cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily; This superfamily is composed of cys-based phosphatases, which includes classical protein tyrosine phosphatases (PTPs) as well as dual-specificity phosphatases (DUSPs or DSPs). They are characterized by a CxxxxxR conserved catalytic loop (where C is the catalytic cysteine, x is any amino acid, and R is an arginine). PTPs are part of the tyrosine phosphorylation/dephosphorylation regulatory mechanism, and are important in the response of the cells to physiologic and pathologic changes in their environment. DUSPs show more substrate diversity (including RNA and lipids) and include pTyr, pSer, and pThr phosphatases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910032 210 PSNFVSPEDLDIPGHASKDRYKTILPNPQSRVCLGRAQSQ-EDGDYINANYIRGYDGKEKVYIATQGPMPNTVSDFWEMV 288
Cdd:cd14612    1 PPNFVSPEELDIPGHASKDRYKTILPNPQSRVCLRRAGSQeEEGSYINANYIRGYDGKEKAYIATQGPMLNTVSDFWEMV 80

                         90
                 ....*....|....*....
gi 767910032 289 WQEEVSLIVMLTQLREGKE 307
Cdd:cd14612   81 WQEECPIIVMITKLKEKKE 99

catalytic domain of tyrosine-protein phosphatase non-receptor type 7; Tyrosine-protein phosphatase non-receptor type 7 (PTPN7), also called hematopoietic protein-tyrosine phosphatase (HePTP) or LC-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. PTPN7/HePTP 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. PTPN7/HePTP is found exclusively in the white blood cells in bone marrow, thymus, spleen, lymph nodes and all myeloid and lymphoid cell lines. It negatively regulates T-cell activation and proliferation, and is often dysregulated in the preleukemic disorder myelodysplastic syndrome, as well as in acute myelogenous leukemia.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910032 210 PSNFVSPEDLDIPGHASKDRYKTILPNPQSRVCLGRAQSQ-EDGDYINANYIRGYDGKEKVYIATQGPMPNTVSDFWEMV 288
Cdd:cd14612    1 PPNFVSPEELDIPGHASKDRYKTILPNPQSRVCLRRAGSQeEEGSYINANYIRGYDGKEKAYIATQGPMLNTVSDFWEMV 80

                         90
                 ....*....|....*....
gi 767910032 289 WQEEVSLIVMLTQLREGKE 307
Cdd:cd14612   81 WQEECPIIVMITKLKEKKE 99

Protein-tyrosine phosphatase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910032  224 HASKDRYKTILPNPQSRVCLGRaqSQEDGDYINANYIRGYdGKEKVYIATQGPMPNTVSDFWEMVWQEEVSLIVMLTQLR 303
Cdd:pfam00102   1 NLEKNRYKDVLPYDHTRVKLTG--DPGPSDYINASYIDGY-KKPKKYIATQGPLPNTVEDFWRMVWEEKVTIIVMLTELE 77

                  ..
gi 767910032  304 EG 305
Cdd:pfam00102  78 EK 79

Protein tyrosine phosphatase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910032 200 KQLEEEFLKIPSNFVSPEDLDIPGHASKDRYKTILPNPQSRVclgraqsQEDGDYINANYIRGYDGKekVYIATQGPMPN 279
Cdd:COG5599   18 SRLSTLTNELAPSHNDPQYLQNINGSPLNRFRDIQPYKETAL-------RANLGYLNANYIQVIGNH--RYIATQYPLEE 88

                         90       100
                 ....*....|....*....|....*...
gi 767910032 280 TVSDFWEMVWQEEVSLIVMLTQLREGKE 307
Cdd:COG5599   89 QLEDFFQMLFDNNTPVLVVLASDDEISK 116

catalytic domain of tyrosine-protein phosphatase non-receptor type 7; Tyrosine-protein phosphatase non-receptor type 7 (PTPN7), also called hematopoietic protein-tyrosine phosphatase (HePTP) or LC-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. PTPN7/HePTP 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. PTPN7/HePTP is found exclusively in the white blood cells in bone marrow, thymus, spleen, lymph nodes and all myeloid and lymphoid cell lines. It negatively regulates T-cell activation and proliferation, and is often dysregulated in the preleukemic disorder myelodysplastic syndrome, as well as in acute myelogenous leukemia.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910032 210 PSNFVSPEDLDIPGHASKDRYKTILPNPQSRVCLGRAQSQ-EDGDYINANYIRGYDGKEKVYIATQGPMPNTVSDFWEMV 288
Cdd:cd14612    1 PPNFVSPEELDIPGHASKDRYKTILPNPQSRVCLRRAGSQeEEGSYINANYIRGYDGKEKAYIATQGPMLNTVSDFWEMV 80

                         90
                 ....*....|....*....
gi 767910032 289 WQEEVSLIVMLTQLREGKE 307
Cdd:cd14612   81 WQEECPIIVMITKLKEKKE 99

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910032 202 LEEEFLKIPSNFVSPEDLDIPGHASKDRYKTILPNPQSRVCLgRAQSQED--GDYINANYIRGYDGKEKVYIATQGPMPN 279
Cdd:cd14613    3 LQAEFFEIPMNFVDPKEYDIPGLVRKNRYKTILPNPHSRVCL-TSPDQDDplSSYINANYIRGYGGEEKVYIATQGPTVN 81

                         90       100
                 ....*....|....*....|....*...
gi 767910032 280 TVSDFWEMVWQEEVSLIVMLTQLREGKE 307
Cdd:cd14613   82 TVGDFWRMVWQERSPIIVMITNIEEMNE 109

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910032 226 SKDRYKTILPNPQSRVCLGRAQSQED-GDYINANYIRGYDGKEKVYIATQGPMPNTVSDFWEMVWQEEVSLIVMLTQLRE 304
Cdd:cd14611    1 TKNRYKTILPNPHSRVCLKPKNSNDSlSTYINANYIRGYGGKEKAFIATQGPMINTVNDFWQMVWQEDSPVIVMITKLKE 80

                 ...
gi 767910032 305 GKE 307
Cdd:cd14611   81 KNE 83

catalytic domain of LAR family receptor-type tyrosine-protein phosphatases, repeat 1; 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 catalytic PTP domain (repeat 1).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767910032 227 KDRYKTILPNPQSRVCLGRAQSQEDGDYINANYIRGYDgKEKVYIATQGPMPNTVSDFWEMVWQEEVSLIVMLTQLRE 304
Cdd:cd14553    6 KNRYANVIAYDHSRVILQPIEGVPGSDYINANYCDGYR-KQNAYIATQGPLPETFGDFWRMVWEQRSATIVMMTKLEE 82

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 767910032 227 KDRYKTILPNPQSRVCLGRAQSQEDGDYINANYIRGYDGkEKVYIATQGPMPNTVSDFWEMVWQEEVSLIVM 298
Cdd:cd14603   33 KNRYKDILPYDQTRVILSLLQEEGHSDYINANFIKGVDG-SRAYIATQGPLSHTVLDFWRMIWQYGVKVILM 103

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 767910032 225 ASKDRYKTILPNPQSRVCLGRAQSQEDG-DYINANYIR------GYDGKEKVYIATQGPMPNTVSDFWEMVWQEEVSLIV 297
Cdd:cd14544    2 KGKNRYKNILPFDHTRVILKDRDPNVPGsDYINANYIRnenegpTTDENAKTYIATQGCLENTVSDFWSMVWQENSRVIV 81

                         90
                 ....*....|.
gi 767910032 298 MLT-QLREGKE 307
Cdd:cd14544   82 MTTkEVERGKN 92

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 767910032 227 KDRYKTILPNPQSRVCLGRAQSQEDGDYINANYIRGYDGKeKVYIATQGPMPNTVSDFWEMVWQEEVSLIVM 298
Cdd:cd14602    1 KNRYKDILPYDHSRVELSLITSDEDSDYINANFIKGVYGP-RAYIATQGPLSTTLLDFWRMIWEYSVLIIVM 71

