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 2462615543 727 TGHMILSYMEDHLKNKNRLEKEWEALCAYQAEPNSSFVAQREENVPKNRSLAVLTYDHSRVLLKAENSHSHSDYINASPI 806
Cdd:cd14610     1 TGHMILSYMEDHLKNKNRLEKEWEALCAYQAEPNATNVAQREENVQKNRSLAVLPYDHSRIILKAENSHSHSDYINASPI 80

                          90       100
                  ....*....|....*....|....*.
gi 2462615543 807 MDHDPRNPAYIATQGPLPATVADFWQ 832
Cdd:cd14610    81 MDHDPRNPAYIATQGPLPATVADFWQ 106

RESP18 domain; This domain is found in the glucocorticoid-responsive protein regulated endocrine-specific protein 18 (RESP18) and in the N-terminal extracellular region of receptor-type tyrosine-protein phosphatases containing the protein-tyrosine phosphatase receptor IA-2 domain (pfam11548).

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462615543  75 SPVaLQRLRVALQKLSGTGFTWQDDYTQYVMDQELADLPKTYLRRP-----EASSPARPS 129
Cdd:pfam14948  18 APV-FQHLQVVLHQIVPQGLFWKDDLTQDVMTQKMEHISRLHPQDPclkdgKAVFPTRTT 76

PTP-like domain of receptor-type tyrosine-protein phosphatase N2; Receptor-type tyrosine-protein phosphatase N2 (PTPRN2 or R-PTP-N2), also called islet cell autoantigen-related protein (IAR), ICAAR, phogrin, or IA-2beta, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). It consists of a large ectodomain that contains a RESP18HD (regulated endocrine-specific protein 18 homology domain), followed by a transmembrane segment, and a single, catalytically-impaired, PTP domain. It is mainly expressed in neuropeptidergic neurons and peptide-secreting endocrine cells, including insulin-producing pancreatic beta-cells. It may function as a phosphatidylinositol phosphatase to regulate insulin secretion. It is also required for normal accumulation of the neurotransmitters norepinephrine, dopamine and serotonin in the brain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462615543 727 TGHMILSYMEDHLKNKNRLEKEWEALCAYQAEPNSSFVAQREENVPKNRSLAVLTYDHSRVLLKAENSHSHSDYINASPI 806
Cdd:cd14610     1 TGHMILSYMEDHLKNKNRLEKEWEALCAYQAEPNATNVAQREENVQKNRSLAVLPYDHSRIILKAENSHSHSDYINASPI 80

                          90       100
                  ....*....|....*....|....*.
gi 2462615543 807 MDHDPRNPAYIATQGPLPATVADFWQ 832
Cdd:cd14610    81 MDHDPRNPAYIATQGPLPATVADFWQ 106

Protein tyrosine phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462615543  745 LEKEWEALCAYQAEPNSSFVAQREENVPKNRSLAVLTYDHSRVLLKAENsHSHSDYINASPIMDHDPRNpAYIATQGPLP 824
Cdd:smart00194   2 LEEEFEKLDRLKPDDESCTVAAFPENRDKNRYKDVLPYDHTRVKLKPPP-GEGSDYINASYIDGPNGPK-AYIATQGPLP 79

                   ....*...
gi 2462615543  825 ATVADFWQ 832
Cdd:smart00194  80 STVEDFWR 87

protein tyrosine phosphatase; Provisional

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462615543 766 QREENVPKNRSLAVLTYDHSRVLLKAeNSHSHSDYINASPImDHDPRNPAYIATQGPLPATVADFWQGI 834
Cdd:PHA02747   47 EKPENQPKNRYWDIPCWDHNRVILDS-GGGSTSDYIHANWI-DGFEDDKKFIATQGPFAETCADFWKAV 113

RESP18 domain; This domain is found in the glucocorticoid-responsive protein regulated endocrine-specific protein 18 (RESP18) and in the N-terminal extracellular region of receptor-type tyrosine-protein phosphatases containing the protein-tyrosine phosphatase receptor IA-2 domain (pfam11548).

