ASAH1_RAT
ID ASAH1_RAT Reviewed; 394 AA.
AC Q6P7S1; Q9EQJ6;
DT 16-JUN-2009, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=Acid ceramidase {ECO:0000305};
DE Short=AC;
DE Short=ACDase;
DE Short=Acid CDase;
DE EC=3.5.1.23 {ECO:0000250|UniProtKB:Q13510};
DE AltName: Full=Acylsphingosine deacylase;
DE AltName: Full=N-acylethanolamine hydrolase ASAH1 {ECO:0000250|UniProtKB:Q13510};
DE EC=3.5.1.- {ECO:0000250|UniProtKB:Q13510};
DE AltName: Full=N-acylsphingosine amidohydrolase;
DE Contains:
DE RecName: Full=Acid ceramidase subunit alpha {ECO:0000250|UniProtKB:Q13510};
DE Contains:
DE RecName: Full=Acid ceramidase subunit beta {ECO:0000250|UniProtKB:Q13510};
DE Flags: Precursor;
GN Name=Asah1 {ECO:0000312|RGD:621568};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RA Frenck J., Sol-Church K., McKay C., Mason R.;
RT "Complete coding sequence of rat ceramidase.";
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pituitary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-258, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24090084; DOI=10.1021/pr400783j;
RA Parker B.L., Thaysen-Andersen M., Solis N., Scott N.E., Larsen M.R.,
RA Graham M.E., Packer N.H., Cordwell S.J.;
RT "Site-specific glycan-peptide analysis for determination of N-glycoproteome
RT heterogeneity.";
RL J. Proteome Res. 12:5791-5800(2013).
CC -!- FUNCTION: Lysosomal ceramidase that hydrolyzes sphingolipid ceramides
CC into sphingosine and free fatty acids at acidic pH (By similarity).
CC Ceramides, sphingosine, and its phosphorylated form sphingosine-1-
CC phosphate are bioactive lipids that mediate cellular signaling pathways
CC regulating several biological processes including cell proliferation,
CC apoptosis and differentiation (By similarity). Has a higher catalytic
CC efficiency towards C12-ceramides versus other ceramides (By
CC similarity). Also catalyzes the reverse reaction allowing the synthesis
CC of ceramides from fatty acids and sphingosine (By similarity). For the
CC reverse synthetic reaction, the natural sphingosine D-erythro isomer is
CC more efficiently utilized as a substrate compared to D-erythro-
CC dihydrosphingosine and D-erythro-phytosphingosine, while the fatty
CC acids with chain lengths of 12 or 14 carbons are the most efficiently
CC used (By similarity). Has also an N-acylethanolamine hydrolase activity
CC (By similarity). By regulating the levels of ceramides, sphingosine and
CC sphingosine-1-phosphate in the epidermis, mediates the calcium-induced
CC differentiation of epidermal keratinocytes (By similarity). Also
CC indirectly regulates tumor necrosis factor/TNF-induced apoptosis (By
CC similarity). By regulating the intracellular balance between ceramides
CC and sphingosine, in adrenocortical cells, probably also acts as a
CC regulator of steroidogenesis (By similarity).
CC {ECO:0000250|UniProtKB:Q13510}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an N-acylsphing-4-enine + H2O = a fatty acid + sphing-4-enine;
CC Xref=Rhea:RHEA:20856, ChEBI:CHEBI:15377, ChEBI:CHEBI:28868,
CC ChEBI:CHEBI:52639, ChEBI:CHEBI:57756; EC=3.5.1.23;
CC Evidence={ECO:0000250|UniProtKB:Q13510};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-dodecanoylsphing-4-enine = dodecanoate + sphing-4-
CC enine; Xref=Rhea:RHEA:41291, ChEBI:CHEBI:15377, ChEBI:CHEBI:18262,
CC ChEBI:CHEBI:57756, ChEBI:CHEBI:72956;
CC Evidence={ECO:0000250|UniProtKB:Q13510};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41292;
CC Evidence={ECO:0000250|UniProtKB:Q13510};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:41293;
CC Evidence={ECO:0000250|UniProtKB:Q13510};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-tetradecanoylsphing-4-enine = sphing-4-enine +
CC tetradecanoate; Xref=Rhea:RHEA:41287, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:30807, ChEBI:CHEBI:57756, ChEBI:CHEBI:72957;
CC Evidence={ECO:0000250|UniProtKB:Q13510};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:41289;
CC Evidence={ECO:0000250|UniProtKB:Q13510};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-hexadecanoylsphing-4-enine = hexadecanoate + sphing-4-
CC enine; Xref=Rhea:RHEA:38891, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:57756, ChEBI:CHEBI:72959;
CC Evidence={ECO:0000250|UniProtKB:Q13510};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38892;
CC Evidence={ECO:0000250|UniProtKB:Q13510};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:38893;
CC Evidence={ECO:0000250|UniProtKB:Q13510};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-octadecanoylsphing-4-enine = octadecanoate + sphing-4-
CC enine; Xref=Rhea:RHEA:41279, ChEBI:CHEBI:15377, ChEBI:CHEBI:25629,
CC ChEBI:CHEBI:57756, ChEBI:CHEBI:72961;
CC Evidence={ECO:0000250|UniProtKB:Q13510};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41280;
CC Evidence={ECO:0000250|UniProtKB:Q13510};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:41281;
CC Evidence={ECO:0000250|UniProtKB:Q13510};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-dodecanoyl-(4R)-hydroxysphinganine = (4R)-
CC hydroxysphinganine + dodecanoate; Xref=Rhea:RHEA:41303,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:18262, ChEBI:CHEBI:64124,
CC ChEBI:CHEBI:78001; Evidence={ECO:0000250|UniProtKB:Q13510};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:41305;
CC Evidence={ECO:0000250|UniProtKB:Q13510};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(dodecanoyl)-sphinganine = dodecanoate + sphinganine;
CC Xref=Rhea:RHEA:45448, ChEBI:CHEBI:15377, ChEBI:CHEBI:18262,
CC ChEBI:CHEBI:57817, ChEBI:CHEBI:85261;
CC Evidence={ECO:0000250|UniProtKB:Q13510};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:45450;
CC Evidence={ECO:0000250|UniProtKB:Q13510};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(acetyl)-sphing-4-enine = acetate + sphing-4-enine;
CC Xref=Rhea:RHEA:58484, ChEBI:CHEBI:15377, ChEBI:CHEBI:30089,
CC ChEBI:CHEBI:46979, ChEBI:CHEBI:57756;
CC Evidence={ECO:0000250|UniProtKB:Q13510};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58485;
CC Evidence={ECO:0000250|UniProtKB:Q13510};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(hexanoyl)sphing-4-enine = hexanoate + sphing-4-enine;
CC Xref=Rhea:RHEA:41295, ChEBI:CHEBI:15377, ChEBI:CHEBI:17120,
CC ChEBI:CHEBI:57756, ChEBI:CHEBI:63867;
CC Evidence={ECO:0000250|UniProtKB:Q13510};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41296;
CC Evidence={ECO:0000250|UniProtKB:Q13510};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-octanoylsphing-4-enine = octanoate + sphing-4-enine;
CC Xref=Rhea:RHEA:45092, ChEBI:CHEBI:15377, ChEBI:CHEBI:25646,
CC ChEBI:CHEBI:45815, ChEBI:CHEBI:57756;
CC Evidence={ECO:0000250|UniProtKB:Q13510};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45093;
CC Evidence={ECO:0000250|UniProtKB:Q13510};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(9Z-octadecenoyl)-sphing-4-enine = (9Z)-octadecenoate
CC + sphing-4-enine; Xref=Rhea:RHEA:41299, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:57756, ChEBI:CHEBI:77996;
CC Evidence={ECO:0000250|UniProtKB:Q13510};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41300;
CC Evidence={ECO:0000250|UniProtKB:Q13510};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-dodecanoylethanolamine = dodecanoate + ethanolamine;
CC Xref=Rhea:RHEA:45456, ChEBI:CHEBI:15377, ChEBI:CHEBI:18262,
CC ChEBI:CHEBI:57603, ChEBI:CHEBI:85263;
CC Evidence={ECO:0000250|UniProtKB:Q13510};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45457;
CC Evidence={ECO:0000250|UniProtKB:Q13510};
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000250|UniProtKB:Q13510}.
CC -!- SUBUNIT: Heterodimer; disulfide-linked. The heterodimer is composed of
CC the disulfide-linked alpha and beta chains produced by autocatalytic
CC cleavage of the precursor. {ECO:0000250|UniProtKB:Q13510}.
CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000250|UniProtKB:Q13510}. Secreted
CC {ECO:0000250|UniProtKB:Q13510}. Note=Secretion is extremely low and
CC localization to lysosomes is mannose-6-phosphate receptor-dependent.
CC {ECO:0000250|UniProtKB:Q13510}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q13510}.
CC -!- PTM: Proteolytically cleaved into two chains alpha and beta that remain
CC associated via a disulfide bond. Cleavage gives rise to a conformation
CC change that activates the enzyme. The same catalytic Cys residue
CC mediates the autoproteolytic cleavage and subsequent hydrolysis of
CC lipid substrates. The beta chain may undergo an additional C-terminal
CC processing. {ECO:0000250|UniProtKB:Q13510}.
CC -!- SIMILARITY: Belongs to the acid ceramidase family. {ECO:0000305}.
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DR EMBL; AF214647; AAG43956.1; -; mRNA.
DR EMBL; BC061540; AAH61540.1; -; mRNA.
DR RefSeq; NP_445859.2; NM_053407.3.
DR AlphaFoldDB; Q6P7S1; -.
DR SMR; Q6P7S1; -.
DR BioGRID; 249967; 1.
DR IntAct; Q6P7S1; 2.
DR STRING; 10116.ENSRNOP00000013463; -.
DR BindingDB; Q6P7S1; -.
DR ChEMBL; CHEMBL2331070; -.
DR DrugCentral; Q6P7S1; -.
DR MEROPS; C89.001; -.
DR GlyGen; Q6P7S1; 4 sites, 4 N-linked glycans (1 site).
DR iPTMnet; Q6P7S1; -.
DR SwissPalm; Q6P7S1; -.
DR jPOST; Q6P7S1; -.
DR PaxDb; Q6P7S1; -.
DR PRIDE; Q6P7S1; -.
DR GeneID; 84431; -.
DR KEGG; rno:84431; -.
DR CTD; 427; -.
DR RGD; 621568; Asah1.
DR VEuPathDB; HostDB:ENSRNOG00000010034; -.
DR eggNOG; ENOG502QVBG; Eukaryota.
DR HOGENOM; CLU_054401_0_0_1; -.
DR InParanoid; Q6P7S1; -.
DR OrthoDB; 745108at2759; -.
DR PhylomeDB; Q6P7S1; -.
DR TreeFam; TF313219; -.
DR BRENDA; 3.5.1.23; 5301.
DR BRENDA; 3.5.1.60; 5301.
DR Reactome; R-RNO-1660662; Glycosphingolipid metabolism.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR UniPathway; UPA00222; -.
DR PRO; PR:Q6P7S1; -.
DR Proteomes; UP000002494; Chromosome 16.
DR Bgee; ENSRNOG00000010034; Expressed in ovary and 20 other tissues.
DR ExpressionAtlas; Q6P7S1; baseline and differential.
DR Genevisible; Q6P7S1; RN.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0102121; F:ceramidase activity; IEA:UniProtKB-EC.
DR GO; GO:0017064; F:fatty acid amide hydrolase activity; IEA:InterPro.
DR GO; GO:0016810; F:hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds; IBA:GO_Central.
DR GO; GO:0016811; F:hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides; ISO:RGD.
DR GO; GO:0017040; F:N-acylsphingosine amidohydrolase activity; ISS:UniProtKB.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; ISS:UniProtKB.
DR GO; GO:0046513; P:ceramide biosynthetic process; ISS:UniProtKB.
DR GO; GO:0046514; P:ceramide catabolic process; ISS:UniProtKB.
DR GO; GO:0006631; P:fatty acid metabolic process; IEA:InterPro.
DR GO; GO:0030216; P:keratinocyte differentiation; ISS:UniProtKB.
DR GO; GO:0030324; P:lung development; IDA:RGD.
DR GO; GO:0062098; P:regulation of programmed necrotic cell death; ISS:UniProtKB.
DR GO; GO:0050810; P:regulation of steroid biosynthetic process; ISS:UniProtKB.
DR GO; GO:0010033; P:response to organic substance; IDA:RGD.
DR GO; GO:0046512; P:sphingosine biosynthetic process; ISS:UniProtKB.
DR InterPro; IPR016699; Acid_ceramidase-like.
DR InterPro; IPR029130; Acid_ceramidase_N.
DR InterPro; IPR029132; CBAH/NAAA_C.
DR Pfam; PF02275; CBAH; 1.
DR Pfam; PF15508; NAAA-beta; 1.
DR PIRSF; PIRSF017632; Acid_ceramidase-like; 1.
PE 1: Evidence at protein level;
KW Disulfide bond; Glycoprotein; Hydrolase; Lipid metabolism; Lysosome;
KW Reference proteome; Secreted; Signal; Sphingolipid metabolism; Zymogen.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..394
FT /note="Acid ceramidase"
FT /id="PRO_0000378102"
FT CHAIN 21..141
FT /note="Acid ceramidase subunit alpha"
FT /evidence="ECO:0000250|UniProtKB:Q13510"
FT /id="PRO_0000446284"
FT CHAIN 142..394
FT /note="Acid ceramidase subunit beta"
FT /evidence="ECO:0000250|UniProtKB:Q13510"
FT /id="PRO_0000446285"
FT ACT_SITE 142
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q13510"
FT SITE 161
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250|UniProtKB:Q13510"
FT SITE 319
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250|UniProtKB:Q13510"
FT SITE 332
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250|UniProtKB:Q13510"
FT CARBOHYD 194
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 258
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0007744|PubMed:24090084"
FT CARBOHYD 285
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 341
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 30..339
FT /note="Interchain (between alpha and beta subunits)"
FT /evidence="ECO:0000250|UniProtKB:Q13510"
FT DISULFID 387..391
FT /evidence="ECO:0000250|UniProtKB:A0A0P6JG37"
FT CONFLICT 375
FT /note="V -> G (in Ref. 1; AAG43956)"
FT /evidence="ECO:0000305"
FT CONFLICT 379
FT /note="Q -> P (in Ref. 1; AAG43956)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 394 AA; 44443 MW; 27608539E1E9ED20 CRC64;
MLGRSLLTWV LAAAVTCAQA QQVPPWTEDC RKSTYPPSGP TYRGPVPWYT INLDLPPYKR
WHELLAHKAP VLRTLVNSIS NLVNAFVPSG KIMQMVDEKL PGLIGSIPGP FGEEMRGIAD
VTGIPLGEII SFNIFYELFT MCTSIITEDG KGHLLHGRNM DFGIFLGWNI NNNTWVVTEE
LKPLTVNLDF QRNNKTVFKA TSFAGYVGML TGFKPGLLSL TLNERFSLNG GYLGILEWMF
GKKNAQWVGF ITRSVLENST SYEEAKNILT KTKITAPAYF ILGGNQSGEG CVITRERKES
LDVYELDPKH GRWYVVQTNY DRWKNTLFLD DRRTPAKKCL NHTTQKNLSF ATIYDVLSTK
PVLNKLTVFT TLIDVTKDQF ESHLRDCPDP CIGW
