ASAH2_RAT
ID ASAH2_RAT Reviewed; 761 AA.
AC Q91XT9;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Neutral ceramidase {ECO:0000305};
DE Short=N-CDase;
DE Short=NCDase;
DE EC=3.5.1.- {ECO:0000269|PubMed:10488143, ECO:0000269|PubMed:11328816};
DE EC=3.5.1.23 {ECO:0000269|PubMed:10488143, ECO:0000269|PubMed:11278489, ECO:0000269|PubMed:11328816, ECO:0000269|PubMed:15123644, ECO:0000269|PubMed:15217782};
DE AltName: Full=Acylsphingosine deacylase 2;
DE AltName: Full=N-acylsphingosine amidohydrolase 2;
DE Contains:
DE RecName: Full=Neutral ceramidase soluble form {ECO:0000305|PubMed:12499379};
GN Name=Asah2;
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], PROTEIN SEQUENCE OF 223-245; 261-273; 601-619
RP AND 701-729, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP GLYCOSYLATION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=11328816; DOI=10.1074/jbc.m102233200;
RA Mitsutake S., Tani M., Okino N., Mori K., Ichinose S., Omori A., Iida H.,
RA Nakamura T., Ito M.;
RT "Purification, characterization, molecular cloning, and subcellular
RT distribution of neutral ceramidase of rat kidney.";
RL J. Biol. Chem. 276:26249-26259(2001).
RN [2]
RP PROTEIN SEQUENCE OF 80-100, SUBCELLULAR LOCATION, TOPOLOGY, GLYCOSYLATION,
RP MUTAGENESIS OF SER-44; 50-SER--THR-71 AND SER-77, AND PROTEOLYTIC CLEAVAGE
RP AFTER ASN-79.
RX PubMed=12499379; DOI=10.1074/jbc.m207932200;
RA Tani M., Iida H., Ito M.;
RT "O-glycosylation of mucin-like domain retains the neutral ceramidase on the
RT plasma membranes as a type II integral membrane protein.";
RL J. Biol. Chem. 278:10523-10530(2003).
RN [3]
RP PROTEIN SEQUENCE OF 311-327; 635-648 AND 737-753.
RX PubMed=10781606; DOI=10.1074/jbc.m002522200;
RA El Bawab S., Roddy P., Qian T., Bielawska A., Lemasters J.J., Hannun Y.A.;
RT "Molecular cloning and characterization of a human mitochondrial
RT ceramidase.";
RL J. Biol. Chem. 275:21508-21513(2000).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=10488143; DOI=10.1074/jbc.274.39.27948;
RA El Bawab S., Bielawska A., Hannun Y.A.;
RT "Purification and characterization of a membrane-bound nonlysosomal
RT ceramidase from rat brain.";
RL J. Biol. Chem. 274:27948-27955(1999).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=11330410; DOI=10.1023/a:1010792031910;
RA Lundgren P., Nilsson A., Duan R.D.;
RT "Distribution and properties of neutral ceramidase activity in rat
RT intestinal tract.";
RL Dig. Dis. Sci. 46:765-772(2001).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY
RP REGULATION.
RX PubMed=11278489; DOI=10.1074/jbc.m009331200;
RA El Bawab S., Birbes H., Roddy P., Szulc Z.M., Bielawska A., Hannun Y.A.;
RT "Biochemical characterization of the reverse activity of rat brain
RT ceramidase. A CoA-independent and fumonisin B1-insensitive ceramide
RT synthase.";
RL J. Biol. Chem. 276:16758-16766(2001).
RN [7]
RP INDUCTION.
RX PubMed=11457826; DOI=10.1074/jbc.m102153200;
RA Franzen R., Pautz A., Braeutigam L., Geisslinger G., Pfeilschifter J.,
RA Huwiler A.;
RT "Interleukin-1beta induces chronic activation and de novo synthesis of
RT neutral ceramidase in renal mesangial cells.";
RL J. Biol. Chem. 276:35382-35389(2001).
