Molecule Information

General Information of the Molecule (ID: Mol04305)

• Name: Aldehyde dehydrogenase 1A1 (ALDH1A1) ,Homo sapiens
• Synonyms: 3-deoxyglucosone dehydrogenase ; ALDH-E1; ALHDII; Aldehyde dehydrogenase family 1 member A1 ; Aldehyde dehydrogenase, cytosolic ; Retinal dehydrogenase 1
• Molecule Type: Protein
• Gene Name: ALDH1A1
• Gene ID: 216
• Sequence:
  MSSSGTPDLPVLLTDLKIQYTKIFINNEWHDSVSGKKFPVFNPATEEELCQVEEGDKEDV
  DKAVKAARQAFQIGSPWRTMDASERGRLLYKLADLIERDRLLLATMESMNGGKLYSNAY
  L NDLAGCIKTLRYCAGWADKIQGRTIPIDGNFFTYTRHEPIGVCGQIIPWNFPLVMLIW
  KI GPALSCGNTVVVKPAEQTPLTALHVASLIKEAGFPPGVVNIVPGYGPTAGAAISSHM
  DID KVAFTGSTEVGKLIKEAAGKSNLKRVTLELGGKSPCIVLADADLDNAVEFAHHGVF
  YHQG QCCIAASRIFVEESIYDEFVRRSVERAKKYILGNPLTPGVTQGPQIDKEQYDKIL
  DLIES GKKEGAKLECGGGPWGNKGYFVQPTVFSNVTDEMRIAKEEIFGPVQQIMKFKSL
  DDVIKR ANNTFYGLSAGVFTKDIDKAITISSALQAGTVWVNCYGVVSAQCPFGGFKMSG
  NGRELGE YGFHEYTEVKTVTVKISQKNS
• Function: Cytosolic dehydrogenase that catalyzes the irreversibleoxidation of a wide range of aldehydes to their correspondingcarboxylic acid . Functionsdownstream of retinol dehydrogenases and catalyzes the oxidation ofretinaldehyde into retinoic acid, the second step in the oxidation ofretinol/vitamin A into retinoic acid . This pathway iscrucial to control the levels of retinol and retinoic acid, twoimportant molecules which excess can be teratogenic and cytotoxic . Also oxidizes aldehydes resulting from lipid peroxidationlike -4-hydroxynon-2-enal/HNE, malonaldehyde and hexanal that formprotein adducts and are highly cytotoxic. By participating for instanceto the clearance of -4-hydroxynon-2-enal/HNE in the lens epitheliumprevents the formation of HNE-protein adducts and lens opacification. Also functionsdownstream of fructosamine-3-kinase in the fructosamine degradationpathway by catalyzing the oxidation of 3-deoxyglucosone, thecarbohydrate product of fructosamine 3-phosphate decomposition, whichis itself a potent glycating agent that may react with lysine andarginine side-chains of proteins . Also has anaminobutyraldehyde dehydrogenase activity and is probably part of analternative pathway for the biosynthesis of GABA/4-aminobutanoate inmidbrain, thereby playing a role in GABAergic synaptic transmission . {ECO:0000250|UniProtKB:P24549,ECO:0000269|PubMed:12941160, ECO:0000269|PubMed:15623782,ECO:0000269|PubMed:17175089, ECO:0000269|PubMed:19296407,ECO:0000269|PubMed:25450233, ECO:0000269|PubMed:26373694}.
• Uniprot ID: AL1A1_HUMAN
• Ensembl ID: ENSG0000016509213
• HGNC ID: HGNC:402

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Abatacept

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Autoimmune disease [ICD-11: 4A4Z.0] [1]

• Resistant Disease: Autoimmune disease [ICD-11: 4A4Z.0]
• Resistant Drug: Abatacept
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vivo Model: Th17-mediated EAD model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Mechanism Description: Abatacept-resistant memory Th17 cells exhibit genes for aldehyde dehydrogenases. Memory-phenotype pTh17 cells exhibit a unique metabolic pathway that may involve ALDH for both survival and function.

References

• Ref 1: Targeting abatacept-resistant T-helper-17 cells by aldehyde dehydrogenase inhibition. iScience. 2023 Dec 9;27(1):108646.