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 1907161265   1 MISLMRKYQEHEDVPICIHCSAGCGRTGAICAIDYTWNLLKAGKIPEEFNVFNLIQEMRTQRHSAVQTKEQYELVHRAIA 80
Cdd:cd14604   211 MISLMRKYQEHEDVPICIHCSAGCGRTGAICAIDYTWNLLKAGKIPEEFNVFNLIQEMRTQRHSAVQTKEQYELVHRAIA 290

                  ....*..
gi 1907161265  81 QLFEKQL 87
Cdd:cd14604   291 QLFEKQL 297

catalytic domain of tyrosine-protein phosphatase non-receptor type 12; Tyrosine-protein phosphatase non-receptor type 12 (PTPN12), also called PTP-PEST or protein-tyrosine phosphatase G1 (PTPG1), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN12 is characterized as a tumor suppressor and a pivotal regulator of EGFR/HER2 signaling. It regulates various physiological processes, including cell migration, immune response, and neuronal activity, by dephosphorylating multiple substrates including HER2, FAK, PYK2, PSTPIP, WASP, p130Cas, paxillin, Shc, catenin, c-Abl, ArgBP2, p190RhoGAP, RhoGDI, cell adhesion kinase beta, and Rho GTPase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161265   1 MISLMRKYQEHEDVPICIHCSAGCGRTGAICAIDYTWNLLKAGKIPEEFNVFNLIQEMRTQRHSAVQTKEQYELVHRAIA 80
Cdd:cd14604   211 MISLMRKYQEHEDVPICIHCSAGCGRTGAICAIDYTWNLLKAGKIPEEFNVFNLIQEMRTQRHSAVQTKEQYELVHRAIA 290

                  ....*..
gi 1907161265  81 QLFEKQL 87
Cdd:cd14604   291 QLFEKQL 297

Protein-tyrosine phosphatase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161265   1 MISLMRKYQEHEDV-PICIHCSAGCGRTGAICAIDYTWNLLKAGkipEEFNVFNLIQEMRTQRHSAVQTKEQYELVHRAI 79
Cdd:pfam00102 156 LLRKVRKSSLDGRSgPIVVHCSAGIGRTGTFIAIDIALQQLEAE---GEVDIFQIVKELRSQRPGMVQTLEQYIFLYDAI 232

                  ..
gi 1907161265  80 AQ 81
Cdd:pfam00102 233 LE 234

Protein tyrosine phosphatase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161265   1 MISLMRKYQEHEDV---PICIHCSAGCGRTGAICAIDYTWNLLKAGKIpEEFNVFNLIQEMRTQR-HSAVQTKEQY-ELV 75
Cdd:COG5599   191 LADLIDKKEKIKDPdklLPVVHCRAGVGRTGTLIACLALSKSINALVQ-ITLSVEEIVIDMRTSRnGGMVQTSEQLdVLV 269

                  ....*.
gi 1907161265  76 HRAIAQ 81
Cdd:COG5599   270 KLAEQQ 275

catalytic domain of tyrosine-protein phosphatase non-receptor type 12; Tyrosine-protein phosphatase non-receptor type 12 (PTPN12), also called PTP-PEST or protein-tyrosine phosphatase G1 (PTPG1), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN12 is characterized as a tumor suppressor and a pivotal regulator of EGFR/HER2 signaling. It regulates various physiological processes, including cell migration, immune response, and neuronal activity, by dephosphorylating multiple substrates including HER2, FAK, PYK2, PSTPIP, WASP, p130Cas, paxillin, Shc, catenin, c-Abl, ArgBP2, p190RhoGAP, RhoGDI, cell adhesion kinase beta, and Rho GTPase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161265   1 MISLMRKYQEHEDVPICIHCSAGCGRTGAICAIDYTWNLLKAGKIPEEFNVFNLIQEMRTQRHSAVQTKEQYELVHRAIA 80
Cdd:cd14604   211 MISLMRKYQEHEDVPICIHCSAGCGRTGAICAIDYTWNLLKAGKIPEEFNVFNLIQEMRTQRHSAVQTKEQYELVHRAIA 290

