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 108802609 151 MQEFMTGTSHSVKQLQFTKWPDHGTPASADSFIKYIRYARKSHLTGPMVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNI 230
Cdd:cd14596   95 LVEKETGENRLIKHLQFTTWPDHGTPQSSDQLVKFICYMRKVHNTGPIVVHCSAGIGRAGVLICVDVLLSLIEKDLSFNI 174

                         90       100       110
                 ....*....|....*....|....*....|...
gi 108802609 231 MDIVAQMREQRSGMVQTKEQYHFCYDIVLEVLR 263
Cdd:cd14596  175 KDIVREMRQQRYGMIQTKDQYLFCYKVVLEVLQ 207

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 108802609 151 MQEFMTGTSHSVKQLQFTKWPDHGTPASADSFIKYIRYARKSHLTGPMVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNI 230
Cdd:cd14596   95 LVEKETGENRLIKHLQFTTWPDHGTPQSSDQLVKFICYMRKVHNTGPIVVHCSAGIGRAGVLICVDVLLSLIEKDLSFNI 174

                         90       100       110
                 ....*....|....*....|....*....|...
gi 108802609 231 MDIVAQMREQRSGMVQTKEQYHFCYDIVLEVLR 263
Cdd:cd14596  175 KDIVREMRQQRYGMIQTKDQYLFCYKVVLEVLQ 207

Protein tyrosine phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 108802609   156 TGTSHSVKQLQFTKWPDHGTPASADSFIKYIRYARK--SHLTGPMVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDI 233
Cdd:smart00194 153 CSETRTVTHYHYTNWPDHGVPESPESILDLIRAVRKsqSTSTGPIVVHCSAGVGRTGTFIAIDILLQQLEAGKEVDIFEI 232

                           90       100
                   ....*....|....*....|....*..
gi 108802609   234 VAQMREQRSGMVQTKEQYHFCYDIVLE 260
Cdd:smart00194 233 VKELRSQRPGMVQTEEQYIFLYRAILE 259

protein tyrosine phosphatase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 108802609 158 TSHSVKQLQFTKWPDHGTPASADSFIKYIR------------YARKSHLTGPMVVHCSAGIGRTGVFLCVDVVFCAIVKN 225
Cdd:PHA02747 180 DSRKISHFQCSEWFEDETPSDHPDFIKFIKiidinrkksgklFNPKDALLCPIVVHCSDGVGKTGIFCAVDICLNQLVKR 259

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 108802609 226 CSFNIMDIVAQMREQRSGMVQTKEQYHF---CYDIVLEVLRKLLTLD 269
Cdd:PHA02747 260 KAICLAKTAEKIREQRHAGIMNFDDYLFiqpGYEVLHYFLSKIKAID 306

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 108802609 151 MQEFMTGTSHSVKQLQFTKWPDHGTPASADSFIKYIRYARKSHLTGPMVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNI 230
Cdd:cd14596   95 LVEKETGENRLIKHLQFTTWPDHGTPQSSDQLVKFICYMRKVHNTGPIVVHCSAGIGRAGVLICVDVLLSLIEKDLSFNI 174

                         90       100       110
                 ....*....|....*....|....*....|...
gi 108802609 231 MDIVAQMREQRSGMVQTKEQYHFCYDIVLEVLR 263
Cdd:cd14596  175 KDIVREMRQQRYGMIQTKDQYLFCYKVVLEVLQ 207

Protein-tyrosine phosphatase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 108802609  142 EEKTAAYDIMQEFM-----TGTSHSVKQLQFTKWPDHGTPASADSFIKYIRYARKSHL---TGPMVVHCSAGIGRTGVFL 213
Cdd:pfam00102 108 EKEDEKDYTVRTLEvsnggSEETRTVKHFHYTGWPDHGVPESPNSLLDLLRKVRKSSLdgrSGPIVVHCSAGIGRTGTFI 187

