or PTPkappa), belongs to the type IIb subfamily of receptor protein tyrosine phosphatases (RPTPs), which belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRK is widely expressed and has been shown to stimulate cell motility and neurite outgrowth. It is required for anti-proliferative and pro-migratory effects of TGF-beta, suggesting a role in regulation, maintenance, and restoration of cell adhesion. It is a potential tumour suppressor in primary central nervous system lymphomas, colorectal cancer, and breast cancer. It contains an extracellular region with an Meprin-A5 (neuropilin)-mu (MAM) domain, an immunoglobulin (Ig) domain, and four fibronectin type III (FN3) repeats, a transmembrane domain, and an intracellular segment with a juxtamembrane domain similar to the cytoplasmic domain of classical cadherins and two tandem PTP domains. This model represents the first (repeat 1) PTP domain.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 17507407  16 PVVVHCSAGVGRSGTIVGISLIMDkMIQGINCKDMKKLVEEIRNQRHYAIQTEAQYMYIHRVLLE 80
Cdd:cd14631 152 PIVVHCSAGAGRTGCYIVIDIMLD-MAEREGVVDIYNCVKALRSRRINMVQTEEQYIFIHDAILE 215

catalytic domain of receptor-type tyrosine-protein phosphatase Q; Receptor-type tyrosine-protein phosphatase Q (PTPRQ or R-PTP-Q), also called phosphatidylinositol phosphatase PTPRQ, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRQ is a member of the R3 subfamily of receptor-type phosphotyrosine phosphatases (RPTP), characterized by a unique modular composition consisting of multiple extracellular fibronectin type III (FN3) repeats (18 in PTPRQ) and a single (most RPTP subtypes have two) cytoplasmic catalytic PTP domain. It displays low tyrosine-protein phosphatase activity; rather, it functions as a phosphatidylinositol phosphatase required for auditory processes. It regulates the levels of phosphatidylinositol 4,5-bisphosphate (PIP2) in the basal region of hair bundles. It can dephosphorylate a broad range of phosphatidylinositol phosphates, including phosphatidylinositol 3,4,5-trisphosphate and most phosphatidylinositol monophosphates and diphosphates.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 17507407  13 DTNPVVVHCSAGVGRSGTIVGisliMDKMIQGINCK---DMKKLVEEIRNQRHYAIQTEAQYMYIHR 76
Cdd:cd14616 162 DNTPMIVHCSAGVGRTGVFIA----LDHLTQHINDHdfvDIYGLVAELRSERMCMVQNLAQYIFLHQ 224

PTP-like domain of receptor-type tyrosine-protein phosphatase-like N and N2; Receptor-type tyrosine-protein phosphatase-like N (PTPRN) and N2 (PTPRN2) belong to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). They consist of a large ectodomain that contains a RESP18HD (regulated endocrine-specific protein 18 homology domain), followed by a transmembrane segment, and a single, catalytically-impaired, PTP domain. They are mainly expressed in neuropeptidergic neurons and peptide-secreting endocrine cells, including insulin-producing pancreatic beta-cells, and are involved in involved in the generation, cargo storage, traffic, exocytosis and recycling of insulin secretory granules, as well as in beta-cell proliferation. They also are major autoantigens in type 1 diabetes and are involved in the regulation of insulin secretion.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 17507407  16 PVVVHCSAGVGRSGTIVGISLIMDKMIQGINCKDMKKLVEEIRNQRHYAIQTEAQY 71
Cdd:cd14546 141 PIVVHCSDGAGRTGTYILIDMVLNRMAKGAKEIDIAATLEHLRDQRPGMVKTKDQF 196