                  ....*..
gi 1907161265  81 QLFEKQL 87
Cdd:cd14604   291 QLFEKQL 297

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161265   1 MISLMRKYQEHEDVPICIHCSAGCGRTGAICAIDYTWNLLKAGKIPEEFNVFNLIQEMRTQRHSAVQTKEQYELVHRAIA 80
Cdd:cd14602   152 LIWDVRCYQEDDSVPICIHCSAGCGRTGVICAIDYTWMLLKDGIIPENFSVFSLIQEMRTQRPSLVQTKEQYELVYNAVI 231

                  ...
gi 1907161265  81 QLF 83
Cdd:cd14602   232 ELF 234

Protein tyrosine phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161265    1 MISLMRKYQEHEDVPICIHCSAGCGRTGAICAIDYTWNLLKAGKipeEFNVFNLIQEMRTQRHSAVQTKEQYELVHRAIA 80
Cdd:smart00194 182 LIRAVRKSQSTSTGPIVVHCSAGVGRTGTFIAIDILLQQLEAGK---EVDIFEIVKELRSQRPGMVQTEEQYIFLYRAIL 258

                   .
gi 1907161265   81 Q 81
Cdd:smart00194 259 E 259

Protein tyrosine phosphatase, catalytic domain motif;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161265    1 MISLMRKYQEHEDV--PICIHCSAGCGRTGAICAIDYTWNLLKAGKipEEFNVFNLIQEMRTQRHSAVQTKEQYELVHRA 78
Cdd:smart00404  25 LLRAVKKNLNQSESsgPVVVHCSAGVGRTGTFVAIDILLQQLEAEA--GEVDIFDTVKELRSQRPGMVQTEEQYLFLYRA 102

                   ...
gi 1907161265   79 IAQ 81
Cdd:smart00404 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 1907161265   1 MISLMRKYQEHEDVPICIHCSAGCGRTGAICAIDYTWNLLKAGKipeEFNVFNLIQEMRTQRHSAVQTKEQYELVHR 77
Cdd:cd00047   127 LVRRVRKEARKPNGPIVVHCSAGVGRTGTFIAIDILLERLEAEG---EVDVFEIVKALRKQRPGMVQTLEQYEFIYE 200

catalytic domain of tyrosine-protein phosphatase non-receptor type 20 and type 13; Tyrosine-protein phosphatase non-receptor type 20 (PTPN20) and type 13 (PTPN13, also known as PTPL1) belong 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. Human PTPN13 is an important regulator of tumor aggressiveness.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161265   2 ISLMRKYqeHEDVPICIHCSAGCGRTGAICAIDYTWNLLKAGKipeEFNVFNLIQEMRTQRHSAVQTKEQYELVHRAIAQ 81
Cdd:cd14538   131 IRYMRRI--HNSGPIVVHCSAGIGRTGVLITIDVALGLIERDL---PFDIQDIVKDLREQRQGMIQTKDQYIFCYKACLE 205

catalytic domain of receptor-type tyrosine-protein phosphatase A and E, repeat 2; Receptor-type tyrosine-protein phosphatase A (PTPRA) and E (PTPRE) belong to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRA and PTPRE share several functions including regulation of Src family kinases and voltage-gated potassium (Kv) channels. They both contain 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 1907161265   1 MISLMRKYQEHE-DVPICIHCSAGCGRTGAICAIDYTWNLLKAGKIpeeFNVFNLIQEMRTQRHSAVQTKEQYELVHRAI 79
Cdd:cd14552   125 LIAAVQKQQQQSgNHPITVHCSAGAGRTGTFCALSTVLERVKAEGV---LDVFQVVKSLRLQRPHMVQTLEQYEFCYKVV 201

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907161265   2 ISLMRKYqeHEDVPICIHCSAGCGRTGAICAIDYTWNLLKAGKipeEFNVFNLIQEMRTQRHSAVQTKEQYELVHRAI 79
Cdd:cd14596   130 ICYMRKV--HNTGPIVVHCSAGIGRAGVLICVDVLLSLIEKDL---SFNIKDIVREMRQQRYGMIQTKDQYLFCYKVV 202

