P30838 (AL3A1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Aldehyde dehydrogenase, dimeric NADP-preferring
EC=1.2.1.5

Alternative name(s):
ALDHIII
Aldehyde dehydrogenase 3
Aldehyde dehydrogenase family 3 member A1

Gene names

Name:	ALDH3A1
Synonyms:	ALDH3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	453 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	ALDHs play a major role in the detoxification of alcohol-derived acetaldehyde. They are involved in the metabolism of corticosteroids, biogenic amines, neurotransmitters, and lipid peroxidation. This protein preferentially oxidizes aromatic aldehyde substrates. It may play a role in the oxidation of toxic aldehydes.
Catalytic activity	An aldehyde + NAD(P)+ + H2O = a carboxylate + NAD(P)H.
Subunit structure	Homodimer.
Subcellular location	Cytoplasm.
Tissue specificity	High levels in stomach, esophagus and lung; low level in the liver and kidney.
Sequence similarities	Belongs to the aldehyde dehydrogenase family.
Biophysicochemical properties	Kinetic parameters: Has a high Km for acetaldehyde.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	NAD NADP
Molecular function	Oxidoreductase
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	aging Inferred from electronic annotation. Source: Compara cellular aldehyde metabolic process Inferred from direct assay Ref.2. Source: UniProtKB positive regulation of cell proliferation Inferred from electronic annotation. Source: Compara response to cAMP Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to glucocorticoid stimulus Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from electronic annotation. Source: Compara response to nutrient Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Inferred from sequence or structural similarity. Source: UniProtKB endoplasmic reticulum Inferred from direct assay. Source: LIFEdb
Molecular_function	3-chloroallyl aldehyde dehydrogenase activity Inferred from electronic annotation. Source: Compara alcohol dehydrogenase (NADP+) activity Inferred from direct assay Ref.2. Source: UniProtKB aldehyde dehydrogenase (NAD) activity Inferred from direct assay Ref.2. Source: UniProtKB aldehyde dehydrogenase [NAD(P)+] activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 453

453

Aldehyde dehydrogenase, dimeric NADP-preferring

PRO_0000056470

Regions

Nucleotide binding

188 – 193

6

NAD or NADP By similarity

Sites

Active site

210

1

Ref.13

Active site

244

1

Ref.13

Amino acid modifications

Modified residue

178

1

N6-acetyllysine Ref.11

Modified residue

194

1

N6-acetyllysine Ref.11

Natural variations

Natural variant

134

1

S → A. Ref.1 Ref.4 Ref.5 Ref.7 Ref.8
Corresponds to variant rs887241 [ dbSNP | Ensembl ].

VAR_018981

Natural variant

309

1

G → E.
Corresponds to variant rs3744692 [ dbSNP | Ensembl ].

VAR_018982

Natural variant

329

1

P → A in allele ALDH3A1*2. Ref.14
Corresponds to variant rs2228100 [ dbSNP | Ensembl ].

VAR_011303

Experimental info

Mutagenesis

244

1

C → S: Abolishes activity. Ref.13

Sequence conflict

12

1

R → P in AAB46377. Ref.2

Sequence conflict

12

1

R → P in AAB26658. Ref.3

Sequence conflict

27

1

I → F in AAA51696. Ref.1

Sequence conflict

170

1

V → L AA sequence Ref.9

Sequence conflict

436

1

D → E AA sequence Ref.9

Secondary structure

1

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453

Helix Strand Turn

Details...

