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Q9NR71 (ASAH2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 97. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Neutral ceramidase

Short name=N-CDase
Short name=NCDase
EC=3.5.1.23
Alternative name(s):
Acylsphingosine deacylase 2
BCDase
LCDase
Short name=hCD
N-acylsphingosine amidohydrolase 2
Non-lysosomal ceramidase

Cleaved into the following chain:

  1. Neutral ceramidase soluble form
Gene names
Name:ASAH2
Synonyms:HNAC1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length780 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Hydrolyzes the sphingolipid ceramide into sphingosine and free fatty acid at an optimal pH of 6.5-8.5. Acts as a key regulator of sphingolipid signaling metabolites by generating sphingosine at the cell surface. Acts as a repressor of apoptosis both by reducing C16-ceramide, thereby preventing ceramide-induced apoptosis, and generating sphingosine, a precursor of the antiapoptotic factor sphingosine 1-phosphate. Probably involved in the digestion of dietary sphingolipids in intestine by acting as a key enzyme for the catabolism of dietary sphingolipids and regulating the levels of bioactive sphingolipid metabolites in the intestinal tract. Ref.2 Ref.7

Catalytic activity

N-acylsphingosine + H2O = a carboxylate + sphingosine. Ref.4 Ref.8

Enzyme regulation

Inhibited by dithiothreitol (DTT), 2-mercaptoethanol, Zn2+, Cu2+ and Fe2+. Enhanced by Na+ and Ca2+, and at lower level Mg2+ and Mn2+.

Subcellular location

Cell membrane; Single-pass type II membrane protein. Note: The neutral ceramidase soluble form is a secreted protein. According to Ref.4, it is mitochondrial. However, they used a shorter form in its N-terminus, which may explain this localization which probably does not exist in vivo. Ref.4 Ref.6

Tissue specificity

Primarily expressed in the intestine (Ref.9). Ubiquitously expressed with higher levels in kidney, skeletal muscle and heart (Ref.4). According to Ref.9, ubiquitous expression attributed to ASAH2 may be actually that of the paralog ASAH2B. Ref.4 Ref.9

Post-translational modification

N-glycosylated. Required for enzyme activity By similarity. Ref.6

O-glycosylated. Required to retain it as a type II membrane protein at the cell surface. Ref.6

Phosphorylated. May prevent ubiquitination and subsequent degradation By similarity.

Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is triggered by nitric oxid By similarity.

Sequence similarities

Belongs to the neutral ceramidase family.

Biophysicochemical properties

Kinetic parameters:

KM=71.4 µM for octanoyl-sphingosine Ref.4 Ref.8

KM=66 µM for palmitoyl-sphingosine

KM=60.1 µM for D-erythro-C12-NBD-ceramide

Vmax=160 µmol/min/mg enzyme with octanoyl-sphingosine as substrate

Vmax=16 µmol/min/mg enzyme with palmitoyl-sphingosine as substrate

Vmax=0.68 nmol/min/mg enzyme with D-erythro-C12-NBD-ceramide as substrate

pH dependence:

Optimum pH is 7.5-9.5.

Sequence caution

The sequence AAL06061.1 differs from that shown. Reason: Erroneous initiation.

The sequence CAI15870.1 differs from that shown. Reason: Erroneous initiation.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9NR71-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q9NR71-2)

The sequence of this isoform differs from the canonical sequence as follows:
     410-444: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 780780Neutral ceramidase
PRO_0000247099
Chain99 – 780682Neutral ceramidase soluble form By similarity
PRO_0000247100

Regions

Topological domain1 – 1212Cytoplasmic Potential
Transmembrane13 – 3321Helical; Signal-anchor for type II membrane protein; Potential
Topological domain34 – 780747Lumenal Potential
Region770 – 78011Required for correct folding and localization By similarity

Sites

Active site3541Nucleophile Ref.8

Amino acid modifications

Glycosylation621O-linked (GalNAc...) Potential
Glycosylation671O-linked (GalNAc...) Potential
Glycosylation681O-linked (GalNAc...) Potential
Glycosylation701O-linked (GalNAc...) Potential
Glycosylation731O-linked (GalNAc...) Potential
Glycosylation741O-linked (GalNAc...) Potential
Glycosylation761O-linked (GalNAc...) Potential
Glycosylation781O-linked (GalNAc...) Potential
Glycosylation791O-linked (GalNAc...) Potential
Glycosylation801O-linked (GalNAc...) Potential
Glycosylation821O-linked (GalNAc...) Potential
Glycosylation841O-linked (GalNAc...) Potential
Glycosylation981N-linked (GlcNAc...) Potential
Glycosylation1511N-linked (GlcNAc...) Potential
Glycosylation2171N-linked (GlcNAc...) Potential
Glycosylation4681N-linked (GlcNAc...) Potential
Glycosylation5641N-linked (GlcNAc...) Potential
Glycosylation7301N-linked (GlcNAc...) Potential
Glycosylation7791O-linked (GalNAc...) Potential