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462615543  75 SPVaLQRLRVALQKLSGTGFTWQDDYTQYVMDQELADLPKTYLRRP-----EASSPARPS 129
Cdd:pfam14948  18 APV-FQHLQVVLHQIVPQGLFWKDDLTQDVMTQKMEHISRLHPQDPclkdgKAVFPTRTT 76

PTP-like domain of receptor-type tyrosine-protein phosphatase N2; Receptor-type tyrosine-protein phosphatase N2 (PTPRN2 or R-PTP-N2), also called islet cell autoantigen-related protein (IAR), ICAAR, phogrin, or IA-2beta, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). It consists of a large ectodomain that contains a RESP18HD (regulated endocrine-specific protein 18 homology domain), followed by a transmembrane segment, and a single, catalytically-impaired, PTP domain. It is mainly expressed in neuropeptidergic neurons and peptide-secreting endocrine cells, including insulin-producing pancreatic beta-cells. It may function as a phosphatidylinositol phosphatase to regulate insulin secretion. It is also required for normal accumulation of the neurotransmitters norepinephrine, dopamine and serotonin in the brain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462615543 727 TGHMILSYMEDHLKNKNRLEKEWEALCAYQAEPNSSFVAQREENVPKNRSLAVLTYDHSRVLLKAENSHSHSDYINASPI 806
Cdd:cd14610     1 TGHMILSYMEDHLKNKNRLEKEWEALCAYQAEPNATNVAQREENVQKNRSLAVLPYDHSRIILKAENSHSHSDYINASPI 80

                          90       100
                  ....*....|....*....|....*.
gi 2462615543 807 MDHDPRNPAYIATQGPLPATVADFWQ 832
Cdd:cd14610    81 MDHDPRNPAYIATQGPLPATVADFWQ 106

Protein-tyrosine phosphatase receptor IA-2; IA-2 is a protein-tyrosine phosphatase receptor that upon exocytosis, the cytoplasmic domain is cleaved and moves to the nucleus where it enhances transcription of the insulin gene. The mature exodomain of IA-2 participates in adhesion to the extracellular matrix and is self-proteolyzed in vitro by reactive oxygen species which may be a new shedding mechanism.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462615543 509 EARGYIVTDRDPLRPEEGRRLVEDVARLLQVPSSAFADVEVLGPAVTFKVSANVQNVTTEDVEKATVDNKDKLEETSGLK 588
Cdd:pfam11548   1 EEYGYIVTDNDPLSWEEGLRLMEKVAELLHLPMSSFADIRVLGPAVTFKVRANNKNLTAADVAKAAVDIKDKLEKETGLK 80

                  ....*....
gi 2462615543 589 ILQTGVGSK 597
Cdd:pfam11548  81 ILQAGVGDK 89

Protein-tyrosine phosphatase;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462615543 770 NVPKNRSLAVLTYDHSRVLLKAENSHShsDYINASPIMDHdPRNPAYIATQGPLPATVADFWQ 832
Cdd:pfam00102   1 NLEKNRYKDVLPYDHTRVKLTGDPGPS--DYINASYIDGY-KKPKKYIATQGPLPNTVEDFWR 60

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
                  ....*....|....*....|....*....|....*
gi 2462615543 800 YINASPIMDHDPRNPAYIATQGPLPATVADFWQGI 834
Cdd:cd14546     1 YINASTIYDHDPRNPAYIATQGPLPHTIADFWQMI 35

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 2462615543 764 VAQREENVPKNRSLAVLTYDHSRVLLKAENSHSHSDYINASPIMD-HDPRnpAYIATQGPLPATVADFWQGI 834
Cdd:cd14604    51 TGEKEENVKKNRYKDILPFDHSRVKLTLKTSSQDSDYINANFIKGvYGPK--AYIATQGPLANTVIDFWRMI 120

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 2462615543 744 RLEKEWEALcayqaEPNSSFV---AQREENVPKNRSLAVLTYDHSRVLLKAENSHSHSDYINASPIMDHDPRNpAYIATQ 820
Cdd:cd14626    17 KFSQEYESI-----DPGQQFTwenSNLEVNKPKNRYANVIAYDHSRVILTSVDGVPGSDYINANYIDGYRKQN-AYIATQ 90

                          90
                  ....*....|....
gi 2462615543 821 GPLPATVADFWQGI 834
Cdd:cd14626    91 GPLPETLSDFWRMV 104

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 2462615543 774 NRSLAVLTYDHSRVLLKAENSHSHSDYINASPIMDHDPRNPAYIATQGPLPATVADFWQ 832
Cdd:cd14547     1 NRYKTILPNEHSRVCLPSVDDDPLSSYINANYIRGYDGEEKAYIATQGPLPNTVADFWR 59

