ID 3HIDH_HUMAN Reviewed; 336 AA. AC P31937; Q546Z2; Q9UDN3; DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot. DT 24-JAN-2001, sequence version 2. DT 11-NOV-2015, entry version 158. DE RecName: Full=3-hydroxyisobutyrate dehydrogenase, mitochondrial; DE Short=HIBADH; DE EC=1.1.1.31; DE Flags: Precursor; GN Name=HIBADH; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Yuji K., Mitani K., Ueno H., Sato Y., Ikawa S., Hangaishi A., RA Ogawa S., Suzuki T., Nakamoto T., Qiao Y., Hirai H.; RT "A new partner gene of the TEL/ETV6, TSL, cloned in acute myeloid RT leukemia with t(7;12)(p15;p13)."; RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Liu Y., Cheng J., Lu Y., Wang G., Zhang L., Chen J., Li L.; RT "Cloning and identification of human gene 1 transactivated by RT hepatitis C virus NS5A protein."; RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Testis; 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., RA Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., RA Waterston R.H., Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP PROTEIN SEQUENCE OF 37-47. RC TISSUE=Liver; RX PubMed=8313870; DOI=10.1002/elps.11501401181; RA Hughes G.J., Frutiger S., Paquet N., Pasquali C., Sanchez J.-C., RA Tissot J.-D., Bairoch A., Appel R.D., Hochstrasser D.F.; RT "Human liver protein map: update 1993."; RL Electrophoresis 14:1216-1222(1993). RN [8] RP CATALYTIC ACTIVITY, PATHWAY, AND TISSUE SPECIFICITY. RX PubMed=16466957; DOI=10.1016/j.ymgme.2005.09.019; RA Loupatty F.J., van der Steen A., Ijlst L., Ruiter J.P., Ofman R., RA Baumgartner M.R., Ballhausen D., Yamaguchi S., Duran M., Wanders R.J.; RT "Clinical, biochemical, and molecular findings in three patients with RT 3-hydroxyisobutyric aciduria."; RL Mol. Genet. Metab. 87:243-248(2006). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., RA Ayoub D., Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [12] RP X-RAY CRYSTALLOGRAPHY (2.38 ANGSTROMS) OF 41-335 OF APOPROTEIN AND IN RP COMPLEX WITH NADH. RG Structural genomics consortium (SGC); RT "Crystal structure of human hydroxyisobutyrate dehydrogenase."; RL Submitted (APR-2006) to the PDB data bank. CC -!- CATALYTIC ACTIVITY: 3-hydroxy-2-methylpropanoate + NAD(+) = 2- CC methyl-3-oxopropanoate + NADH. {ECO:0000269|PubMed:16466957}. CC -!- PATHWAY: Amino-acid degradation; L-valine degradation. CC {ECO:0000269|PubMed:16466957}. CC -!- SUBUNIT: Homodimer. {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Mitochondrion. CC -!- TISSUE SPECIFICITY: Detected in skin fibroblasts. CC {ECO:0000269|PubMed:16466957}. CC -!- SIMILARITY: Belongs to the 3-hydroxyisobutyrate dehydrogenase CC family. {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; AF529362; AAQ09596.1; -; mRNA. DR EMBL; AB050000; BAF42045.1; -; mRNA. DR EMBL; AK316605; BAG38192.1; -; mRNA. DR EMBL; AC007130; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC005091; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH236948; EAL24214.1; -; Genomic_DNA. DR EMBL; CH471073; EAW93897.1; -; Genomic_DNA. DR EMBL; BC032324; AAH32324.1; -; mRNA. DR CCDS; CCDS5414.1; -. DR RefSeq; NP_689953.1; NM_152740.3. DR UniGene; Hs.406758; -. DR