Q62921 (HOIL1_RAT) 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
Protein kinase C-binding protein beta-15
RBCC protein interacting with PKC
Ubiquitin-conjugating enzyme 7-interacting protein 3

Gene names

Name:	Rbck1
Synonyms:	Pkcbpb15, Rbck, Ubce7ip3

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [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 › Rattus

Protein attributes

Sequence length	508 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. 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. Ref.3
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. Interacts 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.
Tissue specificity	Widely expressed.
Domain	The RanBP2-type zinc finger, also called Npl4 zinc finger (NZF), mediates binding to 'M-1'-linked polyubiquitins By similarity. 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. Phosphorylated. In vitro, phosphorylation inhibits auto-ubiquitination activity. Ref.3
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 AAC72243.1 differs from that shown. Reason: Erroneous initiation. The sequence BAA33957.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Coding sequence diversity	Alternative splicing
Domain	Coiled coil Repeat Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay Ref.1. Source: RGD 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	double-stranded DNA binding Inferred from direct assay Ref.1. Source: RGD ubiquitin binding Inferred from sequence or structural similarity. Source: UniProtKB ubiquitin-protein ligase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q62921-1)

Also known as: RBCK1;

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: Q62921-2)

Also known as: RBCK2;

The sequence of this isoform differs from the canonical sequence as follows:
     251-270: RKQQQQEGNYLQHVQLEQRS → GVPAGYHPKQPGGGGILPLH
     271-508: Missing.

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_0000056297
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 – 260	30	Potential
Amino acid modifications
	Modified residue	328	1	Phosphotyrosine By similarity
Natural variations
	Alternative sequence	251 – 270	20	RKQQQ…LEQRS → GVPAGYHPKQPGGGGILPLH in isoform 2.		VSP_005769
	Alternative sequence	271 – 508	238	Missing in isoform 2.		VSP_005770
Experimental info
	Mutagenesis	303	1	C → G: Greatly reduces auto-ubiquitination. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (RBCK1) [UniParc]. Last modified January 15, 2008. Version 3. Checksum: D2E407B254E9FDA6	FASTA	508	57,685
	10 20 30 40 50 60 MDEKTKKAEE MALSLARAVT GGDEQAAIKY ATWLAEQKVP LRVQVKPEVS PTQDIRLCVS 70 80 90 100 110 120 VEDAYMHTVT IWLTVRPDMT VASLKDMVFL DYGFPPSLQQ WVVGQRLARD QETLHSHGIR 130 140 150 160 170 180 RNGDSAYLYL LSARNTSLNP QELQRQRQLR MLEDLGFKDL TLQPRGPLEP VLPKPRTHQE 190 200 210 220 230 240 TGQPDAAPES PPVGWQCPGC TFINKPTRPG CEMCCRARPE AYQIPASYQP DEEERARLAG 250 260 270 280 290 300 EEEALRQYEQ RKQQQQEGNY LQHVQLEQRS LVLNTEPAEC PVCYSVLAPG EAVVLRECLH 310 320 330 340 350 360 TFCRECLQGT IRNSQEAEVS CPFIDNTYSC PGKLLEREIR ALLSPEDYQR FLDLGVSIAE 370 380 390 400 410 420 NRSTLSYHCK TPDCRGWCFF EDDVNEFTCP VCTRVNCLLC KAIHERMNCR EYQDDLAHRA 430 440 450 460 470 480 RNDVAAQQTT EMLRVMLQQG EAMYCPQCRI VVQKKDGCDW IRCTVCHTEI CWVTKGPRWG 490 500 PGGPGDTSGG CRCRVNGIPC HPSCQNCH
	Isoform 2 (RBCK2) [UniParc]. Checksum: D689295BBC4ED744	FASTA	270	30,278
	10 20 30 40 50 60 MDEKTKKAEE MALSLARAVT GGDEQAAIKY ATWLAEQKVP LRVQVKPEVS PTQDIRLCVS 70 80 90 100 110 120 VEDAYMHTVT IWLTVRPDMT VASLKDMVFL DYGFPPSLQQ WVVGQRLARD QETLHSHGIR 130 140 150 160 170 180 RNGDSAYLYL LSARNTSLNP QELQRQRQLR MLEDLGFKDL TLQPRGPLEP VLPKPRTHQE 190 200 210 220 230 240 TGQPDAAPES PPVGWQCPGC TFINKPTRPG CEMCCRARPE AYQIPASYQP DEEERARLAG 250 260 270 EEEALRQYEQ GVPAGYHPKQ PGGGGILPLH

References

[1]	"Molecular cloning and characterization of a novel protein kinase C-interacting protein with structural motifs related to RBCC family proteins." Tokunaga C., Kuroda S.I., Tatematsu K., Nakagawa N., Ono Y., Kikkawa U. Biochem. Biophys. Res. Commun. 244:353-359(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION. Strain: Sprague-Dawley. Tissue: Brain.
[2]	"Molecular cloning and characterization of RBCK2, a splicing variant of a RBCC family protein, RBCK1." Tokunaga C., Takematsu K., Kuroda S.I., Nakagawa N., Kikkawa U. FEBS Lett. 435:11-15(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 2). Tissue: Brain.
[3]	"Identification of ubiquitin ligase activity of RBCK1 and its inhibition by splice variant RBCK2 and protein kinase Cbeta." Tatematsu K., Yoshimoto N., Okajima T., Tanizawa K., Kuroda S. J. Biol. Chem. 283:11575-11585(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, AUTO-UBIQUITINATION, PHOSPHORYLATION, RING-TYPE ZINC FINGERS, MUTAGENESIS OF CYS-303.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U48248 mRNA. Translation: AAC72243.1. Different initiation. AB007133 Genomic DNA. Translation: BAA33953.1. AB011369 mRNA. Translation: BAA33957.1. Different initiation.
IPI	IPI00210189. IPI00231840.
PIR	JC5983.
RefSeq	NP_068532.2. NM_021764.1.
UniGene	Rn.37161.
3D structure databases
ProteinModelPortal	Q62921.
SMR	Q62921. Positions 192-230.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-7261390.
PTM databases
PhosphoSite	Q62921.
Proteomic databases
PaxDb	Q62921.
PRIDE	Q62921.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	60383.
KEGG	rno:60383.
UCSC	RGD:708404. rat.
Organism-specific databases
CTD	10616.
RGD	708404. Rbck1.
Phylogenomic databases
eggNOG	NOG249934.
HOVERGEN	HBG061515.
InParanoid	Q62921.
KO	K10630.
OrthoDB	EOG4MW866.
Gene expression databases
ArrayExpress	Q62921.
Genevestigator	Q62921.
GermOnline	ENSRNOG00000006695. Rattus norvegicus.
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
NextBio	612079.

Entry information

Entry name

HOIL1_RAT

Accession

Primary (citable) accession number: Q62921
Secondary accession number(s): Q9QWN4, Q9Z334

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2001
Last sequence update:	January 15, 2008
Last modified:	April 3, 2013
This is version 103 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program