ASAH1_BALAS
ID ASAH1_BALAS Reviewed; 395 AA.
AC A0A383ZFX3;
DT 10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT 07-NOV-2018, sequence version 1.
DT 25-MAY-2022, entry version 16.
DE RecName: Full=Acid ceramidase {ECO:0000303|PubMed:29692406};
DE Short=AC;
DE Short=ACDase {ECO:0000303|PubMed:29692406};
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:0000305|PubMed:29692406};
DE Contains:
DE RecName: Full=Acid ceramidase subunit beta {ECO:0000305|PubMed:29692406};
DE Flags: Precursor;
GN Name=ASAH1 {ECO:0000312|RefSeq:XP_007174053.1};
OS Balaenoptera acutorostrata scammoni (North Pacific minke whale)
OS (Balaenoptera davidsoni).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Whippomorpha; Cetacea; Mysticeti;
OC Balaenopteridae; Balaenoptera.
OX NCBI_TaxID=310752 {ECO:0000312|Proteomes:UP000261681};
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Zheng Y., Li E., Zhan S., Cho Y.S.;
RL Submitted (NOV-2013) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP X-RAY CRYSTALLOGRAPHY (2.34 ANGSTROMS) OF 22-395 OF MUTANT ALA-143,
RP MUTAGENESIS OF CYS-143, ACTIVE SITE, SUBUNIT, GLYCOSYLATION AT ASN-173 AND
RP ASN-259, AND DISULFIDE BOND.
RX PubMed=29692406; DOI=10.1038/s41467-018-03844-2;
RA Gebai A., Gorelik A., Li Z., Illes K., Nagar B.;
RT "Structural basis for the activation of acid ceramidase.";
RL Nat. Commun. 9:1621-1621(2018).
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:0000269|PubMed:29692406}.
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:0000269|PubMed:29692406}.
CC -!- PTM: Proteolytically cleaved into two chains alpha and beta that remain
CC associated via a disulfide bond (PubMed:29692406). Cleavage gives rise
CC to a conformation change that activates the enzyme. The same catalytic
CC Cys residue mediates the autoproteolytic cleavage and subsequent
CC hydrolysis of lipid substrates. The beta chain may undergo an
CC additional C-terminal processing (By similarity).
CC {ECO:0000250|UniProtKB:Q13510, ECO:0000269|PubMed:29692406}.
CC -!- SIMILARITY: Belongs to the acid ceramidase family. {ECO:0000305}.
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DR EMBL; KI537508; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_007174053.1; XM_007173991.1.
DR PDB; 5U84; X-ray; 2.34 A; A/B=22-395.
DR PDBsum; 5U84; -.
DR AlphaFoldDB; A0A383ZFX3; -.
DR SMR; A0A383ZFX3; -.
DR STRING; 9767.XP_007174053.1; -.
DR iPTMnet; A0A383ZFX3; -.
DR GeneID; 103004383; -.
DR KEGG; bacu:103004383; -.
DR CTD; 427; -.
DR UniPathway; UPA00222; -.
DR Proteomes; UP000261681; Unplaced.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
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:0017040; F:N-acylsphingosine amidohydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0006631; P:fatty acid metabolic process; IEA:InterPro.
DR GO; GO:0006665; P:sphingolipid metabolic process; IEA:UniProtKB-UniPathway.
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 3D-structure; Disulfide bond; Glycoprotein; Hydrolase; Lipid metabolism;
KW Lysosome; Reference proteome; Secreted; Signal; Sphingolipid metabolism;
KW Zymogen.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..395
FT /note="Acid ceramidase"
FT /evidence="ECO:0000255"
FT /id="PRO_5016879903"
FT CHAIN 22..142
FT /note="Acid ceramidase subunit alpha"
FT /evidence="ECO:0000250|UniProtKB:Q13510"
FT /id="PRO_0000446620"
FT CHAIN 143..395
FT /note="Acid ceramidase subunit beta"
FT /evidence="ECO:0000250|UniProtKB:Q13510"
FT /id="PRO_0000446621"
FT ACT_SITE 143
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:29692406"
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 173
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:29692406,
FT ECO:0007744|PDB:5U84"
FT CARBOHYD 259
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:29692406,
FT ECO:0007744|PDB:5U84"
FT CARBOHYD 342
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 348
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:0000269|PubMed:29692406,
FT ECO:0007744|PDB:5U84"
FT DISULFID 388..392
FT /evidence="ECO:0000269|PubMed:29692406,
FT ECO:0007744|PDB:5U84"
FT MUTAGEN 143
FT /note="C->A: Loss of autoproteolytic cleavage."
FT /evidence="ECO:0000269|PubMed:29692406"
FT STRAND 43..46
FT /evidence="ECO:0007829|PDB:5U84"
FT STRAND 49..53
FT /evidence="ECO:0007829|PDB:5U84"
FT HELIX 58..60
FT /evidence="ECO:0007829|PDB:5U84"
FT HELIX 63..66
FT /evidence="ECO:0007829|PDB:5U84"
FT HELIX 70..87
FT /evidence="ECO:0007829|PDB:5U84"
FT HELIX 93..99
FT /evidence="ECO:0007829|PDB:5U84"
FT HELIX 101..107
FT /evidence="ECO:0007829|PDB:5U84"
FT HELIX 110..123
FT /evidence="ECO:0007829|PDB:5U84"
FT HELIX 127..136
FT /evidence="ECO:0007829|PDB:5U84"
FT HELIX 137..140
FT /evidence="ECO:0007829|PDB:5U84"
FT STRAND 141..149
FT /evidence="ECO:0007829|PDB:5U84"
FT STRAND 155..164
FT /evidence="ECO:0007829|PDB:5U84"
FT TURN 167..169
FT /evidence="ECO:0007829|PDB:5U84"
FT HELIX 175..182
FT /evidence="ECO:0007829|PDB:5U84"
FT HELIX 183..185
FT /evidence="ECO:0007829|PDB:5U84"
FT STRAND 186..193
FT /evidence="ECO:0007829|PDB:5U84"
FT STRAND 196..204
FT /evidence="ECO:0007829|PDB:5U84"
FT STRAND 211..215
FT /evidence="ECO:0007829|PDB:5U84"
FT TURN 216..218
FT /evidence="ECO:0007829|PDB:5U84"
FT STRAND 219..225
FT /evidence="ECO:0007829|PDB:5U84"
FT HELIX 233..239
FT /evidence="ECO:0007829|PDB:5U84"
FT HELIX 253..259
FT /evidence="ECO:0007829|PDB:5U84"
FT HELIX 263..272
FT /evidence="ECO:0007829|PDB:5U84"
FT STRAND 279..287
FT /evidence="ECO:0007829|PDB:5U84"
FT STRAND 291..296
FT /evidence="ECO:0007829|PDB:5U84"
FT STRAND 298..306
FT /evidence="ECO:0007829|PDB:5U84"
FT HELIX 309..311
FT /evidence="ECO:0007829|PDB:5U84"
FT STRAND 315..318
FT /evidence="ECO:0007829|PDB:5U84"
FT HELIX 334..344
FT /evidence="ECO:0007829|PDB:5U84"
FT HELIX 346..348
FT /evidence="ECO:0007829|PDB:5U84"
FT HELIX 351..357
FT /evidence="ECO:0007829|PDB:5U84"
FT TURN 361..363
FT /evidence="ECO:0007829|PDB:5U84"
FT STRAND 368..375
FT /evidence="ECO:0007829|PDB:5U84"
FT TURN 376..379
FT /evidence="ECO:0007829|PDB:5U84"
FT STRAND 380..386
FT /evidence="ECO:0007829|PDB:5U84"
SQ SEQUENCE 395 AA; 44743 MW; 6031B0343ED4E588 CRC64;
MLGRSRLTFV LLSVTVTCSV AQHVPPWTED CRKSTYPPSG PTYRGPVPWY TINLDLPPYK
RWHELMVDKA PALKVIVNYL KNMINAFEPS GKIVQLVDQK LPGLLGSFPG PFEEEMKGIA
AVTEIPLGEI ILFNIFYEFF TICTSIITED KEGHLLHARN MDFGVFLGWN VNNNTWVVTE
ELKPLTVNLD FQRNSKTVFK AAGFAGYVGM LTGFKPGLFS LTLNERFSTN GGFMGVIEWI
LGKKDAKWIG FIIRSVLENS TSYEEAKTIL TKSKILAPAY FILGGSKSGE GCVITRDRVQ
SLDIYELDPK QGIWYVVQTN YDRWKNPFFL DNRRTPAKMC LNRTTQENIS FATMYDVLST
KPVLNKLTVY TALIDVTKGQ FETYLRDCPD PCIGW