catalytic domain of tyrosine-protein phosphatase non-receptor type 18; Tyrosine-protein phosphatase non-receptor type 18 (PTPN18), also called brain-derived phosphatase, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN18 regulates HER2-mediated cellular functions through defining both its phosphorylation and ubiquitination states. The N-terminal catalytic PTP domain of PTPN18 blocks lysosomal routing and delays the degradation of HER2 by dephosphorylation, and its C-terminal PEST domain promotes K48-linked HER2 ubiquitination and its destruction via the proteasome pathway.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 17507407  13 DTNPVVVHCSAGVGRSGTIVGI----SLIMDKMIQgincKDMK--KLVEEIRNQRHYAIQTEAQYMYIHRVLLEYF 82
Cdd:cd14603 195 GPEPLCVHCSAGCGRTGVICTVdyvrQLLLTQRIP----PDFSifDVVLEMRKQRPAAVQTEEQYEFLYHTVAQMF 266

catalytic domain of receptor-type tyrosine-protein phosphatase M, repeat 1; Receptor-type tyrosine-protein phosphatase M (PTPRM), also known as protein-tyrosine phosphatase mu (R-PTP-mu or PTPmu), belongs to the type IIb subfamily of receptor protein tyrosine phosphatases (RPTPs), which belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRM/PTPmu is a homophilic cell adhesion molecule expressed in CNS neurons and glia. It is required for E-, N-, and R-cadherin-dependent neurite outgrowth. Loss of PTPmu contributes to tumor cell migration and dispersal of human glioblastomas. PTPRM contains an extracellular region with an Meprin-A5 (neuropilin)-mu (MAM) domain, an immunoglobulin (Ig) domain, and four fibronectin type III (FN3) repeats, a transmembrane domain, and an intracellular segment with a juxtamembrane domain similar to the cytoplasmic domain of classical cadherins and two tandem PTP domains. This model represents the first (repeat 1) PTP domain.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 17507407  16 PVVVHCSAGVGRSGTIVGISLIMDkMIQGINCKDMKKLVEEIRNQRHYAIQTEAQYMYIHRVLLE 80
Cdd:cd14633 207 PLVVHCSAGAGRTGCFIVIDIMLD-MAEREGVVDIYNCVRELRSRRVNMVQTEEQYVFIHDAILE 270

Protein tyrosine phosphatase [Signal transduction mechanisms];

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 17507407   4 INLIEAV----NYDTNPVVVHCSAGVGRSGTIVGIsLIMDKMIQ--GINCKDMKKLVEEIRNQR-HYAIQTEAQY 71
Cdd:COG5599 192 ADLIDKKekikDPDKLLPVVHCRAGVGRTGTLIAC-LALSKSINalVQITLSVEEIVIDMRTSRnGGMVQTSEQL 265

dual specificity phosphatase 23; Dual specificity phosphatase 23 (DUSP23), also known as VH1-like phosphatase Z (VHZ) or low molecular mass dual specificity phosphatase 3 (LDP-3), functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. DUSP23 is an atypical DUSP; it contains the catalytic dual specificity phosphatase domain but lacks the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. It is able to enhance activation of JNK and p38 MAPK, and has been shown to dephosphorylate p44-ERK1 (MAPK3) in vitro. It has been associated with cell growth and human primary cancers. It has also been identified as a cell-cell adhesion regulatory protein; it promotes the dephosphorylation of beta-catenin at Tyr 142 and enhances the interaction between alpha- and beta-catenin.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 17507407   3 AINLIEAVNYDTNPVVVHCSAGVGRSGTIVGISLIMDKMIQGInckdmkKLVEEIRNQRHYAIQTEAQYMYI 74
Cdd:cd14504  71 FLDIVEEANAKNEAVLVHCLAGKGRTGTMLACYLVKTGKISAV------DAINEIRRIRPGSIETSEQEKFV 136