Helix

3 – 16

14

Turn

17 – 20

4

Helix

23 – 39

17

Helix

41 – 52

12

Helix

56 – 61

6

Helix

64 – 82

19

Helix

91 – 93

3

Beta strand

96 – 104

9

Beta strand

106 – 111

6

Beta strand

114 – 116

3

Helix

119 – 130

12

Beta strand

134 – 138

5

Helix

144 – 157

14

Turn

160 – 162

3

Helix

170 – 176

7

Beta strand

182 – 188

7

Helix

190 – 201

12

Turn

202 – 204

3

Beta strand

207 – 210

4

Beta strand

216 – 219

4

Helix

225 – 237

13

Helix

238 – 241

4

Beta strand

249 – 252

4

Helix

254 – 256

3

Helix

257 – 272

16

Helix

276 – 278

3

Helix

288 – 298

11

Beta strand

301 – 305

5

Turn

311 – 314

4

Beta strand

319 – 323

5

Helix

329 – 331

3

Beta strand

337 – 344

8

Helix

348 – 357

10

Beta strand

362 – 367

6

Helix

371 – 380

10

Beta strand

384 – 389

6

Helix

393 – 395

3

Helix

406 – 408

3

Helix

416 – 421

6

Beta strand

423 – 430

8

Helix

437 – 442

6

Beta strand

443 – 445

3

Sequences

	Sequence		Length	Mass (Da)
	P30838 [UniParc]. Last modified November 2, 2010. Version 3. Checksum: D35C488A022FAACA	FASTA	453	50,395
	10 20 30 40 50 60 MSKISEAVKR ARAAFSSGRT RPLQFRIQQL EALQRLIQEQ EQELVGALAA DLHKNEWNAY 70 80 90 100 110 120 YEEVVYVLEE IEYMIQKLPE WAADEPVEKT PQTQQDELYI HSEPLGVVLV IGTWNYPFNL 130 140 150 160 170 180 TIQPMVGAIA AGNSVVLKPS ELSENMASLL ATIIPQYLDK DLYPVINGGV PETTELLKER 190 200 210 220 230 240 FDHILYTGST GVGKIIMTAA AKHLTPVTLE LGGKSPCYVD KNCDLDVACR RIAWGKFMNS 250 260 270 280 290 300 GQTCVAPDYI LCDPSIQNQI VEKLKKSLKE FYGEDAKKSR DYGRIISARH FQRVMGLIEG 310 320 330 340 350 360 QKVAYGGTGD AATRYIAPTI LTDVDPQSPV MQEEIFGPVL PIVCVRSLEE AIQFINQREK 370 380 390 400 410 420 PLALYMFSSN DKVIKKMIAE TSSGGVAAND VIVHITLHSL PFGGVGNSGM GSYHGKKSFE 430 440 450 TFSHRRSCLV RPLMNDEGLK VRYPPSPAKM TQH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and complete nucleotide sequence of a cDNA encoding the full-length open reading frame of the human aldehyde dehydrogenase type III gene." Schuuring E.M.D., Verhoeven E., Eckey R., Vos H.L., Michalides R.J.A. Submitted (AUG-1991) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ALA-134. Tissue: Stomach.
[2]	"Human stomach aldehyde dehydrogenase cDNA and genomic cloning, primary structure, and expression in Escherichia coli." Hsu L.C., Chang W.-C., Shibuya A., Yoshida A. J. Biol. Chem. 267:3030-3037(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Stomach.
[3]	"Human stomach aldehyde dehydrogenase, ALDH3." Hsu L.C., Yoshida A. Adv. Exp. Med. Biol. 328:141-152(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Stomach.
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-134.
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-134. Tissue: Cervix and Tongue.
[6]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ALA-134.
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-134. Tissue: Pancreas.
[9]	"Structural features of stomach aldehyde dehydrogenase distinguish dimeric aldehyde dehydrogenase as a 'variable' enzyme. 'Variable' and 'constant' enzymes within the alcohol and aldehyde dehydrogenase families." Yin S.-J., Vagelopoulos N., Wang S.-L., Joernvall H. FEBS Lett. 283:85-88(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 62-453. Tissue: Stomach.
[10]	"Biochemical, immunological, and molecular characterization of a 'high Km' aldehyde dehydrogenase." Eckey R., Timmann R., Hempel J., Agarwal D.P., Goedde H.W. Adv. Exp. Med. Biol. 284:43-52(1991) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[11]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-178 AND LYS-194, MASS SPECTROMETRY.
[12]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]	"Discovery of a novel class of covalent inhibitor for aldehyde dehydrogenases." Khanna M., Chen C.H., Kimble-Hill A., Parajuli B., Perez-Miller S., Baskaran S., Kim J., Dria K., Vasiliou V., Mochly-Rosen D., Hurley T.D. J. Biol. Chem. 286:43486-43494(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.48 ANGSTROMS) IN COMPLEX WITH INHIBITOR, MUTAGENESIS OF CYS-244, ACTIVE SITE.
[14]	"Mutations associated with Sjogren-Larsson syndrome." Tsukamoto N., Chang C., Yoshida A. Ann. Hum. Genet. 61:235-242(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ALA-329.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M74542 mRNA. Translation: AAA51696.1.
M77477 mRNA. Translation: AAB46377.1.
S61044 mRNA. Translation: AAB26658.1.
BT007102 mRNA. Translation: AAP35766.1.
AK292193 mRNA. Translation: BAF84882.1.
AK314584 mRNA. Translation: BAG37160.1.
AC005722 Genomic DNA. No translation available.
CH471212 Genomic DNA. Translation: EAW50909.1.
BC004370 mRNA. Translation: AAH04370.1.
BC008892 mRNA. Translation: AAH08892.1.
BC021194 mRNA. Translation: AAH21194.1.

