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Q9WUB0 (HOIL1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 114. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
RanBP-type and C3HC4-type zinc finger-containing protein 1

EC=6.3.2.-
Alternative name(s):
Heme-oxidized IRP2 ubiquitin ligase 1 homolog
Short name=HOIL-1
UbcM4-interacting protein 28
Ubiquitin-conjugating enzyme 7-interacting protein 3
Gene names
Name:Rbck1
Synonyms:Rbck, Ubce7ip3, Uip28
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length508 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 ('Met-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 By similarity.

Subunit structure

Forms homodimers in vitro By similarity. Component of the LUBAC complex (linear ubiquitin chain assembly complex) which consists of SHARPIN, RBCK1 and RNF31. LUBAC has a MW of approximative 600 kDa suggesting a heteromultimeric assembly of its subunits. Interacts with beta-I-type (PRKCB1) and zeta-type protein kinase C (PRKCZ) and with UBE2L3. Isoform 1and isoform 2interact with IREB2 only in iron-rich conditions. Associates with the TNF-R1 signaling complex (TNF-RSC) in a stimulation-dependent manner. Interacts with EYA1, TAB2, TAB3, MAP3K7 TRAF6 and RIPK1. Interacts with IRF3 By similarity. Ref.7

Domain

The RanBP2-type zinc finger, also called Npl4 zinc finger (NZF), mediates binding to 'Met-1'-linked polyubiquitins.

The UBL domain mediates association with RNF31 via interaction with its UBA domain By similarity.

Post-translational modification

Auto-ubiquitinated. Auto-ubiquitination leads to degradation by the proteasome By similarity.

Phosphorylated. In vitro, phosphorylation inhibits auto-ubiquitination activity By similarity.

Disruption phenotype

Impaired TNF-alpha-mediated NF-kappa-B activation and enhanced JNK-mediated apoptosis. Ref.6

Sequence similarities

Contains 1 IBR-type zinc finger.

Contains 1 RanBP2-type zinc finger.

Contains 2 RING-type zinc fingers.

Contains 1 ubiquitin-like domain.

Sequence caution

The sequence AAD24572.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAH34555.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processUbl conjugation pathway
   DomainCoiled coil
Repeat
Zinc-finger
   LigandMetal-binding
Zinc
   Molecular functionLigase
   PTMAcetylation
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processT cell receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of NF-kappaB transcription factor activity

Inferred from electronic annotation. Source: Ensembl

negative regulation of necroptotic process

Inferred from genetic interaction PubMed 22089168. Source: MGI

positive regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from mutant phenotype Ref.6. Source: UniProtKB

positive regulation of NF-kappaB import into nucleus

Inferred from mutant phenotype Ref.6. Source: UniProtKB

positive regulation of NF-kappaB transcription factor activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of apoptotic process

Inferred from mutant phenotype Ref.6. Source: UniProtKB

positive regulation of extrinsic apoptotic signaling pathway

Inferred from mutant phenotype Ref.6. Source: MGI

proteasome-mediated ubiquitin-dependent protein catabolic process

Inferred from electronic annotation. Source: Ensembl

protein linear polyubiquitination

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentLUBAC complex

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionligase activity

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction Ref.7. Source: IntAct

ubiquitin binding

Inferred from sequence or structural similarity. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Eya1P977672EBI-6141072,EBI-1368503

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 508508RanBP-type and C3HC4-type zinc finger-containing protein 1
PRO_0000056296

Regions

Domain55 – 11965Ubiquitin-like
Zinc finger188 – 22033RanBP2-type
Zinc finger280 – 32546RING-type 1
Zinc finger360 – 40950IBR-type
Zinc finger435 – 46127RING-type 2
Region1 – 268268Interaction with TAB2 By similarity
Region1 – 218218Interaction with IRF3 By similarity
Region69 – 13163Interaction with RNF31 By similarity
Coiled coil231 – 25929 Potential

Amino acid modifications

Modified residue11N-acetylmethionine By similarity
Modified residue3281Phosphotyrosine Ref.5

Experimental info

Sequence conflict3221P → S in BAE38556. Ref.1
Sequence conflict4061H → R in BAC40440. Ref.1

Secondary structure

......... 508
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9WUB0 [UniParc].

Last modified January 15, 2008. Version 2.
Checksum: CBD3B40CD4E55180

FASTA50857,534
        10         20         30         40         50         60 
MDEKTKKAEE MALSLARAVA GGDEQAAIKY ATWLAEQRVP LRVQVKPEVS PTQDIRLCVS 

        70         80         90        100        110        120 
VEDAYMHTVT IWLTVRPDMT VASLKDMVFL DYGFPPSLQQ WVVGQRLARD QETLHSHGIR 

       130        140        150        160        170        180 
RNGDGAYLYL LSARNTSLNP QELQRQRQLR MLEDLGFKDL TLQSRGPLEP VLPKPRTNQE 

       190        200        210        220        230        240 
PGQPDAAPES PPVGWQCPGC TFINKPTRPG CEMCCRARPE TYQIPASYQP DEEERARLAG 

       250        260        270        280        290        300 
EEEALRQYQQ RKQQQQEGNY LQHVQLEQRS LVLNTEPTEC PVCYSVLAPG EAVVLRECLH 

       310        320        330        340        350        360 
TFCRECLQGT IRNSQEAEVA CPFIDSTYSC PGKLLEREIR ALLSPEDYQR FLDLGVSIAE 