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910032 227 KDRYKTILPNPQSRVCLGraqsqEDGDYINANYIRGYDGKEK-VYIATQGPMPNTVSDFWEMVWQEEVSLIVMLTQLREG 305
Cdd:cd14597    6 KNRYKNILPYDTTRVPLG-----DEGGYINASFIKMPVGDEEfVYIACQGPLPTTVADFWQMVWEQKSTVIAMMTQEVEG 80

                 ...
gi 767910032 306 KEL 308
Cdd:cd14597   81 GKI 83

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767910032 228 DRYKTILPNPQSRVCLGRAQSQEDgDYINANYIRGYDGKeKVYIATQGPMPNTVSDFWEMVWQEEVSLIVMLTQLRE 304
Cdd:cd14615    1 NRYNNVLPYDISRVKLSVQSHSTD-DYINANYMPGYNSK-KEFIAAQGPLPNTVKDFWRMVWEKNVYAIVMLTKCVE 75

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767910032 230 YKTILPNPQSRVCLGRAQSQEDGDYINANYIRGYDGKEKvYIATQGPMPNTVSDFWEMVWQEEVSLIVMLTQLREGKE 307
Cdd:cd14620    1 YPNILPYDHSRVILSQLDGIPCSDYINASYIDGYKEKNK-FIAAQGPKQETVNDFWRMVWEQKSATIVMLTNLKERKE 77

PTP-like domain of receptor-type tyrosine-protein phosphatase N2; Receptor-type tyrosine-protein phosphatase N2 (PTPRN2 or R-PTP-N2), also called islet cell autoantigen-related protein (IAR), ICAAR, phogrin, or IA-2beta, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). It consists 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. It is mainly expressed in neuropeptidergic neurons and peptide-secreting endocrine cells, including insulin-producing pancreatic beta-cells. It may function as a phosphatidylinositol phosphatase to regulate insulin secretion. It is also required for normal accumulation of the neurotransmitters norepinephrine, dopamine and serotonin in the brain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910032 211 SNFVSPEDLDIPghasKDRYKTILPNPQSRVCLGRAQSQEDGDYINANYIRGYDGKEKVYIATQGPMPNTVSDFWEMVWQ 290
Cdd:cd14610   35 ATNVAQREENVQ----KNRSLAVLPYDHSRIILKAENSHSHSDYINASPIMDHDPRNPAYIATQGPLPATVADFWQMVWE 110

                         90
                 ....*....|....
gi 767910032 291 EEVSLIVMLTQLRE 304
Cdd:cd14610  111 SGCVVIVMLTPLAE 124

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
                 ....*....|....*....|....*....|....*....|....*....|..
gi 767910032 254 YINANYIRGYDGKEKVYIATQGPMPNTVSDFWEMVWQEEVSLIVMLTQLREG 305
Cdd:cd18533    1 YINASYITLPGTSSKRYIATQGPLPATIGDFWKMIWQNNVGVIVMLTPLVEN 52

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910032 202 LEEEFLKIPSN------FVSPedlDIPGHASKDRYKTILPNPQSRVCLGRAQSQEDGDYINANYIRGYDgKEKVYIATQG 275
Cdd:cd14628   27 MELEFKRLASSkahtsrFISA---NLPCNKFKNRLVNIMPYESTRVCLQPIRGVEGSDYINASFIDGYR-QQKAYIATQG 102

                         90       100       110
                 ....*....|....*....|....*....|...
gi 767910032 276 PMPNTVSDFWEMVWQEEVSLIVMLTQLRE-GKE 307
Cdd:cd14628  103 PLAETTEDFWRMLWEHNSTIVVMLTKLREmGRE 135

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910032 211 SNFVSPedlDIPGHASKDRYKTILPNPQSRVCLGRAQSQEDGDYINANYIRGYDgKEKVYIATQGPMPNTVSDFWEMVWQ 290
Cdd:cd14627   43 SRFISA---NLPCNKFKNRLVNIMPYETTRVCLQPIRGVEGSDYINASFIDGYR-QQKAYIATQGPLAETTEDFWRMLWE 118

