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 1207734461   1 MVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCYDIVLEVLR 66
Cdd:cd14596   142 IVVHCSAGIGRAGVLICVDVLLSLIEKDLSFNIKDIVREMRQQRYGMIQTKDQYLFCYKVVLEVLQ 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1207734461   1 MVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCYDIVLEVLR 66
Cdd:cd14596   142 IVVHCSAGIGRAGVLICVDVLLSLIEKDLSFNIKDIVREMRQQRYGMIQTKDQYLFCYKVVLEVLQ 207

Protein tyrosine phosphatase, catalytic domain;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207734461    1 MVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCYDIVLE 63
Cdd:smart00194 197 IVVHCSAGVGRTGTFIAIDILLQQLEAGKEVDIFEIVKELRSQRPGMVQTEEQYIFLYRAILE 259

protein tyrosine phosphatase; Provisional

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1207734461   1 MVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCYDIVLEVL 65
Cdd:PHA02746  250 IVVHCSAGIGRAGTFCAIDNALEQLEKEKEVCLGEIVLKIRKQRHSSVFLPEQYAFCYKALKYAI 314

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1207734461   1 MVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCYDIVLEVLR 66
Cdd:cd14596   142 IVVHCSAGIGRAGVLICVDVLLSLIEKDLSFNIKDIVREMRQQRYGMIQTKDQYLFCYKVVLEVLQ 207

Protein-tyrosine phosphatase;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207734461   1 MVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCYDIVLE 63
Cdd:pfam00102 172 IVVHCSAGIGRTGTFIAIDIALQQLEAEGEVDIFQIVKELRSQRPGMVQTLEQYIFLYDAILE 234

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1207734461   1 MVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCYDIVLEVL 65
Cdd:cd14597   170 IITHCSAGIGRSGTLICIDVVLGLISKDLDFDISDIVRTMRLQRHGMVQTEDQYIFCYQVILYVL 234

Protein tyrosine phosphatase, catalytic domain motif;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1207734461    1 MVVHCSAGIGRTGVFLCVDVVfCAIVKNCS--FNIMDIVAQMREQRSGMVQTKEQYHFCYDIVLE 63
Cdd:smart00404  42 VVVHCSAGVGRTGTFVAIDIL-LQQLEAEAgeVDIFDTVKELRSQRPGMVQTEEQYLFLYRALLE 105

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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1207734461   1 MVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCY 58
Cdd:cd14543   213 IVVHCSAGIGRTGTFCTLDICLSQLEDVGTLNVMQTVRRMRTQRAFSIQTPDQYYFCY 270

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207734461   1 MVVHCSAGIGRTGVFLCVDVVF---------CAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCYD 59
Cdd:cd18533   145 IIVHCSAGVGRTGTFIALDSLLdelkrglsdSQDLEDSEDPVYEIVNQLRKQRMSMVQTLRQYIFLYD 212

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207734461   1 MVVHCSAGIGRTGVFLCVDVVFCAIVKN--CSFNIMDIVAQMREQRSGMVQTKEQYHFCY 58
Cdd:cd17658   146 IVVHCSAGIGRTGAYCTIHNTIRRILEGdmSAVDLSKTVRKFRSQRIGMVQTQDQYIFCY 205

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207734461   1 MVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCYDIVLE 63
Cdd:cd14553   172 IVVHCSAGVGRTGCFIVIDSMLERIKHEKTVDIYGHVTCLRAQRNYMVQTEDQYIFIHDALLE 234

catalytic domain of the kinase interaction motif (KIM) family of protein-tyrosine phosphatases; The kinase interaction motif (KIM) family of protein-tyrosine phosphatases (PTPs) includes tyrosine-protein phosphatases non-receptor type 7 (PTPN7) and non-receptor type 5 (PTPN5), and protein-tyrosine phosphatase receptor type R (PTPRR). PTPN7 is also called hematopoietic protein-tyrosine phosphatase (HePTP) while PTPN5 is also called striatal-enriched protein-tyrosine phosphatase (STEP). They belong to the family of classical tyrosine-specific PTPs (EC 3.1.3.48) that catalyze the dephosphorylation of phosphotyrosine peptides. KIM-PTPs are characterized by the presence of a 16-amino-acid KIM that binds specifically to members of the MAPK (mitogen-activated protein kinase) family. They are highly specific to the MAPKs ERK1/2 (extracellular-signal-regulated kinase 1/2) and p38, over JNK (c-Jun N-terminal kinase); they dephosphorylate these kinases and thereby critically modulate cell proliferation and differentiation.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1207734461   2 VVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHF 56
Cdd:cd14547   167 VVHCSAGIGRTGCFIATSIGCQQLREEGVVDVLGIVCQLRLDRGGMVQTAEQYEF 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1207734461   1 MVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCYDIVLEVLRK 67
Cdd:cd14601   146 VVVHCSAGIGRTGVLITMETAMCLIECNQPVYPLDIVRTMRDQRAMMIQTPSQYRFVCEAILKVYEE 212