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 108802609  214 CVDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCYDIVLE 260
Cdd:pfam00102 188 AIDIALQQLEAEGEVDIFQIVKELRSQRPGMVQTLEQYIFLYDAILE 234

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 108802609 142 EEKTAAYdIMQEFM-----TGTSHSVKQLQFTKWPDHGTPASADSFIKYIRYARKS--HLTGPMVVHCSAGIGRTGVFLC 214
Cdd:cd00047   80 EEELSDY-TIRTLElspkgCSESREVTHLHYTGWPDHGVPSSPEDLLALVRRVRKEarKPNGPIVVHCSAGVGRTGTFIA 158

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 108802609 215 VDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCYD 256
Cdd:cd00047  159 IDILLERLEAEGEVDVFEIVKALRKQRPGMVQTLEQYEFIYE 200

Protein tyrosine phosphatase, catalytic domain motif;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 108802609   161 SVKQLQFTKWPDHGTPASADSFIKYIRYARKSH----LTGPMVVHCSAGIGRTGVFLCVDVVfCAIVKNCS--FNIMDIV 234
Cdd:smart00404   1 TVKHYHYTGWPDHGVPESPDSILELLRAVKKNLnqseSSGPVVVHCSAGVGRTGTFVAIDIL-LQQLEAEAgeVDIFDTV 79

                           90       100
                   ....*....|....*....|....*.
gi 108802609   235 AQMREQRSGMVQTKEQYHFCYDIVLE 260
Cdd:smart00404  80 KELRSQRPGMVQTEEQYLFLYRALLE 105

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 108802609 156 TGTSHSVKQLQFTKWPDHGTPASADSFIKYIRYARK----SHLTGPMVVHCSAGIGRTGVFLCVDVVF---------CAI 222
Cdd:cd18533   99 DGKVKKVYHIQYKSWPDFGVPDSPEDLLTLIKLKRElndsASLDPPIIVHCSAGVGRTGTFIALDSLLdelkrglsdSQD 178

                         90       100       110
                 ....*....|....*....|....*....|....
gi 108802609 223 VKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCYD 256
Cdd:cd18533  179 LEDSEDPVYEIVNQLRKQRMSMVQTLRQYIFLYD 212

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 108802609 150 IMQEF---MTGTSHSVKQLQFTKWPDHGTPASADSFIKYIRYARKS--HLTGPMVVHCSAGIGRTGVFLCVDVVFCAIVK 224
Cdd:cd14548  111 TIREFkleRGDEVRSVRQFHFTAWPDHGVPEAPDSLLRFVRLVRDYikQEKGPTIVHCSAGVGRTGTFIALDRLLQQIES 190

                         90       100
                 ....*....|....*....|....*....
gi 108802609 225 NCSFNIMDIVAQMREQRSGMVQTKEQYHF 253
Cdd:cd14548  191 EDYVDIFGIVYDLRKHRPLMVQTEAQYIF 219

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 108802609 142 EEKTAAYdIMQEFM-----TGTSHSVKQLQFTKWPDHGTPASADSFIKYIRYARKSHLTG-PMVVHCSAGIGRTGVFLCV 215
Cdd:cd14600  147 EDCTIAY-VFREMLltntqTGEERTVTHLQYVAWPDHGVPDDSSDFLEFVNYVRSKRVENePVLVHCSAGIGRTGVLVTM 225

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 108802609 216 DVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCYDIVLEVLRK 264
Cdd:cd14600  226 ETAMCLTERNQPVYPLDIVRKMRDQRAMMVQTSSQYKFVCEAILRVYEE 274

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 108802609 150 IMQEFM-----TGTSHSVKQLQFTKWPDHGTPASADSFIKYIRYARKSH----LTGPMVVHCSAGIGRTGVFLCVDVVFC 220
Cdd:cd14554  120 ILREFKvtdarDGQSRTVRQFQFTDWPEQGVPKSGEGFIDFIGQVHKTKeqfgQEGPITVHCSAGVGRTGVFITLSIVLE 199

