HOIL1_MOUSE
ID HOIL1_MOUSE Reviewed; 508 AA.
AC Q9WUB0; A2ANR4; Q3TM86; Q8C2I0;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 2.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=RanBP-type and C3HC4-type zinc finger-containing protein 1;
DE EC=2.3.2.31 {ECO:0000250|UniProtKB:Q9BYM8};
DE AltName: Full=Heme-oxidized IRP2 ubiquitin ligase 1 homolog;
DE Short=HOIL-1;
DE AltName: Full=RING-type E3 ubiquitin transferase HOIL-1 {ECO:0000305};
DE AltName: Full=UbcM4-interacting protein 28;
DE AltName: Full=Ubiquitin-conjugating enzyme 7-interacting protein 3;
GN Name=Rbck1; Synonyms=Rbck, Ubce7ip3, Uip28;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=NOD; TISSUE=Lung, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Salivary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 8-508, AND INTERACTION WITH UBE2L3.
RC STRAIN=BALB/cJ; TISSUE=Liver;
RX PubMed=10431818; DOI=10.1016/s0014-5793(99)00823-6;
RA Martinez-Noel G., Niedenthal R., Tamura T., Harbers K.;
RT "A family of structurally related RING finger proteins interacts
RT specifically with the ubiquitin-conjugating enzyme UbcM4.";
RL FEBS Lett. 454:257-261(1999).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-328, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [6]
RP DISRUPTION PHENOTYPE.
RX PubMed=19136968; DOI=10.1038/ncb1821;
RA Tokunaga F., Sakata S., Saeki Y., Satomi Y., Kirisako T., Kamei K.,
RA Nakagawa T., Kato M., Murata S., Yamaoka S., Yamamoto M., Akira S.,
RA Takao T., Tanaka K., Iwai K.;
RT "Involvement of linear polyubiquitylation of NEMO in NF-kappaB
RT activation.";
RL Nat. Cell Biol. 11:123-132(2009).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP INTERACTION WITH EYA1.
RX PubMed=20956555; DOI=10.1128/mcb.01645-09;
RA Landgraf K., Bollig F., Trowe M.O., Besenbeck B., Ebert C., Kruspe D.,
RA Kispert A., Hanel F., Englert C.;
RT "Sipl1 and Rbck1 are novel Eya1-binding proteins with a role in
RT craniofacial development.";
RL Mol. Cell. Biol. 30:5764-5775(2010).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 192-250 IN COMPLEX WITH LINEAR
RP DIUBIQUITIN.
RX PubMed=22139374; DOI=10.1073/pnas.1109088108;
RA Sato Y., Fujita H., Yoshikawa A., Yamashita M., Yamagata A., Kaiser S.E.,
RA Iwai K., Fukai S.;
RT "Specific recognition of linear ubiquitin chains by the Npl4 zinc finger
RT (NZF) domain of the HOIL-1L subunit of the linear ubiquitin chain assembly
RT complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:20520-20525(2011).
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. Functions as an E3 ligase for oxidized
CC IREB2 and both heme and oxygen are necessary for IREB2 ubiquitination.
CC Promotes ubiquitination of TAB2 and IRF3 and their degradation by the
CC proteasome. Component of the LUBAC complex which conjugates linear
CC ('Met-1'-linked) polyubiquitin chains to substrates and plays a key
CC role in NF-kappa-B activation and regulation of inflammation. 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 Linear ubiquitination mediated by the LUBAC complex interferes with
CC TNF-induced cell death and thereby prevents inflammation. LUBAC is
CC recruited to the TNF-R1 signaling complex (TNF-RSC) following
CC polyubiquitination of TNF-RSC components by BIRC2 and/or BIRC3 and to
CC conjugate linear polyubiquitin to IKBKG and possibly other components
CC contributing to the stability of the complex. The LUBAC complex is also
CC involved in innate immunity by conjugating linear polyubiquitin chains
CC at the surface of bacteria invading the cytosol to form the ubiquitin
CC coat surrounding bacteria. LUBAC is not able to initiate formation of
CC the bacterial ubiquitin coat, and can only promote formation of linear
CC polyubiquitins on pre-existing ubiquitin. The bacterial ubiquitin coat
CC acts as an 'eat-me' signal for xenophagy and promotes NF-kappa-B
CC activation. Together with OTULIN, the LUBAC complex regulates the
CC canonical Wnt signaling during angiogenesis. Binds polyubiquitin of
CC different linkage types. {ECO:0000250|UniProtKB:Q9BYM8}.
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:0000250|UniProtKB:Q9BYM8};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q9BYM8}.
CC -!- SUBUNIT: Component of the LUBAC complex (linear ubiquitin chain
CC assembly complex) which consists of SHARPIN, RBCK1 and RNF31. LUBAC has
CC a MW of approximately 600 kDa suggesting a heteromultimeric assembly of
CC its subunits (By similarity). Interacts with beta-I-type (PRKCB1) and
CC zeta-type protein kinase C (PRKCZ) (By similarity). Interacts with
CC UBE2L3 (PubMed:10431818). Interacts with IREB2 only in iron-rich
CC conditions. Associates with the TNF-R1 signaling complex (TNF-RSC) in a
CC stimulation-dependent manner. Interacts with EYA1, TAB2, TAB3, MAP3K7
CC TRAF6 and RIPK1 (PubMed:20956555). Interacts with IRF3 (By similarity).
CC {ECO:0000250|UniProtKB:Q62921, ECO:0000250|UniProtKB:Q9BYM8,
CC ECO:0000269|PubMed:10431818, ECO:0000269|PubMed:20956555}.
CC -!- INTERACTION:
CC Q9WUB0; P97767: Eya1; NbExp=2; IntAct=EBI-6141072, EBI-1368503;
CC Q9WUB0; Q924T7: Rnf31; NbExp=10; IntAct=EBI-6141072, EBI-647680;
CC -!- DOMAIN: The RanBP2-type zinc finger, also called Npl4 zinc finger
CC (NZF), mediates binding to 'Met-1'-linked polyubiquitins.
CC {ECO:0000269|PubMed:22139374}.
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 (By similarity). {ECO:0000250|UniProtKB:Q62921}.
CC -!- PTM: Phosphorylated. In vitro, phosphorylation inhibits auto-
CC ubiquitination activity (By similarity).
CC {ECO:0000250|UniProtKB:Q62921}.
CC -!- DISRUPTION PHENOTYPE: Impaired TNF-alpha-mediated NF-kappa-B activation
CC and enhanced JNK-mediated apoptosis. {ECO:0000269|PubMed:19136968}.
CC -!- SIMILARITY: Belongs to the RBR family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD24572.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAH34555.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK088591; BAC40440.1; -; mRNA.
DR EMBL; AK166075; BAE38556.1; -; mRNA.
DR EMBL; AL831735; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL928568; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC034555; AAH34555.1; ALT_INIT; mRNA.
DR EMBL; AF124663; AAD24572.1; ALT_INIT; mRNA.
DR CCDS; CCDS38273.1; -.
DR RefSeq; NP_001077390.1; NM_001083921.1.
DR RefSeq; NP_062679.2; NM_019705.3.
DR PDB; 3B08; X-ray; 1.70 A; B/E/H/K=192-250.
DR PDB; 3B0A; X-ray; 1.90 A; B/E=192-250.
DR PDB; 5Y3T; X-ray; 2.40 A; A=1-140.
DR PDBsum; 3B08; -.
DR PDBsum; 3B0A; -.
DR PDBsum; 5Y3T; -.
DR AlphaFoldDB; Q9WUB0; -.
DR SMR; Q9WUB0; -.
DR BioGRID; 204899; 15.
DR DIP; DIP-59198N; -.
DR IntAct; Q9WUB0; 4.
DR MINT; Q9WUB0; -.
DR STRING; 10090.ENSMUSP00000105473; -.
DR iPTMnet; Q9WUB0; -.
DR PhosphoSitePlus; Q9WUB0; -.
DR EPD; Q9WUB0; -.
DR MaxQB; Q9WUB0; -.
DR PaxDb; Q9WUB0; -.
DR PeptideAtlas; Q9WUB0; -.
DR PRIDE; Q9WUB0; -.
DR ProteomicsDB; 267013; -.
DR Antibodypedia; 6164; 300 antibodies from 27 providers.
DR DNASU; 24105; -.
DR Ensembl; ENSMUST00000028964; ENSMUSP00000028964; ENSMUSG00000027466.
DR Ensembl; ENSMUST00000109847; ENSMUSP00000105473; ENSMUSG00000027466.
DR GeneID; 24105; -.
DR KEGG; mmu:24105; -.
DR UCSC; uc008nfd.1; mouse.
DR CTD; 10616; -.
DR MGI; MGI:1344372; Rbck1.
DR VEuPathDB; HostDB:ENSMUSG00000027466; -.
DR eggNOG; KOG1815; Eukaryota.
DR GeneTree; ENSGT00940000161130; -.
DR HOGENOM; CLU_014998_1_0_1; -.
DR InParanoid; Q9WUB0; -.
DR OMA; VKCATWL; -.
DR OrthoDB; 1086223at2759; -.
DR PhylomeDB; Q9WUB0; -.
