ASAH2_MOUSE
ID ASAH2_MOUSE Reviewed; 756 AA.
AC Q9JHE3; Q3UWP9; Q8BNP0; Q8BQN7; Q8R236;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Neutral ceramidase {ECO:0000305};
DE Short=N-CDase;
DE Short=NCDase;
DE EC=3.5.1.- {ECO:0000269|PubMed:10652340};
DE EC=3.5.1.23 {ECO:0000269|PubMed:10652340, ECO:0000269|PubMed:10753931, ECO:0000269|PubMed:14557071, ECO:0000269|PubMed:16126722, ECO:0000269|PubMed:16380386};
DE AltName: Full=Acylsphingosine deacylase 2;
DE AltName: Full=N-acylsphingosine amidohydrolase 2;
DE Contains:
DE RecName: Full=Neutral ceramidase soluble form {ECO:0000250|UniProtKB:Q91XT9};
GN Name=Asah2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, TISSUE
RP SPECIFICITY, AND GLYCOSYLATION.
RC TISSUE=Brain, and Liver;
RX PubMed=10753931; DOI=10.1074/jbc.275.15.11229;
RA Tani M., Okino N., Mori K., Tanigawa T., Izu H., Ito M.;
RT "Molecular cloning of the full-length cDNA encoding mouse neutral
RT ceramidase. A novel but highly conserved gene family of neutral/alkaline
RT ceramidases.";
RL J. Biol. Chem. 275:11229-11234(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Adipose tissue, Corpus striatum, Egg, and Lung;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 261-756.
RC STRAIN=FVB/N; TISSUE=Liver;
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 [4]
RP PROTEIN SEQUENCE OF 309-343 AND 592-603, FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND GLYCOSYLATION.
RC TISSUE=Liver;
RX PubMed=10652340; DOI=10.1074/jbc.275.5.3462;
RA Tani M., Okino N., Mitsutake S., Tanigawa T., Izu H., Ito M.;
RT "Purification and characterization of a neutral ceramidase from mouse
RT liver. A single protein catalyzes the reversible reaction in which ceramide
RT is both hydrolyzed and synthesized.";
RL J. Biol. Chem. 275:3462-3468(2000).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=11591392; DOI=10.1016/s0014-5793(01)02878-2;
RA Romiti E., Meacci E., Tanzi G., Becciolini L., Mitsutake S., Farnararo M.,
RA Ito M., Bruni P.;
RT "Localization of neutral ceramidase in caveolin-enriched light membranes of
RT murine endothelial cells.";
RL FEBS Lett. 506:163-168(2001).
RN [6]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH CAV1.
RX PubMed=12921776; DOI=10.1016/s0003-9861(03)00212-1;
RA Romiti E., Meacci E., Donati C., Formigli L., Zecchi-Orlandini S.,
RA Farnararo M., Ito M., Bruni P.;
RT "Neutral ceramidase secreted by endothelial cells is released in part
RT associated with caveolin-1.";
RL Arch. Biochem. Biophys. 417:27-33(2003).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND TISSUE SPECIFICITY.
RX PubMed=14557071; DOI=10.1016/s0378-1119(03)00721-2;
RA Choi M.S., Anderson M.A., Zhang Z., Zimonjic D.B., Popescu N.,
RA Mukherjee A.B.;
RT "Neutral ceramidase gene: role in regulating ceramide-induced apoptosis.";
RL Gene 315:113-122(2003).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=16126722; DOI=10.1074/jbc.m506827200;
RA Tani M., Igarashi Y., Ito M.;
RT "Involvement of neutral ceramidase in ceramide metabolism at the plasma
RT membrane and in extracellular milieu.";
RL J. Biol. Chem. 280:36592-36600(2005).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, DISRUPTION PHENOTYPE, AND TISSUE
RP SPECIFICITY.
RX PubMed=16380386; DOI=10.1074/jbc.m508382200;
RA Kono M., Dreier J.L., Ellis J.M., Allende M.L., Kalkofen D.N.,
RA Sanders K.M., Bielawski J., Bielawska A., Hannun Y.A., Proia R.L.;
RT "Neutral ceramidase encoded by the Asah2 gene is essential for the
RT intestinal degradation of sphingolipids.";
RL J. Biol. Chem. 281:7324-7331(2006).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, AND DISRUPTION
RP PHENOTYPE.
