ID   ACER3_HUMAN             Reviewed;         267 AA.
AC   Q9NUN7; B2RC99;
DT   14-AUG-2001, integrated into UniProtKB/Swiss-Prot.
DT   18-MAY-2010, sequence version 3.
DT   27-MAR-2024, entry version 170.
DE   RecName: Full=Alkaline ceramidase 3;
DE            Short=AlkCDase 3;
DE            Short=Alkaline CDase 3;
DE            EC=3.5.1.- {ECO:0000269|PubMed:11356846, ECO:0000269|PubMed:20068046, ECO:0000269|PubMed:20207939};
DE            EC=3.5.1.23 {ECO:0000269|PubMed:20068046, ECO:0000269|PubMed:20207939, ECO:0000269|PubMed:26792856, ECO:0000269|PubMed:30575723};
DE   AltName: Full=Alkaline dihydroceramidase SB89;
DE   AltName: Full=Alkaline phytoceramidase;
DE            Short=aPHC;
GN   Name=ACER3; Synonyms=APHC, PHCA;
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   ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION,
RP   AND TISSUE SPECIFICITY.
RC   TISSUE=Kidney;
RX   PubMed=11356846; DOI=10.1074/jbc.m102818200;
RA   Mao C., Xu R., Szulc Z.M., Bielawska A., Galadari S.H., Obeid L.M.;
RT   "Cloning and characterization of a novel human alkaline ceramidase. A
RT   mammalian enzyme that hydrolyzes phytoceramide.";
RL   J. Biol. Chem. 276:26577-26588(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA   Li N., Zhang W., Wan T., Chen T., Cao X.;
RL   Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Placenta, and Thalamus;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16554811; DOI=10.1038/nature04632;
RA   Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA   Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA   Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA   Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA   Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA   Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT   "Human chromosome 11 DNA sequence and analysis including novel gene
RT   identification.";
RL   Nature 440:497-500(2006).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Eye;
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   [7]
RP   FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND TISSUE SPECIFICITY.
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   [8]
RP   FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, AND PATHWAY.
RX   PubMed=20068046; DOI=10.1074/jbc.m109.063586;
RA   Hu W., Xu R., Sun W., Szulc Z.M., Bielawski J., Obeid L.M., Mao C.;
RT   "Alkaline ceramidase 3 (ACER3) hydrolyzes unsaturated long-chain ceramides,
RT   and its down-regulation inhibits both cell proliferation and apoptosis.";
RL   J. Biol. Chem. 285:7964-7976(2010).
RN   [9]
RP   FUNCTION, CATALYTIC ACTIVITY, INVOLVEMENT IN PLDECO, VARIANT PLDECO GLY-33,
RP   AND CHARACTERIZATION OF VARIANT PLDECO GLY-33.
RX   PubMed=26792856; DOI=10.1136/jmedgenet-2015-103457;
RA   Edvardson S., Yi J.K., Jalas C., Xu R., Webb B.D., Snider J., Fedick A.,
RA   Kleinman E., Treff N.R., Mao C., Elpeleg O.;
RT   "Deficiency of the alkaline ceramidase ACER3 manifests in early childhood
RT   by progressive leukodystrophy.";
RL   J. Med. Genet. 53:389-396(2016).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 2-244 IN COMPLEX WITH CALCIUM AND
RP   ZINC IONS, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, PATHWAY,
RP   CHARACTERIZATION OF VARIANT PLDECO GLY-33, SUBCELLULAR LOCATION, TOPOLOGY,
RP   AND MUTAGENESIS OF ASP-19; GLU-22; ASN-24; SER-99; TYR-149 AND SER-228.
RX   PubMed=30575723; DOI=10.1038/s41467-018-07864-w;
RA   Vasiliauskaite-Brooks I., Healey R.D., Rochaix P., Saint-Paul J.,
RA   Sounier R., Grison C., Waltrich-Augusto T., Fortier M., Hoh F., Saied E.M.,
RA   Arenz C., Basu S., Leyrat C., Granier S.;
RT   "Structure of a human intramembrane ceramidase explains enzymatic
RT   dysfunction found in leukodystrophy.";
RL   Nat. Commun. 9:5437-5437(2018).
