Reviewed, UniProtKB/Swiss-Prot P51648 (AL3A2_HUMAN)

Names and origin

Protein names

Recommended name:
    Fatty aldehyde dehydrogenase
    EC=1.2.1.3
Alternative name(s):
    Aldehyde dehydrogenase family 3 member A2
    Aldehyde dehydrogenase 10
    Microsomal aldehyde dehydrogenase

Gene names

Name:	ALDH3A2
Synonyms:	ALDH10, FALDH

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	485 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Catalyzes the oxidation of long-chain aliphatic aldehydes to fatty acids. Active on a variety of saturated and unsaturated aliphatic aldehydes between 6 and 24 carbons in length.
Catalytic activity	An aldehyde + NAD(+) + H(2)O = an acid + NADH.
Subcellular location	Endoplasmic reticulum membrane; Single-pass membrane protein; Cytoplasmic side.
Involvement in disease	Defects in ALDH3A2 are the cause of Sjoegren-Larsson syndrome (SLS) [MIM:270200]. SLS is an autosomal recessive neurocutaneous disorder characterized by a combination of severe mental retardation, spastic di- or tetraplegia and congenital ichthyosis (increased keratinization). Ichthyosis is usually evident at birth, neurologic symptoms appear in the first or second year of life. Most patients have an IQ of less than 60. Additional clinical features include glistening white spots on the retina, seizures, short stature and speech defects.
Sequence similarities	Belongs to the aldehyde dehydrogenase family.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Ichthyosis Mental retardation
Domain	Transmembrane
Ligand	NAD
Molecular function	Oxidoreductase
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	cellular aldehyde metabolic process Inferred from electronic annotation. Source: InterPro central nervous system development Ref.1 Traceable author statement. Source: ProtInc epidermis development Ref.1 Traceable author statement. Source: ProtInc lipid metabolic process Ref.1 Traceable author statement. Source: ProtInc oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW peripheral nervous system development Ref.1 Traceable author statement. Source: ProtInc
Cellular component	endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	3-chloroallyl aldehyde dehydrogenase activity Ref.1 Traceable author statement. Source: ProtInc aldehyde dehydrogenase (NAD) activity Inferred from electronic annotation. Source: EC aldehyde dehydrogenase [NAD(P)+] activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P51648-1)

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: P51648-2)

The sequence of this isoform differs from the canonical sequence as follows:
     482-485: AEYY → KYQAVLRRKALLIFLVVHRLRWSSKQR

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 485	485	Fatty aldehyde dehydrogenase		PRO_0000056473
Regions
	Topological domain	1 – 463	463	Cytoplasmic
	Transmembrane	464 – 480	17	Potential
	Nucleotide binding	185 – 190	6	NAD Potential
Sites
	Active site	207	1	By similarity
	Active site	241	1	By similarity
Natural variations
	Alternative sequence	482 – 485	4	AEYY → KYQAVLRRKALLIFLVVHRL RWSSKQR in isoform 2.		VSP_001283
	Natural variant	45	1	I → F in SLS; severe loss of activity.		VAR_017510
	Natural variant	64	1	V → D in SLS; severe loss of activity.		VAR_017511
	Natural variant	106	1	L → R in SLS; severe loss of activity.		VAR_002249
	Natural variant	114	1	P → L in SLS; severe loss of activity.		VAR_017512
	Natural variant	121	1	P → L in SLS; severe loss of activity.		VAR_017513
	Natural variant	184	1	T → M in SLS; severe loss of activity.		VAR_017514
	Natural variant	184	1	T → R in SLS; severe loss of activity.		VAR_017515
	Natural variant	185	1	G → A in SLS; severe loss of activity.		VAR_017516
	Natural variant	214	1	C → Y in SLS; 4% of activity.		VAR_002250
	Natural variant	226	1	C → W in SLS.		VAR_002251
	Natural variant	228	1	R → C in SLS; severe loss of activity.		VAR_017517
	Natural variant	237	1	C → Y in SLS; severe loss of activity.		VAR_017518
	Natural variant	245	1	D → N in SLS; severe loss of activity; originally thought to be a neutral polymorphism.		VAR_002252
	Natural variant	266	1	K → N in SLS; mild reduction of activity; the underlying nucleotide substitution affects transcript stability.		VAR_017519
	Natural variant	279	1	Y → N in SLS; severe loss of activity.		VAR_017520
	Natural variant	314 – 315	2	AP → GAKSTVGA in SLS; 8% of activity.		VAR_002253
	Natural variant	315	1	P → S in SLS; common mutation in Europeans; severe loss of enzymatic activity.		VAR_002254
	Natural variant	328	1	M → I in SLS.		VAR_017521
	Natural variant	365	1	S → L in SLS; severe loss of activity.		VAR_002255
	Natural variant	386	1	N → S in SLS.		VAR_017522
	Natural variant	406	1	G → R in SLS.		VAR_017523
	Natural variant	411	1	H → Y in SLS; severe loss of activity.		VAR_017524
	Natural variant	412	1	G → R in SLS.		VAR_002256
	Natural variant	415	1	S → N in SLS; severe loss of activity.		VAR_017525
	Natural variant	419	1	F → S in SLS; severe loss of activity.		VAR_017526
	Natural variant	423	1	R → H in SLS; severe loss of activity.		VAR_017527
	Natural variant	447	1	K → E in SLS; severe loss of activity.		VAR_017528

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 209601CB5803C7E3	FASTA	485	54,848
	10 20 30 40 50 60 MELEVRRVRQ AFLSGRSRPL RFRLQQLEAL RRMVQEREKD ILTAIAADLC KSEFNVYSQE 70 80 90 100 110 120 VITVLGEIDF MLENLPEWVT AKPVKKNVLT MLDEAYIQPQ PLGVVLIIGA WNYPFVLTIQ 130 140 150 160 170 180 PLIGAIAAGN AVIIKPSELS ENTAKILAKL LPQYLDQDLY IVINGGVEET TELLKQRFDH 190 200 210 220 230 240 IFYTGNTAVG KIVMEAAAKH LTPVTLELGG KSPCYIDKDC DLDIVCRRIT WGKYMNCGQT 250 260 270 280 290 300 CIAPDYILCE ASLQNQIVWK IKETVKEFYG ENIKESPDYE RIINLRHFKR ILSLLEGQKI 310 320 330 340 350 360 AFGGETDEAT RYIAPTVLTD VDPKTKVMQE EIFGPILPIV PVKNVDEAIN FINEREKPLA 370 380 390 400 410 420 LYVFSHNHKL IKRMIDETSS GGVTGNDVIM HFTLNSFPFG GVGSSGMGAY HGKHSFDTFS 430 440 450 460 470 480 HQRPCLLKSL KREGANKLRY PPNSQSKVDW GKFFLLKRFN KEKLGLLLLT FLGIVAAVLV KAEYY
	Isoform 2 [UniParc]. Checksum: DC5AEB20D8B85388		508	57,669
	10 20 30 40 50 60 MELEVRRVRQ AFLSGRSRPL RFRLQQLEAL RRMVQEREKD ILTAIAADLC KSEFNVYSQE 70 80 90 100 110 120 VITVLGEIDF MLENLPEWVT AKPVKKNVLT MLDEAYIQPQ PLGVVLIIGA WNYPFVLTIQ 130 140 150 160 170 180 PLIGAIAAGN AVIIKPSELS ENTAKILAKL LPQYLDQDLY IVINGGVEET TELLKQRFDH 190 200 210 220 230 240 IFYTGNTAVG KIVMEAAAKH LTPVTLELGG KSPCYIDKDC DLDIVCRRIT WGKYMNCGQT 250 260 270 280 290 300 CIAPDYILCE ASLQNQIVWK IKETVKEFYG ENIKESPDYE RIINLRHFKR ILSLLEGQKI 310 320 330 340 350 360 AFGGETDEAT RYIAPTVLTD VDPKTKVMQE EIFGPILPIV PVKNVDEAIN FINEREKPLA 370 380 390 400 410 420 LYVFSHNHKL IKRMIDETSS GGVTGNDVIM HFTLNSFPFG GVGSSGMGAY HGKHSFDTFS 430 440 450 460 470 480 HQRPCLLKSL KREGANKLRY PPNSQSKVDW GKFFLLKRFN KEKLGLLLLT FLGIVAAVLV 490 500 KKYQAVLRRK ALLIFLVVHR LRWSSKQR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sjogren-Larsson syndrome is caused by mutations in the fatty aldehyde dehydrogenase gene." de Laurenzi V., Rogers G.R., Hamrock D.J., Marekov L.N., Steinert P.M., Compton J.G., Markova N., Rizzo W.B. Nat. Genet. 12:52-57(1996) [PubMed: 8528251] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, VARIANTS SLS.
[2]	"Genomic organization and expression of the human fatty aldehyde dehydrogenase gene (FALDH)." Rogers G.R., Markova N.G., De Laurenzi V., Rizzo W.B., Compton J.G. Genomics 39:127-135(1997) [PubMed: 9027499] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2).
[3]	"Human fatty aldehyde dehydrogenase gene (ALDH10): organization and tissue-dependent expression." Chang C., Yoshida A. Genomics 40:80-85(1997) [PubMed: 9070922] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Liver.
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Skin.
[5]	"A missense mutation in the FALDH gene identified in Sjogren-Larsson syndrome patients originating from the northern part of Sweden." Sillen A., Jagell S., Wadelius C. Hum. Genet. 100:201-203(1997) [PubMed: 9254849] [Abstract] Cited for: VARIANT SLS SER-315.
[6]	"Spectrum of mutations and sequence variants in the FALDH gene in patients with Sjoegren-Larsson syndrome." Sillen A., Anton-Lamprecht I., Braun-Quentin C., Kraus C.S., Sayli B.S., Ayuso C., Jagell S., Kuester W., Wadelius C. Hum. Mutat. 12:377-384(1998) [PubMed: 9829906] [Abstract] Cited for: VARIANTS SLS ARG-106; TRP-226; ASN-245; SER-315; LEU-365 AND ARG-412.
[7]	"The molecular basis of Sjoegren-Larsson syndrome: mutation analysis of the fatty aldehyde dehydrogenase gene." Rizzo W.B., Carney G., Lin Z. Am. J. Hum. Genet. 65:1547-1560(1999) [PubMed: 10577908] [Abstract] Cited for: VARIANTS SLS PHE-45; ASP-64; ARG-106; LEU-114; LEU-121; ARG-184; MET-184; ALA-185; CYS-228; TYR-237; ASN-245; ASN-266; ASN-279; SER-315; ILE-328; LEU-365; ARG-406; TYR-411; ASN-415; SER-419; HIS-423 AND GLU-447.
[8]	"A novel point mutation of the FALDH gene in a Japanese family with Sjoegren-Larsson syndrome." Aoki N., Suzuki H., Ito K., Ito M. J. Invest. Dermatol. 114:1065-1066(2000) [PubMed: 10792573] [Abstract] Cited for: VARIANT SLS SER-386.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	L47162 mRNA. Translation: AAB01003.1. U75296 , U75286, U75287, U75288, U75289, U75290, U75291, U75292, U75293, U75294 Genomic DNA. Translation: AAC50966.1. U75295 , U75286, U75287, U75288, U75289, U75290, U75291, U75292, U75293, U75294 Genomic DNA. Translation: AAC50965.1. U46689 mRNA. Translation: AAC51121.1. BC002430 mRNA. Translation: AAH02430.1.
RefSeq	NP_000373.1. NP_001026976.1.
UniGene	Hs.499886
3D structure databases
HSSP	HSSP built from PDB template 1AD3 based on UniProtKB P11883.
ModBase	Search...
PTM databases
PhosphoSite	P51648.
Genome annotation databases
Ensembl	ENSG00000072210. Homo sapiens. [Contig view]
GeneID	224.
KEGG	hsa:224.
Organism-specific databases
H-InvDB	HIX0009873. HIX0013620.
HGNC	HGNC:403. ALDH3A2.
HPA	HPA014769.
MIM	270200. phenotype. 609523. gene.
Orphanet	816. Sjoegren-Larsson syndrome.
PharmGKB	PA24698.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOVERGEN	P51648.
Gene expression databases
ArrayExpress	P51648.
CleanEx	HS_ALDH3A2.
GermOnline	ENSG00000072210. Homo sapiens.
Family and domain databases
InterPro	IPR016160. Ald_DHase_CS. IPR016162. Ald_DHase_N. IPR012394. Ald_DHase_NAD(P). IPR015590. Aldehyde_DHase. [Graphical view]
Gene3D	G3DSA:3.40.605.10. Aldehyde_dehydrogenase_N. 1 hit.
PANTHER	PTHR11699. Aldehyde_dehyd. 1 hit. PTHR11699:SF15. ALDH. 1 hit.
Pfam	PF00171. Aldedh. 1 hit. [Graphical view]
PIRSF	PIRSF036492. ALDH. 1 hit.
PROSITE	PS00070. ALDEHYDE_DEHYDR_CYS. 1 hit. PS00687. ALDEHYDE_DEHYDR_GLU. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00157. NADH.
NextBio	910.
SOURCE	Search...

Entry information

Entry name

AL3A2_HUMAN

Accession

Primary (citable) accession number: P51648
Secondary accession number(s): Q93011, Q96J37

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	November 25, 2008
This is version 86 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)