PTPN11

PTPN11
Structures disponibles PDB Recherche d'orthologue: PDBe RCSB Identifiants PDB 2SHP, 3B7O, 3MOW, 3O5X, 3TKZ, 3TL0, 4DGP, 4DGX, 4GWF, 4H1O, 4JE4, 4JEG, 3ZM0, 3ZM1, 3ZM2, 3ZM3, 4H34, 4JMG, 4NWF, 4NWG, 4OHD, 4OHE, 4OHH, 4OHI, 4OHL, 4PVG, 4RDD, 4QSY, 5DF6, 5IBS, 5EHP, 5EHR, 5I6V, 5IBM
Identifiants
Aliases	PTPN11
IDs externes	OMIM: 176876 MGI: 99511 HomoloGene: 2122 GeneCards: PTPN11
Position du gène (Homme) Chr. Chromosome 12 humain[1] Locus 12q24.13 Début 112,418,351 bp[1] Fin 112,509,918 bp[1]
Position du gène (Souris) Chr. Chromosome 5 (souris)[2] Locus 5|5 F Début 121,268,596 bp[2] Fin 121,329,460 bp[2]
Expression génétique Bgee Humain Souris (orthologue) Fortement exprimé dans internal globus pallidus dorsal motor nucleus of vagus nerve Brodmann area 23 pleura viscéral parietal pleura noyau sous-thalamique pars reticulata inferior olivary nucleus Epithelium of choroid plexus external globus pallidus Fortement exprimé dans corpuscule rénal Epithelium of choroid plexus utricle medullary collecting duct épithélium pigmentaire rétinien substantia nigra corps ciliaire iris endocardial cushion ligne primitive Plus de données d'expression de référence BioGPS Plus de données d'expression de référence
Gene Ontology Fonction moléculaire liaison de phospholipase phosphoprotein phosphatase activity insulin receptor binding phosphatase activity receptor tyrosine kinase binding peptide hormone receptor binding liaison protéique non-membrane spanning protein tyrosine phosphatase activity activité hydrolase phosphatidylinositol-4,5-bisphosphate 3-kinase activity 1-phosphatidylinositol-3-kinase activity cell adhesion molecule binding protein tyrosine phosphatase activity phosphotyrosine residue binding protein domain specific binding D1 dopamine receptor binding insulin receptor substrate binding protein tyrosine kinase binding protein kinase binding Composant cellulaire cytoplasme cytosol mitochondrie noyau nucléoplasme complexe macromoléculaire Processus biologique dephosphorylation megakaryocyte development positive regulation of signal transduction negative regulation of insulin secretion regulation of cell adhesion mediated by integrin atrioventricular canal development intestinal epithelial cell migration organ growth epidermal growth factor receptor signaling pathway negative regulation of growth hormone secretion axonogenesis glucose homeostasis regulation of protein export from nucleus multicellular organism growth regulation of multicellular organism growth processus métabolique lipidique ephrin receptor signaling pathway abortive mitotic cell cycle DNA damage checkpoint signaling protein dephosphorylation T cell costimulation thrombocytopoïèse microvillus organization positive regulation of mitotic cell cycle genitalia development platelet activation fibroblast growth factor receptor signaling pathway développement du cœur développement cérébral regulation of type I interferon-mediated signaling pathway hormone-mediated signaling pathway integrin-mediated signaling pathway Bergmann glial cell differentiation homeostasis of number of cells within a tissue inner ear development platelet-derived growth factor receptor signaling pathway negative regulation of cortisol secretion peptidyl-tyrosine dephosphorylation ERBB signaling pathway negative regulation of hormone secretion triglyceride metabolic process hormone metabolic process positive regulation of hormone secretion negative regulation of cell adhesion mediated by integrin regulation of protein-containing complex assembly face morphogenesis cerebellar cortex formation leukocyte migration multicellular organismal reproductive process phosphatidylinositol phosphate biosynthetic process neurotrophin TRK receptor signaling pathway phosphatidylinositol-3-phosphate biosynthetic process Guidage axonal positive regulation of ERK1 and ERK2 cascade cellular response to epidermal growth factor stimulus positive regulation of protein kinase B signaling cytokine-mediated signaling pathway interleukin-6-mediated signaling pathway cellular response to cytokine stimulus cellular response to mechanical stimulus positive regulation of interferon-beta production positive regulation of interleukin-6 production positive regulation of tumor necrosis factor production positive regulation of glucose import positive regulation of insulin receptor signaling pathway Sources:Amigo / QuickGO
Orthologues Espèces Homme Souris Entrez 5781 19247 Ensembl ENSG00000179295 ENSMUSG00000043733 UniProt Q06124 P35235 RefSeq (mRNA) NM_002834 NM_080601 NM_001330437 NM_001374625 NM_018508 NM_001109992 NM_011202 RefSeq (protéine) NP_001317366 NP_002825 NP_542168 NP_001361554 NP_001103462 NP_035332 Localisation (UCSC) Chr 12: 112.42 – 112.51 Mb Chr 5: 121.27 – 121.33 Mb Publication PubMed [3] [4]
Wikidata
Voir/Editer Humain Voir/Editer Souris

