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UniProtKB - Q9BYM8 (HOIL1_HUMAN)

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Protein

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

Gene

RBCK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.9 Publications

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri193 – 222RanBP2-typePROSITE-ProRule annotationAdd BLAST30
Zinc fingeri282 – 327RING-type 1PROSITE-ProRule annotationAdd BLAST46
Zinc fingeri362 – 411IBR-typeAdd BLAST50
Zinc fingeri437 – 463RING-type 2PROSITE-ProRule annotationAdd BLAST27

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • ubiquitin binding Source: UniProtKB
  • ubiquitin-protein transferase activity Source: UniProtKB
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionTransferase
Biological processHost-virus interaction, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-5357905 Regulation of TNFR1 signaling
R-HSA-5357956 TNFR1-induced NFkappaB signaling pathway
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SIGNORiQ9BYM8

Names & Taxonomyi

Protein namesi
Recommended name:
RanBP-type and C3HC4-type zinc finger-containing protein 1 (EC:2.3.2.27)
Alternative name(s):
HBV-associated factor 4
Heme-oxidized IRP2 ubiquitin ligase 1
Short name:
HOIL-1
Hepatitis B virus X-associated protein 4
RING finger protein 54
RING-type E3 ubiquitin transferase HOIL-1Curated
Ubiquitin-conjugating enzyme 7-interacting protein 3
Gene namesi
Name:RBCK1
Synonyms:C20orf18, RNF54, UBCE7IP3, XAP3, XAP4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

EuPathDBiHostDB:ENSG00000125826.19
HGNCiHGNC:15864 RBCK1
MIMi610924 gene
neXtProtiNX_Q9BYM8

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Involvement in diseasei

Polyglucosan body myopathy 1 with or without immunodeficiency (PGBM1)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease characterized by polyglucosan storage myopathy associated with early-onset progressive muscle weakness and progressive dilated cardiomyopathy, which may necessitate cardiac transplant in severe cases. Some patients present with severe immunodeficiency, invasive bacterial infections and chronic autoinflammation.
See also OMIM:615895
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07138518A → P in PGBM1. 1 Publication1
Natural variantiVAR_071386387N → S in PGBM1. 1 PublicationCorresponds to variant dbSNP:rs566912235EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi282C → S: Binds to IREB2 in iron-treated cells. Reversed iron-induced down-regulation of IREB2. No ubiquitination of heme-loaded IREB2; when associated with S-285. 1 Publication1
Mutagenesisi285C → S: Binds to IREB2 in iron-treated cells. Reversed iron-induced down-regulation of IREB2. No ubiquitination of heme-loaded IREB2; when associated with S-282. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi10616
MalaCardsiRBCK1
MIMi615895 phenotype
OpenTargetsiENSG00000125826
Orphaneti329173 Autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis
397937 Polyglucosan body myopathy
PharmGKBiPA25723

Polymorphism and mutation databases

BioMutaiRBCK1
DMDMi166214993

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000562951 – 510RanBP-type and C3HC4-type zinc finger-containing protein 1Add BLAST510

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei50PhosphoserineCombined sources1
Modified residuei330PhosphotyrosineCombined sources1

Post-translational modificationi

Auto-ubiquitinated. Auto-ubiquitination leads to degradation by the proteasome (By similarity).By similarity
Phosphorylated. In vitro, phosphorylation inhibits auto-ubiquitination activity (By similarity).By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9BYM8
MaxQBiQ9BYM8
PaxDbiQ9BYM8
PeptideAtlasiQ9BYM8
PRIDEiQ9BYM8
ProteomicsDBi79667
79668 [Q9BYM8-3]
79669 [Q9BYM8-4]

PTM databases

iPTMnetiQ9BYM8
PhosphoSitePlusiQ9BYM8

Expressioni

Inductioni

By viral transfection.1 Publication

Gene expression databases

BgeeiENSG00000125826
CleanExiHS_RBCK1
ExpressionAtlasiQ9BYM8 baseline and differential
GenevisibleiQ9BYM8 HS