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1207734461   1 MVVHCSAGIGRTGVFLCVDVVFCAIVKNC---SFNIMDIVAQMREQRSGMVQTKEQYHFCYDIVLEV 64
Cdd:cd14603   199 LCVHCSAGCGRTGVICTVDYVRQLLLTQRippDFSIFDVVLEMRKQRPAAVQTEEQYEFLYHTVAQM 265

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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1207734461   1 MVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCY 58
Cdd:cd14612   184 IVVHCSAGIGRTGCFIATSIGCQQLKDTGKVDILGIVCQLRLDRGGMIQTSEQYQFLH 241

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 1207734461   1 MVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCYDIVLEVL 65
Cdd:cd17667   209 VLVHCSAGVGRTGTYIVIDSMLQQIKDKSTVNVLGFLKHIRTQRNYLVQTEEQYIFIHDALLEAI 273

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1207734461   1 MVVHCSAGIGRTGVFLCVDVVFCAI---VKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCY 58
Cdd:cd14542   141 ICVHCSAGCGRTGTICAIDYVWNLLktgKIPEEFSLFDLVREMRKQRPAMVQTKEQYELVY 201

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207734461   3 VHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCYDIVLEVL 65
Cdd:cd14627   226 VHCSAGVGRTGVFITLSIVLERMRYEGVVDIFQTVKMLRTQRPAMVQTEDEYQFCYQAALEYL 288

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207734461   1 MVVHCSAGIGRTGVFlCVdvVFCAIVK----NCSFNIMDIVAQMREQRSGMVQTKEQYHFCYD 59
Cdd:cd14539   146 IVVHCSSGVGRTGAF-CL--LYAAVQEieagNGIPDLPQLVRKMRQQRKYMLQEKEHLKFCYE 205

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 1207734461   1 MVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCYDIVLEVL 65
Cdd:cd14624   216 MVVHCSAGVGRTGCFIVIDAMLERIKHEKTVDIYGHVTLMRAQRNYMVQTEDQYIFIHDALLEAV 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1207734461   1 MVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCYDIVLEVL 65
Cdd:cd14625   216 IVVHCSAGVGRTGCFIVIDAMLERIKHEKTVDIYGHVTLMRSQRNYMVQTEDQYSFIHDALLEAV 280

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 1207734461   1 MVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCYDIVL 62
Cdd:cd14614   182 MIIHCSAGVGRTGTFIALDRLLQHIRDHEFVDILGLVSEMRSYRMSMVQTEEQYIFIHQCVQ 243

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207734461   1 MVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCYDIVLE 63
Cdd:cd14623   166 ITVHCSAGAGRTGTFCALSTVLERVKAEGILDVFQTVKSLRLQRPHMVQTLEQYEFCYKVVQE 228

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1207734461   1 MVVHCSAGIGRTGVFLCVDVVFCAIVKncSFNIMDIVA---QMREQRSGMVQTKEQYHFCYDIVLE 63
Cdd:cd14546   142 IVVHCSDGAGRTGTYILIDMVLNRMAK--GAKEIDIAAtleHLRDQRPGMVKTKDQFEFVLTAVAE 205

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207734461   1 MVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCYDIVLE 63
Cdd:cd14630   171 IVVHCSAGAGRTGCFIAIDIMLDMAENEGVVDIFNCVRELRAQRVNMVQTEEQYVFVHDAILE 233

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207734461   3 VHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCYDIVLEVL 65
Cdd:cd14628   225 VHCSAGVGRTGVFITLSIVLERMRYEGVVDIFQTVKMLRTQRPAMVQTEDQYQFCYRAALEYL 287

