ID BODG_HUMAN Reviewed; 387 AA. AC O75936; B2R8L7; D3DQZ1; Q6IBJ2; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1998, sequence version 1. DT 27-MAR-2024, entry version 191. DE RecName: Full=Gamma-butyrobetaine dioxygenase; DE EC=1.14.11.1; DE AltName: Full=Gamma-butyrobetaine hydroxylase; DE Short=Gamma-BBH; DE AltName: Full=Gamma-butyrobetaine,2-oxoglutarate dioxygenase; GN Name=BBOX1; Synonyms=BBH, BBOX; 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 [MRNA]. RC TISSUE=Liver; RX PubMed=9753662; DOI=10.1006/bbrc.1998.9343; RA Vaz F.M., van Gool S., Ofman R., Ijlst L., Wanders R.J.A.; RT "Carnitine biosynthesis: identification of the cDNA encoding human gamma- RT butyrobetaine hydroxylase."; RL Biochem. Biophys. Res. Commun. 250:506-510(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Cerebellum; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Kidney; 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 [6] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH ZINC IONS, CATALYTIC RP ACTIVITY, AND SUBUNIT. RX PubMed=20599753; DOI=10.1016/j.bbrc.2010.06.121; RA Tars K., Rumnieks J., Zeltins A., Kazaks A., Kotelovica S., Leonciks A., RA Sharipo J., Viksna A., Kuka J., Liepinsh E., Dambrova M.; RT "Crystal structure of human gamma-butyrobetaine hydroxylase."; RL Biochem. Biophys. Res. Commun. 398:634-639(2010). CC -!- FUNCTION: Catalyzes the formation of L-carnitine from gamma- CC butyrobetaine. CC -!- CATALYTIC ACTIVITY: CC Reaction=2-oxoglutarate + 4-(trimethylamino)butanoate + O2 = carnitine CC + CO2 + succinate; Xref=Rhea:RHEA:24028, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16244, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, CC ChEBI:CHEBI:17126, ChEBI:CHEBI:30031; EC=1.14.11.1; CC Evidence={ECO:0000269|PubMed:20599753}; CC -!- COFACTOR: CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000305}; CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000305}; CC -!- COFACTOR: CC Name=L-ascorbate; Xref=ChEBI:CHEBI:38290; CC -!- PATHWAY: Amine and polyamine biosynthesis; carnitine biosynthesis. CC -!- INTERACTION: CC O75936; O75936: BBOX1; NbExp=6; IntAct=EBI-715662, EBI-715662; CC O75936; A0MZ66-7: SHTN1; NbExp=3; IntAct=EBI-715662, EBI-10171490; CC -!- SUBCELLULAR LOCATION: Cytoplasm. CC -!- TISSUE SPECIFICITY: Highly expressed in kidney; moderately expressed in CC liver; very low expression in brain. CC -!- SIMILARITY: Belongs to the gamma-BBH/TMLD 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; AF082868; AAC64066.1; -; mRNA. DR EMBL; CR456812; CAG33093.1; -; mRNA. DR EMBL; AK313422; BAG36214.1; -; mRNA. DR EMBL; CH471064; EAW68290.1; -; Genomic_DNA. DR EMBL; CH471064; EAW68291.1; -; Genomic_DNA. DR EMBL; BC011034; AAH11034.1; -; mRNA. DR CCDS; CCDS7862.1; -. DR PIR; JE0360; JE0360. DR RefSeq; NP_003977.1; NM_003986.2. DR RefSeq; XP_005253216.1; XM_005253159.2. DR RefSeq; XP_005253217.1; XM_005253160.2. DR RefSeq; XP_005253218.1; XM_005253161.2. DR RefSeq; XP_011518704.1; XM_011520402.1. DR RefSeq; XP_016873892.1; XM_017018403.1. DR PDB; 3MS5; X-ray; 1.82 A; A=1-387. DR PDB; 3N6W; X-ray; 2.00 A; A=1-387. DR PDB; 3O2G; X-ray; 1.78 A; A=1-387. DR PDB; 4BG1; X-ray; 1.89 A; A=1-387. DR PDB; 4BGK; X-ray; 2.18 A; A=1-387. DR PDB; 4BGM; X-ray; 2.40 A; A=1-387. DR PDB; 4BHF; X-ray; 2.05 A; A=1-387. DR PDB; 4BHG; X-ray; 1.85 A; A=1-387. DR PDB; 4BHI; X-ray; 2.15 A; A=1-387. DR PDB; 4C5W; X-ray; 1.70 A; A=1-387. DR PDB; 4C8R; X-ray; 2.82 A; A/B/C/D/E/F=1-387. DR PDB; 4CWD; X-ray; 1.90 A; A=1-387. DR PDBsum; 3MS5; -. DR PDBsum; 3N6W; -. DR PDBsum; 3O2G; -. DR PDBsum; 4BG1; -. DR PDBsum; 4BGK; -. DR PDBsum; 4BGM; -. DR PDBsum; 4BHF; -. DR PDBsum; 4BHG; -. DR PDBsum; 4BHI; -. DR PDBsum; 4C5W; -. DR PDBsum; 4C8R; -. DR PDBsum; 4CWD; -. DR AlphaFoldDB; O75936; -. DR SMR; O75936; -. DR BioGRID; 114008; 28. DR IntAct; O75936; 16. DR MINT; O75936; -. DR STRING; 9606.ENSP00000263182; -. DR BindingDB; O75936; -. DR ChEMBL; CHEMBL2163175; -. DR DrugBank; DB00126; Ascorbic acid. DR DrugCentral; O75936; -. DR iPTMnet; O75936; -. DR PhosphoSitePlus; O75936; -. DR BioMuta; BBOX1; -. DR EPD; O75936; -. DR jPOST; O75936; -. DR MassIVE; O75936; -. DR PaxDb; 9606-ENSP00000263182; -. DR PeptideAtlas; O75936; -. DR ProteomicsDB; 50301; -. DR Antibodypedia; 2001; 453 antibodies from 30 providers. DR DNASU; 8424; -. DR Ensembl; ENST00000263182.8; ENSP00000263182.3; ENSG00000129151.9. DR Ensembl; ENST00000525090.1; ENSP00000433772.1; ENSG00000129151.9. DR Ensembl; ENST00000528583.5; ENSP00000434918.1; ENSG00000129151.9. DR Ensembl; ENST00000529202.5; ENSP00000435781.1; ENSG00000129151.9. DR GeneID; 8424; -. DR KEGG; hsa:8424; -. DR MANE-Select; ENST00000263182.8; ENSP00000263182.3; NM_003986.3; NP_003977.1. DR UCSC; uc001mre.1; human. DR AGR; HGNC:964; -. DR CTD; 8424; -. DR DisGeNET; 8424; -. DR GeneCards; BBOX1; -. DR HGNC; HGNC:964; BBOX1. DR HPA; ENSG00000129151; Group enriched (kidney, liver). DR MIM; 603312; gene. DR neXtProt; NX_O75936; -. DR OpenTargets; ENSG00000129151; -. DR PharmGKB; PA25274; -. DR VEuPathDB; HostDB:ENSG00000129151; -. DR eggNOG; KOG3888; Eukaryota. DR GeneTree; ENSGT00530000063582; -. DR HOGENOM; CLU_021859_2_0_1; -. DR InParanoid; O75936; -. DR OMA; VHITWPN; -. DR OrthoDB; 5485575at2759; -. DR PhylomeDB; O75936; -. DR TreeFam; TF313805; -. DR BioCyc; MetaCyc:HS05246-MONOMER; -. DR BRENDA; 1.14.11.1; 2681. DR PathwayCommons; O75936; -. DR Reactome; R-HSA-71262; Carnitine synthesis. DR SABIO-RK; O75936; -. DR SignaLink; O75936; -. DR SIGNOR; O75936; -. DR UniPathway; UPA00118; -. DR BioGRID-ORCS; 8424; 11 hits in 1158 CRISPR screens. DR ChiTaRS; BBOX1; human. DR EvolutionaryTrace; O75936; -. DR GeneWiki; Gamma-butyrobetaine_dioxygenase; -. DR GenomeRNAi; 8424; -. DR Pharos; O75936; Tchem. DR PRO; PR:O75936; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; O75936; Protein. DR Bgee; ENSG00000129151; Expressed in adult mammalian kidney and 154 other cell types or tissues. DR ExpressionAtlas; O75936; baseline and differential. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central. DR GO; GO:0008336; F:gamma-butyrobetaine dioxygenase activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0005506; F:iron ion binding; IEA:InterPro. DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB. DR GO; GO:0045329; P:carnitine biosynthetic process; IDA:UniProtKB. DR CDD; cd00250; CAS_like; 1. DR DisProt; DP02678; -. DR Gene3D; 3.30.2020.30; -; 1. DR Gene3D; 3.60.130.10; Clavaminate synthase-like; 1. DR InterPro; IPR012775; GBBH-like. DR InterPro; IPR010376; GBBH-like_N. DR InterPro; IPR038492; GBBH-like_N_sf. DR InterPro; IPR042098; TauD-like_sf. DR InterPro; IPR003819; TauD/TfdA-like. DR NCBIfam; TIGR02409; carnitine_bodg; 1. DR PANTHER; PTHR10696:SF33; GAMMA-BUTYROBETAINE DIOXYGENASE; 1. DR PANTHER; PTHR10696; GAMMA-BUTYROBETAINE HYDROXYLASE-RELATED; 1. DR Pfam; PF06155; GBBH-like_N; 1. DR Pfam; PF02668; TauD; 1. DR SUPFAM; SSF51197; Clavaminate synthase-like; 1. DR Genevisible; O75936; HS. PE 1: Evidence at protein level; KW 3D-structure; Carnitine biosynthesis; Cytoplasm; Dioxygenase; Iron; KW Metal-binding; Oxidoreductase; Phosphoprotein; Reference proteome; Zinc. FT CHAIN 1..387 FT /note="Gamma-butyrobetaine dioxygenase" FT /id="PRO_0000207085" FT BINDING 38 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT BINDING 40 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT BINDING 43 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT BINDING 82 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT BINDING 202 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000305" FT BINDING 204 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000305" FT BINDING 347 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000305" FT MOD_RES 351 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9QZU7" FT TURN 1..3 FT /evidence="ECO:0007829|PDB:3O2G" FT STRAND 4..11 FT /evidence="ECO:0007829|PDB:4C5W" FT TURN 12..15 FT /evidence="ECO:0007829|PDB:4C5W" FT STRAND 16..21 FT /evidence="ECO:0007829|PDB:4C5W" FT STRAND 26..30 FT /evidence="ECO:0007829|PDB:4C5W" FT HELIX 31..36 FT /evidence="ECO:0007829|PDB:4C5W" FT TURN 41..43 FT /evidence="ECO:0007829|PDB:4C5W" FT TURN 46..49 FT /evidence="ECO:0007829|PDB:4C5W" FT HELIX 55..57 FT /evidence="ECO:0007829|PDB:4C5W" FT STRAND 65..69 FT /evidence="ECO:0007829|PDB:4C5W" FT STRAND 71..77 FT /evidence="ECO:0007829|PDB:4C5W" FT STRAND 83..87 FT /evidence="ECO:0007829|PDB:4C5W" FT HELIX 88..93 FT /evidence="ECO:0007829|PDB:4C5W" FT HELIX 98..109 FT /evidence="ECO:0007829|PDB:4C5W" FT STRAND 124..126 FT /evidence="ECO:0007829|PDB:4C5W" FT HELIX 127..132 FT /evidence="ECO:0007829|PDB:4C5W" FT HELIX 134..147 FT /evidence="ECO:0007829|PDB:4C5W" FT STRAND 148..153 FT /evidence="ECO:0007829|PDB:4C5W" FT STRAND 157..159 FT /evidence="ECO:0007829|PDB:4CWD" FT HELIX 161..169 FT /evidence="ECO:0007829|PDB:4C5W" FT STRAND 178..184 FT /evidence="ECO:0007829|PDB:4C5W" FT HELIX 192..194 FT /evidence="ECO:0007829|PDB:4C5W" FT STRAND 195..197 FT /evidence="ECO:0007829|PDB:4C5W" FT STRAND 199..202 FT /evidence="ECO:0007829|PDB:4C5W" FT STRAND 208..210 FT /evidence="ECO:0007829|PDB:4C5W" FT STRAND 213..221 FT /evidence="ECO:0007829|PDB:4C5W" FT STRAND 224..226 FT /evidence="ECO:0007829|PDB:4C5W" FT STRAND 229..233 FT /evidence="ECO:0007829|PDB:4C5W" FT HELIX 234..244 FT /evidence="ECO:0007829|PDB:4C5W" FT HELIX 246..252 FT /evidence="ECO:0007829|PDB:4C5W" FT STRAND 256..280 FT /evidence="ECO:0007829|PDB:4C5W" FT STRAND 286..289 FT /evidence="ECO:0007829|PDB:4C5W" FT TURN 293..295 FT /evidence="ECO:0007829|PDB:4C5W" FT HELIX 304..306 FT /evidence="ECO:0007829|PDB:4C5W" FT HELIX 307..322 FT /evidence="ECO:0007829|PDB:4C5W" FT TURN 324..326 FT /evidence="ECO:0007829|PDB:4C5W" FT STRAND 328..330 FT /evidence="ECO:0007829|PDB:4C5W" FT STRAND 337..341 FT /evidence="ECO:0007829|PDB:4C5W" FT TURN 342..344 FT /evidence="ECO:0007829|PDB:4C5W" FT STRAND 345..349 FT /evidence="ECO:0007829|PDB:4C5W" FT STRAND 361..367 FT /evidence="ECO:0007829|PDB:4C5W" FT HELIX 369..383 FT /evidence="ECO:0007829|PDB:4C5W" SQ SEQUENCE 387 AA; 44715 MW; A3BA3F9FA9355DB3 CRC64; MACTIQKAEA LDGAHLMQIL WYDEEESLYP AVWLRDNCPC SDCYLDSAKA RKLLVEALDV NIGIKGLIFD RKKVYITWPD EHYSEFQADW LKKRCFSKQA RAKLQRELFF PECQYWGSEL QLPTLDFEDV LRYDEHAYKW LSTLKKVGIV RLTGASDKPG EVSKLGKRMG FLYLTFYGHT WQVQDKIDAN NVAYTTGKLS FHTDYPALHH PPGVQLLHCI KQTVTGGDSE IVDGFNVCQK LKKNNPQAFQ ILSSTFVDFT DIGVDYCDFS VQSKHKIIEL DDKGQVVRIN FNNATRDTIF DVPVERVQPF YAALKEFVDL MNSKESKFTF KMNPGDVITF DNWRLLHGRR SYEAGTEISR HLEGAYADWD VVMSRLRILR QRVENGN //