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 2462615543 735 MEDHLK----NKN-RLEKEWEALcayqaEPNSSFVAQR---EENVPKNRSLAVLTYDHSRVLLKAENSHSHSDYINASPI 806
Cdd:cd14624     9 LADHIErlkaNDNlKFSQEYESI-----DPGQQFTWEHsnlEVNKPKNRYANVIAYDHSRVLLSAIEGIPGSDYINANYI 83

                          90       100
                  ....*....|....*....|....*...
gi 2462615543 807 MDHDPRNpAYIATQGPLPATVADFWQGI 834
Cdd:cd14624    84 DGYRKQN-AYIATQGALPETFGDFWRMI 110

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462615543 773 KNRSLAVLTYDHSRVLLKAENSHSHSDYINASPIMD-HDPRnpAYIATQGPLPATVADFWQGI 834
Cdd:cd14602     1 KNRYKDILPYDHSRVELSLITSDEDSDYINANFIKGvYGPR--AYIATQGPLSTTLLDFWRMI 61

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462615543 766 QREENVPKNRSLAVLTYDHSRVLLK-AENSHSHSDYINASPIMDH--DPRNPA--YIATQGPLPATVADFWQ 832
Cdd:cd14606    14 QRPENKSKNRYKNILPFDHSRVILQgRDSNIPGSDYINANYVKNQllGPDENAktYIASQGCLEATVNDFWQ 85

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462615543 735 MEDHLKNKNRL-EKEWEAL--CAYQAepnSSFVAQREENVPKNRSLAVLTYDHSRVLLKAENSHSHSDYINASPIMDHDP 811
Cdd:cd14621    17 INRRMADDNKLfREEFNALpaCPIQA---TCEAASKEENKEKNRYVNILPYDHSRVHLTPVEGVPDSDYINASFINGYQE 93

                          90       100
                  ....*....|....*....|...
gi 2462615543 812 RNpAYIATQGPLPATVADFWQGI 834
Cdd:cd14621    94 KN-KFIAAQGPKEETVNDFWRMI 115

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 2462615543 768 EENVPKNRSLAVLTYDHSRVLLKAENshshsDYINASPI-MDHDPRNPAYIATQGPLPATVADFWQ 832
Cdd:cd14597     1 KENRKKNRYKNILPYDTTRVPLGDEG-----GYINASFIkMPVGDEEFVYIACQGPLPTTVADFWQ 61

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462615543 770 NVPKNRSLAVLTYDHSRVLLK-AENSHSHSDYINASPIM------DHDPRNPAYIATQGPLPATVADFWQ 832
Cdd:cd14544     1 NKGKNRYKNILPFDHTRVILKdRDPNVPGSDYINANYIRnenegpTTDENAKTYIATQGCLENTVSDFWS 70

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462615543 761 SSFVAQREENVPKNRSLAVLTYDHSRVLLKAENSHSHSDYINASPIMDHD-PRNpaYIATQGPLPATVADFWQ 832
Cdd:cd14614     3 PHFAADLPVNRCKNRYTNILPYDFSRVKLVSMHEEEGSDYINANYIPGYNsPQE--YIATQGPLPETRNDFWK 73

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462615543 765 AQREENVPKNRSLAVLTYDHSRVLLKAENshshsDYINASPIMDHDPRNP---AYIATQGPLPATVADFWQGI 834
Cdd:cd14600    35 AKLPQNMDKNRYKDVLPYDATRVVLQGNE-----DYINASYVNMEIPSANivnKYIATQGPLPHTCAQFWQVV 102

catalytic domain of receptor-type tyrosine-protein phosphatase V; Receptor-type tyrosine-protein phosphatase V (PTPRV or R-PTP-V), also known as embryonic stem cell protein-tyrosine phosphatase (ES cell phosphatase) or osteotesticular protein-tyrosine phosphatase (OST-PTP), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRV is a member of the R3 subfamily of receptor-type phosphotyrosine phosphatases (RPTP), characterized by a unique modular composition consisting of multiple extracellular fibronectin type III (FN3) repeats and a single (most RPTP subtypes have two) cytoplasmic catalytic PTP domain. In rodents, it may play a role in the maintenance of pluripotency and may function in signaling pathways during bone remodeling. It is the only PTP whose function has been lost between rodent and human. The human OST-PTP gene is a pseudogene.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462615543 774 NRSLAVLTYDHSRVLLKAENSHSHSDYINASPImdhdprnPAY------IATQGPLPATVADFWQ 832
Cdd:cd14618     1 NRYPHVLPYDHSRVRLSQLGGEPHSDYINANFI-------PGYtspqefIATQGPLKKTIEDFWR 58

