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P51648 (AL3A2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 144. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Fatty aldehyde dehydrogenase

EC=1.2.1.3
Alternative name(s):
Aldehyde dehydrogenase 10
Aldehyde dehydrogenase family 3 member A2
Microsomal aldehyde dehydrogenase
Gene names
Name:ALDH3A2
Synonyms:ALDH10, FALDH
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length485 AA.
Sequence statusComplete.
Protein existenceEvidence 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. Responsible for conversion of the sphingosine 1-phosphate (S1P) degradation product hexadecenal to hexadecenoic acid. Ref.9

Catalytic activity

An aldehyde + NAD+ + H2O = a carboxylate + NADH.

Subcellular location

Endoplasmic reticulum membrane; Single-pass membrane protein; Cytoplasmic side.

Involvement in disease

Sjoegren-Larsson syndrome (SLS) [MIM:270200]: An autosomal recessive neurocutaneous disorder characterized by a combination of severe mental retardation, spastic di- or tetraplegia and congenital ichthyosis. Ichthyosis is usually evident at birth with varying degrees of erythema and scaling, 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.10 Ref.11 Ref.12 Ref.13

Sequence similarities

Belongs to the aldehyde dehydrogenase family.

Ontologies

Keywords
   Cellular componentEndoplasmic reticulum
Membrane
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
Ichthyosis
Mental retardation
   DomainTransmembrane
Transmembrane helix
   LigandNAD
   Molecular functionOxidoreductase
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcellular aldehyde metabolic process

Inferred from direct assay PubMed 9133646. Source: UniProtKB

central nervous system development

Inferred from mutant phenotype Ref.1. Source: UniProtKB

epidermis development

Inferred from mutant phenotype Ref.1. Source: UniProtKB

oxidation-reduction process

Inferred from direct assay PubMed 18035827. Source: GOC

peripheral nervous system development

Inferred from mutant phenotype Ref.1. Source: UniProtKB

phytol metabolic process

Inferred from mutant phenotype PubMed 15110319. Source: UniProtKB

sesquiterpenoid metabolic process

Inferred from direct assay PubMed 18035827. Source: UniProtKB

   Cellular_componentendoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

intracellular membrane-bounded organelle

Inferred from direct assay PubMed 9133646. Source: UniProtKB

mitochondrial inner membrane

Inferred from electronic annotation. Source: Ensembl

peroxisome

Inferred from direct assay PubMed 17510064. Source: UniProtKB

   Molecular_functionaldehyde dehydrogenase (NAD) activity

Inferred from direct assay PubMed 9133646. Source: UniProtKB

aldehyde dehydrogenase [NAD(P)+] activity

Inferred from electronic annotation. Source: InterPro

long-chain-alcohol oxidase activity

Inferred from direct assay PubMed 18035827. Source: UniProtKB

long-chain-aldehyde dehydrogenase activity

Inferred from direct assay PubMed 18035827. Source: UniProtKB

medium-chain-aldehyde dehydrogenase activity

Inferred from direct assay PubMed 18035827. Source: UniProtKB

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 485485Fatty aldehyde dehydrogenase
PRO_0000056473

Regions

Topological domain1 – 463463Cytoplasmic
Transmembrane464 – 48017Helical; Potential
Nucleotide binding185 – 1906NAD Potential

Sites

Active site2071 By similarity
Active site2411 By similarity

Natural variations

Alternative sequence482 – 4854AEYY → KYQAVLRRKALLIFLVVHRL RWSSKQR in isoform 2.
VSP_001283
Natural variant451I → F in SLS; severe loss of activity. Ref.12
VAR_017510
Natural variant641V → D in SLS; severe loss of activity. Ref.12
VAR_017511
Natural variant1061L → R in SLS; severe loss of activity. Ref.11 Ref.12
VAR_002249
Natural variant1141P → L in SLS; severe loss of activity. Ref.12
VAR_017512
Natural variant1211P → L in SLS; severe loss of activity. Ref.12
VAR_017513
Natural variant1841T → M in SLS; severe loss of activity. Ref.12
VAR_017514
Natural variant1841T → R in SLS; severe loss of activity. Ref.12
VAR_017515
Natural variant1851G → A in SLS; severe loss of activity. Ref.12
VAR_017516
Natural variant2141C → Y in SLS; 4% of activity.
VAR_002250
Natural variant2261C → W in SLS. Ref.11
VAR_002251
Natural variant2281R → C in SLS; severe loss of activity. Ref.12
Corresponds to variant rs72547566 [ dbSNP | Ensembl ].
VAR_017517
Natural variant2371C → Y in SLS; severe loss of activity. Ref.12
VAR_017518
Natural variant2451D → N in SLS; severe loss of activity; originally thought to be a neutral polymorphism. Ref.11 Ref.12
VAR_002252
Natural variant2661K → N in SLS; mild reduction of activity; the underlying nucleotide substitution affects transcript stability. Ref.12
VAR_017519
Natural variant2791Y → N in SLS; severe loss of activity. Ref.12
VAR_017520
Natural variant314 – 3152AP → GAKSTVGA in SLS; 8% of activity.
VAR_002253
Natural variant3151P → S in SLS; common mutation in Europeans; severe loss of enzymatic activity. Ref.10 Ref.11 Ref.12
VAR_002254
Natural variant3281M → I in SLS. Ref.12
VAR_017521
Natural variant3651S → L in SLS; severe loss of activity. Ref.11 Ref.12
VAR_002255
Natural variant3861N → S in SLS. Ref.13
VAR_017522
Natural variant4061G → R in SLS. Ref.12
VAR_017523
Natural variant4111H → Y in SLS; severe loss of activity. Ref.12
VAR_017524
Natural variant4121G → R in SLS. Ref.11
VAR_002256
Natural variant4151S → N in SLS; severe loss of activity. Ref.12
VAR_017525
Natural variant4191F → S in SLS; severe loss of activity. Ref.12
VAR_017526
Natural variant4231R → H in SLS; severe loss of activity. Ref.12
VAR_017527
Natural variant4471K → E in SLS; severe loss of activity. Ref.12
Corresponds to variant rs67939114 [ dbSNP | Ensembl ].
VAR_017528

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: 209601CB5803C7E3

FASTA48554,848
        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 

« Hide

Isoform 2 [UniParc].

Checksum: DC5AEB20D8B85388
Show »

FASTA50857,669

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Liver.
[4]"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. expand/collapse author list , 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] (ISOFORM 1).
Tissue: Testis and Trachea.
[5]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]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. expand/collapse author list , 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].
[7]"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: Skin.
[8]"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].
[9]"The Sjogren-Larsson syndrome gene encodes a hexadecenal dehydrogenase of the sphingosine 1-phosphate degradation pathway."
Nakahara K., Ohkuni A., Kitamura T., Abe K., Naganuma T., Ohno Y., Zoeller R.A., Kihara A.
Mol. Cell 46:461-471(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"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] [Europe PMC] [Abstract]
Cited for: VARIANT SLS SER-315.
[11]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS SLS ARG-106; TRP-226; ASN-245; SER-315; LEU-365 AND ARG-412.
[12]"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] [Europe PMC] [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.
[13]"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] [Europe PMC] [Abstract]
Cited for: VARIANT SLS SER-386.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L47162 mRNA. Translation: AAB01003.1.
U75296 expand/collapse EMBL AC list , U75286, U75287, U75288, U75289, U75290, U75291, U75292, U75293, U75294 Genomic DNA. Translation: AAC50966.1.
U75295 expand/collapse EMBL AC list , U75286, U75287, U75288, U75289, U75290, U75291, U75292, U75293, U75294 Genomic DNA. Translation: AAC50965.1.
U46689 mRNA. Translation: AAC51121.1.
AK292381 mRNA. Translation: BAF85070.1.
AK315096 mRNA. Translation: BAG37560.1.
CR457422 mRNA. Translation: CAG33703.1.
CH471212 Genomic DNA. Translation: EAW50898.1.
BC002430 mRNA. Translation: AAH02430.1.
CCDSCCDS11210.1. [P51648-1]
CCDS32589.1. [P51648-2]
RefSeqNP_000373.1. NM_000382.2. [P51648-1]
NP_001026976.1. NM_001031806.1. [P51648-2]
UniGeneHs.499886.

3D structure databases

ProteinModelPortalP51648.
SMRP51648. Positions 5-443.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106726. 14 interactions.
IntActP51648. 12 interactions.
STRING9606.ENSP00000345774.

Chemistry

DrugBankDB00157. NADH.

PTM databases

PhosphoSiteP51648.

Polymorphism databases

DMDM1706379.

Proteomic databases

MaxQBP51648.
PaxDbP51648.
PRIDEP51648.

Protocols and materials databases

DNASU224.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000176643; ENSP00000176643; ENSG00000072210. [P51648-1]
ENST00000339618; ENSP00000345774; ENSG00000072210. [P51648-2]
ENST00000395575; ENSP00000378942; ENSG00000072210. [P51648-1]
ENST00000579855; ENSP00000463637; ENSG00000072210. [P51648-1]
ENST00000581518; ENSP00000461916; ENSG00000072210. [P51648-2]
GeneID224.
KEGGhsa:224.
UCSCuc002gwa.1. human. [P51648-2]
uc002gwb.1. human. [P51648-1]

Organism-specific databases

CTD224.
GeneCardsGC17P019551.
HGNCHGNC:403. ALDH3A2.
HPACAB020692.
HPA014769.
MIM270200. phenotype.
609523. gene.
neXtProtNX_P51648.
Orphanet816. Sjogren-Larsson syndrome.
PharmGKBPA24698.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1012.
HOGENOMHOG000271515.
HOVERGENHBG050483.
KOK00128.
OMANYPYQLA.
PhylomeDBP51648.
TreeFamTF314264.

Enzyme and pathway databases

BioCycMetaCyc:HS01061-MONOMER.
SABIO-RKP51648.

Gene expression databases

ArrayExpressP51648.
BgeeP51648.
CleanExHS_ALDH3A2.
GenevestigatorP51648.

Family and domain databases

Gene3D3.40.309.10. 1 hit.
3.40.605.10. 1 hit.
InterProIPR016161. Ald_DH/histidinol_DH.
IPR016163. Ald_DH_C.
IPR016160. Ald_DH_CS_CYS.
IPR029510. Ald_DH_CS_GLU.
IPR016162. Ald_DH_N.
IPR015590. Aldehyde_DH_dom.
IPR012394. Aldehyde_DH_NAD(P).
[Graphical view]
PfamPF00171. Aldedh. 1 hit.
[Graphical view]
PIRSFPIRSF036492. ALDH. 1 hit.
SUPFAMSSF53720. SSF53720. 1 hit.
PROSITEPS00070. ALDEHYDE_DEHYDR_CYS. 1 hit.
PS00687. ALDEHYDE_DEHYDR_GLU. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSALDH3A2. human.
GenomeRNAi224.
NextBio910.
PROP51648.
SOURCESearch...

Entry information

Entry nameAL3A2_HUMAN
AccessionPrimary (citable) accession number: P51648
Secondary accession number(s): Q6I9T3, Q93011, Q96J37
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: July 9, 2014
This is version 144 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM