human-ABHD12

 
Homo sapiens (Human) abhydrolase domain-containing protein 12. Protein C20orf22, flj90542, CT022, 2-arachidonoylglycerol hydrolase, Monoacylglycerol lipase

Comment
This gene is mutated in Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC) disease. is a neurodegenerative disease. Patients present early-onset cataract and hearing loss, retinitis pigmentosa. Both the central and peripheral nervous systems are affected. Other features are demyelinating sensorimotor polyneuropathy and cerebellar ataxia. Fiskerstrand et al. identified the disease in a norwegian family. Mutations in ABHD12 cause the PHARC. Polyneuropathy and ataxia can be mild and symptomes can be close to those of Usher syndrome type 3 as shown by Eisenberg et al. . ABHD12 is a major very long chain lyso-PS lipase in primary mast cells. long-chain lyso-PSs induce secretion of pro-inflammatory cytokines in macrophage signaling and mast cell degranulation (Khandelwal 2021)


Relationship
Block X
Homo sapiens position in NCBI Life Tree :
N link to NCBI taxonomic web page and E link to ESTHER gene locus found in this strain.
> cellular organisms: N E > Eukaryota: N E > Opisthokonta: N E > Metazoa: N E > Eumetazoa: N E > Bilateria: N E > Deuterostomia: N E > Chordata: N E > Craniata: N E > Vertebrata: N E > Gnathostomata: N E > Teleostomi: N E > Euteleostomi: N E > Sarcopterygii: N E > Dipnotetrapodomorpha: N E > Tetrapoda: N E > Amniota: N E > Mammalia: N E > Theria: N E > Eutheria: N E > Boreoeutheria: N E > Euarchontoglires: N E > Primates: N E > Haplorrhini: N E > Simiiformes: N E > Catarrhini: N E > Hominoidea: N E > Hominidae: N E > Homininae: N E > Homo: N E > Homo sapiens: N E

Molecular evidence
Database
18 mutations: Table (ordered Natural and SD mutagenesis) (e.g. : 59kbdel_human-ABHD12, K377X_human-ABHD12, 14kbdel_human-ABHD12 ... more)
No structure
No kinetic
Disease: PHARC Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract -
Substrate: Lyso-PS-(20-4) , PGE2-glyceryl-ester , Lysophosphatidylserine , 2-Arachidonylglycerol ,
Inhibitor: KC01 , Betulinic-acid , DO264 , Maslinic-acid , Dihydrobetulonic-acid , Ursolic-acid ,
>3 Genbank links 3 more: AK075023, AL117442, AL353812
2 UniProt : Q8N2K0, Q5T712
>3 UniProtTrembl links 3 more: Q8N2K0, Q5T712, I3L1V0
>3 Interpro links 3 more: Q8N2K0, Q5T712, I3L1V0
>3 Prodom links 3 more: Q8N2K0, Q5T712, I3L1V0
>3 Pfam links 3 more: Q8N2K0, Q5T712, I3L1V0
>3 PIRSF links 3 more: Q8N2K0, Q5T712, I3L1V0
>3 SUPERFAM links 3 more: Q8N2K0, Q5T712, I3L1V0
>3 QuickSwissBlast links 3 more: Q8N2K0, Q5T712, I3L1V0
1 EntrezGene : 26090
1 SNP : 26090
1 UniGene : 441550
1 HUGO HGNC : 15868
2 OMIM : 612674, 613599
1 Ensembl : ENSG00000100997
 
Sequence
Graphical view for this peptide sequence: human-ABHD12
Colored MSA for ABHD12-PHARC (raw)
MRKRTEPVALEHERCAAAGSSSSGSAAAALDADCRLKQNLRLTGPAAAEP
RCAADAGMKRALGRRKGVWLRLRKILFCVLGLYIAIPFLIKLCPGIQAKL
IFLNFVRVPYFIDLKKPQDQGLNHTCNYYLQPEEDVTIGVWHTVPAVWWK
NAQGKDQMWYEDALASSHPIILYLHGNAGTRGGDHRVELYKVLSSLGYHV
VTFDYRGWGDSVGTPSERGMTYDALHVFDWIKARSGDNPVYIWGHSLGTG
VATNLVRRLCERETPPDALILESPFTNIREEAKSHPFSVIYRYFPGFDWF
FLDPITSSGIKFANDENVKHISCPLLILHAEDDPVVPFQLGRKLYSIAAP
ARSFRDFKVQFVPFHSDLGYRHKYICKSPELPRILREFLGKSEPEHQH
Legend This sequence has been compared to family alignement (MSA)
red => minority aminoacid
blue => majority aminoacid
color intensity => conservation rate
title => sequence position(MSA position)aminoacid rate
Catalytic site
Catalytic site in the MSA

MRKRTEPVALEHERCAAAGSSSSGSAAAALDADCRLKQNLRLTGPAAAEP
RCAADAGMKRALGRRKGVWLRLRKILFCVLGLYIAIPFLIKLCPGIQAKL
IFLNFVRVPYFIDLKKPQDQGLNHTCNYYLQPEEDVTIGVWHTVPAVWWK
NAQGKDQMWYEDALASSHPIILYLHGNAGTRGGDHRVELYKVLSSLGYHV
VTFDYRGWGDSVGTPSERGMTYDALHVFDWIKARSGDNPVYIWGHSLGTG
VATNLVRRLCERETPPDALILESPFTNIREEAKSHPFSVIYRYFPGFDWF
FLDPITSSGIKFANDENVKHISCPLLILHAEDDPVVPFQLGRKLYSIAAP
ARSFRDFKVQFVPFHSDLGYRHKYICKSPELPRILREFLGKSEPEHQH

no DNA




References
30 more
    Title: Fatty acid chain length drives lysophosphatidylserine-dependent immunological outputs
    Khandelwal N, Shaikh M, Mhetre A, Singh S, Sajeevan T, Joshi A, Balaji KN, Chakrapani H, Kamat SS
    Ref: Cell Chemical Biology, :, 2021 : PubMed

            

    Title: The loss of enzymatic activity of the PHARC associated lipase ABHD12 results in increased phagocytosis that causes neuroinflammation
    Singh S, Kamat SS
    Ref: European Journal of Neuroscience, :, 2021 : PubMed

            

    Title: Blockade of the Lysophosphatidylserine Lipase ABHD12 Potentiates Ferroptosis in Cancer Cells
    Kathman SG, Boshart J, Jing H, Cravatt BF
    Ref: ACS Chemical Biology, 15:871, 2020 : PubMed

            


Other Papers


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Mail to: Nicolas Lenfant, Thierry Hotelier, Yves Bourne, Pascale Marchot and Arnaud Chatonnet.
Please cite: Lenfant 2013 Nucleic.Acids.Res. or Marchot Chatonnet 2012 Prot.Pept Lett.
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