BODG_HUMAN
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 03-AUG-2022, entry version 182.
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}.
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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; 26.
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; O75936; -.
DR PeptideAtlas; O75936; -.
DR PRIDE; O75936; -.
DR ProteomicsDB; 50301; -.
DR Antibodypedia; 2001; 397 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 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; SVNILHC; -.
DR OrthoDB; 868657at2759; -.
DR PhylomeDB; O75936; -.
DR TreeFam; TF313805; -.
DR BioCyc; MetaCyc:HS05246-MON; -.
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 UniPathway; UPA00118; -.
DR BioGRID-ORCS; 8424; 11 hits in 1074 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 152 other tissues.
DR ExpressionAtlas; O75936; baseline and differential.
DR Genevisible; O75936; HS.
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 DisProt; DP02678; -.
DR Gene3D; 3.30.2020.30; -; 1.
DR Gene3D; 3.60.130.10; -; 1.
DR InterPro; IPR012775; GBBH.
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 Pfam; PF06155; GBBH-like_N; 1.
DR Pfam; PF02668; TauD; 1.
DR TIGRFAMs; TIGR02409; carnitine_bodg; 1.
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