                         90
                 ....*....|....*...
gi 767910032 291 EEVSLIVMLTQLRE-GKE 307
Cdd:cd14627  119 NNSTIVVMLTKLREmGRE 136

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910032 214 VSPEDLDIPGHASKDRYKTILPNPQSRVCLgRAQSQEDG---DYINANYIRGYDgKEKVYIATQGPMPNTVSDFWEMVWQ 290
Cdd:cd17667   17 ITAEHSNHPDNKHKNRYINILAYDHSRVKL-RPLPGKDSkhsDYINANYVDGYN-KAKAYIATQGPLKSTFEDFWRMIWE 94

                         90
                 ....*....|....
gi 767910032 291 EEVSLIVMLTQLRE 304
Cdd:cd17667   95 QNTGIIVMITNLVE 108

catalytic domain of tyrosine-protein phosphatase non-receptor type 3; Tyrosine-protein phosphatase non-receptor type 3 (PTPN3), also called protein-tyrosine phosphatase H1 (PTP-H1), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN3 interacts with mitogen-activated protein kinase p38gamma and serves as its specific phosphatase. PTPN3 and p38gamma cooperate to promote Ras-induced oncogenesis. PTPN3 is a large modular protein containing an N-terminal FERM domain, a PDZ domain and a C-terminal catalytic PTP domain. Its PDZ domain binds with the PDZ-binding motif of p38gamma and enables efficient tyrosine dephosphorylation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910032 201 QLEEEFLKIPSNFVS----PEDLDipghasKDRYKTILPNPQSRVCLgraqsQEDGDYINANY----IRGYDGKEKvYIA 272
Cdd:cd14600   19 QFEQLYRKKPGLAITcaklPQNMD------KNRYKDVLPYDATRVVL-----QGNEDYINASYvnmeIPSANIVNK-YIA 86

                         90       100       110
                 ....*....|....*....|....*....|..
gi 767910032 273 TQGPMPNTVSDFWEMVWQEEVSLIVMLTQLRE 304
Cdd:cd14600   87 TQGPLPHTCAQFWQVVWEQKLSLIVMLTTLTE 118

catalytic domain of receptor-type tyrosine-protein phosphatase B; Receptor-type tyrosine-protein phosphatase B (PTPRB), also known as receptor-type tyrosine-protein phosphatase beta (R-PTP-beta) or vascular endothelial protein tyrosine phosphatase(VE-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. PTPRB/VE-PTP 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 and a single (most RPTP subtypes have two) cytoplasmic catalytic PTP domain. It is expressed specifically in vascular endothelial cells and it plays an important role in blood vessel remodeling and angiogenesis.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767910032 228 DRYKTILPNPQSRVCLGRAQSQEDGDYINANYIRGYDGKEKvYIATQGPMPNTVSDFWEMVWQEEVSLIVMLTQLRE 304
Cdd:cd14617    1 NRYNNILPYDSTRVKLSNVDDDPCSDYINASYIPGNNFRRE-YIATQGPLPGTKDDFWKMVWEQNVHNIVMVTQCVE 76

catalytic domain of tyrosine-protein phosphatase non-receptor type 21 and type 14; Tyrosine-protein phosphatase non-receptor type 3 (PTPN3) and type 4 (PTPN4) belong to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN3 and PTPN4 are large modular proteins containing an N-terminal FERM domain, a PDZ domain and a C-terminal catalytic PTP domain. PTPN3 interacts with mitogen-activated protein kinase p38gamma and serves as its specific phosphatase. PTPN4 functions in TCR cell signaling, apoptosis, cerebellar synaptic plasticity, and innate immune responses.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 767910032 253 DYINANY----IRGYDGKEKvYIATQGPMPNTVSDFWEMVWQEEVSLIVMLTQLRE 304
Cdd:cd14541    1 DYINANYvnmeIPGSGIVNR-YIAAQGPLPNTCADFWQMVWEQKSTLIVMLTTLVE 55