Le PTPN11 (pour « Tyrosine-protein phosphatase non-receptor type 11 »), ou SHP2, est une protéine tyrosine phosphatase. Son gène est le PTPN11 situé sur le chromosome 12 humain.

Rôles

Il comporte deux domaines SH2^[5]. Ces derniers bloquent l'activité phosphatase de la molécule s'ils sont libres. S'ils sont activés, ils libèrent le site phosphatase permettant son action enzymatique^[6].

Il régule la voie du phosphatidylinositol-3-phosphate^[7].

En médecine

Une mutation du gène est retrouvée dans un cas de syndrome de Noonan sur deux ainsi que dans plusieurs cancers^[8]. Ces mutations entraînent une augmentation variable (suivant la mutation^[9]) de l'activité phosphatase, prolongeant le signal ERK2/MAPK1 facilitant une prolifération cellulaire^[10]. Des mutations sont également retrouvées dans le syndrome LEOPARD^[11].

Notes et références

1. GRCh38: Ensembl release 89: ENSG00000179295 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000043733 - Ensembl, May 2017
3. « Publications PubMed pour l'Homme », sur National Center for Biotechnology Information, U.S. National Library of Medicine
4. « Publications PubMed pour la Souris », sur National Center for Biotechnology Information, U.S. National Library of Medicine
5. Feng G, SHP-2 tyrosine phosphatase: signaling one cell or many, Exp Cell Res, 1999;253:47–54
6. Hof P, Pluskey S, Dhe-Pagganon S, Eck MJ, Shoelson SE, Crystal structure of the tyrosine phosphatase SHP-2, Cell, 1998;92:441–450
7. Wu CJ, O’Rourke DM, Feng GS, Johnson GR, Wang Q, Greene MI, The tyrosine phosphatase SHP-2 is required for mediating phosphatidylinositol 3-kinase/Akt activation by growth factors, Oncogene, 2001;20:6018–6025
8. Keilhack H, David FS, McGregor M, Cantley LC, Neel BG, Diverse biochemical properties of Shp2 mutants, J Biol Chem, 2005;280:30984–30993
9. Niihori T, Aoki Y, Ohashi H et al. Functional analysis of PTPN11/SHP-2 mutants identified in Noonan syndrome and childhood leukemia, J Hum Genet, 2005;50:192–202
10. Fragale A, Tartaglia M, Wu J, Gelb BD, Noonan syndrome-associated SHP2/PTPN11 mutants cause EGF-dependent prolonged GAB1 binding and sustained ERK2/MAPK1 activation, Hum Mutat, 2004;23:267–277
11. Tartaglia M, Martinelli S, Stella L et al. Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease, Am J Hum Genet, 2006;78:279–290