Natural variations

Alternative sequence410 – 44435Missing in isoform 2.
VSP_019928
Natural variant511T → A.
Corresponds to variant rs7067625 [ dbSNP | Ensembl ].
VAR_027064
Natural variant3461A → S.
Corresponds to variant rs993869 [ dbSNP | Ensembl ].
VAR_027065

Experimental info

Mutagenesis2581S → A: Impairs enzyme activity. Ref.8
Mutagenesis3521D → A: Abolishes enzyme activity. Ref.8
Mutagenesis3541S → A: Abolishes enzyme activity. Ref.8
Mutagenesis3621C → A: Abolishes enzyme activity. Ref.8
Mutagenesis3741S → A: Impairs enzyme activity. Ref.8
Mutagenesis3961S → A: No effect. Ref.8
Mutagenesis5951S → A: Impairs enzyme activity. Ref.8
Mutagenesis7291S → A: Impairs enzyme activity. Ref.8
Sequence conflict2741S → P in AAL06061. Ref.1
Sequence conflict2741S → P in AAF86240. Ref.4
Sequence conflict6021T → A in AAL06061. Ref.1
Sequence conflict6021T → A in AAF86240. Ref.4
Sequence conflict6891T → N in CAI17190. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 25, 2006. Version 2.
Checksum: D2BD7947B022A619

FASTA78085,516
        10         20         30         40         50         60 
MAKRTFSNLE TFLIFLLVMM SAITVALLSL LFITSGTIEN HKDLGGHFFS TTQSPPATQG 

        70         80         90        100        110        120 
STAAQRSTAT QHSTATQSST ATQTSPVPLT PESPLFQNFS GYHIGVGRAD CTGQVADINL 

       130        140        150        160        170        180 
MGYGKSGQNA QGILTRLYSR AFIMAEPDGS NRTVFVSIDI GMVSQRLRLE VLNRLQSKYG 

       190        200        210        220        230        240 
SLYRRDNVIL SGTHTHSGPA GYFQYTVFVI ASEGFSNQTF QHMVTGILKS IDIAHTNMKP 

       250        260        270        280        290        300 
GKIFINKGNV DGVQINRSPY SYLQNPQSER ARYSSNTDKE MIVLKMVDLN GDDLGLISWF 

       310        320        330        340        350        360 
AIHPVSMNNS NHLVNSDNVG YASYLLEQEK NKGYLPGQGP FVAAFASSNL GDVSPNILGP 

       370        380        390        400        410        420 
RCINTGESCD NANSTCPIGG PSMCIAKGPG QDMFDSTQII GRAMYQRAKE LYASASQEVT 

       430        440        450        460        470        480 
GPLASAHQWV DMTDVTVWLN STHASKTCKP ALGYSFAAGT IDGVGGLNFT QGKTEGDPFW 

       490        500        510        520        530        540 
DTIRDQILGK PSEEIKECHK PKPILLHTGE LSKPHPWHPD IVDVQIITLG SLAITAIPGE 

       550        560        570        580        590        600 
FTTMSGRRLR EAVQAEFASH GMQNMTVVIS GLCNVYTHYI TTYEEYQAQR YEAASTIYGP 

       610        620        630        640        650        660 
HTLSAYIQLF RNLAKAIATD TVANLSRGPE PPFFKQLIVP LIPSIVDRAP KGRTFGDVLQ 

       670        680        690        700        710        720 
PAKPEYRVGE VAEVIFVGAN PKNSVQNQTH QTFLTVEKYE ATSTSWQIVC NDASWETRFY 

       730        740        750        760        770        780 
WHKGLLGLSN ATVEWHIPDT AQPGIYRIRY FGHNRKQDIL KPAVILSFEG TSPAFEVVTI 

« Hide

Isoform 2 [UniParc].