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 108802609 221 AIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCY 255
Cdd:cd14554  200 RMRYEGVVDVFQTVKLLRTQRPAMVQTEDQYQFCY 234

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        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 108802609 158 TSHSVKQLQFTKWPDHGTPASADSFIKYIRYARK--SHLTGPMVVHCSAGIGRTGVFLCVDVVFCAI---VKNCSFNIMD 232
Cdd:cd14542   99 ESRTVYQFHYTAWPDHGVPSSVDPILDLVRLVRDyqGSEDVPICVHCSAGCGRTGTICAIDYVWNLLktgKIPEEFSLFD 178

                         90       100
                 ....*....|....*....|...
gi 108802609 233 IVAQMREQRSGMVQTKEQYHFCY 255
Cdd:cd14542  179 LVREMRKQRPAMVQTKEQYELVY 201

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 108802609 137 CLKILEEKTAAYDIMQEFMTGT----SHSVKQLQFTKWPDHGTPASADSFIKYIRYARKSHLTG--PMVVHCSAGIGRTG 210
Cdd:cd14603  132 TITLVKEKRLNEEVILRTLKVTfqkeSRSVSHFQYMAWPDHGIPDSPDCMLAMIELARRLQGSGpePLCVHCSAGCGRTG 211

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 108802609 211 VFLCVDVVFCAIVKNC---SFNIMDIVAQMREQRSGMVQTKEQYHFCYDIVLEV 261
Cdd:cd14603  212 VICTVDYVRQLLLTQRippDFSIFDVVLEMRKQRPAAVQTEEQYEFLYHTVAQM 265

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 108802609 156 TGTSHSVKQLQFTKWPDHGTPASADSFIKYIRYAR--------------KSHLTGP-MVVHCSAGIGRTGVFLCVDVVFC 220
Cdd:cd14543  156 TDESRQVTHFQFTSWPDFGVPSSAAALLDFLGEVRqqqalavkamgdrwKGHPPGPpIVVHCSAGIGRTGTFCTLDICLS 235

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 108802609 221 AIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCY 255
Cdd:cd14543  236 QLEDVGTLNVMQTVRRMRTQRAFSIQTPDQYYFCY 270

PTP-like domain of tyrosine-protein phosphatase non-receptor type 23; Tyrosine-protein phosphatase non-receptor type 23 (PTPN23), also called His domain-containing protein tyrosine phosphatase (HD-PTP) or protein tyrosine phosphatase TD14 (PTP-TD14), is a catalytically inactive member of the tyrosine-specific protein tyrosine phosphatase (PTP) family. Human PTPN23 may be involved in the regulation of small nuclear ribonucleoprotein assembly and pre-mRNA splicing by modifying the survival motor neuron (SMN) complex. It plays a role in ciliogenesis and is part of endosomal sorting complex required for transport (ESCRT) pathways. PTPN23 contains five domains: a BRO1-like domain that plays a role in endosomal sorting; a V-domain that interacts with Lys63-linked polyubiquitinated substrates; a central proline-rich region that might recruit SH3-containing proteins; a PTP-like domain; and a proteolytic degradation-targeting motif, also known as a PEST sequence.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 108802609 156 TGTSHSVKQLQFTKWPDHGTPASADSFIKYIR-----YARKSHLTGPMVVHCSAGIGRTGVFlCVdvVFCAIVK----NC 226
Cdd:cd14539   99 TRLSRSVVHLQFTTWPELGLPDSPNPLLRFIEevhshYLQQRSLQTPIVVHCSSGVGRTGAF-CL--LYAAVQEieagNG 175

                         90       100       110
                 ....*....|....*....|....*....|
gi 108802609 227 SFNIMDIVAQMREQRSGMVQTKEQYHFCYD 256
Cdd:cd14539  176 IPDLPQLVRKMRQQRKYMLQEKEHLKFCYE 205

