Q8IWV8 (UBR2_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 99.
History...
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: E3 ubiquitin-protein ligase UBR2 EC=6.3.2.- Alternative name(s): N-recognin-2 Ubiquitin-protein ligase E3-alpha-2 Ubiquitin-protein ligase E3-alpha-II | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Reference proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo![]() |
Protein attributes
| Sequence length | 1755 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | E3 ubiquitin-protein ligase which is a component of the N-end rule pathway. Recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation. Plays a critical role in chromatin inactivation and chromosome-wide transcriptional silencing during meiosis via ubiquitination of histone H2A. Binds leucine and is a negative regulator of the leucine-mTOR signaling pathway, thereby controlling cell growth. Ref.1 Ref.10 |
| Pathway | |
| Subunit structure | Interacts with UBE2B; promotes the UBE2B-H2A interaction and the ubiquitination of histone H2A by UBE2B and UBR2 By similarity. Interacts with RECQL4. Ref.6 |
| Subcellular location | Nucleus By similarity. Note: Associated with chromatin during meiosis. |
| Tissue specificity | Broadly expressed, with highest levels in skeletal muscle, kidney and pancreas. Present in acinar cells of the pancreas (at protein level). Ref.1 Ref.7 |
| Developmental stage | Expressed in fetal pancreas. Ref.7 |
| Domain | The RING-H2 zinc finger is an atypical RING finger with a His ligand in place of the fourth Cys of the classical motif. |
| Sequence similarities | Belongs to the UBR1 family. Contains 1 RING-type zinc finger. Contains 1 UBR-type zinc finger. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| vif | P12504 | 3 | EBI-1237260,EBI-779991 | From a different organism. |
Alternative products
| This entry describes 4 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q8IWV8-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: Q8IWV8-2) The sequence of this isoform differs from the canonical sequence as follows: 397-439: QQLQRDFMED...MLITEENLMS → ERLQSDYVTD...ISAGRSGSPL 440-1755: Missing. | ||||||
| Isoform 3 (identifier: Q8IWV8-3) The sequence of this isoform differs from the canonical sequence as follows: 1-496: Missing. 497-514: RQKFLEGFDAFLELLKCM → MYAGNIPIYKTESRSRNE 1022-1071: SSRDKDKAER...ELFQQTLELD → HNFRVQGTKT...MKTKNSFSRH 1072-1755: Missing. | ||||||
| Note: No experimental confirmation available. | ||||||
| Isoform 4 (identifier: Q8IWV8-4) The sequence of this isoform differs from the canonical sequence as follows: 397-426: QQLQRDFMEDDHERAVSVTALSVQFFTAPT → ERLQSDYVTDDHDREFSVADLSVQIFTVPS | ||||||
| Note: Derived from mouse cDNA data. No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | |||||||||||||||||||
Molecule processing | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1755 | 1755 | E3 ubiquitin-protein ligase UBR2 | PRO_0000056140 | ||||||||||||||||||||
Regions | ||||||||||||||||||||||||
| Zinc finger | 97 – 168 | 72 | UBR-type | |||||||||||||||||||||
| Zinc finger | 1108 – 1214 | 107 | RING-type; atypical | |||||||||||||||||||||
| Coiled coil | 1019 – 1054 | 36 | Potential | |||||||||||||||||||||
Natural variations | ||||||||||||||||||||||||
| Alternative sequence | 1 – 496 | 496 | Missing in isoform 3. | VSP_015166 | ||||||||||||||||||||
| Alternative sequence | 397 – 439 | 43 | QQLQR…ENLMS → ERLQSDYVTDDHDREFSVAD LSVQIFTVPSLFSISAGRSG SPL in isoform 2. | VSP_015167 | ||||||||||||||||||||
| Alternative sequence | 397 – 426 | 30 | QQLQR…FTAPT → ERLQSDYVTDDHDREFSVAD LSVQIFTVPS in isoform 4. | VSP_017130 | ||||||||||||||||||||
| Alternative sequence | 440 – 1755 | 1316 | Missing in isoform 2. | VSP_015168 | ||||||||||||||||||||
| Alternative sequence | 497 – 514 | 18 | RQKFL…LLKCM → MYAGNIPIYKTESRSRNE in isoform 3. | VSP_015169 | ||||||||||||||||||||
| Alternative sequence | 1022 – 1071 | 50 | SSRDK…TLELD → HNFRVQGTKTKLRGREKQRL PDCAEKRSWLRCLKCSGILL MKTKNSFSRH in isoform 3. | VSP_015170 | ||||||||||||||||||||
| Alternative sequence | 1072 – 1755 | 684 | Missing in isoform 3. | VSP_015171 | ||||||||||||||||||||