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:10753931, PubMed:10652340, PubMed:16380386). 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:14557071). Also catalyzes the reverse
CC reaction allowing the synthesis of ceramides from fatty acids and
CC sphingosine (PubMed:10652340, PubMed:21613224). 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:16126722). Also participates in the hydrolysis of ceramides
CC from the extracellular milieu allowing the production of sphingosine-1-
CC phosphate inside and outside cells (PubMed:16126722). This is the case
CC for instance with the digestion of dietary sphingolipids in the
CC intestinal tract (PubMed:16380386). {ECO:0000269|PubMed:10652340,
CC ECO:0000269|PubMed:10753931, ECO:0000269|PubMed:14557071,
CC ECO:0000269|PubMed:16126722, ECO:0000269|PubMed:16380386,
CC ECO:0000269|PubMed:21613224}.
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:10652340, ECO:0000269|PubMed:10753931,
CC ECO:0000269|PubMed:14557071, ECO:0000269|PubMed:16126722,
CC ECO:0000269|PubMed:16380386};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20857;
CC Evidence={ECO:0000305|PubMed:10652340};
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:10652340};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38892;
CC Evidence={ECO:0000269|PubMed:10652340};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:38893;
CC Evidence={ECO:0000269|PubMed:10652340};
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:10652340};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41292;
CC Evidence={ECO:0000305|PubMed:10652340};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:41293;
CC Evidence={ECO:0000269|PubMed:21613224};
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:0000269|PubMed:10652340};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41280;
CC Evidence={ECO:0000305|PubMed:10652340};
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:Q9NR71};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45093;
CC Evidence={ECO:0000250|UniProtKB:Q9NR71};
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-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:Q91XT9};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:41289;
CC Evidence={ECO:0000250|UniProtKB:Q91XT9};
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:Q91XT9};
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:0000250|UniProtKB:Q91XT9};
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:0000250|UniProtKB:Q91XT9};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:41269;
CC Evidence={ECO:0000250|UniProtKB:Q91XT9};
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:10652340};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:43442;
CC Evidence={ECO:0000305|PubMed:10652340};
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:10652340};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45009;
CC Evidence={ECO:0000305|PubMed:10652340};
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: Inhibited by D-erythro-MAPP.
CC {ECO:0000269|PubMed:14557071}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=22.3 mM for C12-4-nitrobenzo-2-oxa-1,3-diazole-ceramide
CC {ECO:0000269|PubMed:10652340};
CC KM=72.4 mM for N-hexadecanoylsphing-4-enine
CC {ECO:0000269|PubMed:10652340};
CC Vmax=29.1 umol/min/mg enzyme with C12-4-nitrobenzo-2-oxa-1,3-diazole-
CC ceramide as substrate {ECO:0000269|PubMed:10652340};
CC Vmax=3.6 umol/min/mg enzyme with N-hexadecanoylsphing-4-enine as
CC substrate {ECO:0000269|PubMed:10652340};
CC pH dependence:
CC Optimum pH is 7.5. {ECO:0000269|PubMed:10652340};
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000269|PubMed:16380386, ECO:0000269|PubMed:21613224}.
CC -!- SUBUNIT: May interact with CAV1. {ECO:0000269|PubMed:12921776}.
CC -!- SUBCELLULAR LOCATION: [Neutral ceramidase]: Cell membrane
CC {ECO:0000269|PubMed:11591392, ECO:0000269|PubMed:12921776,
CC ECO:0000269|PubMed:16126722}; Single-pass type II membrane protein
CC {ECO:0000269|PubMed:16126722}. Membrane raft
CC {ECO:0000269|PubMed:12921776}; Single-pass type II membrane protein
CC {ECO:0000269|PubMed:16126722}. Membrane, caveola
CC {ECO:0000269|PubMed:12921776}; Single-pass type II membrane protein
CC {ECO:0000269|PubMed:16126722}. Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q9NR71}; Single-pass type II membrane protein
CC {ECO:0000269|PubMed:16126722}. 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 (PubMed:12921776). {ECO:0000250|UniProtKB:Q9NR71,
CC ECO:0000269|PubMed:12921776}.
CC -!- SUBCELLULAR LOCATION: [Neutral ceramidase soluble form]: Secreted
CC {ECO:0000269|PubMed:16126722}.
CC -!- TISSUE SPECIFICITY: Widely expressed (PubMed:10753931,
CC PubMed:14557071). Strongly expressed in small intestine and to a lower
CC extent in liver and kidney (PubMed:10753931). Highly expressed in
CC duodenum, jejunum and ileum along the brush border of the small
CC intestine (at protein level) (PubMed:16380386).
