MAPK1

MAPK1
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	1PME, 1TVO, 1WZY, 2OJG, 2OJI, 2OJJ, 2Y9Q, 3D42, 3D44, 3I5Z, 3I60, 3SA0, 3TEI, 3W55, 4FMQ, 4FUX, 4FUY, 4FV0, 4FV1, 4FV2, 4FV3, 4FV4, 4FV5, 4FV6, 4FV7, 4FV8, 4FV9, 4G6N, 4G6O, 4H3P, 4H3Q, 4IZ5, 4IZ7, 4IZA, 4N0S, 4NIF, 4O6E, 4QTA, 4QTE, 4ZZM, 4ZZN, 4ZZO, 5BUE, 5BUI, 5BUJ, 4QP1, 4QP2, 4QP3, 4QP4, 4QP6, 4QP7, 4QP8, 4QP9, 4QPA, 4XJ0, 5BVD, 5BVE, 5BVF, 5AX3, 4ZXT, 5K4I
Identifikatori
Aliasi	MAPK1
Vanjski ID-jevi	OMIM: 176948 MGI: 1346858 HomoloGene: 37670 GeneCards: MAPK1
Lokacija gena (čovjek)
Hrom.	Hromosom 22 (čovjek)
Kraj	21,867,680 bp
Lokacija gena (miš)
Hrom.	Hromosom 16 (miš)
Kraj	16,865,317 bp
Obrazac RNK ekspresije
	; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• phosphatase binding; • ATP binding; • protein kinase activity; • transcription factor binding; • aktivnost sa transferazom; • mitogen-activated protein kinase kinase kinase binding; • phosphotyrosine residue binding; • GO:0001948, GO:0016582 vezivanje za proteine; • protein kinase binding; • vezivanje sa DNK; • nucleotide binding; • RNA polymerase II CTD heptapeptide repeat kinase activity; • protein serine/threonine kinase activity; • kinase activity; • vezivanje identičnih proteina; • MAP kinase activity; • double-stranded DNA binding; • MAP kinase kinase activity;
Ćelijska komponenta	• citoplazma; • citosol; • focal adhesion; • centar organizacije mikrotubula; • mitohondrija; • Kaveole; • dendrite cytoplasm; • citoskelet; • jedro; • Egzosom; • perikaryon; • late endosome; • Golđijev aparat; • Diobeno vreteno; • Akson; • early endosome; • mitotic spindle; • Pseudopodija; • extracellular region; • nukleoplazma; • azurophil granule lumen; • ficolin-1-rich granule lumen; • ćelijska membrana; • GO:0097483, GO:0097481 postsynaptic density; • membrana; • GO:0009327 makromolekulani kompleks;
Biološki proces	• caveolin-mediated endocytosis; • positive regulation of telomere capping; • response to exogenous dsRNA; • cardiac neural crest cell development involved in heart development; • positive regulation of translation; • cellular response to DNA damage stimulus; • platelet activation; • Fc-epsilon receptor signaling pathway; • protein phosphorylation; • face development; • cellular response to granulocyte macrophage colony-stimulating factor stimulus; • regulation of DNA-binding transcription factor activity; • animal organ morphogenesis; • ćelijski ciklus; • ERBB signaling pathway; • GO:0097285 apoptoza; • B cell receptor signaling pathway; • GO:0009373 regulation of transcription, DNA-templated; • regulation of protein stability; • Fc-gamma receptor signaling pathway involved in phagocytosis; • thymus development; • negative regulation of cell differentiation; • ERK1 and ERK2 cascade; • labyrinthine layer blood vessel development; • transcription, DNA-templated; • GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated; • heart development; • GO:0022415 viral process; • response to toxic substance; • regulation of stress-activated MAPK cascade; • chemical synaptic transmission; • growth hormone receptor signaling pathway via JAK-STAT; • cytosine metabolic process; • Fosforilacija; • outer ear morphogenesis; • response to estrogen; • Hemotaksija; • response to lipopolysaccharide; • thyroid gland development; • response to epidermal growth factor; • positive regulation of telomerase activity; • Nocicepcija; • peptidyl-threonine phosphorylation; • trachea formation; • lipopolysaccharide-mediated signaling pathway; • mammary gland epithelial cell proliferation; • GO:0007243 intracellular signal transduction; • lung morphogenesis; • neural crest cell development; • positive regulation of cell migration; • regulation of early endosome to late endosome transport; • response to stress; • positive regulation of telomere maintenance via telomerase; • MAPK cascade; • axon guidance; • fibroblast growth factor receptor signaling pathway; • positive regulation of peptidyl-threonine phosphorylation; • GO:0035404 peptidyl-serine phosphorylation; • positive regulation of cell population proliferation; • regulation of cellular response to heat; • Bergmann glial cell differentiation; • regulation of Golgi inheritance; • T cell receptor signaling pathway; • regulation of cytoskeleton organization; • GO:0072468 Transdukcija signala; • long-term potentiation; • regulation of ossification; • regulation of phosphatidylinositol 3-kinase signaling; • neutrophil degranulation; • Regulacija ekspresije gena; • cellular response to organic substance; • GO:0010260 starenje; • learning or memory; • GO:1901313 positive regulation of gene expression; • diadenosine tetraphosphate biosynthetic process; • regulation of cellular pH; • cellular response to amino acid starvation; • GO:0072353 cellular response to reactive oxygen species; • response to nicotine; • decidualization; • stress-activated MAPK cascade; • positive regulation of cardiac muscle cell proliferation; • cellular response to cadmium ion; • cellular response to tumor necrosis factor; • cellular response to dopamine; • positive regulation of protein import into nucleus;
	Izvori:Amigo / QuickGO
Ortolozi
	5594
	26413
	ENSG00000100030
	ENSMUSG00000063358
	P28482
	P63085
	NM_138957; NM_002745
	NM_001038663; NM_011949; NM_001357115; NM_028991
	NP_002736; NP_620407
	NP_001033752; NP_036079; NP_001344044
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Mitogen–aktivirana protein-kinaza 1, znana i kao MAPK1, p42MAPK i ERK2, jest enzim koji je kod ljudi kodiran genom sa MAPK1 hromosoma 22.^[5]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 360 aminokiselina, a molekulska težina 41.390 Da.