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161265   1 MISLMRKY---QEHEDVPICIHCSAGCGRTGAICAIDytwNLLKAGKIPEEFNVFNLIQEMRTQRHSAVQTKEQYELVHR 77
Cdd:cd17668   130 VLTFVRKAsyaKRHAVGPVVVHCSAGVGRTGTYIVLD---SMLQQIQHEGTVNIFGFLKHIRSQRNYLVQTEEQYVFIHD 206

                  ..
gi 1907161265  78 AI 79
Cdd:cd17668   207 AL 208

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907161265  15 PICIHCSAGCGRTGAICAIDYTWNLLKAGKIpeeFNVFNLIQEMRTQRHSAVQTKEQYELVHRAIAQ 81
Cdd:cd14630   170 PIVVHCSAGAGRTGCFIAIDIMLDMAENEGV---VDIFNCVRELRAQRVNMVQTEEQYVFVHDAILE 233

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907161265   3 SLMRKYQEHEDVPICIHCSAGCGRTGAICAIDYTWNLLKAGKIpeeFNVFNLIQEMRTQRHSAVQTKEQYELVHRAIAQ 81
Cdd:cd14623   153 AVQKQQQQSGNHPITVHCSAGAGRTGTFCALSTVLERVKAEGI---LDVFQTVKSLRLQRPHMVQTLEQYEFCYKVVQE 228

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 1907161265   1 MISLM----RKYQEHEDVPICIHCSAGCGRTGAICAIDytwNLLKAGKIPEEFNVFNLIQEMRTQRHSAVQTKEQYELVH 76
Cdd:cd14622   123 MIDLIaavqKQQQQTGNHPIVVHCSAGAGRTGTFIALS---NILERVKAEGLLDVFQTVKSLRLQRPHMVQTLEQYEFCY 199

                  ...
gi 1907161265  77 RAI 79
Cdd:cd14622   200 RVV 202

catalytic domain of receptor-type tyrosine-protein phosphatase O; Receptor-type tyrosine-protein phosphatase O (PTPRO or R-PTP-O), also known as glomerular epithelial protein 1 or protein tyrosine phosphatase U2 (PTP-U2), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRO 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 essential for sustaining the structure and function of foot processes by regulating tyrosine phosphorylation of podocyte proteins. It has been identified as a synaptic cell adhesion molecule (CAM) that serves as a potent initiator of synapse formation. It is also a tumor suppressor in several types of cancer, such as hepatocellular carcinoma, lung cancer, and breast cancer.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907161265  15 PICIHCSAGCGRTGAICAIDYtwnLLKAGKIPEEFNVFNLIQEMRTQRHSAVQTKEQYELVHRAI 79
Cdd:cd14614   181 PMIIHCSAGVGRTGTFIALDR---LLQHIRDHEFVDILGLVSEMRSYRMSMVQTEEQYIFIHQCV 242

PTP-like domain of receptor-type tyrosine-protein phosphatase C, repeat 2; 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 2.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907161265   1 MISLMRKYQE------HEDVPICIHCSAGCGRTGAICAIdytWNLLKAGKIPEEFNVFNLIQEMRTQRHSAVQTKEQYE 73
Cdd:cd14558   124 MIKSIKQKLPyknskhGRSVPIVVHCSDGSSRTGIFCAL---WNLLESAETEKVVDVFQVVKALRKQRPGMVSTLEQYQ 199

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907161265  15 PICIHCSAGCGRTGAICAIDytwNLLKAGKIPEEFNVFNLIQEMRTQRHSAVQTKEQYELVHRAIAQ 81
Cdd:cd17667   208 PVLVHCSAGVGRTGTYIVID---SMLQQIKDKSTVNVLGFLKHIRTQRNYLVQTEEQYIFIHDALLE 271