CC {ECO:0000269|PubMed:10753931, ECO:0000269|PubMed:14557071,
CC ECO:0000269|PubMed:16380386}.
CC -!- PTM: Proteolytic cleavage of the N-terminus removes the signal-anchor
CC and produces a soluble form of the protein.
CC {ECO:0000250|UniProtKB:Q91XT9}.
CC -!- PTM: N-glycosylated. Required for enzyme activity.
CC {ECO:0000269|PubMed:10652340, ECO:0000269|PubMed:10753931}.
CC -!- PTM: O-glycosylated. Required to retain it as a type II membrane
CC protein at the cell surface. {ECO:0000250|UniProtKB:Q9NR71}.
CC -!- PTM: Phosphorylated. May prevent ubiquitination and subsequent
CC degradation. {ECO:0000250|UniProtKB:Q91XT9}.
CC -!- PTM: Ubiquitinated, leading to its degradation by the proteasome.
CC Ubiquitination is triggered by nitric oxide.
CC {ECO:0000250|UniProtKB:Q91XT9}.
CC -!- DISRUPTION PHENOTYPE: Homozygous knockout mice have a normal life span
CC and do not show obvious abnormalities or major alterations in total
CC ceramide levels in tissues (PubMed:16380386). However, they are
CC deficient in the intestinal digestion of dietary ceramides
CC (PubMed:16380386). A decrease in total ceramides in liver is also
CC observed (PubMed:21613224). {ECO:0000269|PubMed:16380386,
CC ECO:0000269|PubMed:21613224}.
CC -!- SIMILARITY: Belongs to the neutral ceramidase family. {ECO:0000305}.
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DR EMBL; AB037111; BAA94545.1; -; mRNA.
DR EMBL; AB037181; BAA94546.1; -; mRNA.
DR EMBL; AK047692; BAC33126.1; -; mRNA.
DR EMBL; AK080951; BAC38089.1; -; mRNA.
DR EMBL; AK136189; BAE22865.1; -; mRNA.
DR EMBL; AK166100; BAE38571.1; -; mRNA.
DR EMBL; BC022604; AAH22604.1; -; mRNA.
DR CCDS; CCDS29749.1; -.
DR RefSeq; NP_061300.1; NM_018830.1.
DR RefSeq; XP_011245585.1; XM_011247283.2.
DR RefSeq; XP_011245586.1; XM_011247284.2.
DR RefSeq; XP_011245587.1; XM_011247285.2.
DR RefSeq; XP_011245588.1; XM_011247286.2.
DR RefSeq; XP_011245589.1; XM_011247287.2.
DR RefSeq; XP_011245591.1; XM_011247289.1.
DR RefSeq; XP_011245592.1; XM_011247290.2.
DR AlphaFoldDB; Q9JHE3; -.
DR SMR; Q9JHE3; -.
DR STRING; 10090.ENSMUSP00000093830; -.
DR ChEMBL; CHEMBL2146344; -.
DR SwissLipids; SLP:000000216; -.
DR GlyGen; Q9JHE3; 7 sites.
DR iPTMnet; Q9JHE3; -.
DR PhosphoSitePlus; Q9JHE3; -.
DR jPOST; Q9JHE3; -.
DR MaxQB; Q9JHE3; -.
DR PaxDb; Q9JHE3; -.
DR PRIDE; Q9JHE3; -.
DR ProteomicsDB; 281909; -.
DR Antibodypedia; 27845; 237 antibodies from 31 providers.
DR DNASU; 54447; -.
DR Ensembl; ENSMUST00000096119; ENSMUSP00000093830; ENSMUSG00000024887.
DR Ensembl; ENSMUST00000236030; ENSMUSP00000158185; ENSMUSG00000024887.
DR Ensembl; ENSMUST00000236504; ENSMUSP00000157744; ENSMUSG00000024887.
DR Ensembl; ENSMUST00000237104; ENSMUSP00000157424; ENSMUSG00000024887.
DR GeneID; 54447; -.
DR KEGG; mmu:54447; -.
DR UCSC; uc008hew.1; mouse.
DR CTD; 56624; -.
DR MGI; MGI:1859310; Asah2.
DR VEuPathDB; HostDB:ENSMUSG00000024887; -.