catalytic domain of tyrosine-protein phosphatase non-receptor type 22; Tyrosine-protein phosphatase non-receptor type 22 (PTPN22), also called lymphoid phosphatase (LyP), PEST-domain phosphatase (PEP), or hematopoietic cell protein-tyrosine phosphatase 70Z-PEP, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN22 is expressed in hematopoietic cells and it functions as a key regulator of immune homeostasis by inhibiting T-cell receptor signaling through the direct dephosphorylation of Src family kinases (Lck and Fyn), ITAMs of the TCRz/CD3 complex, and other signaling molecules. Mutations in the PTPN22 gene are associated with multiple connective tissue and autoimmune diseases including type 1 diabetes mellitus, rheumatoid arthritis, and systemic lupus erythematosus. PTPN22 contains an N-terminal catalytic PTP domain and four proline-rich regions at the C-terminus.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 17507407  13 DTNPVVVHCSAGVGRSGTIVGISLIMDKMIQGI--NCKDMKKLVEEIRNQRHYAIQTEAQYMYIHRVLLEYF 82
Cdd:cd14602 163 DSVPICIHCSAGCGRTGVICAIDYTWMLLKDGIipENFSVFSLIQEMRTQRPSLVQTKEQYELVYNAVIELF 234

cyclin-dependent kinase inhibitor 3 and similar proteins; This family is composed of eukaryotic cyclin-dependent kinase inhibitor 3 (CDKN3) and related archaeal and bacterial proteins. CDKN3 is also known as kinase-associated phosphatase (KAP), CDK2-associated dual-specificity phosphatase, cyclin-dependent kinase interactor 1 (CDI1), or cyclin-dependent kinase-interacting protein 2 (CIP2). It has been characterized as dual-specificity phosphatase, which function as a protein-serine/threonine phosphatase (EC 3.1.3.16) and protein-tyrosine-phosphatase (EC 3.1.3.48). It dephosphorylates CDK2 at a threonine residue in a cyclin-dependent manner, resulting in the inhibition of G1/S cell cycle progression. It also interacts with CDK1 and controls progression through mitosis by dephosphorylating CDC2. CDKN3 may also function as a tumor suppressor; its loss of function was found in a variety of cancers including glioblastoma and hepatocellular carcinoma. However, it has also been found over-expressed in many cancers such as breast, cervical, lung and prostate cancers, and may also have an oncogenic function.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 17507407   6 LIEAVNYDTNpVVVHCSAGVGRSGTIVGISLIMDKMiqginCKDMKKLVEEIRNQRHYAIQTEAQYMYIHR 76
Cdd:cd14505  99 LLSALENGKK-VLIHCKGGLGRTGLIAACLLLELGD-----TLDPEQAIAAVRALRPGAIQTPKQENFLHQ 163

PTP domain of receptor-type tyrosine-protein phosphatase T, repeat 2; Receptor-type tyrosine-protein phosphatase T (PTPRT), also known as receptor-type tyrosine-protein phosphatase rho (RPTP-rho or PTPrho), belongs to the type IIb subfamily of receptor protein tyrosine phosphatases (RPTPs), which belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRT is highly expressed in the nervous system and it plays a critical role in regulation of synaptic formation and neuronal development. It dephosphorylates a specific tyrosine residue in syntaxin-binding protein 1, a key component of synaptic vesicle fusion machinery, and regulates its binding to syntaxin 1. PTPRT has been identified as a potential candidate gene for autism spectrum disorder (ASD) susceptibility. It contains an extracellular region with an Meprin-A5 (neuropilin)-mu (MAM) domain, an immunoglobulin (Ig) domain, and four fibronectin type III (FN3) repeats, a transmembrane domain, and an intracellular segment with a juxtamembrane domain similar to the cytoplasmic domain of classical cadherins and two tandem PTP domains. This model represents the second (repeat 2) PTP domain.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 17507407  18 VVHCSAGVGRSGTIVGISLIMDkMIQGINCKDMKKLVEEIRNQRHYAIQTEAQYMYIHRVLLE 80
Cdd:cd14634 145 VVHCLNGGGRSGTFCAICSVCE-MIQQQNIIDVFHTVKTLRNNKSNMVETLEQYKFVYEVALE 206