RN [8]
RP PHOSPHORYLATION.
RX PubMed=12359735; DOI=10.1074/jbc.m204034200;
RA Franzen R., Fabbro D., Aschrafi A., Pfeilschifter J., Huwiler A.;
RT "Nitric oxide induces degradation of the neutral ceramidase in rat renal
RT mesangial cells and is counterregulated by protein kinase C.";
RL J. Biol. Chem. 277:46184-46190(2002).
RN [9]
RP UBIQUITINATION.
RX PubMed=12482609; DOI=10.1016/s0014-5793(02)03727-4;
RA Franzen R., Pfeilschifter J., Huwiler A.;
RT "Nitric oxide induces neutral ceramidase degradation by the
RT ubiquitin/proteasome complex in renal mesangial cell cultures.";
RL FEBS Lett. 532:441-444(2002).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, GLYCOSYLATION,
RP MUTAGENESIS OF PHE-756; GLU-757 AND ILE-758, AND REGION.
RX PubMed=15123644; DOI=10.1074/jbc.m404012200;
RA Tani M., Okino N., Sueyoshi N., Ito M.;
RT "Conserved amino acid residues in the COOH-terminal tail are indispensable
RT for the correct folding and localization and enzyme activity of neutral
RT ceramidase.";
RL J. Biol. Chem. 279:29351-29358(2004).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, CATALYTIC ACTIVITY, PATHWAY,
RP AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=15217782; DOI=10.1152/ajpgi.00155.2004;
RA Olsson M., Duan R.-D., Ohlsson L., Nilsson A.;
RT "Rat intestinal ceramidase: purification, properties, and physiological
RT relevance.";
RL Am. J. Physiol. 287:G929-G937(2004).
RN [12]
RP SUBCELLULAR LOCATION.
RX PubMed=21613224; DOI=10.1074/jbc.m110.214866;
RA Novgorodov S.A., Wu B.X., Gudz T.I., Bielawski J., Ovchinnikova T.V.,
RA Hannun Y.A., Obeid L.M.;
RT "Novel pathway of ceramide production in mitochondria: thioesterase and
RT neutral ceramidase produce ceramide from sphingosine and acyl-CoA.";
RL J. Biol. Chem. 286:25352-25362(2011).
CC -!- FUNCTION: Plasma membrane ceramidase that hydrolyzes sphingolipid
CC ceramides into sphingosine and free fatty acids at neutral pH
CC (PubMed:11328816, PubMed:10488143, PubMed:15217782). Ceramides,
CC sphingosine, and its phosphorylated form sphingosine-1-phosphate are
CC bioactive lipids that mediate cellular signaling pathways regulating
CC several biological processes including cell proliferation, apoptosis
CC and differentiation (PubMed:11328816). Also catalyzes the reverse
CC reaction allowing the synthesis of ceramides from fatty acids and
CC sphingosine (PubMed:15123644, PubMed:11278489). Together with
CC sphingomyelinase, participates in the production of sphingosine and
CC sphingosine-1-phosphate from the degradation of sphingomyelin, a
CC sphingolipid enriched in the plasma membrane of cells
CC (PubMed:15217782). Also participates in the hydrolysis of ceramides
CC from the extracellular milieu allowing the production of sphingosine-1-
CC phosphate inside and outside cells. This is the case for instance with
CC the digestion of dietary sphingolipids in the intestinal tract (By
CC similarity). {ECO:0000250|UniProtKB:Q9JHE3,
CC ECO:0000269|PubMed:10488143, ECO:0000269|PubMed:11278489,
CC ECO:0000269|PubMed:11328816, ECO:0000269|PubMed:15123644,
CC ECO:0000269|PubMed:15217782, ECO:0000303|PubMed:11328816}.
