ID   CHDH_HUMAN              Reviewed;         594 AA.
AC   Q8NE62; Q9NY17;
DT   16-FEB-2004, integrated into UniProtKB/Swiss-Prot.
DT   05-MAY-2009, sequence version 2.
DT   27-MAR-2024, entry version 168.
DE   RecName: Full=Choline dehydrogenase, mitochondrial;
DE            Short=CDH;
DE            Short=CHD;
DE            EC=1.1.99.1;
DE   Flags: Precursor;
GN   Name=CHDH;
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 GENOMIC DNA].
RX   PubMed=16641997; DOI=10.1038/nature04728;
RA   Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA   Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA   Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA   Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA   Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA   Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA   Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA   Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA   Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA   Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA   Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA   Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA   Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA   Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA   Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA   Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA   Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA   Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA   Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT   "The DNA sequence, annotation and analysis of human chromosome 3.";
RL   Nature 440:1194-1198(2006).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-78.
RC   TISSUE=Testis;
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   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 113-594.
RC   TISSUE=Kidney;
RA   Bugert P., Hanke S., Chudek J., Kovacs G.;
RT   "Analysis of a putative tumor suppressor gene region of 100 kb at
RT   chromosome 3p21.1 in conventional renal cell carcinoma.";
RL   Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases.
RN   [4]
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., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=A + choline = AH2 + betaine aldehyde; Xref=Rhea:RHEA:17433,
CC         ChEBI:CHEBI:13193, ChEBI:CHEBI:15354, ChEBI:CHEBI:15710,
CC         ChEBI:CHEBI:17499; EC=1.1.99.1;
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC   -!- PATHWAY: Amine and polyamine biosynthesis; betaine biosynthesis via
CC       choline pathway; betaine aldehyde from choline (cytochrome c reductase
CC       route): step 1/1.
CC   -!- INTERACTION:
CC       Q8NE62; Q92876: KLK6; NbExp=3; IntAct=EBI-7127986, EBI-2432309;
CC       Q8NE62; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-7127986, EBI-945833;
CC   -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the GMC oxidoreductase family. {ECO:0000305}.
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DR   EMBL; AC012467; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC034502; AAH34502.1; -; mRNA.
DR   EMBL; AJ272267; CAB75961.1; -; mRNA.
DR   CCDS; CCDS2873.1; -.
DR   RefSeq; NP_060867.2; NM_018397.4.
DR   RefSeq; XP_016862286.1; XM_017006797.1.
DR   RefSeq; XP_016862287.1; XM_017006798.1.
DR   AlphaFoldDB; Q8NE62; -.
DR   SMR; Q8NE62; -.
DR   BioGRID; 120629; 27.
DR   CORUM; Q8NE62; -.
DR   IntAct; Q8NE62; 16.
DR   MINT; Q8NE62; -.
DR   STRING; 9606.ENSP00000319851; -.
DR   DrugBank; DB00122; Choline.
DR   DrugBank; DB14006; Choline salicylate.
DR   iPTMnet; Q8NE62; -.
DR   PhosphoSitePlus; Q8NE62; -.
DR   SwissPalm; Q8NE62; -.
DR   BioMuta; CHDH; -.
DR   DMDM; 229462828; -.
DR   EPD; Q8NE62; -.
DR   jPOST; Q8NE62; -.
DR   MassIVE; Q8NE62; -.
DR   MaxQB; Q8NE62; -.
DR   PaxDb; 9606-ENSP00000319851; -.
DR   PeptideAtlas; Q8NE62; -.
DR   ProteomicsDB; 73126; -.
DR   Pumba; Q8NE62; -.
DR   Antibodypedia; 31431; 161 antibodies from 23 providers.
DR   DNASU; 55349; -.
DR   Ensembl; ENST00000315251.11; ENSP00000319851.5; ENSG00000016391.11.
DR   GeneID; 55349; -.
DR   KEGG; hsa:55349; -.
DR   MANE-Select; ENST00000315251.11; ENSP00000319851.5; NM_018397.5; NP_060867.2.
DR   UCSC; uc003dgz.4; human.
DR   AGR; HGNC:24288; -.
DR   CTD; 55349; -.
DR   DisGeNET; 55349; -.
DR   GeneCards; CHDH; -.
DR   HGNC; HGNC:24288; CHDH.
DR   HPA; ENSG00000016391; Tissue enhanced (kidney, liver).
DR   neXtProt; NX_Q8NE62; -.
DR   OpenTargets; ENSG00000016391; -.
DR   PharmGKB; PA134873121; -.
DR   VEuPathDB; HostDB:ENSG00000016391; -.
DR   eggNOG; KOG1238; Eukaryota.
DR   GeneTree; ENSGT00530000063260; -.
DR   HOGENOM; CLU_002865_7_1_1; -.
DR   InParanoid; Q8NE62; -.
DR   OMA; NHFESCA; -.
DR   OrthoDB; 3382025at2759; -.
DR   PhylomeDB; Q8NE62; -.
DR   TreeFam; TF313911; -.
DR   BioCyc; MetaCyc:HS00375-MONOMER; -.
DR   BRENDA; 1.1.99.1; 2681.
DR   PathwayCommons; Q8NE62; -.
DR   Reactome; R-HSA-6798163; Choline catabolism.