| Natural variant | 172 | 1 | E → D. Corresponds to variant rs6905054 [ dbSNP | Ensembl ]. | VAR_052117 | ||||||||||||||||||||
| Natural variant | 1095 | 1 | A → P. Corresponds to variant rs6917033 [ dbSNP | Ensembl ]. | VAR_059816 | ||||||||||||||||||||
| Natural variant | 1095 | 1 | A → S. Corresponds to variant rs6917033 [ dbSNP | Ensembl ]. | VAR_059817 | ||||||||||||||||||||
| Natural variant | 1095 | 1 | A → T. Ref.5 Corresponds to variant rs6917033 [ dbSNP | Ensembl ]. | VAR_023283 | ||||||||||||||||||||
Experimental info | ||||||||||||||||||||||||
| Sequence conflict | 864 | 1 | K → R in BAC86295. Ref.2 | |||||||||||||||||||||
Secondary structure | ||||||||||||||||||||||||
Helix Strand Turn | ||||||||||||||||||||||||
| Beta strand | 108 – 112 | 5 | ||||||||||||||||||||||
| Turn | 113 – 115 | 3 | ||||||||||||||||||||||
| Beta strand | 116 – 118 | 3 | ||||||||||||||||||||||
| Helix | 125 – 129 | 5 | ||||||||||||||||||||||
| Helix | 132 – 135 | 4 | ||||||||||||||||||||||
| Beta strand | 138 – 142 | 5 | ||||||||||||||||||||||
| Turn | 154 – 156 | 3 | ||||||||||||||||||||||
| Beta strand | 157 – 159 | 3 | ||||||||||||||||||||||
| Turn | 164 – 166 | 3 | ||||||||||||||||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Regulation of protein catabolism by muscle-specific and cytokine-inducible ubiquitin ligase E3alpha-II during cancer cachexia." Kwak K.S., Zhou X., Solomon V., Baracos V.E., Davis J., Bannon A.W., Boyle W.J., Lacey D.L., Han H.Q. Cancer Res. 64:8193-8198(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, FUNCTION. |
| [2] | "Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Testis. |
| [3] | "The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. Beck S.Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [4] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Ovary. |
| [5] | "Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 4:141-150(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 481-1755 (ISOFORMS 1/4), VARIANT THR-1095. Tissue: Brain. |
| [6] | "RECQL4, mutated in the Rothmund-Thomson and RAPADILINO syndromes, interacts with ubiquitin ligases UBR1 and UBR2 of the N-end rule pathway." Yin J., Kwon Y.T., Varshavsky A., Wang W. Hum. Mol. Genet. 13:2421-2430(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RECQL4, IDENTIFICATION BY MASS SPECTROMETRY. |
| [7] | "Deficiency of UBR1, a ubiquitin ligase of the N-end rule pathway, causes pancreatic dysfunction, malformations and mental retardation (Johanson-Blizzard syndrome)." Zenker M., Mayerle J., Lerch M.M., Tagariello A., Zerres K., Durie P.R., Beier M., Hulskamp G., Guzman C., Rehder H., Beemer F.A., Hamel B.C.J., Vanlieferinghen P., Gershoni-Baruch R., Vieira M.W., Dumic M., Auslender R., Gil-da-Silva-Lopes V.L. Reis A.Nat. Genet. 37:1345-1350(2005) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE. |
| [8] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma. |
| [9] | "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell. |
| [10] | "Role of N-end rule ubiquitin ligases UBR1 and UBR2 in regulating the leucine-mTOR signaling pathway." Kume K., Iizumi Y., Shimada M., Ito Y., Kishi T., Yamaguchi Y., Handa H. Genes Cells 15:339-349(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION. |
| [11] | "Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EMBL GenBank DDBJ | AY061884 mRNA. Translation: AAL32101.1. AK125795 mRNA. Translation: BAC86295.1. AL049843, AL136223, AL391814 Genomic DNA. Translation: CAI20399.1. AL049843, AL136223, AL391814 Genomic DNA. Translation: CAI95685.1. AL136223, AL391814 Genomic DNA. Translation: CAI19919.1. AL136223, AL049843, AL391814 Genomic DNA. Translation: CAI19920.1. AL136223, AL049843, AL391814 Genomic DNA. Translation: CAI95666.1. AL391814, AL136223 Genomic DNA. Translation: CAI14737.1. AL391814, AL136223, AL049843 Genomic DNA. Translation: CAI14738.1. AL391814, AL049843, AL136223 Genomic DNA. Translation: CAI95298.1. BC024217 mRNA. Translation: AAH24217.1. BC064512 mRNA. Translation: AAH64512.1. AB002347 mRNA. Translation: BAA20806.1. | ||||||||||||||||||
