Quelltext der Seite Ubiquitin-Protein-Ligase UBR1

{{Infobox Protein
| Name            = UBR1
| Bild            = 
| Bild_legende    = 
| PDB             = 
| Groesse         = 1749 aa
| Kofaktor        = 
| Precursor       = 
| Struktur        = 
| Isoformen       = 2
| HGNCid          = 16808
| Symbol          = UBR1
| AltSymbols      = 
| OMIM            = 605981
| MGIid           = 1277977
| UniProt         = Q8IWV7
| ATC-Code        = 
| CAS             = 
| CASergänzend    = 
| DrugBank        = 
| Wirkstoffklasse = 
| EC-Nummer       = 6.3.2.-
| Peptidase_fam   = 
| Kategorie       = Ligase
| Reaktionsart    = Erzeugung einer [[Peptidbindung]]
| Substrat        = ATP + Ubiquitin + (Protein-)Aminosäure
| Produkte        = AMP + Diphosphat + (Protein-N-)Ubiquitinyl-Aminosäure
| Homolog_fam     = 
| Taxon           = [[Eukaryoten]]<ref>{{PROSITE|PDOC51157}}</ref>
| Taxon_Ausnahme  = 
| Orthologe       = 
{{ Protein Orthologe
    | Spezies1 = Mensch
    | Spezies2 = Maus
    | S1_EntrezGene = 197131
    | S1_Ensembl = ENSG00000159459
    | S1_RefseqmRNA = NM_174916
    | S1_RefseqProtein = NP_777576
    | S1_GenLoc_db = hg38
    | S1_GenLoc_chr = 15
    | S1_GenLoc_start =42942897
    | S1_GenLoc_end =43106088
    | S1_Uniprot = Q8IWV7
    | S2_EntrezGene = 22222
    | S2_Ensembl = ENSMUSG00000027272
    | S2_RefseqmRNA = NM_009461
    | S2_RefseqProtein = NP_033487
    | S2_GenLoc_db = mm10
    | S2_GenLoc_chr = 2
    | S2_GenLoc_start =120860272
    | S2_GenLoc_end =120970729
    | S2_Uniprot = Q2M4I1
  }}
}}
Die '''Ubiquitin-Protein-Ligase UBR1''' (auch '''E3-&alpha;-1''', '''N-Recognin-1''') ist ein [[Enzym]], das an bestimmte [[Protein]]e ein [[Ubiquitin]]-Molekül hängt. Sie gehört zu den [[Ubiquitin-Protein-Ligasen]]. Diese Reaktion ist Teil des ubiquitinabhängigen Proteinabbaus in der [[Proteinqualitätskontrolle]], die in den [[Zelle (Biologie)|Zellen]] aller [[Eukaryoten]] stattfindet. UBR1 ist außerdem am [[Stoffwechsel]] der [[Bauchspeicheldrüse]] beteiligt und kann durch Bindung von [[Leucin]] den [[Leucin-MTOR-Signalweg]] und damit das [[Zellwachstum]] regulieren. [[Mutation]]en im ''UBR1''-[[Gen]] sind beim Menschen für das erbliche [[Johanson-Blizzard-Syndrom]] verantwortlich.<ref>{{UniProt|Q8IWV7}}</ref><ref name="pmid9653112">{{cite journal | author = Kwon YT, Reiss Y, Fried VA, Hershko A, Yoon JK, Gonda DK, Sangan P, Copeland NG, Jenkins NA, [[Alexander Varshavsky|Varshavsky A]] | title = The mouse and human genes encoding the recognition component of the N-end rule pathway | journal = Proc Natl Acad Sci U S A | volume = 95 | issue = 14 | pages = 7898–7903 | year = 1998 | month = Aug | pmid = 9653112 | pmc = 20901 | doi =  }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: UBR1 ubiquitin protein ligase E3 component n-recognin 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=197131| accessdate = 2011-03-05}}</ref>

== Katalysierte Reaktion ==
:<math>\mathrm{ATP + Ubiquitin + (Protein-)Aminosaeure \longrightarrow}</math>
:<math>\mathrm{\longrightarrow AMP + PP_i + (Protein-N-)Ubiquitinyl-Aminosaeure}</math>

Ubiquitin wird mit einem Protein ligiert. Die [[N-End Rule|N-End-Regel]] legt fest, welche Proteine betroffen sind.