DR TreeFam; TF323486; -.
DR Reactome; R-MMU-5357905; Regulation of TNFR1 signaling.
DR Reactome; R-MMU-5357956; TNFR1-induced NFkappaB signaling pathway.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 24105; 29 hits in 75 CRISPR screens.
DR ChiTaRS; Rbck1; mouse.
DR PRO; PR:Q9WUB0; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q9WUB0; protein.
DR Bgee; ENSMUSG00000027466; Expressed in retinal neural layer and 267 other tissues.
DR ExpressionAtlas; Q9WUB0; baseline and differential.
DR Genevisible; Q9WUB0; MM.
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; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005080; F:protein kinase C binding; ISO:MGI.
DR GO; GO:0140311; F:protein sequestering activity; ISO:MGI.
DR GO; GO:0003713; F:transcription coactivator activity; ISO:MGI.
DR GO; GO:0043130; F:ubiquitin binding; ISS:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISO:MGI.
DR GO; GO:0051220; P:cytoplasmic sequestering of protein; ISO:MGI.
DR GO; GO:0042742; P:defense response to bacterium; ISS:UniProtKB.
DR GO; GO:0060546; P:negative regulation of necroptotic process; IGI:MGI.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISO:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IMP:MGI.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISO:MGI.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISO:MGI.
DR GO; GO:0097039; P:protein linear polyubiquitination; ISS:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; ISO:MGI.
DR GO; GO:0050852; P:T cell receptor signaling pathway; ISO:MGI.
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 3D-structure; Acetylation; Coiled coil; Metal-binding; Phosphoprotein;
KW 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_0000056296"
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 163..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..259
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:0007744|PubMed:17947660"
FT CONFLICT 322
FT /note="P -> S (in Ref. 1; BAE38556)"
FT /evidence="ECO:0000305"
FT CONFLICT 406
FT /note="H -> R (in Ref. 1; BAC40440)"
FT /evidence="ECO:0000305"
FT HELIX 5..20
FT /evidence="ECO:0007829|PDB:5Y3T"
FT HELIX 24..36
FT /evidence="ECO:0007829|PDB:5Y3T"
FT STRAND 41..45
FT /evidence="ECO:0007829|PDB:5Y3T"
FT STRAND 55..63
FT /evidence="ECO:0007829|PDB:5Y3T"
FT STRAND 68..75
FT /evidence="ECO:0007829|PDB:5Y3T"
FT HELIX 81..92
FT /evidence="ECO:0007829|PDB:5Y3T"
FT HELIX 96..98
FT /evidence="ECO:0007829|PDB:5Y3T"
FT STRAND 99..107
FT /evidence="ECO:0007829|PDB:5Y3T"
FT STRAND 112..114
FT /evidence="ECO:0007829|PDB:5Y3T"
FT HELIX 115..117
FT /evidence="ECO:0007829|PDB:5Y3T"
FT STRAND 125..130
FT /evidence="ECO:0007829|PDB:5Y3T"
FT STRAND 194..196
FT /evidence="ECO:0007829|PDB:3B08"
FT TURN 198..200
FT /evidence="ECO:0007829|PDB:3B08"
FT TURN 212..214
FT /evidence="ECO:0007829|PDB:3B08"
FT HELIX 232..245
FT /evidence="ECO:0007829|PDB:3B08"
SQ SEQUENCE 508 AA; 57534 MW; CBD3B40CD4E55180 CRC64;
MDEKTKKAEE MALSLARAVA GGDEQAAIKY ATWLAEQRVP LRVQVKPEVS PTQDIRLCVS
VEDAYMHTVT IWLTVRPDMT VASLKDMVFL DYGFPPSLQQ WVVGQRLARD QETLHSHGIR
RNGDGAYLYL LSARNTSLNP QELQRQRQLR MLEDLGFKDL TLQSRGPLEP VLPKPRTNQE
PGQPDAAPES PPVGWQCPGC TFINKPTRPG CEMCCRARPE TYQIPASYQP DEEERARLAG
EEEALRQYQQ RKQQQQEGNY LQHVQLEQRS LVLNTEPTEC PVCYSVLAPG EAVVLRECLH
TFCRECLQGT IRNSQEAEVA CPFIDSTYSC PGKLLEREIR ALLSPEDYQR FLDLGVSIAE
NRSTLSYHCK TPDCRGWCFF EDDVNEFTCP VCTRVNCLLC KAIHEHMNCR EYQDDLALRA
QNDVAARQTT EMLKVMLQQG EAMHCPQCRI VVQKKDGCDW IRCTVCHTEI CWVTKGPRWG
PGGPGDTSGG CRCRVNGIPC HPSCQNCH
