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 915380   274 FLLQAEFFEIPMNFVDPKEYDIPGLVRKNRYKTILPNPHSRVRLTSPDPEDPLSSYINANYIR 336
Cdd:cd14613   1 FLLQAEFFEIPMNFVDPKEYDIPGLVRKNRYKTILPNPHSRVCLTSPDQDDPLSSYINANYIR 63

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 915380   274 FLLQAEFFEIPMNFVDPKEYDIPGLVRKNRYKTILPNPHSRVRLTSPDPEDPLSSYINANYIR 336
Cdd:cd14613   1 FLLQAEFFEIPMNFVDPKEYDIPGLVRKNRYKTILPNPHSRVCLTSPDQDDPLSSYINANYIR 63

Protein-tyrosine phosphatase;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 915380     300 RKNRYKTILPNPHSRVRLTspdPEDPLSSYINANYIRVcSSIPRAF 345
Cdd:pfam00102   3 EKNRYKDVLPYDHTRVKLT---GDPGPSDYINASYIDG-YKKPKKY 44

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 915380   274 FLLQAEFFEIPMNFVDPKEYDIPGLVRKNRYKTILPNPHSRVRLTSPDPEDPLSSYINANYIR 336
Cdd:cd14613   1 FLLQAEFFEIPMNFVDPKEYDIPGLVRKNRYKTILPNPHSRVCLTSPDQDDPLSSYINANYIR 63

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
                ....*....|....*....|....*....|....*
gi 915380   302 NRYKTILPNPHSRVRLTSpDPEDPLSSYINANYIR 336
Cdd:cd14547   1 NRYKTILPNEHSRVCLPS-VDDDPLSSYINANYIR 34

catalytic domain of receptor-type tyrosine-protein phosphatase R; Receptor-type tyrosine-protein phosphatase-like R (PTPRR or R-PTP-R), also called protein-tyrosine phosphatase PCPTP1, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRR is a kinase interaction motif (KIM)-PTP, characterized by the presence of a 16-amino-acid KIM that binds specifically to members of the MAPK (mitogen-activated protein kinase) family. The human and mouse PTPRR gene produces multiple neuronal protein isoforms of varying sizes (in human, PTPPBS-alpha, beta, gamma and delta). All isoforms contain the KIM motif and the catalytic PTP domain. PTPRR-deficient mice show significant defects in fine motor coordination and balance skills that are reminiscent of a mild ataxia.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 915380   301 KNRYKTILPNPHSRVRLTSPDPEDPLSSYINANYIRVCSSIPRAF 345
Cdd:cd14611   2 KNRYKTILPNPHSRVCLKPKNSNDSLSTYINANYIRGYGGKEKAF 46

Protein-tyrosine phosphatase;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 915380     300 RKNRYKTILPNPHSRVRLTspdPEDPLSSYINANYIRVcSSIPRAF 345
Cdd:pfam00102   3 EKNRYKDVLPYDHTRVKLT---GDPGPSDYINASYIDG-YKKPKKY 44

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
                ....*....|....*....|....*....|....*....|....*....|...
gi 915380   284 PMNFVDPKEYDIPGLVRKNRYKTILPNPHSRVRLTSPDPEDPLSSYINANYIR 336
Cdd:cd14606   4 VKNLHQRLEGQRPENKSKNRYKNILPFDHSRVILQGRDSNIPGSDYINANYVK 56

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
                ....*....|....*....|....*....|....*...
gi 915380   299 VRKNRYKTILPNPHSRVRLTSPDPEDPlSSYINANYIR 336
Cdd:cd14604  58 VKKNRYKDILPFDHSRVKLTLKTSSQD-SDYINANFIK 94

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
                ....*....|....*....|....*....|....
gi 915380   302 NRYKTILPNPHSRVRLTSPdPEDPLSSYINANYI 335
Cdd:cd14618   1 NRYPHVLPYDHSRVRLSQL-GGEPHSDYINANFI 33

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
                ....*....|....*....|....*....|....*....|..
gi 915380   294 DIPGLVRKNRYKTILPNPHSRVRLTSPDpEDPLSSYINANYI 335
Cdd:cd14614   8 DLPVNRCKNRYTNILPYDFSRVKLVSMH-EEEGSDYINANYI 48

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
                ....*....|....*....|....*....|....*...
gi 915380   302 NRYKTILPNPHSRVRLTSPDpEDPLSSYINANYIRVCS 339
Cdd:cd14617   1 NRYNNILPYDSTRVKLSNVD-DDPCSDYINASYIPGNN 37

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
                ....*....|....*....|....*....|....*
gi 915380   301 KNRYKTILPNPHSRVRLTSPDpEDPLSSYINANYI 335
Cdd:cd14630   6 KNRYGNIISYDHSRVRLQLLD-GDPHSDYINANYI 39

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
                ....*....|....*....|....*....|....
gi 915380   302 NRYKTILPNPHSRVRLTSPDpeDPLSSYINANYI 335
Cdd:cd14615   1 NRYNNVLPYDISRVKLSVQS--HSTDDYINANYM 32

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
                ....*....|....*....|....*....|....*
gi 915380   301 KNRYKTILPNPHSRVRLTsPDPEDPLSSYINANYI 335
Cdd:cd14621  55 KNRYVNILPYDHSRVHLT-PVEGVPDSDYINASFI 88

catalytic domain of receptor-type tyrosine-protein phosphatase E, repeat 1; Receptor-type tyrosine-protein phosphatase E (PTPRE), also known as receptor-type tyrosine-protein phosphatase epsilon (R-PTP-epsilon), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. The PTPRE gene contains two distinct promoters that generate the two major isoforms: transmembrane (receptor type RPTPe or PTPeM) and cytoplasmic (cyt-PTPe or PTPeC). Receptor type RPTPe plays a critical role in signaling transduction pathways and phosphoprotein network topology in red blood cells, and may also play a role in osteoclast formation and function. It also negatively regulates PDGFRbeta-mediated signaling pathways that are crucial for the pathogenesis of atherosclerosis. cyt-PTPe acts as a negative regulator of insulin receptor signaling in skeletal muscle. It regulates insulin-induced phosphorylation of proteins downstream of the insulin receptor. Receptor type RPTPe contains a small extracellular region, a single transmembrane segment, and an intracellular region two tandem catalytic PTP domains. This model represents the first PTP domain (repeat 1).

                        10        20        30
                ....*....|....*....|....*....|..
gi 915380   304 YKTILPNPHSRVRLTSPDpEDPLSSYINANYI 335
Cdd:cd14620   1 YPNILPYDHSRVILSQLD-GIPCSDYINASYI 31