UniProt:Q9NR71 ASAH2

chain
  • chain:1-780
  • chain:99-780
checksum D2BD7947B022A619
comment
  • FUNCTION Plasma membrane ceramidase that hydrolyzes sphingolipid ceramides into sphingosine and free fatty acids at neutral pH (PubMed:10781606, PubMed:16229686, PubMed:26190575). Ceramides, sphingosine, and its phosphorylated form sphingosine-1-phosphate are bioactive lipids that mediate cellular signaling pathways regulating several biological processes including cell proliferation, apoptosis and differentiation (PubMed:15946935, PubMed:19345744, PubMed:24798654). Also catalyzes the reverse reaction allowing the synthesis of ceramides from fatty acids and sphingosine (PubMed:11278489, PubMed:17475390). Together with sphingomyelinase, participates in the production of sphingosine and sphingosine-1-phosphate from the degradation of sphingomyelin, a sphingolipid enriched in the plasma membrane of cells (PubMed:16061940). Also participates in the hydrolysis of ceramides from the extracellular milieu allowing the production of sphingosine-1-phosphate inside and outside cells (By similarity). This is the case for instance with the digestion of dietary sphingolipids in the intestinal tract (By similarity).CATALYTIC ACTIVITY an N-acylsphing-4-enine + H2O = sphing-4-enine + a fatty acidCATALYTIC ACTIVITY N-dodecanoylsphing-4-enine + H2O = dodecanoate + sphing-4-enineCATALYTIC ACTIVITY N-hexadecanoylsphing-4-enine + H2O = sphing-4-enine + hexadecanoateCATALYTIC ACTIVITY N-octanoylsphing-4-enine + H2O = octanoate + sphing-4-enineCATALYTIC ACTIVITY N-(hexanoyl)sphing-4-enine + H2O = hexanoate + sphing-4-enineCATALYTIC ACTIVITY N-octadecanoylsphing-4-enine + H2O = sphing-4-enine + octadecanoateCATALYTIC ACTIVITY N-tetradecanoylsphing-4-enine + H2O = sphing-4-enine + tetradecanoateCATALYTIC ACTIVITY N-(9Z-octadecenoyl)-sphing-4-enine + H2O = sphing-4-enine + (9Z)-octadecenoateCATALYTIC ACTIVITY N-(15Z-tetracosenoyl)-sphing-4-enine + H2O = (15Z)-tetracosenoate + sphing-4-enineCATALYTIC ACTIVITY sphinganine + hexadecanoate = N-hexadecanoylsphinganine + H2OCATALYTIC ACTIVITY N-(octadecanoyl)-sphinganine + H2O = sphinganine + octadecanoateCOFACTOR Binds 1 zinc ion per subunit.ACTIVITY REGULATION Inhibited by dithiothreitol (DTT) and 2-mercaptoethanol (PubMed:16229686). Activity is mildly stimulated by Ca(2+) and Mg(2+), but is not inhibited by EDTA (PubMed:10781606, PubMed:16229686). Activity is inhibited by millimolar levels of Fe(2+), Zn(2+) and Cu(2+) (PubMed:16229686, PubMed:17475390). Inhibited by cholesterol (PubMed:17475390).BIOPHYSICOCHEMICAL PROPERTIES Optimum pH is 7.5-9.5 for N-hexadecanoylsphing-4-enine (PubMed:10781606). Optimum pH is 7.5 for D-erythro-C12-NBD-ceramide (PubMed:16229686). Optimum pH is 7.5 for N-octanoylsphing-4-enine (PubMed:17475390).PATHWAY Lipid metabolism; sphingolipid metabolism.SUBCELLULAR LOCATION Enriched in exosomes upon stimulation by cytokine (PubMed:24798654). Enriched in caveolae and lipid rafts (By similarity). The localization to the mitochondrion could not be confirmed (PubMed:15845354).SUBCELLULAR LOCATION Primarily expressed in intestine (PubMed:17334805). Ubiquitously expressed with higher levels in kidney, skeletal muscle and heart (PubMed:10781606). The ubiquitous expression observed for ASAH2 might be an experimental artifact due to the paralog ASAH2B (PubMed:17334805).INDUCTION Down-regulated by gemcitabine/GMZ (at protein level) (PubMed:19345744). Down-regulated upon serum starvation (PubMed:19345744).PTM Proteolytic cleavage of the N-terminus removes the signal-anchor and produces a soluble form of the protein.PTM N-glycosylated. Required for enzyme activity.PTM O-glycosylated. Required to retain it as a type II membrane protein at the cell surface.PTM Phosphorylated. May prevent ubiquitination and subsequent degradation.PTM Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is triggered by nitric oxide.SIMILARITY Belongs to the neutral ceramidase family.CAUTION Was proposed to be mitochondrial, based on experiments with an N-terminal GFP-tag (PubMed:10781606). The in vivo localization to the mitochondrion could not be confirmed (PubMed:15845354). However, it has been observed for the mouse (AC Q9JHE3) and rat (AC Q91XT9) orthologs.SEQUENCE CAUTION Truncated N-terminus.