catalytic domain of R3 subfamily receptor-type tyrosine-protein phosphatases and similar proteins; R3 subfamily receptor-type phosphotyrosine phosphatases (RPTP) are 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. Vertebrate members include receptor-type tyrosine-protein phosphatase-like O (PTPRO), J (PTPRJ), Q (PTPRQ), B (PTPRB), V (PTPRV) and H (PTPRH). They belong to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. Most members are PTPs, except for PTPRQ, which dephosphorylates phosphatidylinositide substrates. PTPRV is characterized only in rodents; its function has been lost in humans. Both vertebrate and invertebrate R3 subfamily RPTPs are involved in the control of a variety of cellular processes, including cell growth, differentiation, mitotic cycle and oncogenic transformation.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907161265   2 ISLMRKYQEHEDVPICIHCSAGCGRTGAICAIDYtwnLLKAGKIPEEFNVFNLIQEMRTQRHSAVQTKEQYELVH 76
Cdd:cd14548   150 VRLVRDYIKQEKGPTIVHCSAGVGRTGTFIALDR---LLQQIESEDYVDIFGIVYDLRKHRPLMVQTEAQYIFLH 221

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161265   2 ISLMRKYQEHEDVPICIHCSAGCGRTGAICAIDYTWNLLKAGkipEEFNVFNLIQEMRTQRHSAVQTKEQYELVHRAIAQ 81
Cdd:cd14601   132 VCLVRNKRAGKDEPVVVHCSAGIGRTGVLITMETAMCLIECN---QPVYPLDIVRTMRDQRAMMIQTPSQYRFVCEAILK 208

                  ....
gi 1907161265  82 LFEK 85
Cdd:cd14601   209 VYEE 212

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907161265   7 KYQEHEDVPICIHCSAGCGRTGAICAIDYTWNLLKAGKIpeeFNVFNLIQEMRTQRHSAVQTKEQYELVHRA 78
Cdd:cd14554   168 KEQFGQEGPITVHCSAGVGRTGVFITLSIVLERMRYEGV---VDVFQTVKLLRTQRPAMVQTEDQYQFCYRA 236

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 1907161265  15 PICIHCSAGCGRTGAICAIDYTWNLLKAGKipeEFNVFNLIQEMRTQRHSAVQTKEQYELVHRAI 79
Cdd:cd14620   166 PIVVHCSAGVGRTGTFIVIDAMIDMMHAEQ---KVDVFEFVSRIRNQRPQMVQTDMQYSFIYQAL 227

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 1907161265  15 PICIHCSAGCGRTGAICAIDYTWNLLKAGKIpeeFNVFNLIQEMRTQRHSAVQTKEQYELVHRAIAQ 81
Cdd:cd14631   152 PIVVHCSAGAGRTGCYIVIDIMLDMAEREGV---VDIYNCVKALRSRRINMVQTEEQYIFIHDAILE 215

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 1907161265  15 PICIHCSAGCGRTGAICAIDYTWNLLKAGKIpeeFNVFNLIQEMRTQRHSAVQTKEQYELVHRAIAQ 81
Cdd:cd14633   207 PLVVHCSAGAGRTGCFIVIDIMLDMAEREGV---VDIYNCVRELRSRRVNMVQTEEQYVFIHDAILE 270

catalytic domain of tyrosine-protein phosphatase non-receptor type 21 and type 14; Tyrosine-protein phosphatase non-receptor type 21 (PTPN21) and type 14 (PTPN14) belong to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. Both PTPN21 and PTPN14 contain an N-terminal FERM domain and a C-terminal catalytic PTP domain, separated by a long intervening sequence.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907161265  15 PICIHCSAGCGRTGAICAIDYTWNLLKAGkipEEFNVFNLIQEMRTQRHSAVQTKEQYELVHRAIAQ 81
Cdd:cd14540   154 PTLVHCSAGVGRTGVVILADLMLYCLDHN---EELDIPRVLALLRHQRMLLVQTLAQYKFVYNVLIQ 217

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161265   6 RKYQEHEDVPICIHCSAGCGRTGAICAIDYTWNLLKAGkipEEFNVFNLIQEMRTQRHSAVQTKEQYELVHRAIAQLFEK 85
Cdd:cd14541   136 RQNRVGMVEPTVVHCSAGIGRTGVLITMETAMCLIEAN---EPVYPLDIVRTMRDQRAMLIQTPSQYRFVCEAILRVYEE 212

