Reviewed,
UniProtKB/Swiss-Prot P51648 (AL3A2_HUMAN)
Last modified
November 25, 2008.
Version 86.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
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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 |
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| 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
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
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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: 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. |
Cross-references
Sequence databases | |
|---|---|
| L47162 mRNA. Translation: AAB01003.1. U75296 U75294 Genomic DNA. Translation: AAC50966.1. U75295 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 |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 17 Human chromosome 17: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


