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DUSP1
Identifiers
Aliases	DUSP1, CL100, HVH1, MKP-1, MKP1, PTPN10, dual specificity phosphatase 1
External IDs	OMIM: 600714; MGI: 105120; HomoloGene: 3254; GeneCards: DUSP1; OMA:DUSP1 - orthologs
Gene location (Human) Chr. Chromosome 5 (human) Band 5q35.1 Start 172,768,096 bp End 172,771,195 bp
Gene location (Mouse) Chr. Chromosome 17 (mouse) Band 17 A3.3|17 13.28 cM Start 26,724,564 bp End 26,781,102 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in vena cava nipple urethra mucosa of paranasal sinus skin of thigh mucosa of urinary bladder cardia lower lobe of lung saphenous vein trachea Top expressed in granulocyte stroma of bone marrow endothelial cell of lymphatic vessel right lung right lung lobe plantaris muscle ascending aorta soleus muscle ankle left lobe of liver More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein tyrosine/threonine phosphatase activity phosphatase activity protein tyrosine phosphatase activity protein binding phosphoprotein phosphatase activity MAP kinase tyrosine/serine/threonine phosphatase activity non-membrane spanning protein tyrosine phosphatase activity hydrolase activity protein tyrosine/serine/threonine phosphatase activity growth factor binding protein serine/threonine phosphatase activity mitogen-activated protein kinase binding Cellular component nucleus cytoplasm Biological process positive regulation of apoptotic process response to estradiol response to retinoic acid response to oxidative stress negative regulation of meiotic cell cycle response to calcium ion response to hydrogen peroxide response to testosterone protein dephosphorylation intracellular signal transduction negative regulation of MAP kinase activity negative regulation of MAPK cascade peptidyl-threonine dephosphorylation cell cycle response to light stimulus negative regulation of DNA biosynthetic process negative regulation of ERK1 and ERK2 cascade cellular response to hormone stimulus dephosphorylation regulation of apoptotic process response to glucocorticoid endoderm formation response to organic substance regulation of mitotic cell cycle spindle assembly checkpoint negative regulation of apoptotic process response to cAMP negative regulation of cell population proliferation peptidyl-tyrosine dephosphorylation peptidyl-serine dephosphorylation negative regulation of cell adhesion negative regulation of monocyte chemotaxis negative regulation of p38MAPK cascade cellular response to chemokine Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1843 19252 Ensembl ENSG00000120129 ENSMUSG00000024190 UniProt P28562 P28563 RefSeq (mRNA) NM_004417 NM_013642 RefSeq (protein) NP_004408 NP_038670 Location (UCSC) Chr 5: 172.77 – 172.77 Mb Chr 17: 26.72 – 26.78 Mb PubMed search
Wikidata
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Dual specificity protein phosphatase 1 is an enzyme that in humans is encoded by the DUSP1 gene.

Function

The expression of DUSP1 gene is induced in human skin fibroblasts by oxidative/heat stress and growth factors. It specifies a protein with structural features similar to members of the non-receptor-type protein-tyrosine phosphatase family, and which has significant amino-acid sequence similarity to a Tyr/Ser-protein phosphatase encoded by the late gene H1 of vaccinia virus. The bacterially expressed and purified DUSP1 protein has intrinsic phosphatase activity, and specifically inactivates mitogen-activated protein (MAP) kinase in vitro by the concomitant dephosphorylation of both its phosphothreonine and phosphotyrosine residues. Furthermore, it suppresses the activation of MAP kinase by oncogenic ras in extracts of Xenopus oocytes. Thus, DUSP1 may play an important role in the human cellular response to environmental stress as well as in the negative regulation of cellular proliferation.

Interactions

DUSP1 has been shown to interact with MAPK14, MAPK1 and MAPK8.

References

1. ^ GRCh38: Ensembl release 89: ENSG00000120129 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000024190 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Keyse SM, Emslie EA (Oct 1992). "Oxidative stress and heat shock induce a human gene encoding a protein-tyrosine phosphatase". Nature. 359 (6396): 644–7. Bibcode:1992Natur.359..644K. doi:10.1038/359644a0. PMID 1406996. S2CID 4307895.
6. Martell KJ, Kwak S, Hakes DJ, Dixon JE, Trent JM (Jul 1994). "Chromosomal localization of four human VH1-like protein-tyrosine phosphatases" (PDF). Genomics. 22 (2): 462–4. doi:10.1006/geno.1994.1411. hdl:2027.42/31442. PMID 7806236.
7. "Entrez Gene: DUSP1 dual specificity phosphatase 1".
8. Tanoue T, Yamamoto T, Maeda R, Nishida E (Jul 2001). "A Novel MAPK phosphatase MKP-7 acts preferentially on JNK/SAPK and p38 alpha and beta MAPKs". The Journal of Biological Chemistry. 276 (28): 26629–39. doi:10.1074/jbc.M101981200. PMID 11359773.
9. ^ Slack DN, Seternes OM, Gabrielsen M, Keyse SM (May 2001). "Distinct binding determinants for ERK2/p38alpha and JNK map kinases mediate catalytic activation and substrate selectivity of map kinase phosphatase-1". The Journal of Biological Chemistry. 276 (19): 16491–500. doi:10.1074/jbc.M010966200. PMID 11278799.
10. Calvisi DF, Pinna F, Meloni F, Ladu S, Pellegrino R, Sini M, Daino L, Simile MM, De Miglio MR, Virdis P, Frau M, Tomasi ML, Seddaiu MA, Muroni MR, Feo F, Pascale RM (Jun 2008). "Dual-specificity phosphatase 1 ubiquitination in extracellular signal-regulated kinase-mediated control of growth in human hepatocellular carcinoma". Cancer Research. 68 (11): 4192–200. doi:10.1158/0008-5472.CAN-07-6157. PMID 18519678.