catalytic domain of tyrosine-protein phosphatase non-receptor type 1 and type 2; Tyrosine-protein phosphatase non-receptor type 1 (PTPN1) type 2 (PTPN2) belong to the family of classical tyrosine-specific protein tyrosine phosphatases, (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN1 (or 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 dephosphorylates and regulates the activity of a number of receptor tyrosine kinases, including the insulin receptor, the EGF receptor, and the PDGF receptor. PTPN2 (or TCPTP), a tumor suppressor, dephosphorylates and inactivates EGFRs, Src family kinases, Janus-activated kinases (JAKs)-1 and -3, and signal transducer and activators of transcription (STATs)-1, -3 and -5, in a cell type and context-dependent manner.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462615543 773 KNRSLAVLTYDHSRVLLKAENSHShsDYINASPI-MDHDPRNpaYIATQGPLPATVADFWQ 832
Cdd:cd14545     1 LNRYRDRDPYDHDRSRVKLKQGDN--DYINASLVeVEEAKRS--YILTQGPLPNTSGHFWQ 57

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 2462615543 774 NRSLAVLTYDHSRVLLKAENSHSHSDYINASPIMDHDPRNpAYIATQGPLPATVADFWQ 832
Cdd:cd14617     1 NRYNNILPYDSTRVKLSNVDDDPCSDYINASYIPGNNFRR-EYIATQGPLPGTKDDFWK 58

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462615543 740 KNKNRLEKEWEALCAYQAEPNSSFVAQREENVPKNRSLAVLTYDHSRVLLKAENSHSHSDYINASpIMDHDPRNPAYIAT 819
Cdd:cd14628    22 ENVTGMELEFKRLASSKAHTSRFISANLPCNKFKNRLVNIMPYESTRVCLQPIRGVEGSDYINAS-FIDGYRQQKAYIAT 100

                          90
                  ....*....|...
gi 2462615543 820 QGPLPATVADFWQ 832
Cdd:cd14628   101 QGPLAETTEDFWR 113

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462615543 764 VAQREENVPKNRSLAVLTYDHSRVLLKAENShshsDYINASPI-MDHDPRnpAYIATQGPLPATVADFWQ 832
Cdd:cd14608    19 VAKLPKNKNRNRYRDVSPFDHSRIKLHQEDN----DYINASLIkMEEAQR--SYILTQGPLPNTCGHFWE 82

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462615543 769 ENVPKNRSLAVLTYDHSRVLL-KAENSHSHSDYINASPIM-DHD-PRNPA-----YIATQGPLPATVADFWQ 832
Cdd:cd14605     1 ENKNKNRYKNILPFDHTRVVLhDGDPNEPVSDYINANIIMpEFEtKCNNSkpkksYIATQGCLQNTVNDFWR 72

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462615543 774 NRSLAVLTYDHSRVLLKAENSHSHSDYINASPIMDHDPRNpAYIATQGPLPATVADFWQGI 834
Cdd:cd14616     1 NRFPNIKPYNNNRVKLIADAGVPGSDYINASYISGYLCPN-EFIATQGPLPGTVGDFWRMV 60

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 2462615543 745 LEKEWEALCAYQAEPNSSFVAQREENVPKNRSLAVLTYDHSRVLLKAENSHSHSDYINASpIMDHDPRNPAYIATQGPLP 824
Cdd:cd14629    28 MELEFKLLANSKAHTSRFISANLPCNKFKNRLVNIMPYELTRVCLQPIRGVEGSDYINAS-FIDGYRQQKAYIATQGPLA 106

                  ....*...
gi 2462615543 825 ATVADFWQ 832
Cdd:cd14629   107 ETTEDFWR 114

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
                  ....*....|....*....|....*....|..
gi 2462615543 800 YINASPIMDHDPRNPAYIATQGPLPATVADFW 831
Cdd:cd14539     1 YINASLIEDLTPYCPRFIATQAPLPGTAADFW 32