PDB; 2GF2; X-ray; 2.38 A; A/B/C/D=41-335. DR PDB; 2I9P; X-ray; 2.55 A; A/B/C/D=41-336. DR PDBsum; 2GF2; -. DR PDBsum; 2I9P; -. DR ProteinModelPortal; P31937; -. DR SMR; P31937; 41-335. DR BioGrid; 116289; 5. DR STRING; 9606.ENSP00000265395; -. DR PhosphoSite; P31937; -. DR BioMuta; HIBADH; -. DR DMDM; 12643395; -. DR SWISS-2DPAGE; P31937; -. DR PaxDb; P31937; -. DR PRIDE; P31937; -. DR DNASU; 11112; -. DR Ensembl; ENST00000265395; ENSP00000265395; ENSG00000106049. DR GeneID; 11112; -. DR KEGG; hsa:11112; -. DR UCSC; uc003szf.3; human. DR CTD; 11112; -. DR GeneCards; HIBADH; -. DR HGNC; HGNC:4907; HIBADH. DR HPA; HPA019522; -. DR HPA; HPA021002; -. DR MIM; 608475; gene. DR neXtProt; NX_P31937; -. DR PharmGKB; PA29280; -. DR eggNOG; KOG0409; Eukaryota. DR eggNOG; COG2084; LUCA. DR GeneTree; ENSGT00530000063270; -. DR HOGENOM; HOG000219610; -. DR HOVERGEN; HBG050424; -. DR InParanoid; P31937; -. DR KO; K00020; -. DR OMA; SQTVVTM; -. DR OrthoDB; EOG7NSB31; -. DR PhylomeDB; P31937; -. DR TreeFam; TF314043; -. DR Reactome; R-HSA-70895; Branched-chain amino acid catabolism. DR SABIO-RK; P31937; -. DR UniPathway; UPA00362; -. DR ChiTaRS; HIBADH; human. DR EvolutionaryTrace; P31937; -. DR GeneWiki; 3-hydroxyisobutyrate_dehydrogenase; -. DR GenomeRNAi; 11112; -. DR NextBio; 42238; -. DR PRO; PR:P31937; -. DR Proteomes; UP000005640; Chromosome 7. DR Bgee; P31937; -. DR CleanEx; HS_HIBADH; -. DR ExpressionAtlas; P31937; baseline and differential. DR Genevisible; P31937; HS. DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome. DR GO; GO:0008442; F:3-hydroxyisobutyrate dehydrogenase activity; IDA:UniProtKB. DR GO; GO:0051287; F:NAD binding; IEA:InterPro. DR GO; GO:0004616; F:phosphogluconate dehydrogenase (decarboxylating) activity; IEA:InterPro. DR GO; GO:0009083; P:branched-chain amino acid catabolic process; TAS:Reactome. DR GO; GO:0034641; P:cellular nitrogen compound metabolic process; TAS:Reactome. DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome. DR GO; GO:0006574; P:valine catabolic process; IDA:UniProtKB. DR Gene3D; 1.10.1040.10; -; 1. DR InterPro; IPR002204; 3-OH-isobutyrate_DH-rel_CS. DR InterPro; IPR008927; 6-PGluconate_DH_C-like. DR InterPro; IPR013328; 6PGD_dom_2. DR InterPro; IPR006115; 6PGDH_NADP-bd. DR InterPro; IPR011548; HIBADH. DR InterPro; IPR015815; HIBADH-related. DR InterPro; IPR016040; NAD(P)-bd_dom. DR InterPro; IPR029154; NADP-bd. DR Pfam; PF14833; NAD_binding_11; 1. DR Pfam; PF03446; NAD_binding_2; 1. DR PIRSF; PIRSF000103; HIBADH; 1. DR SUPFAM; SSF48179; SSF48179; 1. DR SUPFAM; SSF51735; SSF51735; 1. DR TIGRFAMs; TIGR01692; HIBADH; 1. DR PROSITE; PS00895; 3_HYDROXYISOBUT_DH; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Branched-chain amino acid catabolism; KW Complete proteome; Direct protein sequencing; Mitochondrion; NAD; KW Oxidoreductase; Reference proteome; Transit peptide. FT TRANSIT 1 36 Mitochondrion. FT {ECO:0000269|PubMed:8313870}. FT CHAIN 37 336 3-hydroxyisobutyrate dehydrogenase, FT mitochondrial. FT /FTId=PRO_0000007158. FT NP_BIND 40 68 NAD. {ECO:0000269|Ref.12}. FT NP_BIND 103 104 NAD. {ECO:0000269|Ref.12}. FT ACT_SITE 209 209 {ECO:0000250}. FT BINDING 