== Funktion ==
Der sogenannte „N-End Rule“-Pfad ist ein proteolytischer Pfad des Ubiquitin-Systems. Die sogenannte Recognition-Komponente dieses Pfades, die diesem Protein entspricht, bindet an den N-terminalen Aminosäure-Rest des Zielproteins und vermittelt so die Erzeugung der substratgebundenen Multiubiquitin-Kette (sog. Polyubiquinierung). Dies führt zum Abbau des Zielproteins. Das hier beschriebene Protein besitzt zwei Zinc-Finger-Domänen. Mutationen in diesem Gen wurden mit der Entstehung des [[Johanson-Blizzard-Syndrom]]s in Verbindung gebracht.<ref name="entrez" />

<!--== Literatur ==
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*{{cite journal  | author=Chiannilkulchai N, Pasturaud P, Richard I, ''et al.'' |title=A primary expression map of the chromosome 15q15 region containing the recessive form of limb-girdle muscular dystrophy (LGMD2A) gene. |journal=Hum. Mol. Genet. |volume=4 |issue= 4 |pages= 717–25 |year= 1995 |pmid= 7633422 |doi=10.1093/hmg/4.4.717  }}
*{{cite journal  | author=Dgany O, Avidan N, Delaunay J, ''et al.'' |title=Congenital dyserythropoietic anemia type I is caused by mutations in codanin-1. |journal=Am. J. Hum. Genet. |volume=71 |issue= 6 |pages= 1467–74 |year= 2003 |pmid= 12434312 |doi=10.1086/344781  }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal  | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=[[Nat. Genet.]] |volume=36 |issue= 1 |pages= 40–5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
*{{cite journal  | author=Beausoleil SA, Jedrychowski M, Schwartz D, ''et al.'' |title=Large-scale characterization of HeLa cell nuclear phosphoproteins. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=101 |issue= 33 |pages= 12130–5 |year= 2004 |pmid= 15302935 |doi= 10.1073/pnas.0404720101 }}
*{{cite journal  | author=Yin J, Kwon YT, [[Alexander Varshavsky|Varshavsky A]], Wang W |title=RECQL4, mutated in the Rothmund-Thomson and RAPADILINO syndromes, interacts with ubiquitin ligases UBR1 and UBR2 of the N-end rule pathway. |journal=Hum. Mol. Genet. |volume=13 |issue= 20 |pages= 2421–30 |year= 2005 |pmid= 15317757 |doi= 10.1093/hmg/ddh269 }}
*{{cite journal  | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
*{{cite journal  | author=Kwak KS, Zhou X, Solomon V, ''et al.'' |title=Regulation of protein catabolism by muscle-specific and cytokine-inducible ubiquitin ligase E3alpha-II during cancer cachexia. |journal=[[Cancer Res.]] |volume=64 |issue= 22 |pages= 8193–8 |year= 2005 |pmid= 15548684 |doi= 10.1158/0008-5472.CAN-04-2102 }}
*{{cite journal  | author=Tasaki T, Mulder LC, Iwamatsu A, ''et al.'' |title=A family of mammalian E3 ubiquitin ligases that contain the UBR box motif and recognize N-degrons. |journal=Mol. Cell. Biol. |volume=25 |issue= 16 |pages= 7120–36 |year= 2005 |pmid= 16055722 |doi= 10.1128/MCB.25.16.7120-7136.2005 }}
*{{cite journal  | author=Stelzl U, Worm U, Lalowski M, ''et al.'' |title=A human protein-protein interaction network: a resource for annotating the proteome. |journal=Cell |volume=122 |issue= 6 |pages= 957–68 |year= 2005 |pmid= 16169070 |doi= 10.1016/j.cell.2005.08.029 }}
*{{cite journal  | author=Zenker M, Mayerle J, Lerch MM, ''et al.'' |title=Deficiency of UBR1, a ubiquitin ligase of the N-end rule pathway, causes pancreatic dysfunction, malformations and mental retardation (Johanson-Blizzard syndrome). |journal=Nat. Genet. |volume=37 |issue= 12 |pages= 1345–50 |year= 2006 |pmid= 16311597 |doi= 10.1038/ng1681 }}
*{{cite journal  | author=Sasaki T, Kojima H, Kishimoto R, ''et al.'' |title=Spatiotemporal regulation of c-Fos by ERK5 and the E3 ubiquitin ligase UBR1, and its biological role. |journal=Mol. Cell |volume=24 |issue= 1 |pages= 63–75 |year= 2006 |pmid= 17018293 |doi= 10.1016/j.molcel.2006.08.005 }}
*{{cite journal  | author=Zou W, Wang J, Zhang DE |title=Negative regulation of ISG15 E3 ligase EFP through its autoISGylation. |journal=[[Biochem. Biophys. Res. Commun.]] |volume=354 |issue= 1 |pages= 321–7 |year= 2007 |pmid= 17222803 |doi= 10.1016/j.bbrc.2006.12.210 }}
*{{cite journal  | author=Sakane A, Hatakeyama S, Sasaki T |title=Involvement of Rabring7 in EGF receptor degradation as an E3 ligase. |journal=Biochem. Biophys. Res. Commun. |volume=357 |issue= 4 |pages= 1058–64 |year= 2007 |pmid= 17462600 |doi= 10.1016/j.bbrc.2007.04.052 }}
*{{cite journal  | author=Wei S, Lin LF, Yang CC, ''et al.'' |title=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. |journal=Mol. Pharmacol. |volume=72 |issue= 3 |pages= 725–33 |year= 2007 |pmid= 17569795 |doi= 10.1124/mol.107.035287 }}-->

== Einzelnachweise ==
<references />

[[Kategorie:Ligase]]
[[Kategorie:Codiert auf Chromosom 15 (Mensch)]]