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
Fin	112,509,918 bp
Position du gène (Souris)
Chr.	Chromosome 5 (souris)
Fin	121,329,460 bp
Expression génétique
	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
	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
	5781
	19247
	ENSG00000179295
	ENSMUSG00000043733
	Q06124
	P35235
	NM_002834; NM_080601; NM_001330437; NM_001374625; NM_018508
	NM_001109992; NM_011202
	NP_001317366; NP_002825; NP_542168; NP_001361554
	NP_001103462; NP_035332
	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

↑ ^{a b et c} GRCh38: Ensembl release 89: ENSG00000179295 - Ensembl, May 2017
↑ ^{a b et c} GRCm38: Ensembl release 89: ENSMUSG00000043733 - Ensembl, May 2017
↑ « Publications PubMed pour l'Homme », sur National Center for Biotechnology Information, U.S. National Library of Medicine
↑ « Publications PubMed pour la Souris », sur National Center for Biotechnology Information, U.S. National Library of Medicine
↑ Feng G, SHP-2 tyrosine phosphatase: signaling one cell or many, Exp Cell Res, 1999;253:47–54
↑ Hof P, Pluskey S, Dhe-Pagganon S, Eck MJ, Shoelson SE, Crystal structure of the tyrosine phosphatase SHP-2, Cell, 1998;92:441–450
↑ 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
↑ Keilhack H, David FS, McGregor M, Cantley LC, Neel BG, Diverse biochemical properties of Shp2 mutants, J Biol Chem, 2005;280:30984–30993
↑ 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
↑ 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
↑ 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

[refGRCh38Ensembl-1] {a b et c} GRCh38: Ensembl release 89: ENSG00000179295 - Ensembl, May 2017

[refGRCm38Ensembl-2] {a b et c} 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

[Feng_1999-5] Feng G, SHP-2 tyrosine phosphatase: signaling one cell or many, Exp Cell Res, 1999;253:47–54

[Hof_1998-6] Hof P, Pluskey S, Dhe-Pagganon S, Eck MJ, Shoelson SE, Crystal structure of the tyrosine phosphatase SHP-2, Cell, 1998;92:441–450

[Wu_2001-7] 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

[Keilhack_2005-8] Keilhack H, David FS, McGregor M, Cantley LC, Neel BG, Diverse biochemical properties of Shp2 mutants, J Biol Chem, 2005;280:30984–30993

[Niihori_2005-9] 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

[Fragale_2004-10] 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

[Tartaglia_2006-11] 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

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