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1207734461   1 MVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCY 58
Cdd:cd14551   144 IVVHCSAGVGRTGTFIVIDAMLDMMHAEGKVDVFGFVSRIRQQRSQMVQTDMQYVFIY 201

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1207734461   1 MVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCYDIVLEVLR 66
Cdd:cd14598   155 VLVHCSAGVGRTGVVILSEIMIACLEHNEMLDIPRVLDMLRQQRMMMVQTLSQYTFVYKVLIQFLK 220

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1207734461   1 MVVHCSAGIGRTGVFLCVDVVfCAIVKNCS-FNIMDIVAQMREQRSGMVQTKEQYHFCYDIV 61
Cdd:cd14613   195 VIVHCSAGIGRTGCFIATSIC-CKQLRNEGvVDILRTTCQLRLDRGGMIQTCEQYQFVHHVL 255

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1207734461   1 MVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCYDIVLEVLR 66
Cdd:cd14599   222 IVVHCSAGVGRTGVVILTELMIGCLEHNEKVEVPVMLRHLREQRMFMIQTIAQYKFVYQVLIQFLK 287

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 1207734461   1 MVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCYDIVLE 63
Cdd:cd14631   153 IVVHCSAGAGRTGCYIVIDIMLDMAEREGVVDIYNCVKALRSRRINMVQTEEQYIFIHDAILE 215

catalytic domain of receptor-type tyrosine-protein phosphatase B; Receptor-type tyrosine-protein phosphatase B (PTPRB), also known as receptor-type tyrosine-protein phosphatase beta (R-PTP-beta) or vascular endothelial protein tyrosine phosphatase(VE-PTP), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRB/VE-PTP is a member of the R3 subfamily of receptor-type phosphotyrosine phosphatases (RPTP), characterized by a unique modular composition consisting of multiple extracellular fibronectin type III (FN3) repeats and a single (most RPTP subtypes have two) cytoplasmic catalytic PTP domain. It is expressed specifically in vascular endothelial cells and it plays an important role in blood vessel remodeling and angiogenesis.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1207734461   2 VVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCY 58
Cdd:cd14617   171 VVHCSAGVGRTGTFIALDRILQQLDSKDSVDIYGAVHDLRLHRVHMVQTECQYVYLH 227

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1207734461   1 MVVHCSAGIGRTGVFLCVDVVFCAIVKN---CSFNIMDIVAQMREQRSGMVQTKEQYHFCYDIVLE 63
Cdd:cd14608   196 VVVHCSAGIGRSGTFCLADTCLLLMDKRkdpSSVDIKKVLLEMRKFRMGLIQTADQLRFSYLAVIE 261

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1207734461   2 VVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHF 56
Cdd:cd14615   168 LVHCSAGVGRTGTFIAIDRLIYQIENENVVDVYGIVYDLRMHRPLMVQTEDQYVF 222

PTP-like domain of receptor-type tyrosine-protein phosphatase N; Receptor-type tyrosine-protein phosphatase-like N (PTPRN or R-PTP-N), also called islet cell antigen 512 (ICA512) or PTP IA-2, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). It consists of a large ectodomain that contains a RESP18HD (regulated endocrine-specific protein 18 homology domain), followed by a transmembrane segment, and a single, catalytically-impaired, PTP domain. PTPRN is located in secretory granules of neuroendocrine cells and is involved in the generation, cargo storage, traffic, exocytosis and recycling of insulin secretory granules, as well as in beta-cell proliferation. It is a major autoantigen in type 1 diabetes and is involved in the regulation of insulin secretion.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1207734461   1 MVVHCSAGIGRTGVFLCVDVVFCAIVKNC-SFNIMDIVAQMREQRSGMVQTKEQYHFCYDIVLE 63
Cdd:cd14609   213 IIVHCSDGAGRTGTYILIDMVLNRMAKGVkEIDIAATLEHVRDQRPGMVRTKDQFEFALTAVAE 276

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1207734461   2 VVHCSAGIGRTGVFlcvdvvfCAIVKNCSF----NIMDI---VAQMREQRSGMVQTKEQYHFCYDIVLE 63
Cdd:cd14634   145 VVHCLNGGGRSGTF-------CAICSVCEMiqqqNIIDVfhtVKTLRNNKSNMVETLEQYKFVYEVALE 206