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:0000269|PubMed:10488143, ECO:0000269|PubMed:11278489,
CC ECO:0000269|PubMed:11328816, ECO:0000269|PubMed:15123644,
CC ECO:0000269|PubMed:15217782};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20857;
CC Evidence={ECO:0000250|UniProtKB:Q9JHE3};
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:0000269|PubMed:10488143, ECO:0000269|PubMed:11278489,
CC ECO:0000269|PubMed:11328816, ECO:0000269|PubMed:15217782};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38892;
CC Evidence={ECO:0000250|UniProtKB:Q9JHE3};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:38893;
CC Evidence={ECO:0000305|PubMed:11278489};
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:0000269|PubMed:11278489};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:41289;
CC Evidence={ECO:0000305|PubMed:11278489};
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:0000269|PubMed:11278489};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41300;
CC Evidence={ECO:0000250|UniProtKB:Q9NR71};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:41301;
CC Evidence={ECO:0000305|PubMed:11278489};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(15Z-tetracosenoyl)-sphing-4-enine = (15Z)-
CC tetracosenoate + sphing-4-enine; Xref=Rhea:RHEA:41267,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:32392, ChEBI:CHEBI:57756,
CC ChEBI:CHEBI:74450; Evidence={ECO:0000269|PubMed:11278489};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:41269;
CC Evidence={ECO:0000305|PubMed:11278489};
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:0000269|PubMed:11328816, ECO:0000269|PubMed:15217782};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45093;
CC Evidence={ECO:0000250|UniProtKB:Q9NR71};
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:0000269|PubMed:11328816, ECO:0000269|PubMed:15123644};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41292;
CC Evidence={ECO:0000250|UniProtKB:Q9JHE3};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:41293;
CC Evidence={ECO:0000250|UniProtKB:Q9JHE3};
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:Q9NR71};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41296;
CC Evidence={ECO:0000250|UniProtKB:Q9NR71};
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:Q9JHE3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41280;
CC Evidence={ECO:0000250|UniProtKB:Q9JHE3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexadecanoate + sphinganine = H2O + N-hexadecanoylsphinganine;
CC Xref=Rhea:RHEA:43440, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:57817, ChEBI:CHEBI:67042;
CC Evidence={ECO:0000269|PubMed:10488143, ECO:0000269|PubMed:11328816};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:43442;
CC Evidence={ECO:0000250|UniProtKB:Q9JHE3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(octadecanoyl)-sphinganine = octadecanoate +
CC sphinganine; Xref=Rhea:RHEA:45008, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:25629, ChEBI:CHEBI:57817, ChEBI:CHEBI:67033;
CC Evidence={ECO:0000269|PubMed:11328816};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45009;
CC Evidence={ECO:0000250|UniProtKB:Q9JHE3};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q9NR71};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q9NR71};
CC -!- ACTIVITY REGULATION: The reverse reaction is inhibited by Zn(2+) and
CC Cu(2+) (PubMed:11278489). Inhibited by cardiolipin and phosphatidic
CC acid (PubMed:11278489). {ECO:0000269|PubMed:11278489}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=71.4 uM for N-(octanoyl)-sphing-4-enine