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 108802609 161 SVKQLQFTKWPDHGTPASADSFIKYIRyaRKSHL---TGPMVVHCSAGIGRTGVFLCVDVVFCAIVKN--CSFNIMDIVA 235
Cdd:cd17658  108 SVLHIQYPEWPDHGVPKDTRSVRELLK--RLYGIppsAGPIVVHCSAGIGRTGAYCTIHNTIRRILEGdmSAVDLSKTVR 185

                         90       100
                 ....*....|....*....|
gi 108802609 236 QMREQRSGMVQTKEQYHFCY 255
Cdd:cd17658  186 KFRSQRIGMVQTQDQYIFCY 205

catalytic domain of type IIb (or R2B) subfamily receptor-type tyrosine-protein phosphatases, repeat 1; The type II (or R2B) subfamily of receptor protein tyrosine phosphatases (RPTPs) include the prototypical member PTPmu (or PTPRM), PCP-2 (or PTPRU), PTPrho (or PTPRT), and PTPkappa (or PTPRK). They belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. Type IIb RPTPs mediate cell-cell adhesion though homophilic interactions; their ligand is an identical molecule on an adjacent cell. No heterophilic interactions between the subfamily members have been observed. They also commonly function as tumor suppressors. They contain an extracellular region with an Meprin-A5 (neuropilin)-mu (MAM) domain, an immunoglobulin (Ig) domain, and four fibronectin type III (FN3) repeats, a transmembrane domain, and an intracellular segment with a juxtamembrane domain similar to the cytoplasmic domain of classical cadherins and two tandem PTP domains. This model represents the first (repeat 1) PTP domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 108802609 160 HSVKQLQFTKWPDHGTPASADSFIKYIRYARKSH--LTGPMVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQM 237
Cdd:cd14555   99 REVRQFHFTGWPDHGVPYHATGLLGFIRRVKASNppSAGPIVVHCSAGAGRTGCYIVIDIMLDMAEREGVVDIYNCVKEL 178

                         90       100
                 ....*....|....*....|...
gi 108802609 238 REQRSGMVQTKEQYHFCYDIVLE 260
Cdd:cd14555  179 RSRRVNMVQTEEQYIFIHDAILE 201

PTP-like domain of receptor-type tyrosine-protein phosphatase F, repeat 2; Receptor-type tyrosine-protein phosphatase F (PTPRF), also known as leukocyte common antigen related (LAR), is the prototypical member of the LAR family of receptor-type tyrosine-protein phosphatases (RPTPs), which belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRF/LAR plays a role for LAR in cadherin complexes where it associates with and dephosphorylates beta-catenin, a pathway which may be critical for cadherin complex stability and cell-cell association. It also regulates focal adhesions through cyclin-dependent kinase-1 and is involved in axon guidance in the developing nervous system. It also functions in regulating insulin signaling. PTPRF contains an extracellular region with three immunoglobulin-like (Ig) domains and four to eight fibronectin type III (FN3) repeats (determined by alternative splicing), a single transmembrane domain, followed by an intracellular region with a membrane-proximal catalytic PTP domain (repeat 1, also called D1) and a membrane-distal non-catalytic PTP-like domain (repeat 2, also called D2). This model represents the 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 108802609 150 IMQEFMT-----GTSHSVKQLQFTKWPDHGTPASADSFIKYIRYARKSH----LTGPMVVHCSAGIGRTGVFLCVDVVFC 220
Cdd:cd14629  167 ILREFKVtdardGQSRTIRQFQFTDWPEQGVPKTGEGFIDFIGQVHKTKeqfgQDGPITVHCSAGVGRTGVFITLSIVLE 246

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 108802609 221 AIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCYDIVLEVL 262
Cdd:cd14629  247 RMRYEGVVDMFQTVKTLRTQRPAMVQTEDQYQLCYRAALEYL 288