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1207734461   2 VVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCYD 59
Cdd:cd14556   144 VVHCLNGVGRSGVFCAISSVCERIKVENVVDVFQAVKTLRNHRPNMVETEEQYKFCYD 201

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207734461   3 VHCSAGIGRTGVFLCVDVVFCAIVKNC---SFNIMDIVAQMREQRSGMVQTKEQYHFCYDIVLEVLRKLL 69
Cdd:cd14604   228 IHCSAGCGRTGAICAIDYTWNLLKAGKipeEFNVFNLIQEMRTQRHSAVQTKEQYELVHRAIAQLFEKQL 297

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
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1207734461   1 MVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHF 56
Cdd:cd14616   166 MIVHCSAGVGRTGVFIALDHLTQHINDHDFVDIYGLVAELRSERMCMVQNLAQYIF 221

protein tyrosine phosphatase; Provisional

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207734461   1 MVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCYDIVLE 63
Cdd:PHA02742  232 ILVHCSAGLDRAGAFCAIDICISKYNERAIIPLLSIVRDLRKQRHNCLSLPQQYIFCYFIVLI 294

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1207734461   1 MVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQY 54
Cdd:cd14557   143 IVVHCSAGVGRTGTYIGIDAMLEGLEAEGRVDVYGYVVKLRRQRCLMVQVEAQY 196

PTP domain of receptor-type tyrosine-protein phosphatase M, repeat 2; 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 second (repeat 2) PTP domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1207734461   2 VVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCYDIVLE 63
Cdd:cd14635   145 VVHCLNGGGRSGTFCAISIVCEMLRHQRAVDVFHAVKTLRNNKPNMVDLLDQYKFCYEVALE 206

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
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1207734461   2 VVHCSAGIGRTGVFLCvdvvfCAIVKNCSFNIMDIVAQMREQR-SGMVQTKEQYHFCYD 59
Cdd:cd14494    60 LVHCKAGVGRTGTLVA-----CYLVLLGGMSAEEAVRIVRLIRpGGIPQTIEQLDFLIK 113

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1207734461   2 VVHCSAGIGRTGVFL-CVdvvfcAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCYD 59
Cdd:cd14505   110 LIHCKGGLGRTGLIAaCL-----LLELGDTLDPEQAIAAVRALRPGAIQTPKQENFLHQ 163

protein tyrosine phosphatase; Provisional

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1207734461   3 VHCSAGIGRTGVFLCVdvvfcAIVKNCSFNIMDIVAQMREQRSGMVQTKeQYHF 56
Cdd:PTZ00242  103 VHCVAGLGRAPILVAL-----ALVEYGGMEPLDAVGFVREKRKGAINQT-QLQF 150

protein tyrosine phosphatase; Provisional

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1207734461   1 MVVHCSAGIGRTGVFLCVDVVFCAIVKNCSFNIMDIVAQMREQRSGMVQTKEQYHFCYDIV 61
Cdd:PHA02740  224 IIIDCIDGISSSAVFCVFDICATEFDKTGMLSIANALKKVRQKKYGCMNCLDDYVFCYHLI 284

protein tyrosine phosphatase-like domain of phosphatase and tensin homolog and similar proteins; Phosphatase and tensin homolog (PTEN) is a tumor suppressor that acts as a dual-specificity protein phosphatase and as a lipid phosphatase. It dephosphorylates phosphoinositide trisphosphate. In addition to PTEN, this family includes tensins, voltage-sensitive phosphatases (VSPs), and auxilins. They all contain a protein tyrosine phosphatase-like domain although not all are active phosphatases. Tensins are intracellular proteins that act as links between the extracellular matrix and the cytoskeleton, and thereby mediate signaling for cell shape and motility, and they may or may not have phosphatase activity. VSPs are phosphoinositide phosphatases with substrates that include phosphatidylinositol-4,5-diphosphate and phosphatidylinositol-3,4,5-trisphosphate. Auxilins are J domain-containing proteins that facilitate Hsc70-mediated dissociation of clathrin from clathrin-coated vesicles, and they do not exhibit phosphatase activity.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1207734461   2 VVHCSAGIGRTGVFLCVDVVFCAIVKNCSfNIMDIVAQMR 41
Cdd:cd14497    99 VVHCKAGKGRTGTVICAYLLYYGQYSTAD-EALEYFAKKR 137