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tisdag 12 juni 2018

(5) RNF149 (Kr.2q11.2), DNAPT2, PA-TM-RING RNF-alaperhe. Ubikitinoi normaalin BRAF. tekijän, mutta ei BRAF-onkogeeniä.

RNF149 (Kr.2q11.2), DNAPTP2 , PA-TM-RING RNF-alaryhm


Yleisesti ilmenevä, eniten luuytimessä, umpilisäkkeessä ja 25 muussa kudoksessa. https://www.ncbi.nlm.nih.gov/gene/284996
Nimi DNAPTP2 tulee sanoista
DNA polyerase transactivated protein 2. tälle proteiinille on havaittu ubikitinaatiosubstraatti joka on normaali mutatoitumaton BRAF.  Mutatoitunut BRAF on onkogeeni, muta siihen ei RNF149 tehoa. Tästä on alla artikkeli ja kaavakuva BRAF- signalointitiestä.

Proteiinin rakenne, prekursori 149RNF on pituudeltaan 400 aminohappoa. Geenin synonyymi nimi DNAPTP2
Rakenteessa on koordinoiva signaalipeptidi: aminohapot 1..32.
Produkti on aminohapot 33..400 RNF149
PA-GRAIL- kaltainen domeeni, aminohapot 43..185.
TM-domeeni, aminohapot 201..221.
UPF0233. Uncharacterized protein Family: aminohapot 204..235.
Zf-RING-2, aminohapot 267..310.
(Huom malignissa melanomassa on mutatoitunut BRAF, jota koetetaan inhiboida  vemurafenib-nimisellä lääkkeellä).

Related articles in PubMed

  1. Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Hillier LW, et al. Nature, 2005 Apr 7. PMID 15815621
  2. The LIFEdb database in 2006. Mehrle A, et al. Nucleic Acids Res, 2006 Jan 1. PMID 16381901, Free PMC Article
  3. From ORFeome to biology: a functional genomics pipeline. Wiemann S, et al. Genome Res, 2004 Oct. PMID 15489336, Free PMC Article
See all (17) citations in PubMed
See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

  1. Data show that RNF149 (RING finger protein 149) interacts with wild-type BRAF.
Ring finger protein 149 is an E3 ubiquitin ligase active on wild-type v-Raf murine sarcoma viral oncogene homolog B1 (BRAF).
Hong SW1, Jin DH, Shin JS, Moon JH, Na YS, Jung KA, Kim SM, Kim JC, Kim KP, Hong YS, Lee JL, Choi EK, Lee JS, Kim TW.
Members of the RAF family (ARAF, BRAF, and CRAF/RAF-1) are involved in a variety of cellular activities, including growth, survival, differentiation, and transformation. An oncogene encodes BRAF, the function of which is linked to MEK activation. BRAF is the most effective RAF kinase in terms of induction of MEK/ERK activity. However, the mechanisms involved in BRAF regulation remain unclear. In the present work, we used a tandem affinity purification approach to show that RNF149 (RING finger protein 149) interacts with wild-type BRAF. The latter protein is a RING domain-containing E3 ubiquitin ligase involved in control of gene transcription, translation, cytoskeletal organization, cell adhesion, and epithelial development. We showed that RNF149 bound directly to the C-terminal kinase-containing domain of wild-type BRAF and induced ubiquitination, followed by proteasome-dependent degradation, of the latter protein. Functionally, RNF149 attenuated the increase in cell growth induced by wild-type BRAF. However, RNF149 did not bind to mutant BRAF or induce ubiquitination thereof. Thus, we show that RNF149 is an E3 ubiquitin ligase active on wild-type BRAF.




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