CC {ECO:0000269|PubMed:15217782};
CC KM=66 uM for N-hexadecanoylsphing-4-enine
CC {ECO:0000269|PubMed:15217782};
CC Vmax=160 umol/min/mg enzyme with N-(octanoyl)-sphing-4-enine as
CC substrate {ECO:0000269|PubMed:15217782};
CC Vmax=16 umol/min/mg enzyme with N-hexadecanoylsphing-4-enine as
CC substrate {ECO:0000269|PubMed:15217782};
CC Vmax=4.4 umol/min/mg enzyme with N-hexadecanoylsphing-4-enine as
CC substrate {ECO:0000269|PubMed:10488143};
CC Vmax=1.2 umol/min/mg enzyme with dihydroceramide as substrate
CC {ECO:0000269|PubMed:10488143};
CC Vmax=0.63 umol/min/mg enzyme toward tetradecanoate for the synthesis
CC of N-tetradecanoylsphing-4-enine (at pH 7.0)
CC {ECO:0000269|PubMed:11278489};
CC Vmax=0.47 umol/min/mg enzyme toward hexadecanoate for the synthesis
CC of N-hexadecanoylsphing-4-enine (at pH 7.0)
CC {ECO:0000269|PubMed:11278489};
CC Vmax=0.28 umol/min/mg enzyme toward (9Z)-octadecenoate for the
CC synthesis of N-(9Z-octadecenoyl)-sphing-4-enine (at pH 7.0)
CC {ECO:0000269|PubMed:11278489};
CC Vmax=0.25 umol/min/mg enzyme toward (15Z)-tetracosenoate for the
CC synthesis of N-(15Z-tetracosenoyl)sphing-4-enine (at pH 7.0)
CC {ECO:0000269|PubMed:11278489};
CC Vmax=0.3 umol/min/mg enzyme toward D-erythro-sphing-4-enine for the
CC synthesis of N-hexadecanoylsphing-4-enine (at pH 7.0)
CC {ECO:0000269|PubMed:11278489};
CC Note=More efficiently hydrolyzes N-lauroylsphingosine/C12:0-ceramides
CC compared to N-palmitoylsphingosine/C16:0-ceramides and N-
CC stearoylsphingosine/C18:0-ceramides (PubMed:11328816). The catalytic
CC efficiency towards dihydroceramides and phytoceramides is very low
CC (PubMed:11328816, PubMed:10488143). For the reverse synthetic
CC reaction exhibits a higher activity with D-erythro-sphing-4-enine and
CC the fatty acid tetradecanoate as substrates (PubMed:11278489).
CC {ECO:0000269|PubMed:10488143, ECO:0000269|PubMed:11278489,
CC ECO:0000269|PubMed:11328816};
CC pH dependence:
CC Optimum pH is 6-7 for N-hexadecanoylsphing-4-enine hydrolysis
CC (PubMed:11328816). Optimum pH is 7-10 for N-hexadecanoylsphing-4-
CC enine hydrolysis (PubMed:10488143). Optimum pH is 6-8 for N-
CC (octanoyl)-sphing-4-enine hydrolysis (PubMed:15217782). Optimum pH is
CC 6.5-7 for hexadecanoate in the reverse reaction (PubMed:11278489).
CC {ECO:0000269|PubMed:10488143, ECO:0000269|PubMed:11278489,
CC ECO:0000269|PubMed:11328816, ECO:0000269|PubMed:15217782};
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000269|PubMed:15217782}.
CC -!- SUBCELLULAR LOCATION: [Neutral ceramidase]: Cell membrane
CC {ECO:0000269|PubMed:11328816, ECO:0000269|PubMed:12499379,
CC ECO:0000269|PubMed:15123644}; Single-pass type II membrane protein
CC {ECO:0000269|PubMed:12499379}. Membrane raft
CC {ECO:0000269|PubMed:11328816}; Single-pass type II membrane protein
CC {ECO:0000269|PubMed:12499379}. Membrane, caveola
CC {ECO:0000250|UniProtKB:Q9JHE3}; Single-pass type II membrane protein
CC {ECO:0000269|PubMed:12499379}. Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q9NR71}; Single-pass type II membrane protein
CC {ECO:0000269|PubMed:12499379}. Mitochondrion
CC {ECO:0000269|PubMed:21613224}. Secreted, extracellular exosome
CC {ECO:0000250|UniProtKB:Q9NR71}. Note=Enriched in exosomes upon
CC stimulation by cytokine (By similarity). Enriched in caveolae and lipid
CC rafts (By similarity). The localization to the mitochondrion could not
CC be confirmed (By similarity). {ECO:0000250|UniProtKB:Q9JHE3,
CC ECO:0000250|UniProtKB:Q9NR71}.