Checksum: B4577FFD1C6397EA
Show »

FASTA74581,718

References

« Hide 'large scale' references
[1]"Neutral ceramidase gene: role in regulating ceramide-induced apoptosis."
Choi M.S., Anderson M.A., Zhang Z., Zimonjic D.B., Popescu N., Mukherjee A.B.
Gene 315:113-122(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Roles for C16-ceramide and sphingosine 1-phosphate in regulating hepatocyte apoptosis in response to tumor necrosis factor-alpha."
Osawa Y., Uchinami H., Bielawski J., Schwabe R.F., Hannun Y.A., Brenner D.A.
J. Biol. Chem. 280:27879-27887(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION.
[3]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"Molecular cloning and characterization of a human mitochondrial ceramidase."
El Bawab S., Roddy P., Qian T., Bielawska A., Lemasters J.J., Hannun Y.A.
J. Biol. Chem. 275:21508-21513(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 20-780 (ISOFORM 1), ENZYME ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, POSSIBLE SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 20-780 (ISOFORM 2).
[6]"Subcellular localization of human neutral ceramidase expressed in HEK293 cells."
Hwang Y.H., Tani M., Nakagawa T., Okino N., Ito M.
Biochem. Biophys. Res. Commun. 331:37-42(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, GLYCOSYLATION.
[7]"Mechanisms of sphingosine and sphingosine 1-phosphate generation in human platelets."
Tani M., Sano T., Ito M., Igarashi Y.
J. Lipid Res. 46:2458-2467(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"Identification of a novel amidase motif in neutral ceramidase."
Galadari S., Wu B.X., Mao C., Roddy P., El Bawab S., Hannun Y.A.
Biochem. J. 393:687-695(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVE SITE, MUTAGENESIS OF SER-258; ASP-352; SER-354; CYS-362; SER-374; SER-396; SER-595 AND SER-729.
[9]"A novel gene derived from a segmental duplication shows perturbed expression in Alzheimer's disease."
Avramopoulos D., Wang R., Valle D., Fallin M.D., Bassett S.S.
Neurogenetics 8:111-120(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY049008 Genomic DNA. Translation: AAL06061.1. Different initiation.
AF449759 mRNA. Translation: AAQ04667.2.
AL450382 Genomic DNA. Translation: CAI15870.1. Different initiation.
AL589794 Genomic DNA. Translation: CAI15766.1. Sequence problems.
AL589794 Genomic DNA. Translation: CAI15767.1. Sequence problems.
AL954360 Genomic DNA. Translation: CAI17190.1.
AF250847 mRNA. Translation: AAF86240.1.
BC107105 mRNA. Translation: AAI07106.1.
RefSeqNP_001137446.1. NM_001143974.1.
NP_063946.2. NM_019893.2.
UniGeneHs.512645.

3D structure databases

ProteinModelPortalQ9NR71.
SMRQ9NR71. Positions 102-778.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121160. 1 interaction.
575684. 1 interaction.
STRING9606.ENSP00000378897.

Chemistry

ChEMBLCHEMBL2021754.

Polymorphism databases

DMDM110832757.

Proteomic databases

PaxDbQ9NR71.
PRIDEQ9NR71.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000329428; ENSP00000329886; ENSG00000188611.
ENST00000395526; ENSP00000378897; ENSG00000188611. [Q9NR71-1]
ENST00000447815; ENSP00000388206; ENSG00000188611. [Q9NR71-2]
GeneID56624.
KEGGhsa:56624.
UCSCuc001jjd.3. human. [Q9NR71-1]
uc009xos.3. human. [Q9NR71-2]

Organism-specific databases

CTD56624.
GeneCardsGC10M051944.
H-InvDBHIX0058802.
HGNCHGNC:18860. ASAH2.
MIM611202. gene.
neXtProtNX_Q9NR71.
PharmGKBPA134977109.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG75118.
HOVERGENHBG080870.
InParanoidQ9NR71.
KOK12349.
OMADTGLHMR.
OrthoDBEOG7WQ7RQ.
PhylomeDBQ9NR71.
TreeFamTF300786.

Enzyme and pathway databases

BRENDA3.5.1.23. 2681.
ReactomeREACT_111217. Metabolism.
SABIO-RKQ9NR71.

Gene expression databases

BgeeQ9NR71.
CleanExHS_ASAH2.
GenevestigatorQ9NR71.

Family and domain databases

InterProIPR006823. Ceramidase_alk.
[Graphical view]
PANTHERPTHR12670. PTHR12670. 1 hit.
PfamPF04734. Ceramidase_alk. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiASAH2.
GenomeRNAi56624.
NextBio62071.
PROQ9NR71.
SOURCESearch...

Entry information

Entry nameASAH2_HUMAN
AccessionPrimary (citable) accession number: Q9NR71
Secondary accession number(s): Q3KNU1 expand/collapse secondary AC list , Q5SNT7, Q5SZP6, Q5SZP7, Q5T1D5, Q71ME6
Entry history
Integrated into UniProtKB/Swiss-Prot: July 25, 2006
Last sequence update: July 25, 2006
Last modified: April 16, 2014
This is version 97 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM