O94788 (AL1A2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Retinal dehydrogenase 2
Short name=RALDH 2
Short name=RalDH2
EC=1.2.1.36

Alternative name(s):
Aldehyde dehydrogenase family 1 member A2
Retinaldehyde-specific dehydrogenase type 2
Short name=RALDH(II)

Gene names

Name:	ALDH1A2
Synonyms:	RALDH2

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	518 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Recognizes as substrates free retinal and cellular retinol-binding protein-bound retinal. Does metabolize octanal and decanal but does not metabolize citral, benzaldehyde, acetaldehyde and propanal efficiently By similarity.
Catalytic activity	Retinal + NAD+ + H2O = retinoate + NADH.
Pathway	Cofactor metabolism; retinol metabolism.
Subunit structure	Homotetramer By similarity.
Subcellular location	Cytoplasm.
Sequence similarities	Belongs to the aldehyde dehydrogenase family.
Sequence caution	The sequence BAA34786.1 differs from that shown. Reason: Erroneous initiation. The sequence BAA34787.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	NAD
Molecular function	Oxidoreductase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	9-cis-retinoic acid biosynthetic process Inferred from electronic annotation. Source: Compara anterior/posterior pattern specification Inferred from electronic annotation. Source: Compara blood vessel development Inferred from electronic annotation. Source: Compara cardiac muscle tissue development Inferred from electronic annotation. Source: Compara cellular response to retinoic acid Inferred from electronic annotation. Source: Compara determination of bilateral symmetry Inferred from electronic annotation. Source: Compara embryonic camera-type eye development Inferred from electronic annotation. Source: Compara embryonic digestive tract development Inferred from electronic annotation. Source: Compara embryonic forelimb morphogenesis Inferred from electronic annotation. Source: Compara face development Inferred from electronic annotation. Source: Compara heart morphogenesis Inferred from electronic annotation. Source: Compara hindbrain development Inferred from electronic annotation. Source: Compara kidney development Inferred from electronic annotation. Source: Compara liver development Inferred from electronic annotation. Source: Compara lung development Inferred from electronic annotation. Source: Compara midgut development Inferred from electronic annotation. Source: Compara morphogenesis of embryonic epithelium Inferred from electronic annotation. Source: Compara negative regulation of cell proliferation Inferred from direct assay PubMed 16166285. Source: UniProtKB neural crest cell development Inferred from electronic annotation. Source: Compara neural tube development Inferred from mutant phenotype PubMed 16237707. Source: UniProtKB neuron differentiation Inferred from electronic annotation. Source: Compara pancreas development Inferred from electronic annotation. Source: Compara pituitary gland development Inferred from electronic annotation. Source: Compara positive regulation of apoptotic process Inferred from electronic annotation. Source: Compara positive regulation of cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of gene expression Inferred from electronic annotation. Source: Compara proximal/distal pattern formation Inferred from electronic annotation. Source: Compara regulation of endothelial cell proliferation Inferred from electronic annotation. Source: Compara response to cytokine stimulus Inferred from direct assay PubMed 18495959. Source: UniProtKB response to estradiol stimulus Inferred from electronic annotation. Source: Compara response to vitamin A Inferred from electronic annotation. Source: Compara retinal metabolic process Inferred from electronic annotation. Source: Compara retinoic acid metabolic process Inferred from sequence or structural similarity. Source: UniProtKB retinoic acid receptor signaling pathway Inferred from electronic annotation. Source: Compara retinol metabolic process Inferred from electronic annotation. Source: UniProtKB-UniPathway ureter maturation Inferred from electronic annotation. Source: Compara vitamin A metabolic process Non-traceable author statement PubMed 8663198. Source: UniProtKB
Cellular_component	cytoplasm Inferred from direct assay PubMed 18495959. Source: UniProtKB cytosol Inferred from electronic annotation. Source: Compara nucleus Inferred from direct assay. Source: HPA perinuclear region of cytoplasm Inferred from electronic annotation. Source: Compara
Molecular_function	3-chloroallyl aldehyde dehydrogenase activity Inferred from sequence or structural similarity. Source: UniProtKB retinal binding Inferred from sequence or structural similarity. Source: UniProtKB retinal dehydrogenase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O94788-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O94788-2)

The sequence of this isoform differs from the canonical sequence as follows:
     229-266: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: O94788-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-39: MTSSKIEMPGEVKADPAALMASLHLLPSPTPNLEIKYTK → MKNQCETVWLKSPIKLKL

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 518	518	Retinal dehydrogenase 2		PRO_0000056422
Regions
	Nucleotide binding	263 – 268	6	NAD By similarity
Sites
	Active site	286	1	Proton acceptor By similarity
	Active site	320	1	Nucleophile By similarity
	Site	187	1	Transition state stabilizer By similarity
Amino acid modifications
	Modified residue	122	1	Phosphothreonine By similarity
Natural variations
	Alternative sequence	1 – 39	39	MTSSK…IKYTK → MKNQCETVWLKSPIKLKL in isoform 3.		VSP_044496
	Alternative sequence	229 – 266	38	Missing in isoform 2.		VSP_017363
	Natural variant	50	1	E → G. Ref.3 Corresponds to variant rs34266719 [ dbSNP | Ensembl ].		VAR_025439
	Natural variant	110	1	A → V. Ref.3 Corresponds to variant rs35365164 [ dbSNP | Ensembl ].		VAR_025440
	Natural variant	348	1	V → I. Ref.1 Ref.2 Ref.3 Ref.6 Corresponds to variant rs4646626 [ dbSNP | Ensembl ].		VAR_025441
	Natural variant	436	1	E → K. Ref.3 Corresponds to variant rs34744827 [ dbSNP | Ensembl ].		VAR_025442
Experimental info
	Sequence conflict	231	1	F → L in BAG64174. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 7, 2006. Version 3. Checksum: AAEE7A886951373F	FASTA	518	56,724
	10 20 30 40 50 60 MTSSKIEMPG EVKADPAALM ASLHLLPSPT PNLEIKYTKI FINNEWQNSE SGRVFPVYNP 70 80 90 100 110 120 ATGEQVCEVQ EADKADIDKA VQAARLAFSL GSVWRRMDAS ERGRLLDKLA DLVERDRAVL 130 140 150 160 170 180 ATMESLNGGK PFLQAFYVDL QGVIKTFRYY AGWADKIHGM TIPVDGDYFT FTRHEPIGVC 190 200 210 220 230 240 GQIIPWNFPL LMFAWKIAPA LCCGNTVVIK PAEQTPLSAL YMGALIKEAG FPPGVINILP 250 260 270 280 290 300 GYGPTAGAAI ASHIGIDKIA FTGSTEVGKL IQEAAGRSNL KRVTLELGGK SPNIIFADAD 310 320 330 340 350 360 LDYAVEQAHQ GVFFNQGQCC TAGSRIFVEE SIYEEFVRRS VERAKRRVVG SPFDPTTEQG 370 380 390 400 410 420 PQIDKKQYNK ILELIQSGVA EGAKLECGGK GLGRKGFFIE PTVFSNVTDD MRIAKEEIFG 430 440 450 460 470 480 PVQEILRFKT MDEVIERANN SDFGLVAAVF TNDINKALTV SSAMQAGTVW INCYNALNAQ 490 500 510 SPFGGFKMSG NGREMGEFGL REYSEVKTVT VKIPQKNS
	Isoform 2 [UniParc]. Checksum: 5AC931BE5ED26AA4	FASTA	480	53,060
	10 20 30 40 50 60 MTSSKIEMPG EVKADPAALM ASLHLLPSPT PNLEIKYTKI FINNEWQNSE SGRVFPVYNP 70 80 90 100 110 120 ATGEQVCEVQ EADKADIDKA VQAARLAFSL GSVWRRMDAS ERGRLLDKLA DLVERDRAVL 130 140 150 160 170 180 ATMESLNGGK PFLQAFYVDL QGVIKTFRYY AGWADKIHGM TIPVDGDYFT FTRHEPIGVC 190 200 210 220 230 240 GQIIPWNFPL LMFAWKIAPA LCCGNTVVIK PAEQTPLSAL YMGALIKEVG KLIQEAAGRS 250 260 270 280 290 300 NLKRVTLELG GKSPNIIFAD ADLDYAVEQA HQGVFFNQGQ CCTAGSRIFV EESIYEEFVR 310 320 330 340 350 360 RSVERAKRRV VGSPFDPTTE QGPQIDKKQY NKILELIQSG VAEGAKLECG GKGLGRKGFF 370 380 390 400 410 420 IEPTVFSNVT DDMRIAKEEI FGPVQEILRF KTMDEVIERA NNSDFGLVAA VFTNDINKAL 430 440 450 460 470 480 TVSSAMQAGT VWINCYNALN AQSPFGGFKM SGNGREMGEF GLREYSEVKT VTVKIPQKNS
	Isoform 3 [UniParc]. Checksum: 27E8A8307A680BB7	FASTA	497	54,673
	10 20 30 40 50 60 MKNQCETVWL KSPIKLKLIF INNEWQNSES GRVFPVYNPA TGEQVCEVQE ADKADIDKAV 70 80 90 100 110 120 QAARLAFSLG SVWRRMDASE RGRLLDKLAD LVERDRAVLA TMESLNGGKP FLQAFYVDLQ 130 140 150 160 170 180 GVIKTFRYYA GWADKIHGMT IPVDGDYFTF TRHEPIGVCG QIIPWNFPLL MFAWKIAPAL 190 200 210 220 230 240 CCGNTVVIKP AEQTPLSALY MGALIKEAGF PPGVINILPG YGPTAGAAIA SHIGIDKIAF 250 260 270 280 290 300 TGSTEVGKLI QEAAGRSNLK RVTLELGGKS PNIIFADADL DYAVEQAHQG VFFNQGQCCT 310 320 330 340 350 360 AGSRIFVEES IYEEFVRRSV ERAKRRVVGS PFDPTTEQGP QIDKKQYNKI LELIQSGVAE 370 380 390 400 410 420 GAKLECGGKG LGRKGFFIEP TVFSNVTDDM RIAKEEIFGP VQEILRFKTM DEVIERANNS 430 440 450 460 470 480 DFGLVAAVFT NDINKALTVS SAMQAGTVWI NCYNALNAQS PFGGFKMSGN GREMGEFGLR 490 EYSEVKTVTV KIPQKNS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"TAL1 and LIM-only proteins synergistically induce retinaldehyde dehydrogenase 2 expression in T-cell acute lymphoblastic leukemia by acting as cofactors for GATA3." Ono Y., Fukuhara N., Yoshie O. Mol. Cell. Biol. 18:6939-6950(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ILE-348.
[2]	"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] (ISOFORMS 1 AND 3), VARIANT ILE-348. Tissue: Testis and Uterus.
[3]	NIEHS SNPs program Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLY-50; VAL-110; ILE-348 AND LYS-436.
[4]	"Analysis of the DNA sequence and duplication history of human chromosome 15." Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C. Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] (ISOFORM 2). Tissue: Testis.
[6]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 302-518 (ISOFORMS 1/2), VARIANT ILE-348. Tissue: Testis.
[7]	"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].
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB015226 mRNA. Translation: BAA34785.1. AB015227 mRNA. Translation: BAA34786.1. Different initiation. AB015228 mRNA. Translation: BAA34787.1. Different initiation. AK128709 mRNA. Translation: BAG54714.1. AK303057 mRNA. Translation: BAG64174.1. DQ322171 Genomic DNA. Translation: ABC40749.1. AC012653 Genomic DNA. No translation available. AC018904 Genomic DNA. No translation available. AC025431 Genomic DNA. No translation available. AC066616 Genomic DNA. No translation available. AC084781 Genomic DNA. No translation available. BC030589 mRNA. Translation: AAH30589.1. AL110299 mRNA. Translation: CAB53740.2.
IPI	IPI00169288. IPI00216805. IPI01011430.
PIR	T14799.
RefSeq	NP_001193826.1. NM_001206897.1. NP_003879.2. NM_003888.3. NP_733797.1. NM_170696.2. NP_733798.1. NM_170697.2.
UniGene	Hs.643455.
3D structure databases
ProteinModelPortal	O94788.
ModBase	Search...
Protein-protein interaction databases
IntAct	O94788. 1 interaction.
STRING	9606.ENSP00000249750.
PTM databases
PhosphoSite	O94788.
Proteomic databases
PaxDb	O94788.
PRIDE	O94788.
Protocols and materials databases
DNASU	8854.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000249750; ENSP00000249750; ENSG00000128918. ENST00000347587; ENSP00000309623; ENSG00000128918. ENST00000537372; ENSP00000438296; ENSG00000128918.
GeneID	8854.
KEGG	hsa:8854.
UCSC	uc002aew.3. human. uc002aey.3. human.
Organism-specific databases
CTD	8854.
GeneCards	GC15M058245.
H-InvDB	HIX0038341.
HGNC	HGNC:15472. ALDH1A2.
HPA	HPA010022.
MIM	603687. gene.
neXtProt	NX_O94788.
PharmGKB	PA24693.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1012.
HOGENOM	HOG000271505.
HOVERGEN	HBG000097.
InParanoid	O94788.
KO	K07249.
OMA	ICEIQEA.
OrthoDB	EOG4Z8XW6.
PhylomeDB	O94788.
Enzyme and pathway databases
BioCyc	MetaCyc:HS05232-MONOMER.
UniPathway	UPA00912.
Gene expression databases
ArrayExpress	O94788.
Bgee	O94788.
CleanEx	HS_ALDH1A2.
Genevestigator	O94788.
GermOnline	ENSG00000128918. 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. [Graphical view]
Pfam	PF00171. Aldedh. 1 hit. [Graphical view]
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
ChiTaRS	ALDH1A2. human.
DrugBank	DB00157. NADH. DB00755. Tretinoin. DB00162. Vitamin A.
GenomeRNAi	8854.
NextBio	33241.
SOURCE	Search...

Entry information

Entry name

AL1A2_HUMAN

Accession

Primary (citable) accession number: O94788
Secondary accession number(s): B3KY52 , B4DZR2, F5H2Y9, Q2PJS6, Q8NHQ4, Q9UBR8, Q9UFY0

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	March 7, 2006
Last modified:	May 1, 2013
This is version 123 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.