created [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53
crossReference
databaseName UniProt
dbId 219328
description
  • recommendedName: fullName evidence="18"Neutral ceramidase shortName: N-CDase shortName: NCDase ecNumber evidence="2"3.5.1.- ecNumber evidence="5 6 8 9 13 15"3.5.1.23 alternativeName: Acylsphingosine deacylase 2 alternativeName: BCDase alternativeName: LCDase shortName: hCD alternativeName: N-acylsphingosine amidohydrolase 2 alternativeName: Non-lysosomal ceramidase component recommendedName: fullName evidence="1"Neutral ceramidase soluble form /component
displayName UniProt:Q9NR71 ASAH2
geneName
  • ASAH2
  • HNAC1
identifier Q9NR71
isSequenceChanged false
keyword
  • 3D-structure
  • Alternative splicing
  • Apoptosis
  • Calcium
  • Cell membrane
  • Disulfide bond
  • Glycoprotein
  • Golgi apparatus
  • Hydrolase
  • Lipid metabolism
  • Membrane
  • Metal-binding
  • Mitochondrion
  • Phosphoprotein
  • Proteomics identification
  • Reference proteome
  • Secreted
  • Signal-anchor
  • Sphingolipid metabolism
  • Transmembrane
  • Transmembrane helix
  • Ubl conjugation
  • Zinc
modified [InstanceEdit:9983091] Weiser, Joel, 2026-02-20
moleculeType Protein
name
  • ASAH2
otherIdentifier
  • 11757085_s_at
  • 11760913_at
  • 16714294
  • 229793_PM_at
  • 229793_at
  • 231791_PM_at
  • 231791_at
  • 3246831
  • 3246832
  • 3246833
  • 3246834
  • 3246835
  • 3246836
  • 3246837
  • 3246838
  • 3246839
  • 3246842
  • 3246843
  • 3246844
  • 3287682
  • 3287683
  • 3287684
  • 3287685
  • 3287690
  • 3287692
  • 3287694
  • 3287696
  • 3287698
  • 3287700
  • 3287702
  • 3287704
  • 3287706
  • 3287710
  • 3287712
  • 3287714
  • 3287716
  • 3287720
  • 3287722
  • 3287724
  • 3289200
  • 3289201
  • 3289202
  • 3289203
  • 3289204
  • 3289205
  • 3289206
  • 3289207
  • 3289208
  • 3289209
  • 3289210
  • 3289211
  • 3289212
  • 3289214
  • 3289215
  • 3289216
  • 3289217
  • 3289219
  • 3289221
  • 3289222
  • 3289223
  • 3289224
  • 3289225
  • 3289226
  • 3289227
  • 3289228
  • 3289229
  • 56624
  • 7927599
  • 7933341
  • 7933597
  • A_23_P161171
  • GE82486
  • GO:0000139
  • GO:0005509
  • GO:0005576
  • GO:0005737
  • GO:0005739
  • GO:0005794
  • GO:0005886
  • GO:0005901
  • GO:0006629
  • GO:0006665
  • GO:0006670
  • GO:0006672
  • GO:0006915
  • GO:0007346
  • GO:0008270
  • GO:0016020
  • GO:0016787
  • GO:0017040
  • GO:0042759
  • GO:0044241
  • GO:0045121
  • GO:0046512
  • GO:0046513
  • GO:0046514
  • GO:0046872
  • GO:0070062
  • GO:0071345
  • GO:2001234
  • HMNXSV003055192
  • Hs.118654.0.A1_3p_at
  • ILMN_1658602
  • ILMN_1776129
  • ILMN_1780786
  • ILMN_1800237
  • PH_hs_0027512
  • TC10001246.hg
  • TC10001287.hg
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • ASAH2_HUMAN
  • Q3KNU1
  • Q5SNT7
  • Q5SZP6
  • Q5SZP7
  • Q5T1D5
  • Q71ME6
sequenceLength 780
species [Species:48887] Homo sapiens
stId uniprot:Q9NR71
url http://purl.uniprot.org/uniprot/Q9NR71
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