DR eggNOG; KOG2232; Eukaryota.
DR GeneTree; ENSGT00390000015792; -.
DR HOGENOM; CLU_011300_2_0_1; -.
DR InParanoid; Q9JHE3; -.
DR OMA; VWHRTNT; -.
DR OrthoDB; 967085at2759; -.
DR PhylomeDB; Q9JHE3; -.
DR TreeFam; TF300786; -.
DR BRENDA; 3.5.1.23; 3474.
DR Reactome; R-MMU-1660662; Glycosphingolipid metabolism.
DR SABIO-RK; Q9JHE3; -.
DR UniPathway; UPA00222; -.
DR BioGRID-ORCS; 54447; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Asah2; mouse.
DR PRO; PR:Q9JHE3; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q9JHE3; protein.
DR Bgee; ENSMUSG00000024887; Expressed in epithelium of small intestine and 224 other tissues.
DR ExpressionAtlas; Q9JHE3; baseline and differential.
DR Genevisible; Q9JHE3; MM.
DR GO; GO:0005901; C:caveola; IDA: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; IDA:MGI.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0017040; F:N-acylsphingosine amidohydrolase activity; IDA:UniProtKB.
DR GO; GO:0070774; F:phytoceramidase activity; ISO:MGI.
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; IEA:Ensembl.
DR GO; GO:0046513; P:ceramide biosynthetic process; IMP: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; IMP: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; ISO:MGI.
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..756
FT /note="Neutral ceramidase"
FT /id="PRO_0000247101"
FT CHAIN 75..756
FT /note="Neutral ceramidase soluble form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000247102"
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..756
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 746..756
FT /note="Required for correct folding and localization"
FT /evidence="ECO:0000250|UniProtKB:Q91XT9"
FT ACT_SITE 330
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT BINDING 110
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9NR71"
FT BINDING 170
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9NR71"
FT BINDING 279
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9NR71"
FT BINDING 516
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9NR71"
FT BINDING 555
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9NR71"
FT BINDING 688
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9NR71"
FT BINDING 690
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
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 SITE 74..75
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:Q91XT9"
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 64
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 193
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 407
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 444
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 338..352
FT /evidence="ECO:0000250|UniProtKB:Q9NR71"
FT DISULFID 345..360
FT /evidence="ECO:0000250|UniProtKB:Q9NR71"
FT DISULFID 424..474
FT /evidence="ECO:0000250|UniProtKB:Q9NR71"
FT CONFLICT 543
FT /note="V -> I (in Ref. 2; BAC38089)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 756 AA; 83509 MW; FFD514E51280D4BE CRC64;
MAKRTFSTLE AFLIFLLVIM TVITVALLTL LFVTSGTIEN HKDSGNHWFS TTLGSTTTQP
PPITQTPNFP SFRNFSGYYI GVGRADCTGQ VSDINLMGYG KNGQNARGLL TRLFSRAFIL
ADPDGSNRMA FVSVELCMIS QRLRLEVLKR LESKYGSLYR RDNVILSAIH THSGPAGFFQ
YTLYILASEG FSNRTFQYIV SGIMKSIDIA HTNLKPGKIF INKGNVANVQ INRSPSSYLL
NPQSERARYS SNTDKEMLVL KLVDLNGEDL GLISWFAIHP VSMNNSNHFV NSDNMGYAAY
LFEQEKNKGY LPGQGPFVAG FASSNLGDVS PNILGPHCVN TGESCDNDKS TCPNGGPSMC
MASGPGQDMF ESTHIIGRII YQKAKELYAS ASQEVTGPVL AAHQWVNMTD VSVQLNATHT
VKTCKPALGY SFAAGTIDGV SGLNITQGTT EGDPFWDTLR DQLLGKPSEE IVECQKPKPI
LLHSGELTIP HPWQPDIVDV QIVTVGSLAI AAIPGELTTM SGRRFREAIK KEFALYGMKD
MTVVIAGLSN VYTHYITTYE EYQAQRYEAA STIYGPHTLS AYIQLFRDLA KAIATDTVAN
MSSGPEPPFF KNLIASLIPN IADRAPIGKH FGDVLQPAKP EYRVGEVVEV IFVGANPKNS
AENQTHQTFL TVEKYEDSVA DWQIMYNDAS WETRFYWHKG ILGLSNATIY WHIPDTAYPG
IYRIRYFGHN RKQELLKPAV ILAFEGISSP FEVVTT