DR   SignaLink; Q8NE62; -.
DR   UniPathway; UPA00529; UER00385.
DR   BioGRID-ORCS; 55349; 13 hits in 1145 CRISPR screens.
DR   ChiTaRS; CHDH; human.
DR   GenomeRNAi; 55349; -.
DR   Pharos; Q8NE62; Tbio.
DR   PRO; PR:Q8NE62; -.
DR   Proteomes; UP000005640; Chromosome 3.
DR   RNAct; Q8NE62; Protein.
DR   Bgee; ENSG00000016391; Expressed in kidney epithelium and 186 other cell types or tissues.
DR   ExpressionAtlas; Q8NE62; baseline and differential.
DR   GO; GO:0005743; C:mitochondrial inner membrane; IBA:GO_Central.
DR   GO; GO:0008812; F:choline dehydrogenase activity; IBA:GO_Central.
DR   GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR   GO; GO:0042426; P:choline catabolic process; TAS:Reactome.
DR   GO; GO:0019285; P:glycine betaine biosynthetic process from choline; IEA:UniProtKB-UniPathway.
DR   Gene3D; 3.50.50.60; FAD/NAD(P)-binding domain; 1.
DR   Gene3D; 3.30.560.10; Glucose Oxidase, domain 3; 1.
DR   InterPro; IPR036188; FAD/NAD-bd_sf.
DR   InterPro; IPR012132; GMC_OxRdtase.
DR   InterPro; IPR000172; GMC_OxRdtase_N.
DR   InterPro; IPR007867; GMC_OxRtase_C.
DR   PANTHER; PTHR11552:SF147; CHOLINE DEHYDROGENASE, MITOCHONDRIAL; 1.
DR   PANTHER; PTHR11552; GLUCOSE-METHANOL-CHOLINE GMC OXIDOREDUCTASE; 1.
DR   Pfam; PF05199; GMC_oxred_C; 1.
DR   Pfam; PF00732; GMC_oxred_N; 1.
DR   PIRSF; PIRSF000137; Alcohol_oxidase; 1.
DR   SUPFAM; SSF54373; FAD-linked reductases, C-terminal domain; 1.
DR   SUPFAM; SSF51905; FAD/NAD(P)-binding domain; 1.
DR   PROSITE; PS00623; GMC_OXRED_1; 1.
DR   PROSITE; PS00624; GMC_OXRED_2; 1.
DR   Genevisible; Q8NE62; HS.
PE   1: Evidence at protein level;
KW   Acetylation; FAD; Flavoprotein; Membrane; Mitochondrion;
KW   Mitochondrion inner membrane; Oxidoreductase; Reference proteome;
KW   Transit peptide.
FT   TRANSIT         1..29
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000250"
FT   CHAIN           30..594
FT                   /note="Choline dehydrogenase, mitochondrial"
FT                   /id="PRO_0000012329"
FT   ACT_SITE        511
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:E4QP00"
FT   BINDING         42..71
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         436
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8BJ64"
FT   MOD_RES         484
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8BJ64"
FT   MOD_RES         484
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8BJ64"
FT   MOD_RES         496
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8BJ64"
FT   MOD_RES         496
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8BJ64"
FT   MOD_RES         580
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8BJ64"
FT   VARIANT         40
FT                   /note="E -> A (in dbSNP:rs9001)"
FT                   /id="VAR_020421"
FT   VARIANT         78
FT                   /note="L -> R (in dbSNP:rs12676)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_055097"
FT   VARIANT         441
FT                   /note="N -> S (in dbSNP:rs34974961)"
FT                   /id="VAR_049357"
FT   CONFLICT        113
FT                   /note="R -> A (in Ref. 3; CAB75961)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   594 AA;  65358 MW;  E9764CD0F325A501 CRC64;
     MWCLLRGLGR PGALARGALG QQQSLGARAL ASAGSESRDE YSYVVVGAGS AGCVLAGRLT
     EDPAERVLLL EAGPKDVLAG SKRLSWKIHM PAALVANLCD DRYNWCYHTE VQRGLDGRVL
     YWPRGRVWGG SSSLNAMVYV RGHAEDYERW QRQGARGWDY AHCLPYFRKA QGHELGASRY
     RGADGPLRVS RGKTNHPLHC AFLEATQQAG YPLTEDMNGF QQEGFGWMDM TIHEGKRWSA
     ACAYLHPALS RTNLKAEAET LVSRVLFEGT RAVGVEYVKN GQSHRAYASK EVILSGGAIN
     SPQLLMLSGI GNADDLKKLG IPVVCHLPGV GQNLQDHLEI YIQQACTRPI TLHSAQKPLR
     KVCIGLEWLW KFTGEGATAH LETGGFIRSQ PGVPHPDIQF HFLPSQVIDH GRVPTQQEAY
     QVHVGPMRGT SVGWLKLRSA NPQDHPVIQP NYLSTETDIE DFRLCVKLTR EIFAQEALAP
     FRGKELQPGS HIQSDKEIDA FVRAKADSAY HPSCTCKMGQ PSDPTAVVDP QTRVLGVENL
     RVVDASIMPS MVSGNLNAPT IMIAEKAADI IKGQPALWDK DVPVYKPRTL ATQR
//