catalytic domain of tyrosine-protein phosphatase non-receptor type 5; Tyrosine-protein phosphatase non-receptor type 5 (PTPN5), also called striatum-enriched protein-tyrosine phosphatase (STEP) or neural-specific PTP, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN5/STEP is a kinase interaction motif (KIM)-PTP, characterized by the presence of a 16-amino-acid KIM that binds specifically to members of the MAPK (mitogen-activated protein kinase) family. It is a CNS-enriched protein that regulates key signaling proteins required for synaptic strengthening, as well as NMDA and AMPA receptor trafficking. PTPN5 is implicated in multiple neurologic and neuropsychiatric disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, and fragile X syndrome.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 17507407  13 DTNPVVVHCSAGVGRSGTIVGISLIMDKMIQGiNCKDMKKLVEEIRNQRHYAIQTEAQYMYIHRVLLEY 81
Cdd:cd14613 191 NCGPVIVHCSAGIGRTGCFIATSICCKQLRNE-GVVDILRTTCQLRLDRGGMIQTCEQYQFVHHVLSLY 258

PTP domain of type IIb (or R2B) subfamily receptor-type tyrosine-protein phosphatases, repeat 2; The type IIb (or R2B) subfamily of receptor protein tyrosine phosphatases (RPTPs) include the prototypical member PTPmu (or PTPRM), PCP-2 (or PTPRU), PTPrho (or PTPRT), and PTPkappa (or PTPRK). They belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. Type IIb RPTPs mediate cell-cell adhesion though homophilic interactions; their ligand is an identical molecule on an adjacent cell. No heterophilic interactions between the subfamily members have been observed. They also commonly function as tumor suppressors. They contain an extracellular region with an Meprin-A5 (neuropilin)-mu (MAM) domain, an immunoglobulin (Ig) domain, and four fibronectin type III (FN3) repeats, a transmembrane domain, and an intracellular segment with a juxtamembrane domain similar to the cytoplasmic domain of classical cadherins and two tandem PTP domains. This model represents the second (repeat 2) PTP domain.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 17507407  12 YDTNPVVVHCSAGVGRSGTIVGISLIMDkMIQGINCKDMKKLVEEIRNQRHYAIQTEAQYMYIH 75
Cdd:cd14556 138 SGEGPIVVHCLNGVGRSGVFCAISSVCE-RIKVENVVDVFQAVKTLRNHRPNMVETEEQYKFCY 200

catalytic domain of receptor-type tyrosine-protein phosphatase R; Receptor-type tyrosine-protein phosphatase-like R (PTPRR or R-PTP-R), also called protein-tyrosine phosphatase PCPTP1, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRR is a kinase interaction motif (KIM)-PTP, characterized by the presence of a 16-amino-acid KIM that binds specifically to members of the MAPK (mitogen-activated protein kinase) family. The human and mouse PTPRR gene produces multiple neuronal protein isoforms of varying sizes (in human, PTPPBS-alpha, beta, gamma and delta). All isoforms contain the KIM motif and the catalytic PTP domain. PTPRR-deficient mice show significant defects in fine motor coordination and balance skills that are reminiscent of a mild ataxia.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 17507407  16 PVVVHCSAGVGRSGTIVGISlimdkmiqgINCKDMKK--------LVEEIRNQRHYAIQTEAQYMYIH 75
Cdd:cd14611 167 PVVVHCSAGIGRTGCFIATT---------IGCQQLKEegvvdvlsIVCQLRVDRGGMVQTSEQYEFVH 225

protein tyrosine phosphatase; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 17507407   16 PVVVHCSAGVGRSGTIVGISLIMDKMIQGINCKdMKKLVEEIRNQRHYAIQTEAQYMYIHRVLLEYFLE 84
Cdd:PHA02746 249 PIVVHCSAGIGRAGTFCAIDNALEQLEKEKEVC-LGEIVLKIRKQRHSSVFLPEQYAFCYKALKYAIIE 316

hypothetical protein; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 17507407   16 PVVVHCSAGVGRSGT--IVGISLIMDKMIQGINckdMKKLVEEIRNQRHYAIQTEAQYMYIHRVlLEYFLEL 85
Cdd:PHA02738 229 PIVVHCNAGLGRTPCycVVDISISRFDACATVS---IPSIVSSIRNQRYYSLFIPFQYFFCYRA-VKRYVNL 296