Ubiquitin protein ligase UBR1

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UBR1
Properties of human protein
Mass / length primary structure 1749 aa
Isoforms 2
Identifier
Gene name UBR1
External IDs
Enzyme classification
EC, category 6.3.2. ,  Ligase
Response type Creation of a peptide bond
Substrate ATP + ubiquitin + (protein) amino acid
Products AMP + diphosphate + (protein-N-) ubiquitinyl amino acid
Occurrence
Parent taxon Eukaryotes
Orthologue
human mouse
Entrez 197131 22222
Ensemble ENSG00000159459 ENSMUSG00000027272
UniProt Q8IWV7 Q2M4I1
Refseq (mRNA) NM_174916 NM_009461
Refseq (protein) NP_777576 NP_033487
Gene locus Chr 15: 42.94 - 43.11 Mb Chr 2: 120.86 - 120.97 Mb
PubMed search 197131 22222

The ubiquitin protein ligase UBR1 (also E3-α-1 , N-Recognin-1 ) is an enzyme that attaches a ubiquitin molecule to certain proteins . it belongs to the ubiquitin protein ligases . This reaction is part of the ubiquitin-dependent protein degradation in protein quality control that takes place in the cells of all eukaryotes . UBR1 is also involved in the metabolism of the pancreas and by binding leucine can regulate the leucine MTOR signaling pathway and thus cell growth . Mutations in UBR1 - gene in humans for hereditary Johanson-Blizzard syndrome responsible.

Catalyzed reaction

Ubiquitin is ligated to a protein. The N-end rule determines which proteins are affected.

function

The so-called “N-End Rule” path is a proteolytic path of the ubiquitin system. The so-called recognition component of this path, which corresponds to this protein, binds to the N-terminal amino acid residue of the target protein and thus mediates the creation of the substrate-bound multiubiquitin chain (so-called polyubiquination). This leads to the degradation of the target protein. The protein described here has two zinc finger domains. Mutations in this gene have been linked to the development of Johanson-Blizzard syndrome .

literature

  • Varshavsky A : The N-end rule: functions, mysteries, uses. . In: Proc. Natl. Acad. Sci. USA . 93, No. 22, 1996, pp. 12142-9. doi : 10.1073 / pnas.93.22.12142 . PMID 8901547 .
  • Chiannilkulchai N, Pasturaud P, Richard I, et al. : A primary expression map of the chromosome 15q15 region containing the recessive form of limb-girdle muscular dystrophy (LGMD2A) gene. . In: Hum. Mol. Genet. . 4, No. 4, 1995, pp. 717-25. doi : 10.1093 / hmg / 4.4.717 . PMID 7633422 .
  • Dgany O, Avidan N, Delaunay J, et al. : Congenital dyserythropoietic anemia type I is caused by mutations in codanin-1. . In: Am. J. Hum. Genet. . 71, No. 6, 2003, pp. 1467-74. doi : 10.1086 / 344781 . PMID 12434312 .
  • Strausberg RL, Feingold EA, Grouse LH, et al. : Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . In: Proc. Natl. Acad. Sci. USA . 99, No. 26, 2003, pp. 16899-903. doi : 10.1073 / pnas.242603899 . PMID 12477932 .
  • Ota T, Suzuki Y, Nishikawa T, et al. : Complete sequencing and characterization of 21,243 full-length human cDNAs. . In: Nat. Genet. . 36, No. 1, 2004, pp. 40-5. doi : 10.1038 / ng1285 . PMID 14702039 .
  • Beausoleil SA, Jedrychowski M, Schwartz D, et al. : Large-scale characterization of HeLa cell nuclear phosphoproteins. . In: Proc. Natl. Acad. Sci. USA . 101, No. 33, 2004, pp. 12130-5. doi : 10.1073 / pnas.0404720101 . PMID 15302935 .
  • Yin J, Kwon YT, Varshavsky A , Wang W: RECQL4, mutated in the Rothmund-Thomson and RAPADILINO syndromes, interacts with ubiquitin ligases UBR1 and UBR2 of the N-end rule pathway. . In: Hum. Mol. Genet. . 13, No. 20, 2005, pp. 2421-30. doi : 10.1093 / hmg / ddh269 . PMID 15317757 .
  • Gerhard DS, Wagner L, Feingold EA, et al. : The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . In: Genome Res. . 14, No. 10B, 2004, pp. 2121-7. doi : 10.1101 / gr.2596504 . PMID 15489334 .
  • Kwak KS, Zhou X, Solomon V, et al. : Regulation of protein catabolism by muscle-specific and cytokine-inducible ubiquitin ligase E3alpha-II during cancer cachexia. . In: Cancer Res . 64, No. 22, 2005, pp. 8193-8. doi : 10.1158 / 0008-5472.CAN-04-2102 . PMID 15548684 .
  • Tasaki T, Mulder LC, Iwamatsu A, et al. : A family of mammalian E3 ubiquitin ligases that contain the UBR box motif and recognize N-degrons. . In: Mol. Cell. Biol . 25, No. 16, 2005, pp. 7120-36. doi : 10.1128 / MCB.25.16.7120-7136.2005 . PMID 16055722 .
  • Stelzl U, Worm U, Lalowski M, et al. : A human protein-protein interaction network: a resource for annotating the proteome. . In: Cell . 122, No. 6, 2005, pp. 957-68. doi : 10.1016 / j.cell.2005.08.029 . PMID 16169070 .
  • Zenker M, Mayerle J, Lerch MM, et al. : Deficiency of UBR1, a ubiquitin ligase of the N-end rule pathway, causes pancreatic dysfunction, malformations and mental retardation (Johanson-Blizzard syndrome). . In: Nat. Genet. . 37, No. 12, 2006, pp. 1345-50. doi : 10.1038 / ng1681 . PMID 16311597 .
  • Sasaki T, Kojima H, Kishimoto R, et al. : Spatiotemporal regulation of c-Fos by ERK5 and the E3 ubiquitin ligase UBR1, and its biological role. . In: Mol. Cell . 24, No. 1, 2006, pp. 63-75. doi : 10.1016 / j.molcel.2006.08.005 . PMID 17018293 .
  • Zou W, Wang J, Zhang DE: Negative regulation of ISG15 E3 ligase EFP through its autoISGylation. . In: Biochem. Biophys. Res. Commun. . 354, No. 1, 2007, pp. 321-7. doi : 10.1016 / j.bbrc.2006.12.210 . PMID 17222803 .
  • Sakane A, Hatakeyama S, Sasaki T: Involvement of Rabring7 in EGF receptor degradation as an E3 ligase. . In: Biochem. Biophys. Res. Commun. . 357, No. 4, 2007, pp. 1058-64. doi : 10.1016 / j.bbrc.2007.04.052 . PMID 17462600 .
  • Wei S, Lin LF, Yang CC, et al. : Thiazolidinediones modulate the expression of beta-catenin and other cell-cycle regulatory proteins by targeting the F-box proteins of Skp1-Cul1-F-box protein E3 ubiquitin ligase independently of peroxisome proliferator-activated receptor gamma. . In: Mol. Pharmacol. . 72, No. 3, 2007, pp. 725-33. doi : 10.1124 / mol.107.035287 . PMID 17569795 .

Individual evidence

  1. ↑ PROSITE : PROSITE documentation PDOC51157 (English)
  2. ↑ UniProt Q8IWV7
  3. ↑ Kwon YT, Reiss Y, Fried VA, Hershko A, Yoon JK, Gonda DK, Sangan P, Copeland NG, Jenkins NA, Varshavsky A : The mouse and human genes encoding the recognition component of the N-end rule pathway . In: Proc Natl Acad Sci USA . 95, No. 14, August 1998, pp. 7898-7903. PMID 9653112 . PMC 20901 (free full text).
  4. ↑ a b Entrez Gene: UBR1 ubiquitin protein ligase E3 component n-recognin 1 . Retrieved March 5, 2011.