CC   -!- FUNCTION: Endoplasmic reticulum and Golgi ceramidase that catalyzes the
CC       hydrolysis of unsaturated long-chain C18:1-, C20:1- and C20:4-
CC       ceramides, dihydroceramides and phytoceramides into sphingoid bases
CC       like sphingosine and free fatty acids at alkaline pH (PubMed:20068046,
CC       PubMed:26792856, PubMed:20207939, PubMed:11356846, PubMed:30575723).
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 (PubMed:20068046). Controls the
CC       generation of sphingosine in erythrocytes, and thereby sphingosine-1-
CC       phosphate in plasma (PubMed:20207939). Through the regulation of
CC       ceramides and sphingosine-1-phosphate homeostasis in the brain may play
CC       a role in neurons survival and function (By similarity). By regulating
CC       the levels of pro-inflammatory ceramides in immune cells and tissues,
CC       may modulate the inflammatory response (By similarity).
CC       {ECO:0000250|UniProtKB:Q9D099, ECO:0000269|PubMed:11356846,
CC       ECO:0000269|PubMed:20068046, ECO:0000269|PubMed:20207939,
CC       ECO:0000269|PubMed:26792856, ECO:0000269|PubMed:30575723,
CC       ECO:0000303|PubMed:20068046}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=an N-acyl-(4R)-4-hydroxysphinganine + H2O = (4R)-
CC         hydroxysphinganine + a fatty acid; Xref=Rhea:RHEA:33555,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:28868, ChEBI:CHEBI:31998,
CC         ChEBI:CHEBI:64124; Evidence={ECO:0000269|PubMed:11356846,
CC         ECO:0000269|PubMed:20068046};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33556;
CC         Evidence={ECO:0000305|PubMed:20068046};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sphing-4-enine =
CC         (5Z,8Z,11Z,14Z)-eicosatetraenoate + sphing-4-enine;
CC         Xref=Rhea:RHEA:45348, ChEBI:CHEBI:15377, ChEBI:CHEBI:32395,
CC         ChEBI:CHEBI:57756, ChEBI:CHEBI:85198;
CC         Evidence={ECO:0000269|PubMed:20068046};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45349;
CC         Evidence={ECO:0000305|PubMed:20068046};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sphinganine =
CC         (5Z,8Z,11Z,14Z)-eicosatetraenoate + sphinganine;
CC         Xref=Rhea:RHEA:45376, ChEBI:CHEBI:15377, ChEBI:CHEBI:32395,
CC         ChEBI:CHEBI:57817, ChEBI:CHEBI:85206;
CC         Evidence={ECO:0000269|PubMed:20068046};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45377;
CC         Evidence={ECO:0000305|PubMed:20068046};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-(4R)-
CC         hydroxysphinganine = (4R)-hydroxysphinganine + (5Z,8Z,11Z,14Z)-
CC         eicosatetraenoate; Xref=Rhea:RHEA:45380, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:32395, ChEBI:CHEBI:64124, ChEBI:CHEBI:85207;
CC         Evidence={ECO:0000269|PubMed:20068046};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45381;
CC         Evidence={ECO:0000305|PubMed:20068046};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + N-(11Z-eicosenoyl)-sphing-4-enine = (11Z)-eicosenoate +
CC         sphing-4-enine; Xref=Rhea:RHEA:45356, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:32426, ChEBI:CHEBI:57756, ChEBI:CHEBI:85284;
CC         Evidence={ECO:0000269|PubMed:20068046};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45357;
CC         Evidence={ECO:0000305|PubMed:20068046};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + N-(11Z-eicosenoyl)-sphinganine = (11Z)-eicosenoate +
CC         sphinganine; Xref=Rhea:RHEA:45360, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:32426, ChEBI:CHEBI:57817, ChEBI:CHEBI:85285;
CC         Evidence={ECO:0000269|PubMed:20068046};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45361;
CC         Evidence={ECO:0000305|PubMed:20068046};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + N-(11Z-eicosenoyl)-(4R)-hydroxysphinganine = (11Z)-
CC         eicosenoate + (4R)-hydroxysphinganine; Xref=Rhea:RHEA:45364,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:32426, ChEBI:CHEBI:64124,
