UniProt Accession

 HOIL1_HUMAN; Q9BYM8; O95623; Q86SL2; Q96BS3; Q9BYM9 

Genbank Protein ID

 U67322; AB107766; AL121747; AL121747; BC000983; BC015219 

Genbank Nucleotide ID

 AAD00162.1; BAC75409.1; CAC17516.1; CAC28312.2; AAH15219.2 

Protein Name

 RanBP-type and C3HC4-type zinc finger-containing protein 1 

Protein Synonyms/Alias

 HBV-associated factor 4; Heme-oxidized IRP2 ubiquitin ligase 1; HOIL-1; Hepatitis B virus X-associated protein 4; RING finger protein 54; Ubiquitin-conjugating enzyme 7-interacting protein 3 

Gene Name

 RBCK1 

Gene Synonyms/Alias

 C20orf18; RNF54; UBCE7IP3; XAP3; XAP4 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
29	GDEQVAMKCAIWLAE	ubiquitination	[1, 2]
158	MLEDLGFKDLTLQPR	ubiquitination	[1, 2, 3, 4, 5, 6]
174	PLEPGPPKPGVPQEP	ubiquitination	[2, 3, 4, 5, 6]
254	LRQYQQRKQQQQEGN	ubiquitination	[2, 3, 4, 6]
335	NTYSCSGKLLEREIK	ubiquitination	[2]
342	KLLEREIKALLTPED	ubiquitination	[2, 3, 6]
412	IHEQMNCKEYQEDLA	ubiquitination	[2]

Reference

 [1] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [4] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [5] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [6] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789] 

Functional Description

 E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, such as UBE2L3/UBCM4, and then transfers it to substrates. Functions as an E3 ligase for oxidized IREB2 and both heme and oxygen are necessary for IREB2 ubiquitination. Promotes ubiquitination of TAB2 and IRF3 and their degradation by the proteasome. Component of the LUBAC complex which conjugates linear ('M-1'-linked) polyubiquitin chains to substrates and plays a key role in NF- kappa-B activation and regulation of inflammation. LUBAC conjugates linear polyubiquitin to IKBKG and RIPK1 and is involved in activation of the canonical NF-kappa-B and the JNK signaling pathways. Linear ubiquitination mediated by the LUBAC complex interferes with TNF-induced cell death and thereby prevents inflammation. LUBAC is proposed to be recruited to the TNF-R1 signaling complex (TNF-RSC) following polyubiquitination of TNF- RSC components by BIRC2 and/or BIRC3 and to conjugate linear polyubiquitin to IKBKG and possibly other components contributing to the stability of the complex. Together with FAM105B/otulin, the LUBAC complex regulates the canonical Wnt signaling during angiogenesis. Binds polyubiquitin of different linkage types. 

Sequence Annotation

 DOMAIN 55 119 Ubiquitin-like.
 ZN_FING 193 222 RanBP2-type.
 ZN_FING 282 327 RING-type 1.
 ZN_FING 362 411 IBR-type.
 ZN_FING 437 463 RING-type 2.
 REGION 1 270 Interaction with TAB2.
 REGION 1 220 Interaction with IRF3.
 REGION 69 131 Interaction with RNF31.
 MOD_RES 330 330 Phosphotyrosine.  

Keyword

 3D-structure; Alternative splicing; Coiled coil; Complete proteome; Host-virus interaction; Ligase; Metal-binding; Phosphoprotein; Reference proteome; Repeat; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 510 AA 

Protein Sequence

Gene Ontology

 GO:0071797; C:LUBAC complex; IDA:UniProtKB.
 GO:0003677; F:DNA binding; IEA:InterPro.
 GO:0043130; F:ubiquitin binding; IDA:UniProtKB.
 GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
 GO:0043065; P:positive regulation of apoptotic process; IEA:Compara.
 GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IDA:UniProtKB.
 GO:0042346; P:positive regulation of NF-kappaB import into nucleus; IEA:Compara.
 GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
 GO:0043161; P:proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
 GO:0097039; P:protein linear polyubiquitination; IDA:UniProtKB.
 GO:0050852; P:T cell receptor signaling pathway; IDA:UniProtKB.
 GO:0006351; P:transcription, DNA-dependent; IEA:InterPro.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 

Interpro

 IPR026261; RBCK1.
 IPR019955; Ubiquitin_supergroup.
 IPR002867; Znf_C6HC.
 IPR001876; Znf_RanBP2.
 IPR001841; Znf_RING.
 IPR013083; Znf_RING/FYVE/PHD.
 IPR017907; Znf_RING_CS. 

Pfam

 PF01485; IBR
 PF13639; zf-RING_2 

SMART

 SM00184; RING
 SM00547; ZnF_RBZ 

PROSITE

 PS50053; UBIQUITIN_2
 PS50119; ZF_BBOX
 PS01358; ZF_RANBP2_1
 PS50199; ZF_RANBP2_2
 PS00518; ZF_RING_1
 PS50089; ZF_RING_2 

PRINTS