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910032 201 QLEEEFLKI-PSNFVSPEDLDIPGHASKDRYKTILPNPQSRVCLGRAQSQEDGDYINANYIRGYDgKEKVYIATQGPMPN 279
Cdd:cd14625   23 KLSQEYESIdPGQQFTWEHSNLEVNKPKNRYANVIAYDHSRVILQPIEGIMGSDYINANYIDGYR-KQNAYIATQGPLPE 101

                         90       100
                 ....*....|....*....|....*
gi 767910032 280 TVSDFWEMVWQEEVSLIVMLTQLRE 304
Cdd:cd14625  102 TFGDFWRMVWEQRSATVVMMTKLEE 126

protein tyrosine phosphatase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910032 206 FLKIPSNFVSPEDldipghASKDRYKTILPNPQSRVCLgRAQSQEDGDYINANYIRGYDgKEKVYIATQGPMPNTVSDFW 285
Cdd:PHA02747  39 FDGLIANFEKPEN------QPKNRYWDIPCWDHNRVIL-DSGGGSTSDYIHANWIDGFE-DDKKFIATQGPFAETCADFW 110

                         90       100
                 ....*....|....*....|....*
gi 767910032 286 EMVWQEEVSLIVMLTQLR--EGKEL 308
Cdd:PHA02747 111 KAVWQEHCSIIVMLTPTKgtNGEEK 135

catalytic domain of tyrosine-protein phosphatase non-receptor type 1; Tyrosine-protein phosphatase non-receptor type 1 (PTPN1), also called protein-tyrosine phosphatase 1B (PTP-1B), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN1/PTP-1B is the first PTP to be purified and characterized and is the prototypical intracellular PTP found in a wide variety of human tissues. It contains an N-terminal catalytic PTP domain, followed by two tandem proline-rich motifs that mediate interaction with SH3-domain-containing proteins, and a small hydrophobic stretch that localizes the enzyme to the endoplasmic reticulum (ER). It dephosphorylates and regulates the activity of a number of receptor tyrosine kinases, including the insulin receptor, the EGF receptor, and the PDGF receptor.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910032 221 IPGHASKDRYKTILPNPQSRVCLgraqSQEDGDYINANYIRGYDGKEKvYIATQGPMPNTVSDFWEMVWQEEVSLIVMLT 300
Cdd:cd14608   22 LPKNKNRNRYRDVSPFDHSRIKL----HQEDNDYINASLIKMEEAQRS-YILTQGPLPNTCGHFWEMVWEQKSRGVVMLN 96

                 ....
gi 767910032 301 QLRE 304
Cdd:cd14608   97 RVME 100

catalytic domain of receptor-type tyrosine-protein phosphatase V; Receptor-type tyrosine-protein phosphatase V (PTPRV or R-PTP-V), also known as embryonic stem cell protein-tyrosine phosphatase (ES cell phosphatase) or osteotesticular protein-tyrosine phosphatase (OST-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. PTPRV 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 and a single (most RPTP subtypes have two) cytoplasmic catalytic PTP domain. In rodents, it may play a role in the maintenance of pluripotency and may function in signaling pathways during bone remodeling. It is the only PTP whose function has been lost between rodent and human. The human OST-PTP gene is a pseudogene.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767910032 228 DRYKTILPNPQSRVCLGRAQSQEDGDYINANYIRGYDGKEKvYIATQGPMPNTVSDFWEMVWQEEVSLIVMLT 300
Cdd:cd14618    1 NRYPHVLPYDHSRVRLSQLGGEPHSDYINANFIPGYTSPQE-FIATQGPLKKTIEDFWRLVWEQQVCNIIMLT 72

catalytic domain of receptor-type tyrosine-protein phosphatase D, repeat 1; Receptor-type tyrosine-protein phosphatase 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 catalytic PTP domain (repeat 1).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910032 201 QLEEEFLKI-PSNFVSPEDLDIPGHASKDRYKTILPNPQSRVCLGRAQSQEDGDYINANYIRGYDgKEKVYIATQGPMPN 279
Cdd:cd14624   23 KFSQEYESIdPGQQFTWEHSNLEVNKPKNRYANVIAYDHSRVLLSAIEGIPGSDYINANYIDGYR-KQNAYIATQGALPE 101