CC -!- SUBCELLULAR LOCATION: [Neutral ceramidase soluble form]: Secreted
CC {ECO:0000269|PubMed:12499379, ECO:0000269|PubMed:15123644}.
CC -!- TISSUE SPECIFICITY: Highly expressed in brain, kidney and heart
CC (PubMed:11328816). Expressed at lower level in other tissues such as
CC liver (PubMed:11328816). Expressed in intestine, kidney and liver (at
CC protein level) (PubMed:11328816, PubMed:11330410). Localizes in the
CC epithelia of the jejunum and ileum (PubMed:11330410).
CC {ECO:0000269|PubMed:11328816, ECO:0000269|PubMed:11330410}.
CC -!- INDUCTION: By interleukin-1-beta in renal mesangial cells.
CC {ECO:0000269|PubMed:11457826}.
CC -!- PTM: Proteolytic cleavage of the N-terminus removes the signal-anchor
CC and produces a soluble form of the protein.
CC {ECO:0000269|PubMed:12499379}.
CC -!- PTM: N-glycosylated (PubMed:11328816, PubMed:15123644). Required for
CC enzyme activity (PubMed:11328816). {ECO:0000269|PubMed:11328816,
CC ECO:0000269|PubMed:15123644}.
CC -!- PTM: O-glycosylated (PubMed:12499379). Required to retain it as a type
CC II membrane protein at the cell surface (PubMed:12499379).
CC {ECO:0000269|PubMed:12499379}.
CC -!- PTM: Phosphorylated. May prevent ubiquitination and subsequent
CC degradation. {ECO:0000269|PubMed:12359735,
CC ECO:0000269|PubMed:12482609}.
CC -!- PTM: Ubiquitinated, leading to its degradation by the proteasome.
CC Ubiquitination is triggered by nitric oxide.
CC {ECO:0000269|PubMed:12482609}.
CC -!- SIMILARITY: Belongs to the neutral ceramidase family. {ECO:0000305}.
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DR EMBL; AB057433; BAB62033.1; -; mRNA.
DR RefSeq; NP_446098.1; NM_053646.2.
DR RefSeq; XP_006231325.1; XM_006231263.1.
DR RefSeq; XP_006231330.1; XM_006231268.3.
DR RefSeq; XP_006231332.1; XM_006231270.1.
DR RefSeq; XP_008758542.1; XM_008760320.2.
DR RefSeq; XP_017444135.1; XM_017588646.1.
DR RefSeq; XP_017444136.1; XM_017588647.1.
DR RefSeq; XP_017444137.1; XM_017588648.1.
DR RefSeq; XP_017444138.1; XM_017588649.1.
DR RefSeq; XP_017444139.1; XM_017588650.1.
DR RefSeq; XP_017444140.1; XM_017588651.1.
DR AlphaFoldDB; Q91XT9; -.
DR SMR; Q91XT9; -.
DR STRING; 10116.ENSRNOP00000016688; -.
DR SwissLipids; SLP:000000682; -.
DR GlyGen; Q91XT9; 16 sites.
DR PaxDb; Q91XT9; -.
DR PRIDE; Q91XT9; -.
DR Ensembl; ENSRNOT00000077135; ENSRNOP00000073116; ENSRNOG00000012196.
DR GeneID; 114104; -.
DR KEGG; rno:114104; -.
DR UCSC; RGD:69410; rat.
DR CTD; 56624; -.
DR RGD; 69410; Asah2.
DR eggNOG; KOG2232; Eukaryota.
DR GeneTree; ENSGT00390000015792; -.
DR InParanoid; Q91XT9; -.
DR OMA; VWHRTNT; -.
DR OrthoDB; 967085at2759; -.
DR PhylomeDB; Q91XT9; -.
DR BRENDA; 3.5.1.23; 5301.
