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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
 
 
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