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MAAAAAAGAG	PEMVRGQVFD	VGPRYTNLSY	IGEGAYGMVC	SAYDNVNKVR
VAIKKISPFE	HQTYCQRTLR	EIKILLRFRH	ENIIGINDII	RAPTIEQMKD
VYIVQDLMET	DLYKLLKTQH	LSNDHICYFL	YQILRGLKYI	HSANVLHRDL
KPSNLLLNTT	CDLKICDFGL	ARVADPDHDH	TGFLTEYVAT	RWYRAPEIML
NSKGYTKSID	IWSVGCILAE	MLSNRPIFPG	KHYLDQLNHI	LGILGSPSQE
DLNCIINLKA	RNYLLSLPHK	NKVPWNRLFP	NADSKALDLL	DKMLTFNPHK
RIEVEQALAH	PYLEQYYDPS	DEPIAEAPFK	FDMELDDLPK	EKLKELIFEE
TARFQPGYRS

Funkcija

Protein kodiran ovim genom član je porodice MAP-kinaza. MAP-kinaze, također poznate kao vanćelijske signalno regulirane kinaze (ERK), djeluju kao integracijska tačka za više biohemijskih signala i uključene su u širok spektar ćelijskih procesa, kao što je proliferacija, diferencijacija, regulacija i razvoj transkripcije. Aktivacija ove kinaze zahtijeva njenu fosforilaciju uzvodnim kinazama. Nakon aktivacije, ova kinaza translocira se u jedro stimuliranih ćelija, gdje fosforilira jedarne mete. Za ovaj gen prijavljene su dvije alternativno prerađene varijante transkripta koje kodiraju isti protein, ali se razlikuju u UTR-u.^[6] MAPK1 contains multiple amino acid sites that are phosphorylated and ubiquitinated.^[7]

Modelni organizmi

U proučavanju funkcije MAPK1 korišteni su modelni organizmi. Uslovna linija nokaut-miša, zvana Mapk1^{tm1a(EUCOMM)Wtsi}^[8]^[9] generirana je kao dio programa Konzorcija za nokaut-miševe—projekta mutageneze visoke propusnosti za generiranje i distribuciju životinjskih modela bolesti zainteresiranim naučnicima.^[10]^[11]^[12]

Fenotip *Mapk1* nokaut-miševa
Svojstvo	Fenotip
Vijabilnost homozigota	Nenormalan
Studija recesivne letalnosti	Nenormalan
Plodnost	Normalan
Tjelesna težina	Normalan
Anksioznost otvorenog polja\|	Normalan
Neurološka procjena	Normalan
Snaga ugriza	Normalan
Test vruće ploče	Normalan
Dismorfologija	Normalan ^[13]
Indirektna kalorimetrija	Normalan
Test tolerancije glukoze	Normalan
Slušni odgovor moždanog stabla	Normalan
DEXA	Normalan
Radiografija	Normalan
Tjelesna temperatura	Normalan
Morfologija OKA	Normalan
klinička hemija	Nenormalan^[14]
Plazmatski imunoglobulini	Normalan
Hematologija	Normalan
Leukociti periferne krvi	Normalan
Mikronukleus test	Normalan
Težina srca	Normalan
Cjelovitost repne epiderme	Normalan
Histopatologija kože	Normalan
Histopatologija mozga	Normalan
Salmonella infekcija	Normalan^[15]
Citrobacter infekcija	Normalan^[16]
Svi testovi i analize su prema^[17]^[18]

Mužjaci i ženke su podvrgnute standardiziranom fenotipskom pregledu, kako bi se utvrdili efekti deleciija.^[17]^[19] Obavljeno je 27 testova na mutantnim miševima i uočene su tri značajne abnormalnosti.^[17] Nijedan homozigotni mutantni embrion nije identifikovan tokom gestacije, pa stoga nijedan nije preživio do odbijanja. Preostali testovi su obavljeni na heterozigotnim mutantnim odraslim miševima, a mužjaci su imali smanjene razine amilaze u cirkulaciji.^[17]

Uslovna delecija "Mapk1" u B-ćelijama pokazala je ulogu MAPK1 u proizvodnji antitijela zavisnih od T-ćelija.^[20] Dominantni mutanti za dobijanje funkcije "Mapk1" kod transgenih miševa pokazao je ulogu MAPK1 u razvoju T-ćelija.^[21] Uslovna inaktivacija "Mapk1" u nervnim progenitorskim ćelijama korteksa u razvoju dovodi do smanjenja debljine korteksa i smanjene proliferacije u nervnim progenitorskim ćelijama.^[22]

Interakcije

Pokazalo se da MAPK1 reaguje sa:

Klinički značaj

Mutacije u MAPK1 su uključene u mnoge tipove kancera.^[61]

Također pogledajte

Vanćelijske signalno regulirane kinaze

Reference

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^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000063358 - Ensembl, maj 2017
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^ Lee IS, Liu Y, Narazaki M, Hibi M, Kishimoto T, Taga T (January 1997). "Vav is associated with signal transducing molecules gp130, Grb2 and Erk2, and is tyrosine phosphorylated in response to interleukin-6". FEBS Lett. 401 (2–3): 133–7. doi:10.1016/s0014-5793(96)01456-1. PMID 9013873. S2CID 32632406.
^ "Expression of MAPK1 in cancer - Summary - The Human Protein Atlas". www.proteinatlas.org.

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