Further reading

• Martell KJ, Angelotti T, Ullrich A (Feb 1998). "The "VH1-like" dual-specificity protein tyrosine phosphatases". Molecules and Cells. 8 (1): 2–11. doi:10.1016/S1016-8478(23)13385-1. PMID 9571625.
• Keyse SM (Apr 1998). "Protein phosphatases and the regulation of MAP kinase activity". Seminars in Cell & Developmental Biology. 9 (2): 143–52. doi:10.1006/scdb.1997.0219. PMID 9599409.
• Abraham SM, Clark AR (Dec 2006). "Dual-specificity phosphatase 1: a critical regulator of innate immune responses". Biochemical Society Transactions. 34 (Pt 6): 1018–23. doi:10.1042/BST0341018. PMID 17073741.
• Raingeaud J, Gupta S, Rogers JS, Dickens M, Han J, Ulevitch RJ, Davis RJ (Mar 1995). "Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine". The Journal of Biological Chemistry. 270 (13): 7420–6. doi:10.1074/jbc.270.13.7420. PMID 7535770.
• Kwak SP, Hakes DJ, Martell KJ, Dixon JE (Feb 1994). "Isolation and characterization of a human dual specificity protein-tyrosine phosphatase gene". The Journal of Biological Chemistry. 269 (5): 3596–604. doi:10.1016/S0021-9258(17)41905-3. PMID 8106404.
• Emslie EA, Jones TA, Sheer D, Keyse SM (May 1994). "The CL100 gene, which encodes a dual specificity (Tyr/Thr) MAP kinase phosphatase, is highly conserved and maps to human chromosome 5q34". Human Genetics. 93 (5): 513–6. doi:10.1007/BF00202814. PMID 8168826. S2CID 12590731.
• Sun H, Charles CH, Lau LF, Tonks NK (Nov 1993). "MKP-1 (3CH134), an immediate early gene product, is a dual specificity phosphatase that dephosphorylates MAP kinase in vivo". Cell. 75 (3): 487–93. doi:10.1016/0092-8674(93)90383-2. PMID 8221888. S2CID 29988777.
• Charles CH, Sun H, Lau LF, Tonks NK (Jun 1993). "The growth factor-inducible immediate-early gene 3CH134 encodes a protein-tyrosine-phosphatase". Proceedings of the National Academy of Sciences of the United States of America. 90 (11): 5292–6. Bibcode:1993PNAS...90.5292C. doi:10.1073/pnas.90.11.5292. PMC 46702. PMID 8389479.
• Alessi DR, Smythe C, Keyse SM (Jul 1993). "The human CL100 gene encodes a Tyr/Thr-protein phosphatase which potently and specifically inactivates MAP kinase and suppresses its activation by oncogenic ras in Xenopus oocyte extracts". Oncogene. 8 (7): 2015–20. PMID 8390041.
• Brondello JM, Pouysségur J, McKenzie FR (Dec 1999). "Reduced MAP kinase phosphatase-1 degradation after p42/p44MAPK-dependent phosphorylation". Science. 286 (5449): 2514–7. doi:10.1126/science.286.5449.2514. PMID 10617468.
• Hutter D, Chen P, Barnes J, Liu Y (Nov 2000). "Catalytic activation of mitogen-activated protein (MAP) kinase phosphatase-1 by binding to p38 MAP kinase: critical role of the p38 C-terminal domain in its negative regulation". The Biochemical Journal. 352 (1): 155–63. doi:10.1042/0264-6021:3520155. PMC 1221442. PMID 11062068.
• Slack DN, Seternes OM, Gabrielsen M, Keyse SM (May 2001). "Distinct binding determinants for ERK2/p38alpha and JNK map kinases mediate catalytic activation and substrate selectivity of map kinase phosphatase-1". The Journal of Biological Chemistry. 276 (19): 16491–500. doi:10.1074/jbc.M010966200. PMID 11278799.
• Manzano RG, Montuenga LM, Dayton M, Dent P, Kinoshita I, Vicent S, Gardner GJ, Nguyen P, Choi YH, Trepel J, Auersperg N, Birrer MJ (Jun 2002). "CL100 expression is down-regulated in advanced epithelial ovarian cancer and its re-expression decreases its malignant potential". Oncogene. 21 (28): 4435–47. doi:10.1038/sj.onc.1205542. hdl:10171/20183. PMID 12080474.
• Imasato A, Desbois-Mouthon C, Han J, Kai H, Cato AC, Akira S, Li JD (Dec 2002). "Inhibition of p38 MAPK by glucocorticoids via induction of MAPK phosphatase-1 enhances nontypeable Haemophilus influenzae-induced expression of toll-like receptor 2". The Journal of Biological Chemistry. 277 (49): 47444–50. doi:10.1074/jbc.M208140200. PMID 12356755.
• Lasa M, Abraham SM, Boucheron C, Saklatvala J, Clark AR (Nov 2002). "Dexamethasone causes sustained expression of mitogen-activated protein kinase (MAPK) phosphatase 1 and phosphatase-mediated inhibition of MAPK p38". Molecular and Cellular Biology. 22 (22): 7802–11. doi:10.1128/MCB.22.22.7802-7811.2002. PMC 134716. PMID 12391149.
• Denkert C, Schmitt WD, Berger S, Reles A, Pest S, Siegert A, Lichtenegger W, Dietel M, Hauptmann S (Dec 2002). "Expression of mitogen-activated protein kinase phosphatase-1 (MKP-1) in primary human ovarian carcinoma". International Journal of Cancer. 102 (5): 507–13. doi:10.1002/ijc.10746. PMID 12432554. S2CID 45750943.

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