                         90       100
                 ....*....|....*....|....*
gi 767910032 280 TVSDFWEMVWQEEVSLIVMLTQLRE 304
Cdd:cd14624  102 TFGDFWRMIWEQRSATVVMMTKLEE 126

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 767910032 254 YINANYIRGYDGKEKVYIATQGPMPNTVSDFWEMVWQEEVSLIVMLTQLREG 305
Cdd:cd14546    1 YINASTIYDHDPRNPAYIATQGPLPHTIADFWQMIWEQGCVVIVMLTRLQEN 52

catalytic domain of tyrosine-protein phosphatase non-receptor type 22, type 18 and type 12; Tyrosine-protein phosphatase non-receptor type 22 (PTPN22), type 18 (PTPN18) and type 12 (PTPN12) belong 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. TPN18 regulates HER2-mediated cellular functions through defining both its phosphorylation and ubiquitination states. PTPN12 is characterized as a tumor suppressor and a pivotal regulator of EGFR/HER2 signaling.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 767910032 254 YINANYIRGYDGkEKVYIATQGPMPNTVSDFWEMVWQEEVSLIVM 298
Cdd:cd14542    1 YINANFIKGVSG-SKAYIATQGPLPNTVLDFWRMIWEYNVQVIVM 44

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
                 ....*....|....*....|....*....|....*....|....*....|...
gi 767910032 254 YINANYIRGYDGKEK-VYIATQGPMPNTVSDFWEMVWQEEVSLIVMLTQLREG 305
Cdd:cd14596    1 YINASYITMPVGEEElFYIATQGPLPSTIDDFWQMVWENRSDVIAMMTREVER 53

catalytic domain of receptor-type tyrosine-protein phosphatase U, repeat 1; Receptor-type tyrosine-protein phosphatase U (PTPRU), also known as pancreatic carcinoma phosphatase 2 (PCP-2), 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. PTPRU/PCP-2 is the most distant member of the type IIb subfamily and may have a distinct biological function other than cell-cell aggregation. It localizes to the adherens junctions and directly binds and dephosphorylates beta-catenin, and regulates the balance between signaling and adhesive beta-catenin. It plays an important role in the maintenance of epithelial integrity. PTPRU 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
                 ....*....|....*....|....*....|....*....|....*....|.
gi 767910032 254 YINANYIRGYDgKEKVYIATQGPMPNTVSDFWEMVWQEEVSLIVMLTQLRE 304
Cdd:cd14632    1 YINANYIDGYH-RSNHFIATQGPKQEMVYDFWRMVWQEHCSSIVMITKLVE 50

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
                 ....*....|....*....|....*....|....*....|....*....|.
gi 767910032 254 YINANYIRGYDgKEKVYIATQGPMPNTVSDFWEMVWQEEVSLIVMLTQLRE 304
Cdd:cd17668    1 YINANYVDGYN-KPKAYIAAQGPLKSTAEDFWRMIWEHNVEVIVMITNLVE 50

