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RPS6KB1

S Wikipedije, slobodne enciklopedije
RPS6KB1
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

3A60, 3A61, 3A62, 3WE4, 3WF5, 3WF6, 3WF7, 3WF8, 3WF9, 4L3J, 4L3L, 4L42, 4L43, 4L44, 4L45, 4L46, 4RLO, 4RLP

Identifikatori
AliasiRPS6KB1
Vanjski ID-jeviOMIM: 608938 MGI: 1270849 HomoloGene: 81703 GeneCards: RPS6KB1
Lokacija gena (čovjek)
Hromosom 17 (čovjek)
Hrom.Hromosom 17 (čovjek)[1]
Hromosom 17 (čovjek)
Genomska lokacija za RPS6KB1
Genomska lokacija za RPS6KB1
Bend17q23.1Početak59,893,046 bp[1]
Kraj59,950,574 bp[1]
Lokacija gena (miš)
Hromosom 11 (miš)
Hrom.Hromosom 11 (miš)[2]
Hromosom 11 (miš)
Genomska lokacija za RPS6KB1
Genomska lokacija za RPS6KB1
Bend11|11 CPočetak86,498,871 bp[2]
Kraj86,544,805 bp[2]
Obrazac RNK ekspresije


Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija• aktivnost sa transferazom
• protein kinase activity
• nucleotide binding
• peptide binding
• GO:0001948, GO:0016582 vezivanje za proteine
• vezivanje identičnih proteina
• protein serine/threonine/tyrosine kinase activity
• ATP binding
• kinase activity
• protein serine/threonine kinase activity
• ribosomal protein S6 kinase activity
• PDZ domain binding
• protein phosphatase 2A binding
Ćelijska komponenta• citoplazma
• citosol
• membrana
• sinapsa
• nukleoplazma
• cell surface
• mitochondrial outer membrane
• međućelijske veze
• mitohondrija
• perinuklearno područje citoplazme
• neuron projection
• jedro
Biološki proces• germ cell development
• response to amino acid
• response to glucagon
• GO:1904578 response to organic cyclic compound
• protein kinase B signaling
• response to nutrient
• Fosforilacija
• regulation of glucose import
• response to testosterone
• negative regulation of extrinsic apoptotic signaling pathway
• cellular response to growth factor stimulus
• skeletal muscle contraction
• response to mechanical stimulus
• GO:0010260 starenje
• response to leucine
• GO:1904579 cellular response to organic cyclic compound
• positive regulation of mitotic cell cycle
• negative regulation of apoptotic process
• response to heat
• response to glucocorticoid
• response to glucose
• response to peptide hormone
• behavioral fear response
• positive regulation of translation
• response to organic substance
• positive regulation of smooth muscle cell migration
• response to tumor necrosis factor
• response to insulin
• response to lipopolysaccharide
• GO:1903105 negative regulation of insulin receptor signaling pathway
• cellular response to hormone stimulus
• Dugoročno pamćenje
• response to wounding
• response to organonitrogen compound
• response to electrical stimulus involved in regulation of muscle adaptation
• skeletal muscle atrophy
• ćelijski ciklus
• response to ethanol
• positive regulation of translational initiation
• Ćelijska migracija
• response to toxic substance
• positive regulation of skeletal muscle tissue growth
• regulation of translation
• phosphatidylinositol-mediated signaling
• GO:0072468 Transdukcija signala
• positive regulation of smooth muscle cell proliferation
• GO:0097285 apoptoza
• protein phosphorylation
• cellular response to dexamethasone stimulus
• cellular response to insulin stimulus
• G1/S transition of mitotic cell cycle
• GO:0035404 peptidyl-serine phosphorylation
• TOR signaling
• cellular response to interferon-gamma
• long-chain fatty acid import into cell
• GO:0007243 intracellular signal transduction
• response to nutrient levels
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez

6198

72508

Ensembl

ENSG00000108443

ENSMUSG00000020516

UniProt

P23443

Q8BSK8

RefSeq (mRNK)

NM_001272042
NM_001272043
NM_001272044
NM_001272060
NM_003161

NM_001114334
NM_028259
NM_001363162

RefSeq (bjelančevina)
NP_001258971
NP_001258972
NP_001258973
NP_001258989
NP_003152

NP_001356598
NP_001356599
NP_001356600
NP_001356601
NP_001356602
NP_001356603
NP_001356604
NP_001356605
NP_001356606
NP_001356607
NP_001356608

NP_001107806
NP_082535
NP_001350091

Lokacija (UCSC)Chr 17: 59.89 – 59.95 MbChr 11: 86.5 – 86.54 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Ribosomna protein S6 kinaza beta-1 (S6K1), znana i kao p70S6 kinaza (p70S6K, p70-S6K), je enzim (preciznije protein-kinaza) koji je kod ljudi kodiran genom RPS6KB1.[5][6] To je serin / treonin kinaza koja djeluje nizvodno od PIP3 i fosfoinozitid-ovisne kinaze-1 u PI3 kinaznom putu.[7] Kao što i samo ime govori, njegov cilj supstrat je ribosomski protein S6.[8] Sintezu proteina na ribosomu nducira fosforilacija S6.

Fosforilacija p70S6K na treoninu 389 korištena je kao obilježje aktivacije od mTOR i u korelaciji je s inhibicijom autofagija u različitim situacijama. Međutim, nekoliko nedavnih studija sugerira da aktivnost p70S6K ima pozitivniju ulogu u porastu autofagije.[9][10]

Aminokiselinska sekvenca

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Dužina polipeptidnog lanca je 525 aminokiselina, a molekulska težina 59.140 Da.[11].

