ID MSRB3_HUMAN Reviewed; 192 AA. AC Q8IXL7; B4DR19; B7ZAQ0; Q6UXS2; DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot. DT 05-APR-2011, sequence version 2. DT 27-MAR-2024, entry version 163. DE RecName: Full=Methionine-R-sulfoxide reductase B3; DE Short=MsrB3; DE EC=1.8.4.12 {ECO:0000250|UniProtKB:Q9JLC3}; DE EC=1.8.4.14 {ECO:0000250|UniProtKB:Q9JLC3}; DE Flags: Precursor; GN Name=MSRB3; ORFNames=UNQ1965/PRO4487; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Esophageal carcinoma, Teratocarcinoma, and Uterus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Uterus; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Pancreas; 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 [5] RP FUNCTION, COFACTOR, SUBCELLULAR LOCATION, AND ALTERNATIVE SPLICING. RX PubMed=14699060; DOI=10.1091/mbc.e03-08-0629; RA Kim H.-Y., Gladyshev V.N.; RT "Methionine sulfoxide reduction in mammals: characterization of methionine- RT R-sulfoxide reductases."; RL Mol. Biol. Cell 15:1055-1064(2004). RN [6] RP TISSUE SPECIFICITY. RX PubMed=15914630; DOI=10.1167/iovs.05-0018; RA Marchetti M.A., Pizarro G.O., Sagher D., Deamicis C., Brot N., RA Hejtmancik J.F., Weissbach H., Kantorow M.; RT "Methionine sulfoxide reductases B1, B2, and B3 are present in the human RT lens and confer oxidative stress resistance to lens cells."; RL Invest. Ophthalmol. Vis. Sci. 46:2107-2112(2005). RN [7] RP MUTAGENESIS OF HIS-141 AND ASN-160, AND SUBUNIT. RX PubMed=16262444; DOI=10.1371/journal.pbio.0030375; RA Kim H.-Y., Gladyshev V.N.; RT "Different catalytic mechanisms in mammalian selenocysteine- and cysteine- RT containing methionine-R-sulfoxide reductases."; RL PLoS Biol. 3:2080-2089(2005). RN [8] RP VARIANT DFNB74 GLY-89, FUNCTION, ALTERNATIVE SPLICING, AND TISSUE RP SPECIFICITY. RX PubMed=21185009; DOI=10.1016/j.ajhg.2010.11.010; RA Ahmed Z.M., Yousaf R., Lee B.C., Khan S.N., Lee S., Lee K., Husnain T., RA Rehman A.U., Bonneux S., Ansar M., Ahmad W., Leal S.M., Gladyshev V.N., RA Belyantseva I.A., Van Camp G., Riazuddin S., Friedman T.B., Riazuddin S.; RT "Functional null mutations of MSRB3 encoding methionine sulfoxide reductase RT are associated with human deafness DFNB74."; RL Am. J. Hum. Genet. 88:19-29(2011). CC -!- FUNCTION: Catalyzes the reduction of free and protein-bound methionine CC sulfoxide to methionine. Isoform 2 is essential for hearing. CC {ECO:0000269|PubMed:14699060, ECO:0000269|PubMed:21185009}. CC -!- CATALYTIC ACTIVITY: CC Reaction=[thioredoxin]-disulfide + H2O + L-methionyl-[protein] = CC [thioredoxin]-dithiol + L-methionyl-(R)-S-oxide-[protein]; CC Xref=Rhea:RHEA:24164, Rhea:RHEA-COMP:10698, Rhea:RHEA-COMP:10700, CC Rhea:RHEA-COMP:12313, Rhea:RHEA-COMP:12314, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:16044, ChEBI:CHEBI:29950, ChEBI:CHEBI:45764, CC ChEBI:CHEBI:50058; EC=1.8.4.12; CC Evidence={ECO:0000250|UniProtKB:Q9JLC3}; CC -!