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907161265   7 KYQEHEDVPICIHCSAGCGRTGAICAIDYTWNLLKAGKIpeeFNVFNLIQEMRTQRHSAVQTKEQYELVHRA 78
Cdd:cd14628   214 KEQFGQDGPISVHCSAGVGRTGVFITLSIVLERMRYEGV---VDIFQTVKMLRTQRPAMVQTEDQYQFCYRA 282

Protein tyrosine phosphatase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161265   1 MISLMRKYQEHEDV---PICIHCSAGCGRTGAICAIDYTWNLLKAGKIpEEFNVFNLIQEMRTQR-HSAVQTKEQY-ELV 75
Cdd:COG5599   191 LADLIDKKEKIKDPdklLPVVHCRAGVGRTGTLIACLALSKSINALVQ-ITLSVEEIVIDMRTSRnGGMVQTSEQLdVLV 269

                  ....*.
gi 1907161265  76 HRAIAQ 81
Cdd:COG5599   270 KLAEQQ 275

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 1907161265  15 PICIHCSAGCGRTGAICAIDytwNLLKAGKIPEEFNVFNLIQEMRTQRHSAVQTKEQYELVHRAIAQ 81
Cdd:cd14625   215 PIVVHCSAGVGRTGCFIVID---AMLERIKHEKTVDIYGHVTLMRSQRNYMVQTEDQYSFIHDALLE 278

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 1907161265   1 MISLMRKYQEHEDV-----PICIHCSAGCGRTGAICAIDYTWNLLKAgkiPEEFNVFNLIQEMRTQRHSAVQTKEQYELV 75
Cdd:cd14612   164 LLRLVAEVEESRQTaaspgPIVVHCSAGIGRTGCFIATSIGCQQLKD---TGKVDILGIVCQLRLDRGGMIQTSEQYQFL 240

                  ....*.
gi 1907161265  76 HRAIAQ 81
Cdd:cd14612   241 HHTLAL 246

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907161265  12 EDVPICIHCSAGCGRTGAICAIDYTWNLlkagkIPEEFNVFNL--IQEMRTQRHSAVQTKEQYELVHRAIAQLFEK 85
Cdd:cd14600   204 ENEPVLVHCSAGIGRTGVLVTMETAMCL-----TERNQPVYPLdiVRKMRDQRAMMVQTSSQYKFVCEAILRVYEE 274

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907161265  15 PICIHCSAGCGRTGAICAIDYTWNLLKAGKIpeeFNVFNLIQEMRTQRHSAVQTKEQYELVHRAI 79
Cdd:cd14618   168 PTLVHCSAGVGRSGTFIALDRLLRQLKEEKV---VDVFNTVYILRMHRYLMIQTLSQYIFLHSCI 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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907161265   7 KYQEHEDVPICIHCSAGCGRTGAICAIDYTWNLLKAGKIpeeFNVFNLIQEMRTQRHSAVQTKEQYELVHRA 78
Cdd:cd14627   215 KEQFGQDGPISVHCSAGVGRTGVFITLSIVLERMRYEGV---VDIFQTVKMLRTQRPAMVQTEDEYQFCYQA 283

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907161265  15 PICIHCSAGCGRTGAICAIDytwnLLKAGKIPeefnVFNLIQEMRTQR-HSAVQTKEQYELVHR 77
Cdd:cd14494    58 PVLVHCKAGVGRTGTLVACY----LVLLGGMS----AEEAVRIVRLIRpGGIPQTIEQLDFLIK 113

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907161265  15 PICIHCSAGCGRTGAICAIDYTWNLLKAGKipeEFNVFNLIQEMRTQRHSAVQTKEQYELVHRAIAQ 81
Cdd:cd14621   224 AIVVHCSAGVGRTGTFIVIDAMLDMMHAER---KVDVYGFVSRIRAQRCQMVQTDMQYVFIYQALLE 287

