ASAH2_DANRE
ID ASAH2_DANRE Reviewed; 743 AA.
AC Q5W7F1;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 07-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 102.
DE RecName: Full=Neutral ceramidase {ECO:0000305};
DE Short=N-CDase;
DE Short=NCDase;
DE EC=3.5.1.23 {ECO:0000269|PubMed:15271994};
DE AltName: Full=Acylsphingosine deacylase 2;
DE AltName: Full=N-acylsphingosine amidohydrolase 2;
DE Short=znCD;
GN Name=asah2;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, SUBCELLULAR LOCATION,
RP GLYCOSYLATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=15271994; DOI=10.1074/jbc.m405598200;
RA Yoshimura Y., Tani M., Okino N., Iida H., Ito M.;
RT "Molecular cloning and functional analysis of zebrafish neutral
RT ceramidase.";
RL J. Biol. Chem. 279:44012-44022(2004).
CC -!- FUNCTION: Plasma membrane ceramidase that hydrolyzes sphingolipid
CC ceramides into sphingosine and free fatty acids at neutral pH
CC (PubMed:15271994). 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. Also catalyzes the
CC reverse reaction allowing the synthesis of ceramides from fatty acids
CC and sphingosine. Together with sphingomyelinase, participates in the
CC production of sphingosine and sphingosine-1-phosphate from the
CC degradation of sphingomyelin, a sphingolipid enriched in the plasma
CC membrane of cells (By similarity). Also participates in the hydrolysis
CC of ceramides from the extracellular milieu allowing the production of
CC sphingosine-1-phosphate inside and outside cells (By similarity).
CC {ECO:0000250|UniProtKB:Q9JHE3, ECO:0000250|UniProtKB:Q9NR71,
CC ECO:0000269|PubMed:15271994}.
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:15271994};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20857;
CC Evidence={ECO:0000250|UniProtKB:Q9JHE3};
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:15271994};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41292;
CC Evidence={ECO:0000250|UniProtKB:Q9NR71};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:41293;
CC Evidence={ECO:0000250|UniProtKB:Q9JHE3};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q9NR71};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q9NR71};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.5 for N-dodecanoylsphing-4-enine hydrolysis.
CC {ECO:0000269|PubMed:15271994};
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000269|PubMed:15271994}.
CC -!- SUBCELLULAR LOCATION: [Neutral ceramidase]: Cell membrane
CC {ECO:0000269|PubMed:15271994}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q91XT9}. Membrane raft
CC {ECO:0000250|UniProtKB:Q9JHE3}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q91XT9}. Membrane, caveola
CC {ECO:0000250|UniProtKB:Q9JHE3}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q91XT9}. Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q9NR71}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q91XT9}. Mitochondrion
CC {ECO:0000250|UniProtKB:Q9NR71}. Secreted, extracellular exosome
CC {ECO:0000250|UniProtKB:Q9NR71}.
CC -!- TISSUE SPECIFICITY: Detected in intestine (at protein level).
CC {ECO:0000269|PubMed:15271994}.
CC -!- DEVELOPMENTAL STAGE: Expressed and active during embryonic development.
CC {ECO:0000269|PubMed:15271994}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:15271994}.
CC -!- PTM: O-glycosylated. {ECO:0000269|PubMed:15271994}.
CC -!- DISRUPTION PHENOTYPE: Fishes display severe embryonic morphological and
CC cellular abnormalities such as abnormal morphogenesis in the head and
CC tail, pericardial edema, defect of blood cell circulation, and an
CC increase of apoptotic cells, especially in the head and neural tube
CC regions, at 36 hours post-fertilization. {ECO:0000269|PubMed:15271994}.
CC -!- SIMILARITY: Belongs to the neutral ceramidase family. {ECO:0000305}.
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DR EMBL; AB194413; BAD69590.1; -; mRNA.
DR RefSeq; NP_001007764.1; NM_001007763.1.
DR AlphaFoldDB; Q5W7F1; -.
DR SMR; Q5W7F1; -.
DR STRING; 7955.ENSDARP00000024847; -.
DR PaxDb; Q5W7F1; -.
DR Ensembl; ENSDART00000146650; ENSDARP00000119244; ENSDARG00000012829.
DR GeneID; 493602; -.
DR KEGG; dre:493602; -.
DR CTD; 56624; -.
DR ZFIN; ZDB-GENE-041112-1; asah2.
DR eggNOG; KOG2232; Eukaryota.
DR GeneTree; ENSGT00390000015792; -.
DR HOGENOM; CLU_011300_2_0_1; -.
DR InParanoid; Q5W7F1; -.
DR OMA; VWHRTNT; -.