- CATALYTIC ACTIVITY: CC Reaction=[thioredoxin]-disulfide + H2O + L-methionine = [thioredoxin]- CC dithiol + L-methionine (R)-S-oxide; Xref=Rhea:RHEA:21260, Rhea:RHEA- CC COMP:10698, Rhea:RHEA-COMP:10700, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:29950, ChEBI:CHEBI:50058, ChEBI:CHEBI:57844, CC ChEBI:CHEBI:58773; EC=1.8.4.14; CC Evidence={ECO:0000250|UniProtKB:Q9JLC3}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000269|PubMed:14699060}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:14699060}; CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:16262444}. CC -!- INTERACTION: CC Q8IXL7; Q08379: GOLGA2; NbExp=3; IntAct=EBI-8634060, EBI-618309; CC Q8IXL7; Q9UKN5: PRDM4; NbExp=3; IntAct=EBI-8634060, EBI-2803427; CC Q8IXL7; P15884: TCF4; NbExp=3; IntAct=EBI-8634060, EBI-533224; CC Q8IXL7; Q15654: TRIP6; NbExp=3; IntAct=EBI-8634060, EBI-742327; CC Q8IXL7-2; Q8WXK3-2: ASB13; NbExp=3; IntAct=EBI-10699187, EBI-12015080; CC Q8IXL7-2; Q8N9N5-2: BANP; NbExp=3; IntAct=EBI-10699187, EBI-11524452; CC Q8IXL7-2; P56545-3: CTBP2; NbExp=5; IntAct=EBI-10699187, EBI-10171902; CC Q8IXL7-2; Q96AZ1: EEF1AKMT3; NbExp=3; IntAct=EBI-10699187, EBI-12108304; CC Q8IXL7-2; Q12805: EFEMP1; NbExp=3; IntAct=EBI-10699187, EBI-536772; CC Q8IXL7-2; P56537: EIF6; NbExp=3; IntAct=EBI-10699187, EBI-372243; CC Q8IXL7-2; A1KXE4-2: FAM168B; NbExp=3; IntAct=EBI-10699187, EBI-12193763; CC Q8IXL7-2; Q13643: FHL3; NbExp=3; IntAct=EBI-10699187, EBI-741101; CC Q8IXL7-2; Q08379: GOLGA2; NbExp=3; IntAct=EBI-10699187, EBI-618309; CC Q8IXL7-2; O15354: GPR37; NbExp=3; IntAct=EBI-10699187, EBI-15639515; CC Q8IXL7-2; P28799: GRN; NbExp=3; IntAct=EBI-10699187, EBI-747754; CC Q8IXL7-2; P28799-2: GRN; NbExp=3; IntAct=EBI-10699187, EBI-25860013; CC Q8IXL7-2; O60333-2: KIF1B; NbExp=3; IntAct=EBI-10699187, EBI-10975473; CC Q8IXL7-2; Q15323: KRT31; NbExp=3; IntAct=EBI-10699187, EBI-948001; CC Q8IXL7-2; O76011: KRT34; NbExp=3; IntAct=EBI-10699187, EBI-1047093; CC Q8IXL7-2; Q6A162: KRT40; NbExp=3; IntAct=EBI-10699187, EBI-10171697; CC Q8IXL7-2; P80188: LCN2; NbExp=3; IntAct=EBI-10699187, EBI-11911016; CC Q8IXL7-2; Q86YW9: MED12L; NbExp=3; IntAct=EBI-10699187, EBI-3957138; CC Q8IXL7-2; A6NJ78-4: METTL15; NbExp=3; IntAct=EBI-10699187, EBI-10174029; CC Q8IXL7-2; Q8WXB1: METTL21A; NbExp=3; IntAct=EBI-10699187, EBI-8652459; CC Q8IXL7-2; A0A0C4DFN3: MGLL; NbExp=3; IntAct=EBI-10699187, EBI-12866138; CC Q8IXL7-2; P07196: NEFL; NbExp=3; IntAct=EBI-10699187, EBI-475646; CC Q8IXL7-2; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-10699187, EBI-79165; CC Q8IXL7-2; Q58EX7: PLEKHG4; NbExp=3; IntAct=EBI-10699187, EBI-949255; CC Q8IXL7-2; P78424: POU6F2; NbExp=3; IntAct=EBI-10699187, EBI-12029004; CC Q8IXL7-2; Q04864-2: REL; NbExp=3; IntAct=EBI-10699187, EBI-10829018; CC Q8IXL7-2; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-10699187, EBI-396669; CC Q8IXL7-2; Q9GZS3: SKIC8; NbExp=3; IntAct=EBI-10699187, EBI-358545; CC Q8IXL7-2; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-10699187, EBI-5235340; CC Q8IXL7-2; P36406: TRIM23; NbExp=3; IntAct=EBI-10699187, EBI-740098; CC Q8IXL7-2; Q6NVU6: UFSP1; NbExp=3; IntAct=EBI-10699187, EBI-12068150; CC Q8IXL7-2; O76024: WFS1; NbExp=3; IntAct=EBI-10699187, EBI-720609; CC Q8IXL7-2; Q9H0C1: ZMYND12; NbExp=3; IntAct=EBI-10699187, EBI-12030590; CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Endoplasmic reticulum. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Mitochondrion. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=A; CC IsoId=Q8IXL7-1; Sequence=Displayed; CC Name=2; Synonyms=B, C, D; CC IsoId=Q8IXL7-2; Sequence=VSP_040883; CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:15914630, CC ECO:0000269|PubMed:21185009}. CC -!- DISEASE: Deafness, autosomal recessive, 74 (DFNB74) [MIM:613718]: A CC form of non-syndromic sensorineural deafness characterized by CC prelingual, bilateral, profound hearing loss. Sensorineural deafness CC results from damage to the neural receptors of the inner ear, the nerve CC pathways to the brain, or the area of the brain that receives sound CC information. {ECO:0000269|PubMed:21185009}. Note=The disease is caused CC by variants affecting the gene represented in this entry. A nonsense CC mutation affecting exclusively mitochondrial isoform 2 is sufficient to CC produce hearing loss. CC -!- MISCELLANEOUS: [Isoform 2]: Has a transit peptide. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the MsrB Met sulfoxide reductase family. CC {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; AY358229; AAQ88596.1; -; mRNA. DR EMBL; AK293084; BAF85773.1; -; mRNA. DR EMBL; AK299065; BAG61131.1; -; mRNA. DR EMBL; AK316365; BAH14736.1; -; mRNA. DR EMBL; BX648776; CAI46018.1; -; mRNA. DR EMBL; BC040053; AAH40053.1; -; mRNA. DR CCDS; CCDS31853.1; -. [Q8IXL7-2] DR CCDS; CCDS8973.1; -. [Q8IXL7-1] DR RefSeq; NP_001026849.1; NM_001031679.2. [Q8IXL7-2] DR RefSeq; NP_001180389.1; NM_001193460.1. [Q8IXL7-2] DR RefSeq; NP_001180390.1; NM_001193461.1. [Q8IXL7-2] DR RefSeq; NP_932346.1; NM_198080.3. [Q8IXL7-1] DR PDB; 6QA0; X-ray; 1.71 A; A/B=31-169. DR PDBsum; 6QA0; -. DR AlphaFoldDB; Q8IXL7; -. DR SMR; Q8IXL7; -. DR BioGRID; 128990; 89. DR IntAct; Q8IXL7; 46. DR MINT; Q8IXL7; -. DR STRING; 9606.ENSP00000347324; -. DR ChEMBL; CHEMBL3509604; -. DR iPTMnet; Q8IXL7; -. DR PhosphoSitePlus; Q8IXL7; -. DR BioMuta; MSRB3; -. DR DMDM; 327478523; -. DR EPD; Q8IXL7; -. DR jPOST; Q8IXL7; -. DR MassIVE; Q8IXL7; -. DR MaxQB; Q8IXL7; -. DR PaxDb; 9606-ENSP00000347324; -. DR PeptideAtlas; Q8IXL7; -. DR ProteomicsDB; 71024; -. [Q8IXL7-1] DR ProteomicsDB; 71025; -. [Q8IXL7-2] DR Pumba; Q8IXL7; -. DR Antibodypedia; 2870; 150 antibodies from 22 providers. DR DNASU; 253827; -. DR Ensembl; ENST00000308259.10; ENSP00000312274.6; ENSG00000174099.12. [Q8IXL7-2] DR Ensembl; ENST00000355192.8; ENSP00000347324.3; ENSG00000174099.12. [Q8IXL7-1] DR Ensembl; ENST00000535664.5; ENSP00000441650.1; ENSG00000174099.12. [Q8IXL7-2] DR Ensembl; ENST00000614640.4; ENSP00000481483.1; ENSG00000174099.12. [Q8IXL7-2] DR Ensembl; ENST00000642404.1; ENSP00000496008.1; ENSG00000174099.12. [Q8IXL7-2] DR Ensembl; ENST00000642411.1; ENSP00000494265.1; ENSG00000174099.12. [Q8IXL7-2] DR Ensembl; ENST00000646299.1; ENSP00000494941.1; ENSG00000174099.12. [Q8IXL7-2] DR GeneID; 253827; -. DR KEGG; hsa:253827; -. DR MANE-Select; ENST00000308259.10; ENSP00000312274.6; NM_001031679.3; NP_001026849.1. [Q8IXL7-2] DR UCSC; uc001ssm.3; human. [Q8IXL7-1] DR AGR; HGNC:27375; -. DR CTD; 253827; -. DR DisGeNET; 253827; -. DR GeneCards; MSRB3; -. DR HGNC; HGNC:27375; MSRB3. DR HPA; ENSG00000174099; Low tissue specificity. DR MalaCards; MSRB3; -. DR MIM; 613718; phenotype. DR MIM; 613719; gene. DR neXtProt; NX_Q8IXL7; -. DR OpenTargets; ENSG00000174099; -. DR Orphanet; 90636; Rare autosomal recessive non-syndromic sensorineural deafness type DFNB. DR PharmGKB; PA134991350; -. DR VEuPathDB; HostDB:ENSG00000174099; -. DR eggNOG; KOG0856; Eukaryota. DR GeneTree; ENSGT00940000155240; -. DR InParanoid; Q8IXL7; -. DR OMA; DEQWRAE; -. DR OrthoDB; 1074224at2759; -. DR PhylomeDB; Q8IXL7; -. DR TreeFam; TF329147; -. DR BRENDA; 1.8.4.12; 2681. DR BRENDA; 1.8.4.B3; 2681. DR PathwayCommons; Q8IXL7; -. DR Reactome; R-HSA-5676934; Protein repair. DR SignaLink; Q8IXL7; -. DR BioGRID-ORCS; 253827; 9 hits in 1151 CRISPR screens. DR ChiTaRS; MSRB3; human. DR GenomeRNAi; 253827; -. DR Pharos; Q8IXL7; Tbio. DR PRO; PR:Q8IXL7; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q8IXL7; Protein. DR Bgee; ENSG00000174099; Expressed in saphenous vein and 185 other cell types or tissues. DR ExpressionAtlas; Q8IXL7; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HGNC-UCL. DR GO; GO:0005739; C:mitochondrion; IDA:HGNC-UCL. DR GO; GO:0033745; F:L-methionine-(R)-S-oxide reductase activity; IEA:UniProtKB-EC. DR GO; GO:0033743; F:peptide-methionine (R)-S-oxide reductase activity; IDA:HGNC-UCL. DR GO; GO:0008270; F:zinc ion binding; IDA:HGNC-UCL. DR GO; GO:0030091; P:protein repair; IDA:HGNC-UCL. DR GO; GO:0006979; P:response to oxidative stress; IEA:InterPro. DR Gene3D; 2.170.150.20; Peptide methionine sulfoxide reductase; 1. DR HAMAP; MF_01400; MsrB; 1. DR InterPro; IPR028427; Met_Sox_Rdtase_MsrB. DR InterPro; IPR002579; Met_Sox_Rdtase_MsrB_dom. DR InterPro; IPR011057; Mss4-like_sf. DR NCBIfam; TIGR00357; peptide-methionine (R)-S-oxide reductase MsrB; 1. DR PANTHER; PTHR10173; METHIONINE SULFOXIDE REDUCTASE; 1. DR PANTHER; PTHR10173:SF52; METHIONINE-R-SULFOXIDE REDUCTASE B3; 1. DR Pfam; PF01641; SelR; 1. DR SUPFAM; SSF51316; Mss4-like; 1. DR PROSITE; PS51790; MSRB; 1. DR Genevisible; Q8IXL7; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Deafness; Disease variant; KW Endoplasmic reticulum; Metal-binding; Mitochondrion; KW Non-syndromic deafness; Oxidoreductase; Phosphoprotein; Reference proteome; KW Signal; Zinc. FT SIGNAL 1..32 FT /evidence="ECO:0000255" FT CHAIN 33..192 FT /note="Methionine-R-sulfoxide reductase B3" FT /id="PRO_0000327240" FT DOMAIN 47..169 FT /note="MsrB" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01126" FT REGION 169..192 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 189..192 FT /note="Endoplasmic reticulum retention signal" FT /evidence="ECO:0000250" FT ACT_SITE 158 FT /note="Nucleophile" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01126" FT BINDING 86 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01126" FT BINDING 89 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01126" FT BINDING 135 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01126" FT BINDING 138 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01126" FT MOD_RES 42 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8BU85" FT MOD_RES 183 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8BU85" FT VAR_SEQ 1..31 FT /note="MSPRRTLPRPLSLCLSLCLCLCLAAALGSAQ -> MSAFNLLHLVTKSQPVA FT LRACGLP (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:17974005" FT /id="VSP_040883" FT VARIANT 89 FT /note="C -> G (in DFNB74; abolishes zinc-binding and FT enzymatic activity; dbSNP:rs387907088)" FT /evidence="ECO:0000269|PubMed:21185009" FT /id="VAR_064904" FT MUTAGEN 141 FT /note="H->G: 30-fold reduction in activity." FT /evidence="ECO:0000269|PubMed:16262444" FT MUTAGEN 160 FT /note="N->F: 7000-fold reduction in activity." FT /evidence="ECO:0000269|PubMed:16262444" FT MUTAGEN 160 FT /note="N->Y: 500-fold reduction in activity." FT /evidence="ECO:0000269|PubMed:16262444" FT CONFLICT 49 FT /note="E -> G (in Ref. 2; BAH14736)" FT /evidence="ECO:0000305" FT TURN 35..39 FT /evidence="ECO:0007829|PDB:6QA0" FT HELIX 47..53 FT /evidence="ECO:0007829|PDB:6QA0" FT HELIX 56..64 FT /evidence="ECO:0007829|PDB:6QA0" FT TURN 74..77 FT /evidence="ECO:0007829|PDB:6QA0" FT STRAND 81..86 FT /evidence="ECO:0007829|PDB:6QA0" FT TURN 87..89 FT /evidence="ECO:0007829|PDB:6QA0" FT STRAND 92..95 FT /evidence="ECO:0007829|PDB:6QA0" FT HELIX 96..98 FT /evidence="ECO:0007829|PDB:6QA0" FT STRAND 108..111 FT /evidence="ECO:0007829|PDB:6QA0" FT STRAND 117..123 FT /evidence="ECO:0007829|PDB:6QA0" FT HELIX 125..127 FT /evidence="ECO:0007829|PDB:6QA0" FT STRAND 130..135 FT /evidence="ECO:0007829|PDB:6QA0" FT TURN 136..138 FT /evidence="ECO:0007829|PDB:6QA0" FT STRAND 141..147 FT /evidence="ECO:0007829|PDB:6QA0" FT TURN 151..153 FT /evidence="ECO:0007829|PDB:6QA0" FT STRAND 156..159 FT /evidence="ECO:0007829|PDB:6QA0" FT HELIX 161..163 FT /evidence="ECO:0007829|PDB:6QA0" FT STRAND 164..168 FT /evidence="ECO:0007829|PDB:6QA0" SQ SEQUENCE 192 AA; 20702 MW; C3326F6103369083 CRC64; MSPRRTLPRP LSLCLSLCLC LCLAAALGSA QSGSCRDKKN CKVVFSQQEL RKRLTPLQYH VTQEKGTESA FEGEYTHHKD PGIYKCVVCG TPLFKSETKF DSGSGWPSFH DVINSEAITF TDDFSYGMHR VETSCSQCGA HLGHIFDDGP RPTGKRYCIN SAALSFTPAD SSGTAEGGSG VASPAQADKA EL //