IPI

IPI00296183.

PIR

A42584.

RefSeq

NP_000682.3. NM_000691.4.
NP_001128639.1. NM_001135167.1.
NP_001128640.1. NM_001135168.1.

UniGene

Hs.531682.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3SZA	X-ray	1.48	A/B	1-453	[»]
3SZB	X-ray	1.51	A/B	1-453	[»]

ProteinModelPortal

P30838.

SMR

P30838. Positions 2-453.

ModBase

Search...

Protein-protein interaction databases

IntAct

P30838. 2 interactions.

STRING

9606.ENSP00000225740.

PTM databases

PhosphoSite

P30838.

Polymorphism databases

DMDM

311033473.

Proteomic databases

PaxDb

P30838.

PRIDE

P30838.

Protocols and materials databases

DNASU

218.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000225740; ENSP00000225740; ENSG00000108602.
ENST00000444455; ENSP00000388469; ENSG00000108602.
ENST00000457500; ENSP00000411821; ENSG00000108602.

GeneID

218.

KEGG

hsa:218.

UCSC

uc002gwj.3. human.

Organism-specific databases

CTD

218.

GeneCards

GC17M019641.

H-InvDB

HIX0013622.

HGNC

HGNC:405. ALDH3A1.

HPA

CAB045957.
HPA051150.

MIM

100660. gene.

neXtProt

NX_P30838.

PharmGKB

PA24697.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1012.

HOGENOM

HOG000271515.

HOVERGEN

HBG050483.

KO

K00129.

Enzyme and pathway databases

SABIO-RK

P30838.

Gene expression databases

ArrayExpress

P30838.

Bgee

P30838.

CleanEx

HS_ALDH3A1.

Genevestigator

P30838.

GermOnline

ENSG00000108602. Homo sapiens.

Family and domain databases

Gene3D

3.40.309.10. 1 hit.
3.40.605.10. 1 hit.

InterPro

IPR016161. Ald_DH/histidinol_DH.
IPR016163. Ald_DH_C.
IPR016160. Ald_DH_CS.
IPR016162. Ald_DH_N.
IPR015590. Aldehyde_DH_dom.
IPR012394. Aldehyde_DH_NAD(P).
[Graphical view]

PANTHER

PTHR11699:SF15. PTHR11699:SF15. 1 hit.

Pfam

PF00171. Aldedh. 1 hit.
[Graphical view]

PIRSF

PIRSF036492. ALDH. 1 hit.

SUPFAM

SSF53720. Aldehyde_DH/Histidinol_DH. 1 hit.

PROSITE

PS00070. ALDEHYDE_DEHYDR_CYS. 1 hit.
PS00687. ALDEHYDE_DEHYDR_GLU. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL3578.

ChiTaRS

ALDH3A1. human.

DrugBank

DB00157. NADH.

EvolutionaryTrace

P30838.

GenomeRNAi

218.

NextBio

882.

SOURCE

Search...

Entry information

Entry name

AL3A1_HUMAN

Accession

Primary (citable) accession number: P30838
Secondary accession number(s): A8K828, Q9BT37

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1993
Last sequence update:	November 2, 2010
Last modified:	May 1, 2013
This is version 131 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.