Interactioni

Subunit structurei

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 approximately 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. Interacts with PRKCH. Isoform 1 and isoform 2 interact 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 similarity9 Publications
(Microbial infection) Interacts with hepatitis B virus/HBV protein HBx; this interaction is required to activate transcription of the viral genome.1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • ubiquitin binding Source: UniProtKB
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi115862, 88 interactors
CORUMiQ9BYM8
DIPiDIP-47737N
IntActiQ9BYM8, 54 interactors
MINTiQ9BYM8
STRINGi9606.ENSP00000348632

Structurei

Secondary structure

1510
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi55 – 66Combined sources12
Beta strandi69 – 75Combined sources7
Helixi81 – 92Combined sources12
Helixi96 – 98Combined sources3
Beta strandi99 – 103Combined sources5
Beta strandi106 – 108Combined sources3
Helixi115 – 117Combined sources3
Beta strandi125 – 130Combined sources6
Beta strandi194 – 197Combined sources4
Turni200 – 202Combined sources3
Beta strandi214 – 216Combined sources3

3D structure databases

ProteinModelPortaliQ9BYM8
SMRiQ9BYM8
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9BYM8

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini55 – 119Ubiquitin-likePROSITE-ProRule annotationAdd BLAST65

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 270Interaction with TAB21 PublicationAdd BLAST270
Regioni1 – 220Interaction with IRF31 PublicationAdd BLAST220
Regioni69 – 131Interaction with RNF311 PublicationAdd BLAST63

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili233 – 261Sequence analysisAdd BLAST29

Domaini

The RanBP2-type zinc finger, also called Npl4 zinc finger (NZF), mediates binding to 'Met-1'-linked polyubiquitins.By similarity
The UBL domain mediates association with RNF31 via interaction with its UBA domain.1 Publication

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri193 – 222RanBP2-typePROSITE-ProRule annotationAdd BLAST30
Zinc fingeri282 – 327RING-type 1PROSITE-ProRule annotationAdd BLAST46
Zinc fingeri362 – 411IBR-typeAdd BLAST50
Zinc fingeri437 – 463RING-type 2PROSITE-ProRule annotationAdd BLAST27

Keywords - Domaini

Coiled coil, Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1815 Eukaryota
ENOG410XP9Y LUCA
GeneTreeiENSGT00530000063620
HOVERGENiHBG061515
InParanoidiQ9BYM8
KOiK10630
OMAiQGEAMRC
OrthoDBiEOG091G04QK
PhylomeDBiQ9BYM8
TreeFamiTF323486

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR002867 IBR_dom
IPR026261 RBCK1
IPR029071 Ubiquitin-like_domsf
IPR000626 Ubiquitin_dom
IPR027370 Znf-RING_LisH
IPR001876 Znf_RanBP2
IPR036443 Znf_RanBP2_sf
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR017907 Znf_RING_CS
PANTHERiPTHR22770:SF35 PTHR22770:SF35, 1 hit
PfamiView protein in Pfam
PF01485 IBR, 1 hit
PF13445 zf-RING_UBOX, 1 hit
SMARTiView protein in SMART
SM00184 RING, 1 hit
SM00547 ZnF_RBZ, 1 hit
SUPFAMiSSF54236 SSF54236, 1 hit
SSF90209 SSF90209, 1 hit
PROSITEiView protein in PROSITE
PS50053 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

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Experimental confirmation may be lacking for some isoforms.
Isoform 1 (identifier: Q9BYM8-1) [UniParc]FASTAAdd to basket
Also known as: HOIL-1L

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.