1020304050
MRRRRRRDGFYPAPDFRDREAEDMAGVFDIDLDQPEDAGSEDELEEGGQL
NESMDHGGVGPYELGMEHCEKFEISETSVNRGPEKIRPECFELLRVLGKG
GYGKVFQVRKVTGANTGKIFAMKVLKKAMIVRNAKDTAHTKAERNILEEV
KHPFIVDLIYAFQTGGKLYLILEYLSGGELFMQLEREGIFMEDTACFYLA
EISMALGHLHQKGIIYRDLKPENIMLNHQGHVKLTDFGLCKESIHDGTVT
HTFCGTIEYMAPEILMRSGHNRAVDWWSLGALMYDMLTGAPPFTGENRKK
TIDKILKCKLNLPPYLTQEARDLLKKLLKRNAASRLGAGPGDAGEVQAHP
FFRHINWEELLARKVEPPFKPLLQSEEDVSQFDSKFTRQTPVDSPDDSTL
SESANQVFLGFTYVAPSVLESVKEKFSFEPKIRSPRRFIGSPRTPVSPVK
FSPGDFWGRGASASTANPQTPVEYPMETSGIEQMDVTMSGEASAPLPIRQ
PNSGPYKKQAFPMISKRPEHLRMNL
Simboli

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

Funkcija

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Ovaj gen kodira člana RSK porodice serin / treonin kinaza. Ova kinaza sadrži dva neidentična katalitska domena kinaze i fosforilira nekoliko ostataka ribosomskog proteina S6. Aktivnost kinaze ovog proteina dovodi do povećanja sinteze proteina i proliferacije ćelija. Pojačanje regije DNK koja kodira ovaj gen i prekomerna ekspresija ove kinaze uočene su u nekim ćelijskim linijama karcinoma dojke. Opisana su alternativna mjesta translacije i varijante prerađenih transkripata, ali nisu detaljno okarakterizirana.

mTOR

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P70S6 kinaza je nizvodna meta signalizacije mTOR (cilj sisarskog rapamicina), posebno mTORC1, kompleksa koji sadrži mTOR, a karakterizira se uključivanjem Raptora, a ne Riktora (mTORC2). mTOR se može aktivirati putem mehanizma sličnog AND-vratima u lizosomu, integrirajući signale o faktorima rasta i bioraspoloživosti važnih molekula. Naprimjer, aminokiseline poput arginina i leucina mogu podstaknuti lizosomsko regrutiranje mTORC1. Kada se nađe u lizosomu, mTOR može aktivirati Rheb, malu GTPazu, koja se nalazi u lizosomu, u svom stanju vezanom za GTP. Aktivnost reb GTPaze stimulira (i samim tim smanjuje kapacitet za aktiviranje mTOR) uzvodnim TSC kompleksom, koji je inhibiran IGF signalizacijom. Stoga se AND ulaz sastoji od pravilne lokalizacije dovoljnom količinom aminokiselina i aktivacije faktorima rasta. Jednom kada je mTOR pravilno lokaliziran i aktiviran, može fosforilirati nizvodne ciljeve kao što su p70S6K, 4EBP i ULK1, koji su važni za regulaciju anaboličke/ kataboličke ravnoteže proteina. Fizička vježba aktivira sintezu proteina, fosforilacijom (aktivacijom) p70S6K na putu koji ovisi o mTOR, konkretno mTORC1. To je dokazano upotrebom inhibitora mTOR-a, rapamicina, za blokiranje povećanja mišićne mase, uprkos povećanom opterećenju (npr. vježbanjem). Pokazalo se da vježba povećava nivo IGF-1 u mišićima, indukujući tako signalni put IGF-1/PI3K/Akt/p70S6K, a samim tim povećanu sintezu proteina potrebnih za izgradnju mišića.

Klinički značaj

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Inhibicija proteina S6K1, ili njegov nedostatak, usporava proizvodnju masnih ćelija, ometanjem i usporavanjem početne "faze posvećenosti" njihovom formiranju. Studija bi mogla imati implikacije na liječenje gojaznosti.[12]

Amplifikacija regije DNK koja kodira ovaj gen i prekomerna ekspresija ove kinaze uočena je kod nekih karcinoma dojke u ćelijskim linijama.

Sljedeći put, za koji je P70 predložio njegovosudjelovanje, produžuje i rast mišića. P70 se fosforilira pasivnim istezanjem u mišićima. Ovo je možda jedna od mnogih proteinskih kinaza uključenih u izgradnju mišića.[13]

U svom neaktivnom stanju, S6K1 je vezan za eIF3 i odvaja se nakon fosforilacije, pomoću mTOR/Raptor-a. Slobodni S6K1 tada može fosforilirati svoje brojne ciljeve, uključujući eIF4B.[14]

Interakcije

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Pokazano je da P70-S6 kinaza 1 komunicira sa:

Također pogledajte

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Reference

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000108443 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020516 - Ensembl, maj 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.
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  6. ^ "Entrez Gene: RPS6KB1 ribosomal protein S6 kinase, 70kDa, polypeptide 1".
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  24. ^ Isotani S, Hara K, Tokunaga C, Inoue H, Avruch J, Yonezawa K (Nov 1999). "Immunopurified mammalian target of rapamycin phosphorylates and activates p70 S6 kinase alpha in vitro". The Journal of Biological Chemistry. 274 (48): 34493–8. doi:10.1074/jbc.274.48.34493. PMID 10567431.
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  37. ^ a b Panasyuk G, Nemazanyy I, Filonenko V, Gout I (maj 2008). "Ribosomal protein S6 kinase 1 interacts with and is ubiquitinated by ubiquitin ligase ROC1". Biochemical and Biophysical Research Communications. 369 (2): 339–43. doi:10.1016/j.bbrc.2008.02.016. PMID 18279656.

Vanjski linkovi

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