| IPI | IPI00217407. IPI00445539. IPI00640085. IPI00640329. | ||||||||||||||||||
| RefSeq | NP_001171730.1. NM_001184801.1. NP_056070.1. NM_015255.2. | ||||||||||||||||||
| UniGene | Hs.529925. | ||||||||||||||||||
3D structure databases | |||||||||||||||||||
| PDBe RCSB PDB PDBj |
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| ProteinModelPortal | Q8IWV8. | ||||||||||||||||||
| ModBase | Search... | ||||||||||||||||||
Protein-protein interaction databases | |||||||||||||||||||
| DIP | DIP-38165N. | ||||||||||||||||||
| IntAct | Q8IWV8. 7 interactions. | ||||||||||||||||||
| STRING | 9606.ENSP00000361990. | ||||||||||||||||||
PTM databases | |||||||||||||||||||
| PhosphoSite | Q8IWV8. | ||||||||||||||||||
Polymorphism databases | |||||||||||||||||||
| DMDM | 73622073. | ||||||||||||||||||
Proteomic databases | |||||||||||||||||||
| PaxDb | Q8IWV8. | ||||||||||||||||||
| PRIDE | Q8IWV8. | ||||||||||||||||||
Protocols and materials databases | |||||||||||||||||||
| StructuralBiologyKnowledgebase | Search... | ||||||||||||||||||
Genome annotation databases | |||||||||||||||||||
| Ensembl | ENST00000372883; ENSP00000361974; ENSG00000024048. ENST00000372899; ENSP00000361990; ENSG00000024048. ENST00000372901; ENSP00000361992; ENSG00000024048. ENST00000372903; ENSP00000361994; ENSG00000024048. | ||||||||||||||||||
| GeneID | 23304. | ||||||||||||||||||
| KEGG | hsa:23304. | ||||||||||||||||||
| UCSC | uc003osf.3. human. uc011dur.2. human. uc011dus.2. human. | ||||||||||||||||||
Organism-specific databases | |||||||||||||||||||
| CTD | 23304. | ||||||||||||||||||
| GeneCards | GC06P042531. | ||||||||||||||||||
| HGNC | HGNC:21289. UBR2. | ||||||||||||||||||
| HPA | HPA027869. HPA027880. | ||||||||||||||||||
| MIM | 609134. gene. | ||||||||||||||||||
| neXtProt | NX_Q8IWV8. | ||||||||||||||||||
| PharmGKB | PA128394621. | ||||||||||||||||||
| HUGE | Search... | ||||||||||||||||||
| GenAtlas | Search... | ||||||||||||||||||
Phylogenomic databases | |||||||||||||||||||
| eggNOG | NOG310244. | ||||||||||||||||||
| HOGENOM | HOG000231769. | ||||||||||||||||||
| HOVERGEN | HBG080426. | ||||||||||||||||||
| KO | K10626. | ||||||||||||||||||
| OMA | PVLPPFC. | ||||||||||||||||||
| OrthoDB | EOG42NHZG. | ||||||||||||||||||
| PhylomeDB | Q8IWV8. | ||||||||||||||||||
Enzyme and pathway databases | |||||||||||||||||||
| Reactome | REACT_6900. Immune System. | ||||||||||||||||||
| UniPathway | UPA00143. | ||||||||||||||||||
Gene expression databases | |||||||||||||||||||
| ArrayExpress | Q8IWV8. | ||||||||||||||||||
| Bgee | Q8IWV8. | ||||||||||||||||||
| CleanEx | HS_UBR2. | ||||||||||||||||||
| Genevestigator | Q8IWV8. | ||||||||||||||||||
| GermOnline | ENSG00000024048. Homo sapiens. | ||||||||||||||||||
Family and domain databases | |||||||||||||||||||
| Gene3D | 3.30.1390.10. 1 hit. | ||||||||||||||||||
| InterPro | IPR003769. ClpS_core. IPR014719. Ribosomal_L7/12_C/ClpS-like. IPR003126. Znf_N-recognin. IPR013993. Znf_N-recognin_met. IPR001841. Znf_RING. [Graphical view] | ||||||||||||||||||
| Pfam | PF02617. ClpS. 1 hit. PF02207. zf-UBR. 1 hit. [Graphical view] | ||||||||||||||||||
| SMART | SM00184. RING. 1 hit. SM00396. ZnF_UBR1. 1 hit. [Graphical view] | ||||||||||||||||||
| SUPFAM | SSF54736. Ribosomal_L7/12_C/ClpS-like. 1 hit. | ||||||||||||||||||
| PROSITE | PS00518. ZF_RING_1. False negative. PS50089. ZF_RING_2. False negative. PS51157. ZF_UBR. 1 hit. [Graphical view] | ||||||||||||||||||
| ProtoNet | Search... | ||||||||||||||||||
Other | |||||||||||||||||||
| EvolutionaryTrace | Q8IWV8. | ||||||||||||||||||
| GenomeRNAi | 23304. | ||||||||||||||||||
| NextBio | 45149. | ||||||||||||||||||
| SOURCE | Search... | ||||||||||||||||||
Entry information
| Entry name | UBR2_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q8IWV8 Secondary accession number(s): O15057 Q6ZUD0 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 6 Human chromosome 6: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PATHWAY comments Index of metabolic and biosynthesis pathways |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with