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 108802609 154 FMTGTSH--SVKQLQFTKWPDHGTPASADSFIKYIRYARKSHL--TGPMVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFN 229
Cdd:cd14624  168 YKNGSSEkrEVRQFQFTAWPDHGVPEHPTPFLAFLRRVKTCNPpdAGPMVVHCSAGVGRTGCFIVIDAMLERIKHEKTVD 247

                         90       100       110
                 ....*....|....*....|....*....|...
gi 108802609 230 IMDIVAQMREQRSGMVQTKEQYHFCYDIVLEVL 262
Cdd:cd14624  248 IYGHVTLMRAQRNYMVQTEDQYIFIHDALLEAV 280

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 108802609 162 VKQLQFTKWPDHGTPASADSFIKYIRYARKSHL--TGPMVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMRE 239
Cdd:cd14625  178 VRQFQFTAWPDHGVPEYPTPFLAFLRRVKTCNPpdAGPIVVHCSAGVGRTGCFIVIDAMLERIKHEKTVDIYGHVTLMRS 257

                         90       100
                 ....*....|....*....|...
gi 108802609 240 QRSGMVQTKEQYHFCYDIVLEVL 262
Cdd:cd14625  258 QRNYMVQTEDQYSFIHDALLEAV 280

catalytic domain of tyrosine-protein phosphatase non-receptor type 11; Tyrosine-protein phosphatase non-receptor type 11 (PTPN11), also called SH2 domain-containing tyrosine phosphatase 2 (SHP-2 or SHP2), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN11 promotes the activation of the RAS/Mitogen-Activated Protein Kinases (MAPK) Extracellular-Regulated Kinases 1/2 (ERK1/2) pathway, a canonical signaling cascade that plays key roles in various cellular processes, including proliferation, survival, differentiation, migration, or metabolism. It also regulates the phosphoinositide 3-kinase (PI3K)/AKT pathway, a fundamental cascade that functions in cell survival, proliferation, migration, morphogenesis, and metabolism. PTPN11 dysregulation is associated with several developmental diseases and malignancies, such as Noonan syndrome and juvenile myelomonocytic leukemia. It contains two tandem SH2 domains, a catalytic PTP domain, and a C-terminal tail with regulatory properties.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 108802609 143 EKTAAYD-IMQEF------MTGTSHSVKQLQFTKWPDHGTPASAD---SFIKYIRYARKSHL-TGPMVVHCSAGIGRTGV 211
Cdd:cd14605  118 KESAAHDyILRELklskvgQGNTERTVWQYHFRTWPDHGVPSDPGgvlDFLEEVHHKQESIMdAGPVVVHCSAGIGRTGT 197

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 108802609 212 FLCVDVVFCAIVK---NCSFNIMDIVAQMREQRSGMVQTKEQYHFCY 255
Cdd:cd14605  198 FIVIDILIDIIREkgvDCDIDVPKTIQMVRSQRSGMVQTEAQYRFIY 244

catalytic domain of receptor-type tyrosine-protein phosphatase H; Receptor-type tyrosine-protein phosphatase H (PTPRH or R-PTP-H), also known as stomach cancer-associated protein tyrosine phosphatase 1 (SAP-1), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRH 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 localized specifically at microvilli of the brush border in gastrointestinal epithelial cells. It plays a role in intestinal immunity by regulating CEACAM20 through tyrosine dephosphorylation. It is also a negative regulator of integrin-mediated signaling and may contribute to contact inhibition of cell growth and motility.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 108802609 155 MTGTSHSVKQLQFTKWPDHGTPASADSFIKYIRYARK---SHL-TGPMVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNI 230
Cdd:cd14619  122 EEQKTLSVRHFHFTAWPDHGVPSSTDTLLAFRRLLRQwldQTMsGGPTVVHCSAGVGRTGTLIALDVLLQQLQSEGLLGP 201