       370        380        390        400        410        420 
NRSTLSYHCK TPDCRGWCFF EDDVNEFTCP VCTRVNCLLC KAIHEHMNCR EYQDDLALRA 

       430        440        450        460        470        480 
QNDVAARQTT EMLKVMLQQG EAMHCPQCRI VVQKKDGCDW IRCTVCHTEI CWVTKGPRWG 

       490        500 
PGGPGDTSGG CRCRVNGIPC HPSCQNCH 

« Hide

References

« Hide 'large scale' references
[1]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: NOD.
Tissue: Lung and Thymus.
[2]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[3]"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].
Strain: FVB/N.
Tissue: Salivary gland.
[4]"A family of structurally related RING finger proteins interacts specifically with the ubiquitin-conjugating enzyme UbcM4."
Martinez-Noel G., Niedenthal R., Tamura T., Harbers K.
FEBS Lett. 454:257-261(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 8-508.
Strain: BALB/c.
Tissue: Liver.
[5]"Quantitative time-resolved phosphoproteomic analysis of mast cell signaling."
Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R.
J. Immunol. 179:5864-5876(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-328, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Mast cell.
[6]"Involvement of linear polyubiquitylation of NEMO in NF-kappaB activation."
Tokunaga F., Sakata S., Saeki Y., Satomi Y., Kirisako T., Kamei K., Nakagawa T., Kato M., Murata S., Yamaoka S., Yamamoto M., Akira S., Takao T., Tanaka K., Iwai K.
Nat. Cell Biol. 11:123-132(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[7]"Sipl1 and Rbck1 are novel Eya1-binding proteins with a role in craniofacial development."
Landgraf K., Bollig F., Trowe M.O., Besenbeck B., Ebert C., Kruspe D., Kispert A., Hanel F., Englert C.
Mol. Cell. Biol. 30:5764-5775(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EYA1.
[8]"Specific recognition of linear ubiquitin chains by the Npl4 zinc finger (NZF) domain of the HOIL-1L subunit of the linear ubiquitin chain assembly complex."
Sato Y., Fujita H., Yoshikawa A., Yamashita M., Yamagata A., Kaiser S.E., Iwai K., Fukai S.
Proc. Natl. Acad. Sci. U.S.A. 108:20520-20525(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 192-250 IN COMPLEX WITH LINEAR DIUBIQUITIN.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK088591 mRNA. Translation: BAC40440.1.
AK166075 mRNA. Translation: BAE38556.1.
AL831735, AL928568 Genomic DNA. Translation: CAM24727.1.
AL928568, AL831735 Genomic DNA. Translation: CAM23203.1.
BC034555 mRNA. Translation: AAH34555.1. Different initiation.
AF124663 mRNA. Translation: AAD24572.1. Different initiation.
CCDSCCDS38273.1.
RefSeqNP_001077390.1. NM_001083921.1.
NP_062679.2. NM_019705.3.
UniGeneMm.182145.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3B08X-ray1.70B/E/H/K192-250[»]
3B0AX-ray1.90B/E192-250[»]
ProteinModelPortalQ9WUB0.
SMRQ9WUB0. Positions 51-139, 192-249, 276-324.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid204899. 8 interactions.
DIPDIP-59198N.
IntActQ9WUB0. 2 interactions.

PTM databases

PhosphoSiteQ9WUB0.

Proteomic databases

PaxDbQ9WUB0.
PRIDEQ9WUB0.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000028964; ENSMUSP00000028964; ENSMUSG00000027466.
ENSMUST00000109847; ENSMUSP00000105473; ENSMUSG00000027466.
GeneID24105.
KEGGmmu:24105.
UCSCuc008nfd.1. mouse.

Organism-specific databases

CTD10616.
MGIMGI:1344372. Rbck1.

Phylogenomic databases

eggNOGNOG249934.
GeneTreeENSGT00530000063620.
HOVERGENHBG061515.
InParanoidQ9WUB0.
KOK10630.
OMAQDIRLWV.
OrthoDBEOG7PGDQN.
PhylomeDBQ9WUB0.
TreeFamTF323486.

Gene expression databases

BgeeQ9WUB0.
GenevestigatorQ9WUB0.

Family and domain databases

Gene3D3.30.40.10. 1 hit.
InterProIPR000626. Ubiquitin-like.
IPR029071. Ubiquitin-rel_dom.
IPR002867. Znf_C6HC.
IPR001876. Znf_RanBP2.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PfamPF01485. IBR. 2 hits.
PF13639. zf-RING_2. 1 hit.
[Graphical view]
SMARTSM00184. RING. 1 hit.
SM00547. ZnF_RBZ. 1 hit.
[Graphical view]
SUPFAMSSF54236. SSF54236. 1 hit.
PROSITEPS50053. UBIQUITIN_2. 1 hit.
PS01358. ZF_RANBP2_1. 1 hit.
PS50199. ZF_RANBP2_2. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSRBCK1. mouse.
NextBio304117.
PROQ9WUB0.
SOURCESearch...

Entry information

Entry nameHOIL1_MOUSE
AccessionPrimary (citable) accession number: Q9WUB0
Secondary accession number(s): A2ANR4, Q3TM86, Q8C2I0
Entry history
Integrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: January 15, 2008
Last modified: July 9, 2014
This is version 114 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot