ASAH1_PANTR
ID ASAH1_PANTR Reviewed; 395 AA.
AC A5A6P2;
DT 16-JUN-2009, integrated into UniProtKB/Swiss-Prot.
DT 12-JUN-2007, sequence version 1.
DT 03-AUG-2022, entry version 76.
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:0000250|UniProtKB:Q13510};
OS Pan troglodytes (Chimpanzee).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pan.
OX NCBI_TaxID=9598;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Subsp. verus; TISSUE=Skin;
RX PubMed=17574350; DOI=10.1016/j.gene.2007.04.013;
RA Sakate R., Suto Y., Imanishi T., Tanoue T., Hida M., Hayasaka I.,
RA Kusuda J., Gojobori T., Hashimoto K., Hirai M.;
RT "Mapping of chimpanzee full-length cDNAs onto the human genome unveils
RT large potential divergence of the transcriptome.";
RL Gene 399:1-10(2007).
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; AB222170; BAF62415.1; -; mRNA.
DR RefSeq; NP_001092030.1; NM_001098560.1.
DR AlphaFoldDB; A5A6P2; -.
DR SMR; A5A6P2; -.
DR STRING; 9598.ENSPTRP00000034295; -.
DR MEROPS; C89.001; -.
DR PaxDb; A5A6P2; -.
DR PRIDE; A5A6P2; -.
DR Ensembl; ENSPTRT00000037110; ENSPTRP00000034295; ENSPTRG00000020027.
DR GeneID; 464022; -.
DR KEGG; ptr:464022; -.
DR CTD; 427; -.
DR VGNC; VGNC:53738; ASAH1.
DR eggNOG; ENOG502QVBG; Eukaryota.
DR GeneTree; ENSGT00530000063548; -.
DR HOGENOM; CLU_054401_0_0_1; -.
DR InParanoid; A5A6P2; -.
DR TreeFam; TF313219; -.
DR UniPathway; UPA00222; -.
DR Proteomes; UP000002277; Chromosome 8.
DR Bgee; ENSPTRG00000020027; Expressed in heart and 21 other tissues.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
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: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: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: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 2: Evidence at transcript level;
KW Disulfide bond; Glycoprotein; Hydrolase; Lipid metabolism; Lysosome;
KW Reference proteome; Secreted; Signal; Sphingolipid metabolism; Zymogen.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..395
FT /note="Acid ceramidase"
FT /id="PRO_0000378101"
FT CHAIN 22..142
FT /note="Acid ceramidase subunit alpha"
FT /evidence="ECO:0000250|UniProtKB:Q13510"
FT /id="PRO_0000446282"
FT CHAIN 143..395
FT /note="Acid ceramidase subunit beta"
FT /evidence="ECO:0000250|UniProtKB:Q13510"
FT /id="PRO_0000446283"
FT ACT_SITE 143
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q13510"
FT SITE 162
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250|UniProtKB:Q13510"
FT SITE 320
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250|UniProtKB:Q13510"
FT SITE 333
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250|UniProtKB:Q13510"
FT CARBOHYD 195
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 259
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 286
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 342
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 31..340
FT /note="Interchain (between alpha and beta subunits)"
FT /evidence="ECO:0000250|UniProtKB:Q13510"
FT DISULFID 388..392
FT /evidence="ECO:0000250|UniProtKB:A0A0P6JG37"
SQ SEQUENCE 395 AA; 44697 MW; 95F276721883EF4B CRC64;
MPGRSRVALV LLAAAVSCAV AQHAPPWTED CRKSTYPPSG PTYRGPVPWY TINLDLPPYK
RWHELMLDKA PMLKVIVNSL KNMINTFVPS GKIVQVVDEK LPGLLGNFPG PFEEEMKGIA
AVTDIPLGEI ISFNIFYELF TICTSIVAED KKGHLIHGRN MDFGVFLGWN INNDTWVITE
QLKPLTVNLD FQRNNKTVFK ASSFAGYVGM LTGFKPGLFS LSLNERFSIN GGYLGILEWI
LGKKDAMWIG FLTRTVLENS TSYEEAKNLL TKTKILAPAY FILGGNQSGE GCVITRDRKE
SLDVYELDAK QGRWYVVQTN YDRWKHPFFL DDRRTPAKMC LNRTSQENIS FETMYDVLST
KPVLNKLTVY TTLIDVTKGQ FETYLRDCPD PCIGW
