HOIL1_RAT
ID HOIL1_RAT Reviewed; 508 AA.
AC Q62921; Q9QWN4; Q9Z334;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 3.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=RanBP-type and C3HC4-type zinc finger-containing protein 1;
DE EC=2.3.2.31 {ECO:0000305|PubMed:18303026};
DE AltName: Full=Heme-oxidized IRP2 ubiquitin ligase 1 homolog;
DE Short=HOIL-1;
DE AltName: Full=Protein kinase C-binding protein beta-15;
DE AltName: Full=RBCC protein interacting with PKC {ECO:0000303|PubMed:9514928};
DE AltName: Full=RING-type E3 ubiquitin transferase HOIL-1 {ECO:0000305};
DE AltName: Full=Ubiquitin-conjugating enzyme 7-interacting protein 3;
GN Name=Rbck1; Synonyms=Pkcbpb15, Rbck, Ubce7ip3;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH PRKCB1 AND PRKCZ,
RP AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=9514928; DOI=10.1006/bbrc.1998.8270;
RA Tokunaga C., Kuroda S.I., Tatematsu K., Nakagawa N., Ono Y., Kikkawa U.;
RT "Molecular cloning and characterization of a novel protein kinase C-
RT interacting protein with structural motifs related to RBCC family
RT proteins.";
RL Biochem. Biophys. Res. Commun. 244:353-359(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=9755849; DOI=10.1016/s0014-5793(98)01029-1;
RA Tokunaga C., Takematsu K., Kuroda S.I., Nakagawa N., Kikkawa U.;
RT "Molecular cloning and characterization of RBCK2, a splicing variant of a
RT RBCC family protein, RBCK1.";
RL FEBS Lett. 435:11-15(1998).
RN [3]
RP FUNCTION, AUTOUBIQUITINATION, PHOSPHORYLATION, RING-TYPE ZINC FINGERS, AND
RP MUTAGENESIS OF CYS-303.
RX PubMed=18303026; DOI=10.1074/jbc.m706961200;
RA Tatematsu K., Yoshimoto N., Okajima T., Tanizawa K., Kuroda S.;
RT "Identification of ubiquitin ligase activity of RBCK1 and its inhibition by
RT splice variant RBCK2 and protein kinase Cbeta.";
RL J. Biol. Chem. 283:11575-11585(2008).
CC -!- FUNCTION: E3 ubiquitin-protein ligase, which accepts ubiquitin from
CC specific E2 ubiquitin-conjugating enzymes, such as UBE2L3/UBCM4, and
CC then transfers it to substrates (By similarity). Functions as an E3
CC ligase for oxidized IREB2 and both heme and oxygen are necessary for
CC IREB2 ubiquitination (By similarity). Promotes ubiquitination of TAB2
CC and IRF3 and their degradation by the proteasome (PubMed:18303026).
CC Component of the LUBAC complex which conjugates linear ('Met-1'-linked)
CC polyubiquitin chains to substrates and plays a key role in NF-kappa-B
CC activation and regulation of inflammation (By similarity). LUBAC
CC conjugates linear polyubiquitin to IKBKG and RIPK1 and is involved in
CC activation of the canonical NF-kappa-B and the JNK signaling pathways
CC (By similarity). Linear ubiquitination mediated by the LUBAC complex
CC interferes with TNF-induced cell death and thereby prevents
CC inflammation (By similarity). LUBAC is recruited to the TNF-R1
CC signaling complex (TNF-RSC) following polyubiquitination of TNF-RSC
CC components by BIRC2 and/or BIRC3 and to conjugate linear polyubiquitin
CC to IKBKG and possibly other components contributing to the stability of
CC the complex (By similarity). The LUBAC complex is also involved in
CC innate immunity by conjugating linear polyubiquitin chains at the
CC surface of bacteria invading the cytosol to form the ubiquitin coat
CC surrounding bacteria (By similarity). LUBAC is not able to initiate
CC formation of the bacterial ubiquitin coat, and can only promote
CC formation of linear polyubiquitins on pre-existing ubiquitin (By
CC similarity). The bacterial ubiquitin coat acts as an 'eat-me' signal
CC for xenophagy and promotes NF-kappa-B activation (By similarity).
CC Together with OTULIN, the LUBAC complex regulates the canonical Wnt
CC signaling during angiogenesis (By similarity). Binds polyubiquitin of
CC different linkage types (By similarity). {ECO:0000250|UniProtKB:Q9BYM8,
CC ECO:0000269|PubMed:18303026}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + [acceptor protein]-N(6)-ubiquitinyl-L-lysine.;
CC EC=2.3.2.31; Evidence={ECO:0000305|PubMed:18303026};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000305|PubMed:18303026}.
CC -!- SUBUNIT: Component of the LUBAC complex (linear ubiquitin chain
CC assembly complex) which consists of SHARPIN, RBCK1 and RNF31 (By
CC similarity). LUBAC has a MW of approximately 600 kDa suggesting a
CC heteromultimeric assembly of its subunits (By similarity). Interacts
CC with beta-I-type (PRKCB1) and zeta-type protein kinase C (PRKCZ)
CC (PubMed:9514928). Interacts with UBE2L3 (By similarity). Interacts with
CC IREB2 only in iron-rich conditions (By similarity). Associates with the
CC TNF-R1 signaling complex (TNF-RSC) in a stimulation-dependent manner
CC (By similarity). Interacts with EYA1, TAB2, TAB3, MAP3K7 TRAF6 and
CC RIPK1. Interacts with IRF3 (By similarity).
CC {ECO:0000250|UniProtKB:Q9BYM8, ECO:0000250|UniProtKB:Q9WUB0,
CC ECO:0000269|PubMed:9514928}.
CC -!- INTERACTION:
CC Q62921; P55036: PSMD4; Xeno; NbExp=3; IntAct=EBI-7266339, EBI-359318;
CC Q62921; P0CG48: UBC; Xeno; NbExp=2; IntAct=EBI-7266339, EBI-3390054;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=RBCK1;
CC IsoId=Q62921-1; Sequence=Displayed;
CC Name=2; Synonyms=RBCK2;
CC IsoId=Q62921-2; Sequence=VSP_005769, VSP_005770;
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:9514928}.
CC -!- DOMAIN: The RanBP2-type zinc finger, also called Npl4 zinc finger
CC (NZF), mediates binding to 'Met-1'-linked polyubiquitins.
CC {ECO:0000250|UniProtKB:Q9WUB0}.
CC -!- DOMAIN: The UBL domain mediates association with RNF31 via interaction
CC with its UBA domain. {ECO:0000250|UniProtKB:Q9BYM8}.
CC -!- PTM: Auto-ubiquitinated. Auto-ubiquitination leads to degradation by
CC the proteasome. {ECO:0000269|PubMed:18303026}.
CC -!- PTM: Phosphorylated. In vitro, phosphorylation inhibits auto-
CC ubiquitination activity. {ECO:0000269|PubMed:18303026}.
CC -!- SIMILARITY: Belongs to the RBR family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC72243.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAA33957.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; U48248; AAC72243.1; ALT_INIT; mRNA.
DR EMBL; AB007133; BAA33953.1; -; Genomic_DNA.
DR EMBL; AB011369; BAA33957.1; ALT_INIT; mRNA.
DR PIR; JC5983; JC5983.
DR RefSeq; NP_068532.2; NM_021764.1. [Q62921-1]
DR AlphaFoldDB; Q62921; -.
DR SMR; Q62921; -.
DR BioGRID; 248810; 4.
DR IntAct; Q62921; 2.
DR MINT; Q62921; -.
DR STRING; 10116.ENSRNOP00000047637; -.
DR iPTMnet; Q62921; -.
DR PhosphoSitePlus; Q62921; -.
DR PaxDb; Q62921; -.
DR GeneID; 60383; -.
DR KEGG; rno:60383; -.
DR UCSC; RGD:708404; rat. [Q62921-1]
DR CTD; 10616; -.
DR RGD; 708404; Rbck1.
DR eggNOG; KOG1815; Eukaryota.
DR InParanoid; Q62921; -.
DR OrthoDB; 1086223at2759; -.
DR PhylomeDB; Q62921; -.
DR BRENDA; 2.3.2.27; 5301.
DR Reactome; R-RNO-5357905; Regulation of TNFR1 signaling.
DR Reactome; R-RNO-5357956; TNFR1-induced NFkappaB signaling pathway.
DR Reactome; R-RNO-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR PRO; PR:Q62921; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0071797; C:LUBAC complex; ISS:UniProtKB.
DR GO; GO:0000151; C:ubiquitin ligase complex; IBA:GO_Central.
DR GO; GO:0003690; F:double-stranded DNA binding; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005080; F:protein kinase C binding; IPI:RGD.
DR GO; GO:0043130; F:ubiquitin binding; ISS:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISO:RGD.
DR GO; GO:0042742; P:defense response to bacterium; ISS:UniProtKB.
DR GO; GO:0060546; P:negative regulation of necroptotic process; ISO:RGD.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:RGD.
DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISO:RGD.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:RGD.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISO:RGD.
DR GO; GO:0097039; P:protein linear polyubiquitination; ISS:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; ISO:RGD.
DR GO; GO:0050852; P:T cell receptor signaling pathway; ISO:RGD.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR026261; RBCK1/SHARPIN.
DR InterPro; IPR044066; TRIAD_supradom.
DR InterPro; IPR000626; Ubiquitin-like_dom.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR InterPro; IPR027370; Znf-RING_LisH.
DR InterPro; IPR001876; Znf_RanBP2.
DR InterPro; IPR036443; Znf_RanBP2_sf.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR PANTHER; PTHR22770:SF35; PTHR22770:SF35; 1.
DR Pfam; PF13445; zf-RING_UBOX; 1.
DR SMART; SM00184; RING; 1.
DR SMART; SM00547; ZnF_RBZ; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR SUPFAM; SSF90209; SSF90209; 1.
DR PROSITE; PS51873; TRIAD; 1.
DR PROSITE; PS50053; UBIQUITIN_2; 1.
DR PROSITE; PS01358; ZF_RANBP2_1; 1.
DR PROSITE; PS50199; ZF_RANBP2_2; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Coiled coil; Metal-binding;
KW Phosphoprotein; Reference proteome; Repeat; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..508
FT /note="RanBP-type and C3HC4-type zinc finger-containing
FT protein 1"
FT /id="PRO_0000056297"
FT DOMAIN 55..119
FT /note="Ubiquitin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT ZN_FING 188..220
FT /note="RanBP2-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00322"
FT ZN_FING 280..330
FT /note="RING-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT ZN_FING 349..409
FT /note="IBR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT ZN_FING 445..474
FT /note="RING-type 2; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT REGION 1..268
FT /note="Interaction with TAB2"
FT /evidence="ECO:0000250|UniProtKB:Q9BYM8"
FT REGION 1..218
FT /note="Interaction with IRF3"
FT /evidence="ECO:0000250|UniProtKB:Q9BYM8"
FT REGION 69..131
FT /note="Interaction with RNF31"
FT /evidence="ECO:0000250|UniProtKB:Q9BYM8"
FT REGION 161..191
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 276..504
FT /note="TRIAD supradomain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT COILED 231..260
FT /evidence="ECO:0000255"
FT ACT_SITE 458
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 280
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 283
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 298
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 300
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 303
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 306
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 321
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 330
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 369
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 374
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 389
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 392
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 397
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 400
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 404
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 409
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 445
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 448
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 463
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 466
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q9BYM8"
FT MOD_RES 50
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BYM8"
FT MOD_RES 328
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9BYM8"
FT VAR_SEQ 251..270
FT /note="RKQQQQEGNYLQHVQLEQRS -> GVPAGYHPKQPGGGGILPLH (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:9755849"
FT /id="VSP_005769"
FT VAR_SEQ 271..508
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9755849"
FT /id="VSP_005770"
FT MUTAGEN 303
FT /note="C->G: Greatly reduces auto-ubiquitination."
FT /evidence="ECO:0000269|PubMed:18303026"
SQ SEQUENCE 508 AA; 57685 MW; D2E407B254E9FDA6 CRC64;
MDEKTKKAEE MALSLARAVT GGDEQAAIKY ATWLAEQKVP LRVQVKPEVS PTQDIRLCVS
VEDAYMHTVT IWLTVRPDMT VASLKDMVFL DYGFPPSLQQ WVVGQRLARD QETLHSHGIR
RNGDSAYLYL LSARNTSLNP QELQRQRQLR MLEDLGFKDL TLQPRGPLEP VLPKPRTHQE
TGQPDAAPES PPVGWQCPGC TFINKPTRPG CEMCCRARPE AYQIPASYQP DEEERARLAG
EEEALRQYEQ RKQQQQEGNY LQHVQLEQRS LVLNTEPAEC PVCYSVLAPG EAVVLRECLH
TFCRECLQGT IRNSQEAEVS CPFIDNTYSC PGKLLEREIR ALLSPEDYQR FLDLGVSIAE
NRSTLSYHCK TPDCRGWCFF EDDVNEFTCP VCTRVNCLLC KAIHERMNCR EYQDDLAHRA
RNDVAAQQTT EMLRVMLQQG EAMYCPQCRI VVQKKDGCDW IRCTVCHTEI CWVTKGPRWG
PGGPGDTSGG CRCRVNGIPC HPSCQNCH