DR Reactome; R-RNO-1660662; Glycosphingolipid metabolism.
DR SABIO-RK; Q91XT9; -.
DR UniPathway; UPA00222; -.
DR PRO; PR:Q91XT9; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000012196; Expressed in duodenum and 18 other tissues.
DR Genevisible; Q91XT9; RN.
DR GO; GO:0005901; C:caveola; ISS:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; ISS:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0102121; F:ceramidase activity; IEA:UniProtKB-EC.
DR GO; GO:0071633; F:dihydroceramidase activity; IDA:UniProtKB.
DR GO; GO:0017040; F:N-acylsphingosine amidohydrolase activity; IDA:UniProtKB.
DR GO; GO:0070774; F:phytoceramidase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; ISO:RGD.
DR GO; GO:0046513; P:ceramide biosynthetic process; IDA:UniProtKB.
DR GO; GO:0046514; P:ceramide catabolic process; IDA:UniProtKB.
DR GO; GO:0006672; P:ceramide metabolic process; ISS:UniProtKB.
DR GO; GO:0044241; P:lipid digestion; ISS:UniProtKB.
DR GO; GO:0042759; P:long-chain fatty acid biosynthetic process; IBA:GO_Central.
DR GO; GO:2001234; P:negative regulation of apoptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:0007346; P:regulation of mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0010033; P:response to organic substance; IDA:RGD.
DR GO; GO:0046512; P:sphingosine biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006670; P:sphingosine metabolic process; ISS:UniProtKB.
DR Gene3D; 2.60.40.2300; -; 1.
DR InterPro; IPR006823; Ceramidase_alk.
DR InterPro; IPR038445; NCDase_C_sf.
DR InterPro; IPR031331; NEUT/ALK_ceramidase_C.
DR InterPro; IPR031329; NEUT/ALK_ceramidase_N.
DR PANTHER; PTHR12670; PTHR12670; 1.
DR Pfam; PF04734; Ceramidase_alk; 1.
DR Pfam; PF17048; Ceramidse_alk_C; 1.
PE 1: Evidence at protein level;
KW Apoptosis; Calcium; Cell membrane; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Golgi apparatus; Hydrolase; Lipid metabolism;
KW Membrane; Metal-binding; Mitochondrion; Phosphoprotein; Reference proteome;
KW Secreted; Signal-anchor; Sphingolipid metabolism; Transmembrane;
KW Transmembrane helix; Ubl conjugation; Zinc.
FT CHAIN 1..761
FT /note="Neutral ceramidase"
FT /id="PRO_0000247103"
FT CHAIN 80..761
FT /note="Neutral ceramidase soluble form"
FT /evidence="ECO:0000269|PubMed:12499379"
FT /id="PRO_0000247104"
FT TOPO_DOM 1..11
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 12..32
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 33..761
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 43..76
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 751..761
FT /note="Required for correct folding and localization"
FT /evidence="ECO:0000269|PubMed:15123644"
FT ACT_SITE 335
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT BINDING 115
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9NR71"
FT BINDING 175
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9NR71"
FT BINDING 284
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9NR71"
FT BINDING 521
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9NR71"
FT BINDING 560
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9NR71"
FT BINDING 693
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9NR71"
FT BINDING 695
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9NR71"
FT BINDING 698
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9NR71"
FT SITE 79..80
FT /note="Cleavage"
FT /evidence="ECO:0000269|PubMed:12499379"
FT CARBOHYD 51
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 52
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 56
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 57
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 58
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 60
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 61
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 63
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 64
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 66
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 68
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 69
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 71
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 198
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 412
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 449
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 343..357
FT /evidence="ECO:0000250|UniProtKB:Q9NR71"
FT DISULFID 350..365
FT /evidence="ECO:0000250|UniProtKB:Q9NR71"
FT DISULFID 429..479
FT /evidence="ECO:0000250|UniProtKB:Q9NR71"
FT MUTAGEN 44
FT /note="S->A: Abolishes O-glycosylation and localization at
FT the cell surface; when associated with A-50; A-51; A-52; A-
FT 56; A-57; A-58; A-60; A-61; A-62; A-63; A-65; A-76; A-68;
FT A-69; A-71 and A-77."
