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 27-MAR-2024, entry version 185. 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 8IM5; NMR; -; A=192-250. DR PDBsum; 3B08; -. DR PDBsum; 3B0A; -. DR PDBsum; 5Y3T; -. DR PDBsum; 8IM5; -. DR AlphaFoldDB; Q9WUB0; -. DR SMR; Q9WUB0; -. DR BioGRID; 204899; 16. DR DIP; DIP-59198N; -. DR IntAct; Q9WUB0; 4. DR MINT; Q9WUB0; -. DR STRING; 10090.ENSMUSP00000105473; -. DR iPTMnet; Q9WUB0; -. DR PhosphoSitePlus; Q9WUB0; -. DR SwissPalm; Q9WUB0; -. DR EPD; Q9WUB0; -. DR MaxQB; Q9WUB0; -. DR PaxDb; 10090-ENSMUSP00000105473; -. DR PeptideAtlas; Q9WUB0; -. DR ProteomicsDB; 267013; -. DR Pumba; Q9WUB0; -. DR Antibodypedia; 6164; 325 antibodies from 28 providers. DR DNASU; 24105; -. DR Ensembl; ENSMUST00000028964.14; ENSMUSP00000028964.8; ENSMUSG00000027466.16. DR Ensembl; ENSMUST00000109847.9; ENSMUSP00000105473.3; ENSMUSG00000027466.16. DR GeneID; 24105; -. DR KEGG; mmu:24105; -. DR UCSC; uc008nfd.1; mouse. DR AGR; MGI:1344372; -. 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; CRCRMNG; -. DR OrthoDB; 2903477at2759; -. DR PhylomeDB; Q9WUB0; -. DR TreeFam; TF323486; -. DR Reactome; R-MMU-5357786; TNFR1-induced proapoptotic signaling. DR Reactome; R-MMU-5357905; Regulation of TNFR1 signaling. DR Reactome; R-MMU-5357956; TNFR1-induced NF-kappa-B signaling pathway. DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 24105; 30 hits in 80 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 271 other cell types or tissues. DR ExpressionAtlas; Q9WUB0; baseline and differential. DR GO; GO:0071797; C:LUBAC complex; IDA:MGI. 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:1990757; F:ubiquitin ligase activator activity; IDA:MGI. 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:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IMP:UniProtKB. DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IMP:MGI. DR GO; GO:1901224; P:positive regulation of non-canonical NF-kappaB signal transduction; 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; IMP:MGI. DR GO; GO:0050852; P:T cell receptor signaling pathway; ISO:MGI. DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; TAS:MGI. DR CDD; cd20345; BRcat_RBR_HOIL1; 1. DR CDD; cd16633; mRING-HC-C3HC3D_RBR_HOIL1; 1. DR CDD; cd20358; Rcat_RBR_HOIL1; 1. DR CDD; cd01799; Ubl_HOIL1; 1. DR Gene3D; 1.20.120.1750; -; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR Gene3D; 2.30.30.380; Zn-finger domain of Sec23/24; 1. DR InterPro; IPR047558; BRcat_RBR_HOIL1. DR InterPro; IPR047559; HOIL1_RBR_mRING-HC-C3HC3D. DR InterPro; IPR047557; Rcat_RBR_HOIL1. DR InterPro; IPR044066; TRIAD_supradom. DR InterPro; IPR000626; Ubiquitin-like_dom. DR InterPro; IPR029071; Ubiquitin-like_domsf. DR InterPro; IPR027370; Znf-RING_euk. 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; RANBP-TYPE AND C3HC4-TYPE ZINC FINGER-CONTAINING PROTEIN 1; 1. DR PANTHER; PTHR22770; UBIQUITIN CONJUGATING ENZYME 7 INTERACTING PROTEIN-RELATED; 1. DR Pfam; PF13445; zf-RING_UBOX; 1. DR SMART; SM00184; RING; 1. DR SMART; SM00547; ZnF_RBZ; 1. DR SUPFAM; SSF90209; Ran binding protein zinc finger-like; 1. DR SUPFAM; SSF57850; RING/U-box; 3. DR SUPFAM; SSF54236; Ubiquitin-like; 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. DR Genevisible; Q9WUB0; MM. 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 //