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 767910032 240 RVCLGRAQSQEDGDYINANYIRGYDgKEKVYIATQGPMPNTVSDFWEMVWQEEVSLIVMLTQLRE 304
Cdd:cd14631    1 RVILQPVEDDPSSDYINANYIDGYQ-RPSHYIATQGPVHETVYDFWRMIWQEQSACIVMVTNLVE 64

catalytic domain of receptor-type tyrosine-protein phosphatase C, repeat 1; Receptor-type tyrosine-protein phosphatase C (PTPRC), also known as CD45, leukocyte common antigen (LCA) or GP180, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRC/CD45 is found in all nucleated hematopoietic cells and is an essential regulator of T- and B-cell antigen receptor signaling. It controls immune response, both positively and negatively, by dephosphorylating a number of signaling molecules such as the Src family kinases, the CD3zeta chain of TCY, and ZAP-70 kinase. Mutations in the human PTPRC/CD45 gene are associated with severe combined immunodeficiency (SCID) and multiple sclerosis. PTPRC/CD45 contains an extracellular receptor-like region with fibronectin type III (FN3) repeats, a short transmembrane segment, and a cytoplasmic region comprising of a membrane proximal catalytically active PTP domain (repeat 1 or D1) and a membrane distal catalytically impaired PTP-like domain (repeat 2, or D2). This model represents repeat 1.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 767910032 254 YINANYIRGYDGKEKvYIATQGPMPNTVSDFWEMVWQEEVSLIVMLTQLREG 305
Cdd:cd14557    1 YINASYIDGFKEPRK-YIAAQGPKDETVDDFWRMIWEQKSTVIVMVTRCEEG 51

Protein tyrosine phosphatase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910032 200 KQLEEEFLKIPSNFVSPEDLDIPGHASKDRYKTILPNPQSRVclgraqsQEDGDYINANYIRGYDGKekVYIATQGPMPN 279
Cdd:COG5599   18 SRLSTLTNELAPSHNDPQYLQNINGSPLNRFRDIQPYKETAL-------RANLGYLNANYIQVIGNH--RYIATQYPLEE 88

                         90       100
                 ....*....|....*....|....*...
gi 767910032 280 TVSDFWEMVWQEEVSLIVMLTQLREGKE 307
Cdd:COG5599   89 QLEDFFQMLFDNNTPVLVVLASDDEISK 116

catalytic domain of receptor-type tyrosine-protein phosphatase A, repeat 2; Receptor-type tyrosine-protein phosphatase A (PTPRA), also known as receptor-type tyrosine-protein phosphatase alpha (R-PTP-alpha), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRA is a positive regulator of Src and Src family kinases via dephosphorylation of the Src-inhibitory tyrosine 527. Thus, it affects transformation and tumorigenesis, inhibition of proliferation, cell cycle arrest, integrin signaling, neuronal differentiation and outgrowth, and ion channel activity. It is also involved in interleukin-1 signaling in fibroblasts through its interaction with the focal adhesion targeting domain of focal adhesion kinase. PTPRA comprises a small extracellular domain, a transmembrane segment, and an intracellular region containing two tandem catalytic PTP domains. This model represents the second PTP domain (repeat 2).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910032 229 RYKTILPNPQSRVCLGRAQSQEDGDYINANYIRGYDGKEKvYIATQGPMPNTVSDFWEMVWQEEVSLIVMLTQLRE-GKE 307
Cdd:cd14623    1 RVLQIIPYEFNRVIIPVKRGEENTDYVNASFIDGYRQKDS-YIASQGPLQHTIEDFWRMIWEWKSCSIVMLTELEErGQE 79

catalytic domain of tyrosine-protein phosphatase non-receptor type 4; Tyrosine-protein phosphatase non-receptor type 4 (PTPN4), also called protein-tyrosine phosphatase MEG1, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN4 functions in TCR cell signaling, apoptosis, cerebellar synaptic plasticity, and innate immune responses. It specifically inhibits the TRIF-dependent TLR4 pathway by suppressing tyrosine phosphorylation of TRAM. It is a large modular protein containing an N-terminal FERM domain, a PDZ domain and a C-terminal catalytic PTP domain; the PDZ domain regulates the catalytic activity of PTPN4.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 767910032 253 DYINANYIR---GYDGKEKVYIATQGPMPNTVSDFWEMVWQEEVSLIVML-TQLREGK 306
Cdd:cd14601    1 DYINANYINmeiPSSSIINRYIACQGPLPNTCSDFWQMTWEQGSSMVVMLtTQVERGR 58