DR OrthoDB; 967085at2759; -.
DR PhylomeDB; Q5W7F1; -.
DR TreeFam; TF300786; -.
DR BRENDA; 3.5.1.23; 928.
DR Reactome; R-DRE-1660662; Glycosphingolipid metabolism.
DR UniPathway; UPA00222; -.
DR PRO; PR:Q5W7F1; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 12.
DR Bgee; ENSDARG00000012829; Expressed in intestine and 7 other tissues.
DR GO; GO:0016324; C:apical plasma membrane; IDA:ZFIN.
DR GO; GO:0005901; C:caveola; IEA:UniProtKB-SubCell.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:ZFIN.
DR GO; GO:0005576; C:extracellular region; IBA:GO_Central.
DR GO; GO:0000139; C:Golgi membrane; IDA:ZFIN.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:ZFIN.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:ZFIN.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0102121; F:ceramidase activity; IEA:UniProtKB-EC.
DR GO; GO:0017040; F:N-acylsphingosine amidohydrolase activity; IDA:ZFIN.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0046513; P:ceramide biosynthetic process; ISS:UniProtKB.
DR GO; GO:0046514; P:ceramide catabolic process; ISS:UniProtKB.
DR GO; GO:0006672; P:ceramide metabolic process; IDA:ZFIN.
DR GO; GO:0042759; P:long-chain fatty acid biosynthetic process; IBA:GO_Central.
DR GO; GO:0007346; P:regulation of mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0046512; P:sphingosine biosynthetic process; ISS: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 Calcium; Cell membrane; Developmental protein; Disulfide bond;
KW Glycoprotein; Golgi apparatus; Hydrolase; Lipid metabolism; Membrane;
KW Metal-binding; Mitochondrion; Reference proteome; Secreted; Signal-anchor;
KW Sphingolipid metabolism; Transmembrane; Transmembrane helix; Zinc.
FT CHAIN 1..743
FT /note="Neutral ceramidase"
FT /id="PRO_0000247105"
FT TOPO_DOM 1..14
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 15..35
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 36..743
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 40..60
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 312
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT BINDING 151
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9NR71"
FT BINDING 260
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9NR71"
FT BINDING 498
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9NR71"
FT BINDING 538
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9NR71"
FT BINDING 672
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9NR71"
FT BINDING 674
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9NR71"
FT BINDING 677
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9NR71"
FT CARBOHYD 265
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 331
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 389
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 398
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 451
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 661
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 720
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 320..334
FT /evidence="ECO:0000250|UniProtKB:Q9NR71"
FT DISULFID 327..342
FT /evidence="ECO:0000250|UniProtKB:Q9NR71"
FT DISULFID 406..456
FT /evidence="ECO:0000250|UniProtKB:Q9NR71"
SQ SEQUENCE 743 AA; 82069 MW; 7D2DC7395BA8CF70 CRC64;
MASKSRRLSG LEISLIVLFL LMTAVSVALI TVLALKQESD KKEEVTPEEP SPSVTPPEKP
YLIGVGRADC TGPVADLPMM GYANTDQTAR GLHTRLFSRA FIVDDGNKRV VFVTSDIGMV
SQRLRLEVFQ ALKEKYGDLY RQDNVVLSGT HTHSGVGGYF QYTLFMITSK GYIKPSIQAI
VSGIVKSIDI AHRNLRPGRI FINKGQVADS NFNRSPHSYM NNPEEERNRY EFNTDKQIVV
LKFTDLDGDG IGLLSWFAVH PVSMNYTNRM VSSDNLGYAS YIFEQEKNIG FLPGEKGPFV
AGFSSSNLGD SSPNIRGPVC VNTGLKCDYI NSSCPVGGKK ACIAFGPGED MFESTRIIGE
NMFKIAKELY GSAKQELHGP VYGAHQWVNM TDETVQFNST HTGRTCKPAL GHSFAAGTTD
GGGEFNFLQG DTEGDPFWDG IRDAVLGPPS NETKACHQPK PILFSTGEMD SPLPWHPAIV
DVQIITIGSL AVVAVPGEFT TMSGRRIREA VKRELEVKEP FTNAEVVVAG LCNIYTHYIT
TYEEYQIQRY EGASTIFGPH TLSAYIQRYR GLAKAIAHGT IGELPKGPEP PFFDEDKLFN
QVRDPVADVA PVGTTFGDVL QEVNPVYKVG EIASVTFVSG NPRHSGDIRD TTLVTVERFH
NDTGSWEIIH NDASWETRFH WIKGLAGRSQ AKVEWHIPQT AQAGTYQIQY FGHYKQTTEN
TTVITPYVGT SAAFKVARSF YYF