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907161265  15 PICIHCSAGCGRTGAICAIDytwNLLKAGKIPEEFNVFNLIQEMRTQRHSAVQTKEQYELVHRAIAQ 81
Cdd:cd14624   215 PMVVHCSAGVGRTGCFIVID---AMLERIKHEKTVDIYGHVTLMRAQRNYMVQTEDQYIFIHDALLE 278

protein tyrosine phosphatase; Provisional

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907161265  15 PICIHCSAGCGRTGAICAIDYTWN-LLKAGKIPEEFNVFNLiqemRTQRHSAVQTKEQYELVH 76
Cdd:PHA02747  231 PIVVHCSDGVGKTGIFCAVDICLNqLVKRKAICLAKTAEKI----REQRHAGIMNFDDYLFIQ 289

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907161265  15 PICIHCSAGCGRTGAICAIdYtwnLLKAGKIPEEfnvfNLIQEMRTQRHSAVQTKEQYELV 75
Cdd:cd14504    84 AVLVHCLAGKGRTGTMLAC-Y---LVKTGKISAV----DAINEIRRIRPGSIETSEQEKFV 136

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161265  18 IHCSAGCGRTGAICAidyTWnLLKAGKIPEEfnvfnLIQEMRTQRHSAVQTKEQYELVHR 77
Cdd:COG2453    85 VHCRGGIGRTGTVAA---AY-LVLLGLSAEE-----ALARVRAARPGAVETPAQRAFLER 135

YopH and related bacterial protein tyrosine phosphatases; Yersinia outer protein H (YopH) belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. YopH is an essential virulence determinant of the pathogenic bacterium by dephosphorylating several focal adhesion proteins including p130Cas in human epithelial cells, resulting in the disruption of focal adhesions and cell detachment from the extracellular matrix. It contains an N-terminal domain that contains signals required for TTSS-mediated delivery of YopH into host cells and a C-terminal catalytic PTP domain.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1907161265  18 IHCSAGCGRTGAICAIdytwnlLKAGKIPEEFNVFNLIQEMRTQR-HSAVQTKEQYEL 74
Cdd:cd14559   173 IHCRAGVGRTGQLAAA------MELNKSPNNLSVEDIVSDMRTSRnGKMVQKDEQLDT 224

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907161265   1 MISLMRKYQEHEDVP---ICIHCSAGCGRTGAICAIDYTWNLLKAGKIpeeFNVFNLIQEMRTQRHSAVQTKEQYELVH 76
Cdd:cd14634   126 VVRRLEKWQEQYDGRegrTVVHCLNGGGRSGTFCAICSVCEMIQQQNI---IDVFHTVKTLRNNKSNMVETLEQYKFVY 201

catalytic domain of tyrosine-protein phosphatase non-receptor type 2; Tyrosine-protein phosphatase non-receptor type 2 (PTPN2), also called T-cell protein-tyrosine phosphatase (TCPTP), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN2, a tumor suppressor, dephosphorylates and inactivates EGFRs, Src family kinases, Janus-activated kinases (JAKs)-1 and -3, and signal transducer and activators of transcription (STATs)-1, -3 and -5, in a cell type and context-dependent manner. It is deleted in 6% of all T-cell acute lymphoblastic leukemias and is associated with constitutive JAK1/STAT5 signaling and tumorigenesis.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907161265  12 EDVPICIHCSAGCGRTGAICAIDyTWNLLKAGKIPEEFNVFNLIQEMRTQRHSAVQTKEQYELVHRAI 79
Cdd:cd14607   191 EHGPAVVHCSAGIGRSGTFSLVD-TCLVLMEKKDPDSVDIKQVLLDMRKYRMGLIQTPDQLRFSYMAV 257

protein tyrosine phosphatase domain of PTP domain-containing protein 1; protein tyrosine phosphatase domain-containing protein 1 (PTPDC1) is an uncharacterized non-receptor class protein-tyrosine phosphatase (PTP). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. Small interfering RNA (siRNA) knockdown of the ptpdc1 gene is associated with elongated cilia.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907161265  12 EDVPICIHCSAGCGRTG-AICAIdytwnLLKAGKIPEEfnvfNLIQEMRTQRHSAVQTKEQYELVH 76
Cdd:cd14506   108 EGGKVAVHCHAGLGRTGvLIACY-----LVYALRMSAD----QAIRLVRSKRPNSIQTRGQVLCVR 164