FT /evidence="ECO:0000269|PubMed:12499379"
FT MUTAGEN 50..71
FT /note="STTQGPTTTQSSPTTQTPTTQT->AAAQGPAAAQAAPAAQAPAAQA:
FT Abolishes O-glycosylation and localization at the cell
FT surface; when associated with A-44 and A-77."
FT /evidence="ECO:0000269|PubMed:12499379"
FT MUTAGEN 77
FT /note="S->A: Abolishes O-glycosylation and localization at
FT the cell surface; when associated with A-44; A-50; A-51; A-
FT 52; A-56; A-57; A-58; A-60; A-61; A-62; A-63; A-65; A-76;
FT A-68; A-69 and A-71."
FT /evidence="ECO:0000269|PubMed:12499379"
FT MUTAGEN 756
FT /note="F->I: No effect."
FT /evidence="ECO:0000269|PubMed:15123644"
FT MUTAGEN 756
FT /note="F->R,D: Loss of function."
FT /evidence="ECO:0000269|PubMed:15123644"
FT MUTAGEN 757
FT /note="E->R: No effect."
FT /evidence="ECO:0000269|PubMed:15123644"
FT MUTAGEN 758
FT /note="I->F: Impairs enzyme activity."
FT /evidence="ECO:0000269|PubMed:15123644"
FT MUTAGEN 758
FT /note="I->R,D: Loss of function."
FT /evidence="ECO:0000269|PubMed:15123644"
FT MUTAGEN 758
FT /note="I->V: No effect."
FT /evidence="ECO:0000269|PubMed:15123644"
FT CONFLICT 325
FT /note="G -> N (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 761 AA; 83488 MW; 68B91BC78AEB6324 CRC64;
MAKRTFSSLE AFLIFLLVMM TAITVALLTL LFVTSGTIEN HKDSGNHWVS TTQGPTTTQS
SPTTQTPTTQ TPDLPPSQNF SGYYIGVGRA DCTGQVSDIN LMGYGKNGQN AQGLLTRLFS
RAFILADPDG SNRMAFVSVE LCMISQRLRL EVLKRLQSKY GSLYRRDNVI LSATHTHSGP
AGFFQYTLYI LASEGFSNRT FQYIVSGIVK SIDIAHTNLK PGKVLINKGN VANVQINRSP
SSYLQNPPSE RARYSSDTDK EMVVLKLVDL NGEDLGLISW FAVHPVSMNN SNHLVNSDNM
GYAAYLFEQE KNRGYLPGQG PFVAGFASSN LGDVSPNILG PHCVNTGESC DNDKSTCPSG
GPSMCMASGP GQDMFESTHI IGRVIYQKAK ELHASASQEV TGPVLTAHQW VNMTDVSVQL
NATHTVKTCK AALGYSFAAG TIDGVSGLNI TQGTTEGNLF WDTLRDQLLG KPSEEIIECQ
KPKPILIHTG ELTKPHPWQP DIVDIQIVTL GSLAIAAIPG EFTTMSGRRL REAVKKEFAL
YGMKDMTVVI AGLSNVYTHY ITTYEEYQAQ RYEAASTIYG PHTLSAYIQL FRALAKAIAT
DTVANMSSGP EPPFFKNLIG SLIPNIADRA PIGKQFGDVL QPAKPEYRVG EVVEVVFVGA
NPKNSAENQT HQTFLTVEKY EDSVANWQIM HNDASWETRF YWHKGVLGLS NATIHWHIPD
TALPGVYRIR YFGHNRKQEL LKPAVILAFE GISSPFEIVT T