CC         ChEBI:CHEBI:85286; Evidence={ECO:0000269|PubMed:20068046};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45365;
CC         Evidence={ECO:0000305|PubMed:20068046};
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:20068046, ECO:0000269|PubMed:26792856};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41300;
CC         Evidence={ECO:0000305|PubMed:20068046};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + N-(9Z-octadecenoyl)-sphinganine = (9Z)-octadecenoate +
CC         sphinganine; Xref=Rhea:RHEA:45372, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:30823, ChEBI:CHEBI:57817, ChEBI:CHEBI:74100;
CC         Evidence={ECO:0000269|PubMed:20068046, ECO:0000269|PubMed:30575723};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45373;
CC         Evidence={ECO:0000305|PubMed:20068046};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + N-(9Z-octadecenoyl)-(4R)-hydroxysphinganine = (4R)-
CC         hydroxysphinganine + (9Z)-octadecenoate; Xref=Rhea:RHEA:45368,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:30823, ChEBI:CHEBI:64124,
CC         ChEBI:CHEBI:85204; Evidence={ECO:0000269|PubMed:20068046};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45369;
CC         Evidence={ECO:0000305|PubMed:20068046};
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:20068046, ECO:0000269|PubMed:20207939,
CC         ECO:0000269|PubMed:26792856};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20857;
CC         Evidence={ECO:0000305|PubMed:20068046};
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:20068046, ECO:0000269|PubMed:20207939};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33552;
CC         Evidence={ECO:0000305|PubMed:20068046};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000269|PubMed:30575723};
CC   -!- ACTIVITY REGULATION: Activated by 5 mM Ca(2+) and inhibited by 5 mM
CC       Zn(2+). {ECO:0000269|PubMed:11356846}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       pH dependence:
CC         Optimum pH is 9.5. {ECO:0000269|PubMed:11356846};
CC   -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC       {ECO:0000269|PubMed:20068046, ECO:0000269|PubMed:20207939,
CC       ECO:0000269|PubMed:30575723}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000269|PubMed:11356846}; Multi-pass membrane protein
CC       {ECO:0000269|PubMed:11356846, ECO:0000269|PubMed:30575723}. Golgi
CC       apparatus membrane {ECO:0000269|PubMed:11356846}; Multi-pass membrane
CC       protein {ECO:0000269|PubMed:11356846, ECO:0000269|PubMed:30575723}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q9NUN7-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9NUN7-2; Sequence=VSP_039162, VSP_039163;
CC   -!- TISSUE SPECIFICITY: Ubiquitously expressed. Highly expressed in
CC       placenta (PubMed:11356846). Expressed in erythrocytes
CC       (PubMed:20207939). {ECO:0000269|PubMed:11356846,
CC       ECO:0000269|PubMed:20207939}.
CC   -!- DISEASE: Leukodystrophy, progressive, early childhood-onset (PLDECO)
CC       [MIM:617762]: A form of leukodystrophy, a disorder of myelin production
CC       or maintenance affecting the central nervous system. PELCO features
CC       include neurological regression between 6 and 13 months of age, truncal
CC       hypotonia, appendicular spasticity, dystonia, optic disk pallor,
CC       peripheral neuropathy and neurogenic bladder. Brain imaging shows
CC       progressive diffuse abnormal white matter signals, cerebral atrophy,
CC       and thin corpus callosum. Sural nerve biopsy shows decreased
CC       myelination. PLDECO inheritance is autosomal recessive.
CC       {ECO:0000269|PubMed:26792856, ECO:0000269|PubMed:30575723}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- SIMILARITY: Belongs to the alkaline ceramidase family. {ECO:0000305}.
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DR   EMBL; AF214454; AAK71923.1; -; mRNA.
DR   EMBL; AF327353; AAL56013.1; -; mRNA.
DR   EMBL; AK002100; BAA92085.1; -; mRNA.
DR   EMBL; AK315000; BAG37496.1; -; mRNA.
DR   EMBL; AP000752; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AP002498; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AP003119; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471076; EAW75010.1; -; Genomic_DNA.
DR   EMBL; BC073853; AAH73853.1; -; mRNA.
DR   CCDS; CCDS8247.1; -. [Q9NUN7-1]
DR   RefSeq; NP_060837.3; NM_018367.6. [Q9NUN7-1]
DR   PDB; 6G7O; X-ray; 2.70 A; A=2-244.
DR   PDB; 6YXH; X-ray; 2.60 A; A=2-244.
DR   PDBsum; 6G7O; -.
DR   PDBsum; 6YXH; -.
DR   AlphaFoldDB; Q9NUN7; -.
DR   SMR; Q9NUN7; -.
DR   BioGRID; 120612; 10.
DR   IntAct; Q9NUN7; 1.
DR   STRING; 9606.ENSP00000434480; -.
DR   SwissLipids; SLP:000000680; -.
DR   iPTMnet; Q9NUN7; -.
DR   PhosphoSitePlus; Q9NUN7; -.
DR   BioMuta; ACER3; -.
DR   DMDM; 296439452; -.
DR   MassIVE; Q9NUN7; -.
DR   PaxDb; 9606-ENSP00000434480; -.
DR   PeptideAtlas; Q9NUN7; -.
DR   ProteomicsDB; 82700; -. [Q9NUN7-1]
DR   ProteomicsDB; 82701; -. [Q9NUN7-2]
DR   TopDownProteomics; Q9NUN7-1; -. [Q9NUN7-1]
DR   Antibodypedia; 53464; 134 antibodies from 25 providers.
DR   DNASU; 55331; -.
DR   Ensembl; ENST00000532485.6; ENSP00000434480.1; ENSG00000078124.13. [Q9NUN7-1]
DR   GeneID; 55331; -.
DR   KEGG; hsa:55331; -.
DR   MANE-Select; ENST00000532485.6; ENSP00000434480.1; NM_018367.7; NP_060837.3.
DR   UCSC; uc009yum.2; human. [Q9NUN7-1]
DR   AGR; HGNC:16066; -.
DR   CTD; 55331; -.
DR   DisGeNET; 55331; -.
DR   GeneCards; ACER3; -.
DR   HGNC; HGNC:16066; ACER3.
DR   HPA; ENSG00000078124; Low tissue specificity.
DR   MalaCards; ACER3; -.
DR   MIM; 617036; gene.
DR   MIM; 617762; phenotype.
DR   neXtProt; NX_Q9NUN7; -.
DR   OpenTargets; ENSG00000078124; -.
DR   Orphanet; 502444; Alkaline ceramidase 3 deficiency.
DR   PharmGKB; PA33256; -.
DR   VEuPathDB; HostDB:ENSG00000078124; -.
DR   eggNOG; KOG2329; Eukaryota.
DR   GeneTree; ENSGT00730000110920; -.
DR   InParanoid; Q9NUN7; -.
DR   OMA; IMFEPLR; -.
DR   OrthoDB; 2910516at2759; -.
DR   PhylomeDB; Q9NUN7; -.
DR   TreeFam; TF313019; -.
DR   BRENDA; 3.5.1.23; 2681.
DR   PathwayCommons; Q9NUN7; -.
DR   Reactome; R-HSA-428157; Sphingolipid metabolism.
DR   SignaLink; Q9NUN7; -.
DR   UniPathway; UPA00222; -.
DR   BioGRID-ORCS; 55331; 15 hits in 1156 CRISPR screens.
DR   ChiTaRS; ACER3; human.
DR   GeneWiki; ACER3; -.
DR   GenomeRNAi; 55331; -.
DR   Pharos; Q9NUN7; Tbio.
DR   PRO; PR:Q9NUN7; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; Q9NUN7; Protein.
DR   Bgee; ENSG00000078124; Expressed in endothelial cell and 195 other cell types or tissues.
DR   ExpressionAtlas; Q9NUN7; baseline and differential.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR   GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB.
DR   GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR   GO; GO:0005509; F:calcium ion binding; IDA: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; IDA:UniProtKB.
DR   GO; GO:0046514; P:ceramide catabolic process; IDA:UniProtKB.
DR   GO; GO:0006954; P:inflammatory response; IEA:Ensembl.
DR   GO; GO:0042552; P:myelination; IMP:UniProtKB.
DR   GO; GO:0071602; P:phytosphingosine biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB.
DR   GO; GO:0043067; P:regulation of programmed cell death; IDA:UniProtKB.
DR   GO; GO:0006665; P:sphingolipid metabolic process; TAS:Reactome.
DR   GO; GO:0046512; P:sphingosine biosynthetic process; IDA:UniProtKB.
DR   InterPro; IPR008901; ACER.
DR   PANTHER; PTHR46187; ALKALINE CERAMIDASE 3; 1.
DR   PANTHER; PTHR46187:SF3; ALKALINE CERAMIDASE 3; 1.
DR   Pfam; PF05875; Ceramidase; 1.
DR   Genevisible; Q9NUN7; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Calcium; Disease variant;
KW   Endoplasmic reticulum; Golgi apparatus; Hydrolase; Leukodystrophy;
KW   Lipid metabolism; Membrane; Metal-binding; Reference proteome;
KW   Sphingolipid metabolism; Transmembrane; Transmembrane helix; Zinc.
FT   CHAIN           1..267
FT                   /note="Alkaline ceramidase 3"
FT                   /id="PRO_0000212463"
FT   TOPO_DOM        1..33
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:30575723"
FT   TRANSMEM        34..55
FT                   /note="Helical"
FT                   /evidence="ECO:0000269|PubMed:30575723"
FT   TOPO_DOM        56..61
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000269|PubMed:30575723"
FT   TRANSMEM        62..82
FT                   /note="Helical"
FT                   /evidence="ECO:0000269|PubMed:30575723"
FT   TOPO_DOM        83..87
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:30575723"
FT   TRANSMEM        88..108
FT                   /note="Helical"
FT                   /evidence="ECO:0000269|PubMed:30575723"
FT   TOPO_DOM        109..118
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000269|PubMed:30575723"
FT   TRANSMEM        119..139
FT                   /note="Helical"
FT                   /evidence="ECO:0000269|PubMed:30575723"
FT   TOPO_DOM        140..141
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:30575723"
FT   TRANSMEM        142..162
FT                   /note="Helical"
FT                   /evidence="ECO:0000269|PubMed:30575723"
FT   TOPO_DOM        163..173
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000269|PubMed:30575723"
FT   TRANSMEM        174..194
FT                   /note="Helical"
FT                   /evidence="ECO:0000269|PubMed:30575723"
FT   TOPO_DOM        195..215
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:30575723"
FT   TRANSMEM        216..236
FT                   /note="Helical"
FT                   /evidence="ECO:0000269|PubMed:30575723"
FT   TOPO_DOM        237..267
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000269|PubMed:30575723"
FT   BINDING         19
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000269|PubMed:30575723,
FT                   ECO:0007744|PDB:6G7O"
FT   BINDING         20
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000269|PubMed:30575723,
FT                   ECO:0007744|PDB:6G7O"
FT   BINDING         22
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000269|PubMed:30575723,
FT                   ECO:0007744|PDB:6G7O"
FT   BINDING         24
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000269|PubMed:30575723,
FT                   ECO:0007744|PDB:6G7O"
FT   BINDING         33
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000269|PubMed:30575723,
FT                   ECO:0007744|PDB:6G7O"
FT   BINDING         81
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000269|PubMed:30575723,
FT                   ECO:0007744|PDB:6G7O"
FT   BINDING         217
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000269|PubMed:30575723,
FT                   ECO:0007744|PDB:6G7O"
FT   BINDING         221
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000269|PubMed:30575723,
FT                   ECO:0007744|PDB:6G7O"
FT   VAR_SEQ         1..133
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_039162"
FT   VAR_SEQ         134..145
FT                   /note="TVYLKVKEPIFH -> MAQSRLIGTSTS (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_039163"
FT   VARIANT         33
FT                   /note="E -> G (in PLDECO; impaired protein stability;
FT                   strongly decreased enzyme activity; decreased ceramide
FT                   catabolic process; in fibroblasts of patients homozygous
FT                   for the mutation; dbSNP:rs1554988032)"
FT                   /evidence="ECO:0000269|PubMed:26792856,
FT                   ECO:0000269|PubMed:30575723"
FT                   /id="VAR_081205"
FT   MUTAGEN         19
FT                   /note="D->G: Mildly decreased enzyme activity."
FT                   /evidence="ECO:0000269|PubMed:30575723"
FT   MUTAGEN         22
FT                   /note="E->G: Strongly decreased enzyme activity."
FT                   /evidence="ECO:0000269|PubMed:30575723"
FT   MUTAGEN         24
FT                   /note="N->G: Strongly decreased enzyme activity."
FT                   /evidence="ECO:0000269|PubMed:30575723"
FT   MUTAGEN         99
FT                   /note="S->A: No effect on enzyme activity."
FT                   /evidence="ECO:0000269|PubMed:30575723"
FT   MUTAGEN         149
FT                   /note="Y->A: Decreased enzyme activity."
FT                   /evidence="ECO:0000269|PubMed:30575723"
FT   MUTAGEN         228
FT                   /note="S->A: No effect on enzyme activity."
FT                   /evidence="ECO:0000269|PubMed:30575723"
FT   CONFLICT        52
FT                   /note="V -> I (in Ref. 1; AAK71923, 2; AAL56013, 3;
FT                   BAG37496, 5; EAW75010 and 6; AAH73853)"
FT                   /evidence="ECO:0000305"
FT   STRAND          32..34
FT                   /evidence="ECO:0007829|PDB:6YXH"
FT   HELIX           35..38
FT                   /evidence="ECO:0007829|PDB:6YXH"
FT   HELIX           39..43
FT                   /evidence="ECO:0007829|PDB:6YXH"
FT   HELIX           45..56
FT                   /evidence="ECO:0007829|PDB:6YXH"
FT   HELIX           61..83
FT                   /evidence="ECO:0007829|PDB:6YXH"
FT   HELIX           86..109
FT                   /evidence="ECO:0007829|PDB:6YXH"
FT   HELIX           119..138
FT                   /evidence="ECO:0007829|PDB:6YXH"
FT   HELIX           142..166
FT                   /evidence="ECO:0007829|PDB:6YXH"
FT   HELIX           169..171
FT                   /evidence="ECO:0007829|PDB:6YXH"
FT   HELIX           172..194
FT                   /evidence="ECO:0007829|PDB:6YXH"
FT   HELIX           199..203
FT                   /evidence="ECO:0007829|PDB:6YXH"
FT   HELIX           209..212
FT                   /evidence="ECO:0007829|PDB:6YXH"
FT   HELIX           216..243
FT                   /evidence="ECO:0007829|PDB:6YXH"
SQ   SEQUENCE   267 AA;  31552 MW;  CFD2A901F12A5918 CRC64;
     MAPAADREGY WGPTTSTLDW CEENYSVTWY IAEFWNTVSN LIMIIPPMFG AVQSVRDGLE
     KRYIASYLAL TVVGMGSWCF HMTLKYEMQL LDELPMIYSC CIFVYCMFEC FKIKNSVNYH
     LLFTLVLFSL IVTTVYLKVK EPIFHQVMYG MLVFTLVLRS IYIVTWVYPW LRGLGYTSLG
     IFLLGFLFWN IDNIFCESLR NFRKKVPPII GITTQFHAWW HILTGLGSYL HILFSLYTRT
     LYLRYRPKVK FLFGIWPVIL FEPLRKH
//