AL1B1_HUMAN
ID AL1B1_HUMAN Reviewed; 517 AA.
AC P30837; B2R8F0; Q8WX76; Q9BV45;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 4.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=Aldehyde dehydrogenase X, mitochondrial;
DE EC=1.2.1.3;
DE AltName: Full=Aldehyde dehydrogenase 5;
DE AltName: Full=Aldehyde dehydrogenase family 1 member B1;
DE Flags: Precursor;
GN Name=ALDH1B1; Synonyms=ALDH5, ALDHX;
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 [GENOMIC DNA], AND VARIANTS LEU-107 AND MET-253.
RC TISSUE=Testis;
RX PubMed=2061311; DOI=10.1016/s0021-9258(18)98890-3;
RA Hsu L.C., Chang W.-C.;
RT "Cloning and characterization of a new functional human aldehyde
RT dehydrogenase gene.";
RL J. Biol. Chem. 266:12257-12265(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS LEU-107 AND MET-253.
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT MET-253.
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., 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].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS LEU-107 AND MET-253.
RC TISSUE=Eye;
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 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., Buerckstuemmer T.,
RA 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 [7]
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).
RN [8]
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., Ayoub D.,
RA 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 [9]
RP VARIANTS VAL-86 AND LEU-107.
RX PubMed=8244338; DOI=10.1007/bf00216454;
RA Sherman D., Dave V., Hsu L.C., Peters T.J., Yoshida A.;
RT "Diverse polymorphism within a short coding region of the human aldehyde
RT dehydrogenase-5 (ALDH5) gene.";
RL Hum. Genet. 92:477-480(1993).
CC -!- FUNCTION: ALDHs play a major role in the detoxification of alcohol-
CC derived acetaldehyde. They are involved in the metabolism of
CC corticosteroids, biogenic amines, neurotransmitters, and lipid
CC peroxidation.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an aldehyde + H2O + NAD(+) = a carboxylate + 2 H(+) + NADH;
CC Xref=Rhea:RHEA:16185, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17478, ChEBI:CHEBI:29067, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; EC=1.2.1.3;
CC -!- PATHWAY: Alcohol metabolism; ethanol degradation; acetate from ethanol:
CC step 2/2.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix.
CC -!- TISSUE SPECIFICITY: Liver, testis and to a lesser extent in brain.
CC -!- SIMILARITY: Belongs to the aldehyde dehydrogenase 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; M63967; AAA96830.1; -; Genomic_DNA.
DR EMBL; BT007418; AAP36086.1; -; mRNA.
DR EMBL; AK313344; BAG36147.1; -; mRNA.
DR EMBL; AL135785; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001619; AAH01619.1; -; mRNA.
DR CCDS; CCDS6615.1; -.
DR PIR; A40872; A40872.
DR RefSeq; NP_000683.3; NM_000692.4.
DR AlphaFoldDB; P30837; -.
DR SMR; P30837; -.
DR BioGRID; 106721; 145.
DR IntAct; P30837; 43.
DR MINT; P30837; -.
DR STRING; 9606.ENSP00000366927; -.
DR BindingDB; P30837; -.
DR ChEMBL; CHEMBL4881; -.
DR DrugBank; DB00157; NADH.
DR GlyGen; P30837; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P30837; -.
DR PhosphoSitePlus; P30837; -.
DR SwissPalm; P30837; -.
DR BioMuta; ALDH1B1; -.
DR DMDM; 311033472; -.
DR REPRODUCTION-2DPAGE; IPI00103467; -.
DR EPD; P30837; -.
DR jPOST; P30837; -.
DR MassIVE; P30837; -.
DR MaxQB; P30837; -.
DR PaxDb; P30837; -.
DR PeptideAtlas; P30837; -.
DR PRIDE; P30837; -.
DR ProteomicsDB; 54740; -.
DR Antibodypedia; 12074; 292 antibodies from 35 providers.
DR DNASU; 219; -.
DR Ensembl; ENST00000377698.4; ENSP00000366927.3; ENSG00000137124.8.
DR GeneID; 219; -.
DR KEGG; hsa:219; -.
DR MANE-Select; ENST00000377698.4; ENSP00000366927.3; NM_000692.5; NP_000683.3.
DR UCSC; uc004aay.4; human.
DR CTD; 219; -.
DR DisGeNET; 219; -.
DR GeneCards; ALDH1B1; -.
DR HGNC; HGNC:407; ALDH1B1.
DR HPA; ENSG00000137124; Tissue enhanced (liver, smooth muscle).
DR MIM; 100670; gene.
DR neXtProt; NX_P30837; -.
DR OpenTargets; ENSG00000137124; -.
DR PharmGKB; PA24695; -.
DR VEuPathDB; HostDB:ENSG00000137124; -.
DR eggNOG; KOG2450; Eukaryota.
DR GeneTree; ENSGT00940000162530; -.
DR HOGENOM; CLU_005391_0_2_1; -.
DR InParanoid; P30837; -.
DR OrthoDB; 153834at2759; -.
DR PhylomeDB; P30837; -.
DR TreeFam; TF300455; -.
DR BRENDA; 1.2.1.3; 2681.
DR PathwayCommons; P30837; -.
DR Reactome; R-HSA-71384; Ethanol oxidation.
DR SABIO-RK; P30837; -.
DR SignaLink; P30837; -.
DR UniPathway; UPA00780; UER00768.