« Hide

        10         20         30         40         50
MDEKTKKAEE MALSLTRAVA GGDEQVAMKC AIWLAEQRVP LSVQLKPEVS 
        60         70         80         90        100
PTQDIRLWVS VEDAQMHTVT IWLTVRPDMT VASLKDMVFL DYGFPPVLQQ 
       110        120        130        140        150
WVIGQRLARD QETLHSHGVR QNGDSAYLYL LSARNTSLNP QELQRERQLR 
       160        170        180        190        200
MLEDLGFKDL TLQPRGPLEP GPPKPGVPQE PGRGQPDAVP EPPPVGWQCP 
       210        220        230        240        250
GCTFINKPTR PGCEMCCRAR PEAYQVPASY QPDEEERARL AGEEEALRQY 
       260        270        280        290        300
QQRKQQQQEG NYLQHVQLDQ RSLVLNTEPA ECPVCYSVLA PGEAVVLREC 
       310        320        330        340        350
LHTFCRECLQ GTIRNSQEAE VSCPFIDNTY SCSGKLLERE IKALLTPEDY 
       360        370        380        390        400
QRFLDLGISI AENRSAFSYH CKTPDCKGWC FFEDDVNEFT CPVCFHVNCL 
       410        420        430        440        450
LCKAIHEQMN CKEYQEDLAL RAQNDVAARQ TTEMLKVMLQ QGEAMRCPQC 
       460        470        480        490        500
QIVVQKKDGC DWIRCTVCHT EICWVTKGPR WGPGGPGDTS GGCRCRVNGI 
       510
PCHPSCQNCH
Length:510
Mass (Da):57,572
Last modified:January 15, 2008 - v2
Checksum:iC6EF957B1F152FF2
GO
Isoform 2 (identifier: Q9BYM8-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-55: MDEKTKKAEEMALSLTRAVAGGDEQVAMKCAIWLAEQRVPLSVQLKPEVSPTQDI → MGTATPDGREDQE

Show »
Length:468
Mass (Da):52,936
Checksum:i5B4420D28508EE16
GO
Isoform 3 (identifier: Q9BYM8-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-55: MDEKTKKAEEMALSLTRAVAGGDEQVAMKCAIWLAEQRVPLSVQLKPEVSPTQDI → MGTATPDGREDQE
     253-272: RKQQQQEGNYLQHVQLDQRS → GVPAGHHPQQPGGGGLLPLH
     273-510: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:230
Mass (Da):25,654
Checksum:i8EDB1C28B96BF8D4
GO

Sequence cautioni

The sequence AAH15219 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti236E → D in BAC75409 (PubMed:12629548).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07138518A → P in PGBM1. 1 Publication1
Natural variantiVAR_071386387N → S in PGBM1. 1 PublicationCorresponds to variant dbSNP:rs566912235EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0057661 – 55MDEKT…PTQDI → MGTATPDGREDQE in isoform 2 and isoform 3. 3 PublicationsAdd BLAST55
Alternative sequenceiVSP_005767253 – 272RKQQQ…LDQRS → GVPAGHHPQQPGGGGLLPLH in isoform 3. 1 PublicationAdd BLAST20
Alternative sequenceiVSP_005768273 – 510Missing in isoform 3. 1 PublicationAdd BLAST238

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U67322 mRNA Translation: AAD00162.1
AB107766 mRNA Translation: BAC75409.1
AL121747 Genomic DNA No translation available.
BC000983 mRNA No translation available.
BC015219 mRNA Translation: AAH15219.2 Different initiation.
CCDSiCCDS12998.1 [Q9BYM8-3]
CCDS13000.2 [Q9BYM8-1]
RefSeqiNP_006453.1, NM_006462.5 [Q9BYM8-3]
NP_112506.2, NM_031229.3 [Q9BYM8-1]
UniGeneiHs.247280
Hs.29546

Genome annotation databases

EnsembliENST00000353660; ENSP00000254960; ENSG00000125826 [Q9BYM8-3]
ENST00000356286; ENSP00000348632; ENSG00000125826 [Q9BYM8-1]
GeneIDi10616
KEGGihsa:10616
UCSCiuc002wdp.5 human [Q9BYM8-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiHOIL1_HUMAN
AccessioniPrimary (citable) accession number: Q9BYM8
Secondary accession number(s): O95623
, Q86SL2, Q96BS3, Q9BYM9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: January 15, 2008
Last modified: July 18, 2018
This is version 178 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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