ACER2_HUMAN
ID ACER2_HUMAN Reviewed; 275 AA.
AC Q5QJU3; A2A3R8; Q569G5; Q5VZR7; Q71RD2;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 25-JUL-2006, sequence version 2.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Alkaline ceramidase 2 {ECO:0000305};
DE Short=AlkCDase 2;
DE Short=Alkaline CDase 2;
DE Short=haCER2;
DE EC=3.5.1.- {ECO:0000269|PubMed:20207939, ECO:0000269|PubMed:20628055};
DE EC=3.5.1.23 {ECO:0000269|PubMed:16940153, ECO:0000269|PubMed:20089856, ECO:0000269|PubMed:20207939};
DE AltName: Full=Acylsphingosine deacylase 3-like;
DE AltName: Full=N-acylsphingosine amidohydrolase 3-like;
GN Name=ACER2 {ECO:0000312|HGNC:HGNC:23675}; Synonyms=ASAH3L;
GN ORFNames=PP11646;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP PATHWAY, SUBCELLULAR LOCATION, INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=16940153; DOI=10.1096/fj.05-5689com;
RA Xu R., Jin J., Hu W., Sun W., Bielawski J., Szulc Z., Taha T., Obeid L.M.,
RA Mao C.;
RT "Golgi alkaline ceramidase regulates cell proliferation and survival by
RT controlling levels of sphingosine and S1P.";
RL FASEB J. 20:1813-1825(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RX PubMed=15498874; DOI=10.1073/pnas.0404089101;
RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X.,
RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X.,
RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.;
RT "Large-scale cDNA transfection screening for genes related to cancer
RT development and progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Placenta;
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 [5]
RP FUNCTION.
RX PubMed=18945876; DOI=10.1096/fj.08-115634;
RA Sun W., Hu W., Xu R., Jin J., Szulc Z.M., Zhang G., Galadari S.H.,
RA Obeid L.M., Mao C.;
RT "Alkaline ceramidase 2 regulates beta1 integrin maturation and cell
RT adhesion.";
RL FASEB J. 23:656-666(2009).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND PATHWAY.
RX PubMed=20207939; DOI=10.1096/fj.09-153635;
RA Xu R., Sun W., Jin J., Obeid L.M., Mao C.;
RT "Role of alkaline ceramidases in the generation of sphingosine and its
RT phosphate in erythrocytes.";
RL FASEB J. 24:2507-2515(2010).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBSTRATE SPECIFICITY,
RP PATHWAY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, TOPOLOGY,
RP REGION, AND MUTAGENESIS OF 1-MET--GLU-16.
RX PubMed=20089856; DOI=10.1074/jbc.m109.069203;
RA Sun W., Jin J., Xu R., Hu W., Szulc Z.M., Bielawski J., Obeid L.M., Mao C.;
RT "Substrate specificity, membrane topology, and activity regulation of human
RT alkaline ceramidase 2 (ACER2).";
RL J. Biol. Chem. 285:8995-9007(2010).
RN [8]
RP FUNCTION, INDUCTION BY 4-HPR, AND CATALYTIC ACTIVITY.
RX PubMed=20628055; DOI=10.1074/jbc.m110.105296;
RA Mao Z., Sun W., Xu R., Novgorodov S., Szulc Z.M., Bielawski J., Obeid L.M.,
RA Mao C.;
RT "Alkaline ceramidase 2 (ACER2) and its product dihydrosphingosine mediate
RT the cytotoxicity of N-(4-hydroxyphenyl)retinamide in tumor cells.";
RL J. Biol. Chem. 285:29078-29090(2010).
RN [9]
RP FUNCTION, AND INDUCTION BY DNA DAMAGE.
RX PubMed=26943039; DOI=10.18632/oncotarget.7825;
RA Xu R., Wang K., Mileva I., Hannun Y.A., Obeid L.M., Mao C.;
RT "Alkaline ceramidase 2 and its bioactive product sphingosine are novel
RT regulators of the DNA damage response.";
RL Oncotarget 7:18440-18457(2016).
RN [10]
RP FUNCTION, AND INDUCTION BY TP53.
RX PubMed=28294157; DOI=10.1038/srep44573;
RA Wang Y., Zhang C., Jin Y., Wang S., He Q., Liu Z., Ai Q., Lei Y., Li Y.,
RA Song F., Bu Y.;
RT "Alkaline ceramidase 2 is a novel direct target of p53 and induces
RT autophagy and apoptosis through ROS generation.";
RL Sci. Rep. 7:44573-44573(2017).