                         90       100       110
                 ....*....|....*....|....*....|..
gi 108802609 231 MDIVAQMREQRSGMVQTKEQYHFCYDIVLEVL 262
Cdd:cd14619  202 FSFVQKMRENRPLMVQTESQYVFLHQCILDFL 233

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 108802609 157 GTSHSVKQLQFTKWPDHGTPASADSFIKY---IRYARKSHLT-GPMVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMD 232
Cdd:cd14611  123 SQSRSVKHYWYTSWPDHKTPDSAQPLLQLmldVEEDRLASPGrGPVVVHCSAGIGRTGCFIATTIGCQQLKEEGVVDVLS 202

                         90       100
                 ....*....|....*....|...
gi 108802609 233 IVAQMREQRSGMVQTKEQYHFCY 255
Cdd:cd14611  203 IVCQLRVDRGGMVQTSEQYEFVH 225

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 108802609 162 VKQLQFTKWPDHGTPASADSFIKYIRYAR--KSHLTGPMVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMRE 239
Cdd:cd14630  133 IRQFHFTSWPDHGVPCYATGLLGFVRQVKflNPPDAGPIVVHCSAGAGRTGCFIAIDIMLDMAENEGVVDIFNCVRELRA 212

                         90       100
                 ....*....|....*....|.
gi 108802609 240 QRSGMVQTKEQYHFCYDIVLE 260
Cdd:cd14630  213 QRVNMVQTEEQYVFVHDAILE 233

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 108802609 162 VKQLQFTKWPDHGTPASADSFIKYIRYARKSHL--TGPMVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMRE 239
Cdd:cd14626  172 VRQFQFMAWPDHGVPEYPTPILAFLRRVKACNPpdAGPMVVHCSAGVGRTGCFIVIDAMLERMKHEKTVDIYGHVTCMRS 251

                         90       100
                 ....*....|....*....|.
gi 108802609 240 QRSGMVQTKEQYHFCYDIVLE 260
Cdd:cd14626  252 QRNYMVQTEDQYIFIHEALLE 272

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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 108802609 156 TGTSHSVKQLQFTKWPDHGTPASADSFIKYIRYARKSH--LTGPMVVHCSAGIGRTGVFLCVDVVFCAIVKncSFNIMDI 233
Cdd:cd14546   98 TSETRTVTQFHFLSWPDEGIPASAKPLLEFRRKVNKSYrgRSCPIVVHCSDGAGRTGTYILIDMVLNRMAK--GAKEIDI 175

                         90       100       110
                 ....*....|....*....|....*....|
gi 108802609 234 VA---QMREQRSGMVQTKEQYHFCYDIVLE 260
Cdd:cd14546  176 AAtleHLRDQRPGMVKTKDQFEFVLTAVAE 205

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 108802609 161 SVKQLQFTKWPDHGTPASADSFIKYIRY---ARKSHLtGPMVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQM 237
Cdd:cd17667  170 TVIQYHYTQWPDMGVPEYALPVLTFVRRssaARTPEM-GPVLVHCSAGVGRTGTYIVIDSMLQQIKDKSTVNVLGFLKHI 248

                         90       100
                 ....*....|....*....|....*
gi 108802609 238 REQRSGMVQTKEQYHFCYDIVLEVL 262
Cdd:cd17667  249 RTQRNYLVQTEEQYIFIHDALLEAI 273

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 108802609 162 VKQLQFTKWPDHGTPASADSFIKYIRYAR--KSHLTGPMVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMRE 239
Cdd:cd14616  128 VRQCNFTSWPEHGVPESSAPLIHFVKLVRasRAHDNTPMIVHCSAGVGRTGVFIALDHLTQHINDHDFVDIYGLVAELRS 207

                         90
                 ....*....|....
gi 108802609 240 QRSGMVQTKEQYHF 253
Cdd:cd14616  208 ERMCMVQNLAQYIF 221