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
                  ....*....|....*....|....*....|....*.
gi 2462615543 800 YINASPIMDHDPRN-PAYIATQGPLPATVADFWQGI 834
Cdd:cd17658     1 YINASLVETPASESlPKFIATQGPLPHTFEDFWEMV 36

Protein tyrosine phosphatase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462615543 743 NRLEKEWEALcAYQAEPNSSFvaQREENVPKNRSLAVLTYDHSRVllkaensHSHSDYINASPIMDHDPRNpaYIATQGP 822
Cdd:COG5599    18 SRLSTLTNEL-APSHNDPQYL--QNINGSPLNRFRDIQPYKETAL-------RANLGYLNANYIQVIGNHR--YIATQYP 85

                          90
                  ....*....|..
gi 2462615543 823 LPATVADFWQGI 834
Cdd:COG5599    86 LEEQLEDFFQML 97

catalytic domain of R5 subfamily receptor-type tyrosine-protein phosphatases, repeat 1; The R5 subfamily of receptor-type phosphotyrosine phosphatases (RPTP) is composed of receptor-type tyrosine-protein phosphatase Z (PTPRZ) and G (PTPRG). 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. They are type 1 integral membrane proteins 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
                  ....*....|....*....|....*....|....*
gi 2462615543 800 YINASPImDHDPRNPAYIATQGPLPATVADFWQGI 834
Cdd:cd14549     1 YINANYV-DGYNKARAYIATQGPLPSTFDDFWRMV 34

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
                  ....*....|....*....|....*....|....*
gi 2462615543 800 YINASPIMDHDpRNPAYIATQGPLPATVADFWQGI 834
Cdd:cd14542     1 YINANFIKGVS-GSKAYIATQGPLPNTVLDFWRMI 34

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
                  ....*....|....*....|....*....|...
gi 2462615543 800 YINASpIMDHDPRNPAYIATQGPLPATVADFWQ 832
Cdd:cd14556     1 YINAA-LLDSYKQPAAFIVTQHPLPNTVTDFWR 32

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
                  ....*....|....*....|....*....|....
gi 2462615543 800 YINASPI-MDHDPRNPAYIATQGPLPATVADFWQ 832
Cdd:cd14596     1 YINASYItMPVGEEELFYIATQGPLPSTIDDFWQ 34

hypothetical protein; Provisional

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2462615543 774 NRSLAVLTYDHSRVLLKAENshSHSDYINASPImDHDPRNPAYIATQGPLPATVADFWQ 832
Cdd:PHA02738   53 NRYLDAVCFDHSRVILPAER--NRGDYINANYV-DGFEYKKKFICGQAPTRQTCYDFYR 108

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
                  ....*....|....*....|....*....|....*....|....*..
gi 2462615543 786 RVLLKAENSHSHSDYINASPImDHDPRNPAYIATQGPLPATVADFWQ 832
Cdd:cd14631     1 RVILQPVEDDPSSDYINANYI-DGYQRPSHYIATQGPVHETVYDFWR 46

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

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 2462615543 799 DYINASPImDHDPRNPAYIATQGPLPATVADFWQGI 834
Cdd:cd14622     1 DYINASFI-DGYRQKDYFIATQGPLAHTVEDFWRMV 35

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
                  ....*....|....*....|....*....|....*..
gi 2462615543 799 DYINASPIMDHDPRNP---AYIATQGPLPATVADFWQ 832
Cdd:cd14601     1 DYINANYINMEIPSSSiinRYIACQGPLPNTCSDFWQ 37

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
                  ....*....|....*....|....*....|....*
gi 2462615543 800 YINASPImDHDPRNPAYIATQGPLPATVADFWQGI 834
Cdd:cd14555     1 YINANYI-DGYHRPNHYIATQGPMQETVYDFWRMV 34

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
                  ....*....|....*....|....*....|....*.
gi 2462615543 800 YINASPIMDH-DPRNpaYIATQGPLPATVADFWQGI 834
Cdd:cd14557     1 YINASYIDGFkEPRK--YIAAQGPKDETVDDFWRMI 34

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

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 2462615543 800 YINASpIMDHDPRNPAYIATQGPLPATVADFWQGI 834
Cdd:cd17668     1 YINAN-YVDGYNKPKAYIAAQGPLKSTAEDFWRMI 34