RN [11]
RP FUNCTION, AND INDUCTION BY TP53.
RX PubMed=29229990; DOI=10.1038/s41418-017-0018-y;
RA Xu R., Garcia-Barros M., Wen S., Li F., Lin C.L., Hannun Y.A., Obeid L.M.,
RA Mao C.;
RT "Tumor suppressor p53 links ceramide metabolism to DNA damage response
RT through alkaline ceramidase 2.";
RL Cell Death Differ. 25:841-856(2018).
CC -!- FUNCTION: Golgi ceramidase that catalyzes the hydrolysis of ceramides
CC into sphingoid bases like sphingosine and free fatty acids at alkaline
CC pH (PubMed:16940153, PubMed:18945876, PubMed:20207939,
CC PubMed:20089856). Ceramides, sphingosine, and its phosphorylated form
CC sphingosine-1-phosphate are bioactive lipids that mediate cellular
CC signaling pathways regulating several biological processes including
CC cell proliferation, apoptosis and differentiation (PubMed:20207939).
CC Has a better catalytic efficiency towards unsaturated long-chain
CC ceramides, including C18:1-, C20:1- and C24:1-ceramides
CC (PubMed:16940153, PubMed:18945876, PubMed:20207939, PubMed:20089856).
CC Saturated long-chain ceramides and unsaturated very long-chain
CC ceramides are also good substrates, whereas saturated very long-chain
CC ceramides and short-chain ceramides are poor substrates
CC (PubMed:20089856). Also hydrolyzes dihydroceramides to produce
CC dihydrosphingosine (PubMed:20207939, PubMed:20628055). It is the
CC ceramidase that controls the levels of circulating sphingosine-1-
CC phosphate and dihydrosphingosine-1-phosphate in plasma through their
CC production by hematopoietic cells (By similarity). Regulates cell
CC proliferation, autophagy and apoptosis by the production of sphingosine
CC and sphingosine-1-phosphate (PubMed:16940153, PubMed:26943039,
CC PubMed:28294157, PubMed:29229990). As part of a p53/TP53-dependent
CC pathway, promotes for instance autophagy and apoptosis in response to
CC DNA damage (PubMed:26943039, PubMed:28294157, PubMed:29229990). Through
CC the production of sphingosine, may also regulate the function of the
CC Golgi complex and regulate the glycosylation of proteins
CC (PubMed:18945876). {ECO:0000250|UniProtKB:Q8VD53,
CC ECO:0000269|PubMed:16940153, ECO:0000269|PubMed:18945876,
CC ECO:0000269|PubMed:20089856, ECO:0000269|PubMed:20207939,
CC ECO:0000269|PubMed:20628055, ECO:0000269|PubMed:26943039,
CC ECO:0000269|PubMed:28294157, ECO:0000269|PubMed:29229990,
CC ECO:0000303|PubMed:20207939}.
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:16940153,
CC ECO:0000269|PubMed:20089856};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41268;
CC Evidence={ECO:0000269|PubMed:16940153};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-eicosanoyl-sphing-4-enine = eicosanoate + sphing-4-
CC enine; Xref=Rhea:RHEA:41275, ChEBI:CHEBI:15377, ChEBI:CHEBI:32360,
CC ChEBI:CHEBI:57756, ChEBI:CHEBI:72962;
CC Evidence={ECO:0000269|PubMed:20089856};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41276;
CC Evidence={ECO:0000305|PubMed:20089856};
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:20089856};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41280;
CC Evidence={ECO:0000305|PubMed:20089856};
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:16940153, ECO:0000269|PubMed:20089856};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38892;
CC Evidence={ECO:0000269|PubMed:16940153};
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:20089856};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41288;
CC Evidence={ECO:0000305|PubMed:20089856};
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:20089856};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41292;
CC Evidence={ECO:0000305|PubMed:20089856};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-tetracosanoyl-sphing-4-enine = sphing-4-enine +
CC tetracosanoate; Xref=Rhea:RHEA:41283, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:31014, ChEBI:CHEBI:57756, ChEBI:CHEBI:72965;
CC Evidence={ECO:0000269|PubMed:16940153, ECO:0000269|PubMed:20089856};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41284;
CC Evidence={ECO:0000269|PubMed:16940153};
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:0000269|PubMed:20089856};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41296;
CC Evidence={ECO:0000305|PubMed:20089856};
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:20089856};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41300;
CC Evidence={ECO:0000305|PubMed:20089856};
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:16940153, ECO:0000269|PubMed:20089856,
CC ECO:0000269|PubMed:20207939};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20857;
CC Evidence={ECO:0000269|PubMed:20207939};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an N-acylsphinganine + H2O = a fatty acid + sphinganine;
CC Xref=Rhea:RHEA:33551, ChEBI:CHEBI:15377, ChEBI:CHEBI:28868,
CC ChEBI:CHEBI:31488, ChEBI:CHEBI:57817;
CC Evidence={ECO:0000269|PubMed:20207939, ECO:0000269|PubMed:20628055};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33552;
CC Evidence={ECO:0000269|PubMed:20207939};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q9NUN7};
CC -!- ACTIVITY REGULATION: Specifically activated by lumenal, but not
CC cytosolic Ca(2+). Inhibited by Zn(2+) or Cu(2+). Mg(2+) or Mn(2+) have
CC no effect on ceramidase activity (PubMed:20089856). Inhibited by De-
CC MAPP (PubMed:20207939). {ECO:0000269|PubMed:20089856,
CC ECO:0000269|PubMed:20207939}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=224 uM for D-erythro-C(6:0)-ceramide (at 37 degrees Celsius and pH
CC 9.0) {ECO:0000269|PubMed:20089856};
CC KM=134 uM for D-erythro-C(12:0)-ceramide (at 37 degrees Celsius and
CC pH 9.0) {ECO:0000269|PubMed:20089856};
CC KM=115 uM for D-erythro-C(14:0)-ceramide (at 37 degrees Celsius and
CC pH 9.0) {ECO:0000269|PubMed:20089856};
CC KM=99 uM for D-erythro-C(16:0)-ceramide (at 37 degrees Celsius and pH
CC 9.0) {ECO:0000269|PubMed:20089856};
CC KM=95 uM for D-erythro-C(18:0)-ceramide (at 37 degrees Celsius and pH
CC 9.0) {ECO:0000269|PubMed:20089856};
CC KM=77 uM for D-erythro-C(18:1)-ceramide (at 37 degrees Celsius and pH
CC 9.0) {ECO:0000269|PubMed:20089856};
CC KM=91 uM for D-erythro-C(20:0)-ceramide (at 37 degrees Celsius and pH
CC 9.0) {ECO:0000269|PubMed:20089856};
CC KM=72 uM for D-erythro-C(20:1)-ceramide (at 37 degrees Celsius and pH
CC 9.0) {ECO:0000269|PubMed:20089856};
CC KM=143 uM for D-erythro-C(24:0)-ceramide (at 37 degrees Celsius and
CC pH 9.0) {ECO:0000269|PubMed:20089856};
CC KM=81 uM for D-erythro-C(24:1)-ceramide (at 37 degrees Celsius and pH
CC 9.0) {ECO:0000269|PubMed:20089856};
CC Vmax=5 pmol/min/mg enzyme with D-erythro-C(6:0)-ceramide as substrate
CC {ECO:0000269|PubMed:20089856};
CC Vmax=11 pmol/min/mg enzyme with D-erythro-C(12:0)-ceramide as
CC substrate {ECO:0000269|PubMed:20089856};
CC Vmax=11 pmol/min/mg enzyme with D-erythro-C(14:0)-ceramide as
CC substrate {ECO:0000269|PubMed:20089856};
CC Vmax=24 pmol/min/mg enzyme with D-erythro-C(16:0)-ceramide as
CC substrate {ECO:0000269|PubMed:20089856};
CC Vmax=26 pmol/min/mg enzyme with D-erythro-C(18:0)-ceramide as
CC substrate {ECO:0000269|PubMed:20089856};
CC Vmax=35 pmol/min/mg enzyme with D-erythro-C(18:1)-ceramide as
CC substrate {ECO:0000269|PubMed:20089856};
CC Vmax=29 pmol/min/mg enzyme with D-erythro-C(20:0)-ceramide as
CC substrate {ECO:0000269|PubMed:20089856};
CC Vmax=38 pmol/min/mg enzyme with D-erythro-C(20:1)-ceramide as
CC substrate {ECO:0000269|PubMed:20089856};
CC Vmax=7 pmol/min/mg enzyme with D-erythro-C(24:0)-ceramide as
CC substrate {ECO:0000269|PubMed:20089856};
CC Vmax=27 pmol/min/mg enzyme with D-erythro-C(24:1)-ceramide as
CC substrate {ECO:0000269|PubMed:20089856};
CC pH dependence:
CC Optimum pH is 7.5-9.0. {ECO:0000269|PubMed:20089856};
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000269|PubMed:16940153, ECO:0000269|PubMed:20089856,
CC ECO:0000269|PubMed:20207939}.
CC -!- INTERACTION:
CC Q5QJU3-2; Q00013: MPP1; NbExp=3; IntAct=EBI-13319881, EBI-711788;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:16940153, ECO:0000269|PubMed:20089856}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:20089856}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q5QJU3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5QJU3-2; Sequence=VSP_020033;
CC Name=3;
CC IsoId=Q5QJU3-3; Sequence=VSP_020033, VSP_020034, VSP_020035;
CC -!- TISSUE SPECIFICITY: Highly expressed in placenta.
CC {ECO:0000269|PubMed:16940153}.
CC -!- INDUCTION: Up-regulated upon serum deprivation (PubMed:16940153). Up-
CC regulated by N-(4-hydroxyphenyl)retinamode/4-HPR (PubMed:20628055). Up-
CC regulated upon DNA damage, in a p53/TP53-dependent manner, resulting in
CC increased levels of sphingosine and sphingosine-1-phosphate (at protein
CC level) (PubMed:26943039, PubMed:28294157, PubMed:29229990).
CC {ECO:0000269|PubMed:16940153, ECO:0000269|PubMed:20628055,
CC ECO:0000269|PubMed:26943039, ECO:0000269|PubMed:28294157,
CC ECO:0000269|PubMed:29229990}.
CC -!- SIMILARITY: Belongs to the alkaline ceramidase family. {ECO:0000305}.
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DR EMBL; AY312516; AAQ85132.1; -; mRNA.
DR EMBL; AF370405; AAQ15241.1; -; mRNA.
DR EMBL; AL158206; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL391834; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC092487; AAH92487.1; -; mRNA.
DR CCDS; CCDS34992.1; -. [Q5QJU3-1]
DR RefSeq; NP_001010887.2; NM_001010887.2. [Q5QJU3-1]
DR RefSeq; XP_005251505.1; XM_005251448.3. [Q5QJU3-2]
DR RefSeq; XP_016870183.1; XM_017014694.1. [Q5QJU3-2]
DR AlphaFoldDB; Q5QJU3; -.
DR SMR; Q5QJU3; -.
DR BioGRID; 131056; 1.
DR IntAct; Q5QJU3; 1.
DR STRING; 9606.ENSP00000342609; -.
DR BindingDB; Q5QJU3; -.
DR ChEMBL; CHEMBL2331067; -.
DR SwissLipids; SLP:000000164; -.
DR GlyGen; Q5QJU3; 1 site.
DR BioMuta; ACER2; -.
DR DMDM; 110832756; -.
DR PaxDb; Q5QJU3; -.
DR PeptideAtlas; Q5QJU3; -.
DR PRIDE; Q5QJU3; -.
DR Antibodypedia; 2873; 68 antibodies from 20 providers.
DR DNASU; 340485; -.
DR Ensembl; ENST00000340967.3; ENSP00000342609.2; ENSG00000177076.6. [Q5QJU3-1]
DR GeneID; 340485; -.
DR KEGG; hsa:340485; -.
DR MANE-Select; ENST00000340967.3; ENSP00000342609.2; NM_001010887.3; NP_001010887.2.
DR UCSC; uc003zny.2; human. [Q5QJU3-1]
DR CTD; 340485; -.
DR DisGeNET; 340485; -.
DR GeneCards; ACER2; -.
DR HGNC; HGNC:23675; ACER2.
DR HPA; ENSG00000177076; Group enriched (stomach, urinary bladder).
DR MIM; 613492; gene.
DR neXtProt; NX_Q5QJU3; -.
DR OpenTargets; ENSG00000177076; -.
DR PharmGKB; PA164714853; -.
DR VEuPathDB; HostDB:ENSG00000177076; -.
DR eggNOG; KOG2329; Eukaryota.
DR GeneTree; ENSGT00730000110920; -.
DR HOGENOM; CLU_088280_0_0_1; -.
DR InParanoid; Q5QJU3; -.
DR OMA; ALFCWIT; -.
DR PhylomeDB; Q5QJU3; -.
DR TreeFam; TF313019; -.
DR BRENDA; 3.5.1.23; 2681.
DR PathwayCommons; Q5QJU3; -.
DR Reactome; R-HSA-1660661; Sphingolipid de novo biosynthesis.
DR SABIO-RK; Q5QJU3; -.
DR SignaLink; Q5QJU3; -.
DR UniPathway; UPA00222; -.
DR BioGRID-ORCS; 340485; 10 hits in 1073 CRISPR screens.
