ACER3_HUMAN
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 03-AUG-2022, entry version 162.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
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; 9.
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; Q9NUN7; -.
DR PeptideAtlas; Q9NUN7; -.
DR PRIDE; Q9NUN7; -.
DR ProteomicsDB; 82700; -. [Q9NUN7-1]
DR ProteomicsDB; 82701; -. [Q9NUN7-2]
DR TopDownProteomics; Q9NUN7-1; -. [Q9NUN7-1]
DR Antibodypedia; 53464; 126 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 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; 969354at2759; -.
DR PhylomeDB; Q9NUN7; -.
DR TreeFam; TF313019; -.
DR BRENDA; 3.5.1.23; 2681.
DR PathwayCommons; Q9NUN7; -.
DR Reactome; R-HSA-1660661; Sphingolipid de novo biosynthesis.
DR SignaLink; Q9NUN7; -.
DR UniPathway; UPA00222; -.
DR BioGRID-ORCS; 55331; 14 hits in 1078 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 193 other tissues.
DR ExpressionAtlas; Q9NUN7; baseline and differential.
DR Genevisible; Q9NUN7; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0030173; C:integral component of Golgi membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of 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:0030148; P:sphingolipid biosynthetic process; TAS:Reactome.
DR GO; GO:0046512; P:sphingosine biosynthetic process; IDA:UniProtKB.
DR InterPro; IPR008901; ACER.
DR PANTHER; PTHR46187; PTHR46187; 1.
DR Pfam; PF05875; Ceramidase; 1.
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