DR BioGRID-ORCS; 219; 10 hits in 1083 CRISPR screens.
DR ChiTaRS; ALDH1B1; human.
DR GeneWiki; ALDH1B1; -.
DR GenomeRNAi; 219; -.
DR Pharos; P30837; Tchem.
DR PRO; PR:P30837; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; P30837; protein.
DR Bgee; ENSG00000137124; Expressed in buccal mucosa cell and 142 other tissues.
DR ExpressionAtlas; P30837; baseline and differential.
DR Genevisible; P30837; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0004029; F:aldehyde dehydrogenase (NAD+) activity; IBA:GO_Central.
DR GO; GO:0043878; F:glyceraldehyde-3-phosphate dehydrogenase (NAD+) (non-phosphorylating) activity; IEA:UniProtKB-EC.
DR GO; GO:0051287; F:NAD binding; ISS:CAFA.
DR GO; GO:0005975; P:carbohydrate metabolic process; NAS:ProtInc.
DR GO; GO:0006068; P:ethanol catabolic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.40.309.10; -; 1.
DR Gene3D; 3.40.605.10; -; 1.
DR InterPro; IPR016161; Ald_DH/histidinol_DH.
DR InterPro; IPR016163; Ald_DH_C.
DR InterPro; IPR016160; Ald_DH_CS_CYS.
DR InterPro; IPR029510; Ald_DH_CS_GLU.
DR InterPro; IPR016162; Ald_DH_N.
DR InterPro; IPR015590; Aldehyde_DH_dom.
DR Pfam; PF00171; Aldedh; 1.
DR SUPFAM; SSF53720; SSF53720; 1.
DR PROSITE; PS00070; ALDEHYDE_DEHYDR_CYS; 1.
DR PROSITE; PS00687; ALDEHYDE_DEHYDR_GLU; 1.
PE 1: Evidence at protein level;
KW Acetylation; Mitochondrion; NAD; Oxidoreductase; Reference proteome;
KW Transit peptide.
FT TRANSIT 1..17
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 18..517
FT /note="Aldehyde dehydrogenase X, mitochondrial"
FT /id="PRO_0000007172"
FT ACT_SITE 285
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007,
FT ECO:0000255|PROSITE-ProRule:PRU10008"
FT ACT_SITE 319
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007,
FT ECO:0000255|PROSITE-ProRule:PRU10008"
FT BINDING 262..267
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT SITE 186
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250"
FT MOD_RES 51
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9CZS1"
FT MOD_RES 52
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9CZS1"
FT MOD_RES 52
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9CZS1"
FT MOD_RES 81
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9CZS1"
FT MOD_RES 364
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9CZS1"
FT MOD_RES 364
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9CZS1"
FT MOD_RES 383
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9CZS1"
FT MOD_RES 383
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9CZS1"
FT MOD_RES 399
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9CZS1"
FT MOD_RES 399
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9CZS1"
FT MOD_RES 414
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9CZS1"
FT MOD_RES 414
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9CZS1"
FT MOD_RES 426
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9CZS1"
FT MOD_RES 426
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9CZS1"
FT MOD_RES 429
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9CZS1"
FT VARIANT 86
FT /note="A -> V (in dbSNP:rs2228093)"
FT /evidence="ECO:0000269|PubMed:8244338"
FT /id="VAR_002257"
FT VARIANT 107
FT /note="R -> L (in dbSNP:rs2073478)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:2061311, ECO:0000269|PubMed:8244338,
FT ECO:0000269|Ref.2"
FT /id="VAR_002258"
FT VARIANT 202
FT /note="T -> I (in dbSNP:rs4646773)"
FT /id="VAR_029891"
FT VARIANT 253
FT /note="V -> M (in dbSNP:rs4878199)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:2061311,
FT ECO:0000269|Ref.2"
FT /id="VAR_029892"
FT CONFLICT 18
FT /note="R -> L (in Ref. 1; AAA96830)"
FT /evidence="ECO:0000305"
FT CONFLICT 164
FT /note="D -> H (in Ref. 1; AAA96830)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 517 AA; 57249 MW; B877BD45FEC70025 CRC64;
MLRFLAPRLL SLQGRTARYS SAAALPSPIL NPDIPYNQLF INNEWQDAVS KKTFPTVNPT
TGEVIGHVAE GDRADVDRAV KAAREAFRLG SPWRRMDASE RGRLLNRLAD LVERDRVYLA
SLETLDNGKP FQESYALDLD EVIKVYRYFA GWADKWHGKT IPMDGQHFCF TRHEPVGVCG
QIIPWNFPLV MQGWKLAPAL ATGNTVVMKV AEQTPLSALY LASLIKEAGF PPGVVNIITG
YGPTAGAAIA QHVDVDKVAF TGSTEVGHLI QKAAGDSNLK RVTLELGGKS PSIVLADADM
EHAVEQCHEA LFFNMGQCCC AGSRTFVEES IYNEFLERTV EKAKQRKVGN PFELDTQQGP
QVDKEQFERV LGYIQLGQKE GAKLLCGGER FGERGFFIKP TVFGGVQDDM RIAKEEIFGP
VQPLFKFKKI EEVVERANNT RYGLAAAVFT RDLDKAMYFT QALQAGTVWV NTYNIVTCHT
PFGGFKESGN GRELGEDGLK AYTEVKTVTI KVPQKNS