DR ChiTaRS; ACER2; human.
DR GeneWiki; ACER2; -.
DR GenomeRNAi; 340485; -.
DR Pharos; Q5QJU3; Tchem.
DR PRO; PR:Q5QJU3; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q5QJU3; protein.
DR Bgee; ENSG00000177076; Expressed in urinary bladder and 109 other tissues.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0030173; C:integral component of Golgi membrane; IDA:UniProtKB.
DR GO; GO:0102121; F:ceramidase activity; IEA:UniProtKB-EC.
DR GO; GO:0071633; F:dihydroceramidase activity; IDA:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0017040; F:N-acylsphingosine amidohydrolase activity; IDA:UniProtKB.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:BHF-UCL.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEP:BHF-UCL.
DR GO; GO:0046514; P:ceramide catabolic process; IMP:UniProtKB.
DR GO; GO:0030330; P:DNA damage response, signal transduction by p53 class mediator; IMP:UniProtKB.
DR GO; GO:0033629; P:negative regulation of cell adhesion mediated by integrin; IDA:UniProtKB.
DR GO; GO:0001953; P:negative regulation of cell-matrix adhesion; IDA:UniProtKB.
DR GO; GO:0010942; P:positive regulation of cell death; IMP:BHF-UCL.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0010506; P:regulation of autophagy; IMP:UniProtKB.
DR GO; GO:0060049; P:regulation of protein glycosylation; IMP:UniProtKB.
DR GO; GO:0032526; P:response to retinoic acid; IDA:UniProtKB.
DR GO; GO:0030148; P:sphingolipid biosynthetic process; TAS:Reactome.
DR GO; GO:0046512; P:sphingosine biosynthetic process; IDA:UniProtKB.
DR InterPro; IPR008901; ACER.
DR PANTHER; PTHR46139; PTHR46139; 1.
DR Pfam; PF05875; Ceramidase; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Glycoprotein; Golgi apparatus; Hydrolase;
KW Lipid metabolism; Membrane; Metal-binding; Reference proteome;
KW Sphingolipid metabolism; Transmembrane; Transmembrane helix; Zinc.
FT CHAIN 1..275
FT /note="Alkaline ceramidase 2"
FT /id="PRO_0000247748"
FT TOPO_DOM 1..32
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 33..53
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 54..62
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 63..83
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 84..86
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 87..107
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 108..124
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 125..142
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 143
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 144..164
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 165..173
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 174..194
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 195..211
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 212..232
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 233..275
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..13
FT /note="Required for proper localization to the Golgi
FT apparatus"
FT /evidence="ECO:0000269|PubMed:20089856"
FT BINDING 18
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9NUN7"
FT BINDING 19
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9NUN7"
FT BINDING 21
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9NUN7"
FT BINDING 23
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9NUN7"
FT BINDING 32
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9NUN7"
FT BINDING 82
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9NUN7"
FT BINDING 211
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9NUN7"
FT BINDING 215
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9NUN7"
FT CARBOHYD 23
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..49
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:15498874"
FT /id="VSP_020033"
FT VAR_SEQ 169..189
FT /note="CDNMRVFKLGLFSGLWWTLAL -> HERNQRRRHRKGGQQGGGDKV (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:15498874"
FT /id="VSP_020034"
FT VAR_SEQ 190..275
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15498874"
FT /id="VSP_020035"
FT VARIANT 134
FT /note="A -> V (in dbSNP:rs10964136)"
FT /id="VAR_027150"
FT MUTAGEN 1..16
FT /note="Missing: Loss of localization to the Golgi. No
FT effect on the ceramidase activity."
FT /evidence="ECO:0000269|PubMed:20089856"
FT CONFLICT 274
FT /note="I -> T (in Ref. 1; AAQ85132)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 275 AA; 31309 MW; 56FD619B53C296B1 CRC64;
MGAPHWWDQL QAGSSEVDWC EDNYTIVPAI AEFYNTISNV LFFILPPICM CLFRQYATCF
NSGIYLIWTL LVVVGIGSVY FHATLSFLGQ MLDELAVLWV LMCALAMWFP RRYLPKIFRN
DRGRFKVVVS VLSAVTTCLA FVKPAINNIS LMTLGVPCTA LLIAELKRCD NMRVFKLGLF
SGLWWTLALF CWISDRAFCE LLSSFNFPYL HCMWHILICL AAYLGCVCFA YFDAASEIPE
QGPVIKFWPN EKWAFIGVPY VSLLCANKKS SVKIT
