Q9WUB0 (HOIL1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	508 AA.
Sequence status	Complete.
Protein existence	Evidence 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 ('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. 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 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 similarity. Ref.8
Domain	The RanBP2-type zinc finger, also called Npl4 zinc finger (NZF), mediates binding to 'M-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.7
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 process	Ubl conjugation pathway
Domain	Coiled coil Repeat Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	T cell receptor signaling pathway Inferred from electronic annotation. Source: Compara negative regulation of NF-kappaB transcription factor activity Inferred from electronic annotation. Source: Compara positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from mutant phenotype Ref.7. Source: UniProtKB positive regulation of NF-kappaB import into nucleus Inferred from mutant phenotype Ref.7. Source: UniProtKB positive regulation of NF-kappaB transcription factor activity Inferred from electronic annotation. Source: Compara positive regulation of apoptotic process Inferred from mutant phenotype Ref.7. Source: UniProtKB proteasomal ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: Compara protein linear polyubiquitination Inferred from sequence or structural similarity. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: InterPro
Cellular_component	LUBAC complex Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	DNA binding Inferred from electronic annotation. Source: InterPro ubiquitin binding Inferred from sequence or structural similarity. Source: UniProtKB ubiquitin-protein ligase activity Inferred from electronic annotation. Source: Compara zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Eya1	P97767	2	EBI-6141072,EBI-1368503

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 508

508

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

PRO_0000056296

Regions

Domain

55 – 119

65

Ubiquitin-like

Zinc finger

188 – 220

33

RanBP2-type

Zinc finger

280 – 325

46

RING-type 1

Zinc finger

360 – 409

50

IBR-type

Zinc finger

435 – 461

27

RING-type 2

Region

1 – 268

268

Interaction with TAB2 By similarity

Region

1 – 218

218

Interaction with IRF3 By similarity

Region

69 – 131

63

Interaction with RNF31 By similarity

Coiled coil

231 – 259

29

Potential

Amino acid modifications

Modified residue

328

1

Phosphotyrosine Ref.5 Ref.6

Experimental info

Sequence conflict

322

1

P → S in BAE38556. Ref.1

Sequence conflict

406

1

H → R in BAC40440. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

508

Helix Strand Turn

Details...

Beta strand

194 – 196

3

Turn

198 – 200

3

Turn

212 – 214

3

Helix

232 – 245

14

Sequences

	Sequence		Length	Mass (Da)
	Q9WUB0 [UniParc]. Last modified January 15, 2008. Version 2. Checksum: CBD3B40CD4E55180	FASTA	508	57,534
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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, MASS SPECTROMETRY. Tissue: Mast cell.
[6]	"Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain." Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P. J. Proteome Res. 7:311-318(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-328, MASS SPECTROMETRY. Tissue: Brain.
[7]	"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.
[8]	"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.
[9]	"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.

IPI

IPI00322839.

RefSeq

NP_001077390.1. NM_001083921.1.
NP_062679.2. NM_019705.3.

UniGene

Mm.182145.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3B08	X-ray	1.70	B/E/H/K	192-250	[»]
3B0A	X-ray	1.90	B/E	192-250	[»]

ProteinModelPortal

Q9WUB0.

SMR

Q9WUB0. Positions 51-139, 192-249.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-59198N.

IntAct

Q9WUB0. 2 interactions.

PTM databases

PhosphoSite

Q9WUB0.

Proteomic databases

PaxDb

Q9WUB0.

PRIDE

Q9WUB0.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000028964; ENSMUSP00000028964; ENSMUSG00000027466.
ENSMUST00000109847; ENSMUSP00000105473; ENSMUSG00000027466.

GeneID

24105.

KEGG

mmu:24105.

UCSC

uc008nfd.1. mouse.

Organism-specific databases

CTD

10616.

MGI

MGI:1344372. Rbck1.

Phylogenomic databases

eggNOG

NOG249934.

GeneTree

ENSGT00530000063620.

HOVERGEN

HBG061515.

InParanoid

Q9WUB0.

KO

K10630.

OMA

QDIRLWV.

OrthoDB

EOG4MW866.

Gene expression databases

ArrayExpress

Q9WUB0.

Bgee

Q9WUB0.

Genevestigator

Q9WUB0.

GermOnline

ENSMUSG00000027466. Mus musculus.

Family and domain databases

Gene3D

3.30.40.10. 1 hit.

InterPro

IPR026261. RBCK1.
IPR019955. Ubiquitin_supergroup.
IPR002867. Znf_C6HC.
IPR001876. Znf_RanBP2.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]

PANTHER

PTHR22770:SF10. PTHR22770:SF10. 1 hit.

Pfam

PF01485. IBR. 2 hits.
PF13639. zf-RING_2. 1 hit.
[Graphical view]

SMART

SM00184. RING. 1 hit.
SM00547. ZnF_RBZ. 1 hit.
[Graphical view]

PROSITE

PS50053. UBIQUITIN_2. 1 hit.
PS50119. ZF_BBOX. False negative.
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]

ProtoNet

Search...

Other

ChiTaRS

RBCK1. mouse.

NextBio

304117.

SOURCE

Search...

Entry information

Entry name

HOIL1_MOUSE

Accession

Primary (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:	May 1, 2013
This is version 102 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program