108 108 NAD. {ECO:0000269|Ref.12}. FT BINDING 134 134 NAD. {ECO:0000269|Ref.12}. FT BINDING 284 284 NAD. {ECO:0000269|Ref.12}. FT MOD_RES 60 60 N6-acetyllysine; alternate. FT {ECO:0000250|UniProtKB:Q99L13}. FT MOD_RES 60 60 N6-succinyllysine; alternate. FT {ECO:0000250|UniProtKB:Q99L13}. FT MOD_RES 76 76 N6-acetyllysine; alternate. FT {ECO:0000250|UniProtKB:Q99L13}. FT MOD_RES 76 76 N6-succinyllysine; alternate. FT {ECO:0000250|UniProtKB:Q99L13}. FT MOD_RES 95 95 N6-succinyllysine. FT {ECO:0000250|UniProtKB:Q99L13}. FT MOD_RES 121 121 N6-acetyllysine. FT {ECO:0000250|UniProtKB:Q99L13}. FT MOD_RES 141 141 N6-succinyllysine. FT {ECO:0000250|UniProtKB:Q99L13}. FT MOD_RES 145 145 N6-acetyllysine. FT {ECO:0000250|UniProtKB:Q99L13}. FT MOD_RES 149 149 N6-acetyllysine; alternate. FT {ECO:0000250|UniProtKB:Q99L13}. FT MOD_RES 149 149 N6-succinyllysine; alternate. FT {ECO:0000250|UniProtKB:Q99L13}. FT MOD_RES 238 238 N6-acetyllysine; alternate. FT {ECO:0000250|UniProtKB:Q99L13}. FT MOD_RES 238 238 N6-succinyllysine; alternate. FT {ECO:0000250|UniProtKB:Q99L13}. FT MOD_RES 242 242 N6-acetyllysine; alternate. FT {ECO:0000250|UniProtKB:Q99L13}. FT MOD_RES 242 242 N6-succinyllysine; alternate. FT {ECO:0000250|UniProtKB:Q99L13}. FT MOD_RES 297 297 N6-succinyllysine. FT {ECO:0000250|UniProtKB:Q99L13}. FT MOD_RES 321 321 N6-acetyllysine; alternate. FT {ECO:0000250|UniProtKB:Q99L13}. FT MOD_RES 321 321 N6-succinyllysine; alternate. FT {ECO:0000250|UniProtKB:Q99L13}. FT STRAND 42 45 {ECO:0000244|PDB:2GF2}. FT HELIX 51 60 {ECO:0000244|PDB:2GF2}. FT STRAND 65 68 {ECO:0000244|PDB:2GF2}. FT HELIX 73 79 {ECO:0000244|PDB:2GF2}. FT TURN 80 82 {ECO:0000244|PDB:2GF2}. FT HELIX 89 95 {ECO:0000244|PDB:2GF2}. FT STRAND 97 101 {ECO:0000244|PDB:2GF2}. FT HELIX 106 114 {ECO:0000244|PDB:2GF2}. FT HELIX 119 121 {ECO:0000244|PDB:2GF2}. FT STRAND 128 131 {ECO:0000244|PDB:2GF2}. FT HELIX 137 149 {ECO:0000244|PDB:2GF2}. FT STRAND 153 156 {ECO:0000244|PDB:2GF2}. FT STRAND 159 161 {ECO:0000244|PDB:2GF2}. FT HELIX 162 168 {ECO:0000244|PDB:2GF2}. FT STRAND 171 177 {ECO:0000244|PDB:2GF2}. FT HELIX 179 181 {ECO:0000244|PDB:2GF2}. FT HELIX 182 189 {ECO:0000244|PDB:2GF2}. FT TURN 190 192 {ECO:0000244|PDB:2GF2}. FT STRAND 193 201 {ECO:0000244|PDB:2GF2}. FT HELIX 204 232 {ECO:0000244|PDB:2GF2}. FT HELIX 237 245 {ECO:0000244|PDB:2GF2}. FT HELIX 252 256 {ECO:0000244|PDB:2GF2}. FT TURN 261 263 {ECO:0000244|PDB:2GF2}. FT STRAND 265 267 {ECO:0000244|PDB:2GF2}. FT HELIX 268 271 {ECO:0000244|PDB:2GF2}. FT STRAND 275 278 {ECO:0000244|PDB:2GF2}. FT HELIX 279 295 {ECO:0000244|PDB:2GF2}. FT HELIX 301 314 {ECO:0000244|PDB:2GF2}. FT TURN 315 317 {ECO:0000244|PDB:2GF2}. FT HELIX 323 325 {ECO:0000244|PDB:2GF2}. FT HELIX 326 330 {ECO:0000244|PDB:2GF2}. SQ SEQUENCE 336 AA; 35329 MW; DA3128774A91AF48 CRC64; MAASLRLLGA ASGLRYWSRR LRPAAGSFAA VCSRSVASKT PVGFIGLGNM GNPMAKNLMK HGYPLIIYDV FPDACKEFQD AGEQVVSSPA DVAEKADRII TMLPTSINAI EAYSGANGIL KKVKKGSLLI DSSTIDPAVS KELAKEVEKM GAVFMDAPVS GGVGAARSGN LTFMVGGVED EFAAAQELLG CMGSNVVYCG AVGTGQAAKI CNNMLLAISM IGTAEAMNLG IRLGLDPKLL AKILNMSSGR CWSSDTYNPV PGVMDGVPSA NNYQGGFGTT LMAKDLGLAQ DSATSTKSPI LLGSLAHQIY RMMCAKGYSK KDFSSVFQFL REEETF //