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Protein

Neutral ceramidase

Gene

Asah2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.3 Publications

Catalytic activityi

N-acylsphingosine + H2O = a carboxylate + sphingosine.2 Publications

Enzyme regulationi

Inhibited by dithiothreitol (DTT), D-erythro-MAPP and 2-mercaptoethanol.1 Publication

Kineticsi

  1. KM=22.3 mM for C12-4-nitrobenzo-2-oxa-1,3-diazole-ceramide1 Publication
  2. KM=72.4 mM for C16-(14)C-ceramide1 Publication
  1. Vmax=29.1 µmol/min/mg enzyme with C12-4-nitrobenzo-2-oxa-1,3-diazole-ceramide as substrate1 Publication
  2. Vmax=3.6 µmol/min/mg enzyme with C16-(14)C-ceramide as substrate1 Publication

pH dependencei

Optimum pH is 7.5.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei330 – 3301NucleophileBy similarity

GO - Molecular functioni

  • ceramidase activity Source: MGI

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • cell proliferation Source: MGI
  • response to organic substance Source: Ensembl
  • sphingolipid metabolic process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Apoptosis, Lipid metabolism, Sphingolipid metabolism

Enzyme and pathway databases

BRENDAi3.5.1.23. 3474.
ReactomeiR-MMU-1660662. Glycosphingolipid metabolism.
SABIO-RKQ9JHE3.

Chemistry

SwissLipidsiSLP:000000216.

Names & Taxonomyi

Protein namesi
Recommended name:
Neutral ceramidase (EC:3.5.1.23)
Short name:
N-CDase
Short name:
NCDase
Alternative name(s):
Acylsphingosine deacylase 2
N-acylsphingosine amidohydrolase 2
Cleaved into the following chain:
Gene namesi
Name:Asah2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:1859310. Asah2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1111CytoplasmicSequence analysisAdd
BLAST
Transmembranei12 – 3221Helical; Signal-anchor for type II membrane proteinSequence analysisAdd
BLAST
Topological domaini33 – 756724LumenalSequence analysisAdd
BLAST

GO - Cellular componenti

  • integral component of membrane Source: UniProtKB-KW
  • membrane Source: MGI
  • mitochondrion Source: MGI
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice have a normal life span and do not show obvious abnormalities or major alterations in total ceramide levels in tissues. They are however deficient in the intestinal degradation of ceramide.1 Publication

Chemistry

ChEMBLiCHEMBL2146344.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 756756Neutral ceramidasePRO_0000247101Add
BLAST
Chaini75 – 756682Neutral ceramidase soluble formBy similarityPRO_0000247102Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi56 – 561O-linked (GalNAc...)Sequence analysis
Glycosylationi57 – 571O-linked (GalNAc...)Sequence analysis
Glycosylationi58 – 581O-linked (GalNAc...)Sequence analysis
Glycosylationi64 – 641O-linked (GalNAc...)Sequence analysis
Glycosylationi193 – 1931N-linked (GlcNAc...)Sequence analysis
Glycosylationi407 – 4071N-linked (GlcNAc...)Sequence analysis
Glycosylationi444 – 4441N-linked (GlcNAc...)Sequence analysis

Post-translational modificationi

N-glycosylated. Required for enzyme activity.2 Publications
O-glycosylated. Required to retain it as a type II membrane protein at the cell surface (By similarity).By similarity
Phosphorylated. May prevent ubiquitination and subsequent degradation (By similarity).By similarity
Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is triggered by nitric oxid (By similarity).By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ9JHE3.
PaxDbiQ9JHE3.
PRIDEiQ9JHE3.

PTM databases

iPTMnetiQ9JHE3.
PhosphoSiteiQ9JHE3.

Expressioni

Tissue specificityi

Widely expressed. Strongly expressed in liver and kidney. Highly expressed in the small intestine along the brush border. Localizes in the apical membranes of proximal and distal tubules, collecting ducts of kidney, endosome-like organelles of hepatocytes, and in the epithelia of the jejunum and ileum.2 Publications

Gene expression databases

BgeeiQ9JHE3.
CleanExiMM_ASAH2.
ExpressionAtlasiQ9JHE3. baseline and differential.
GenevisibleiQ9JHE3. MM.

Interactioni

Protein-protein interaction databases

IntActiQ9JHE3. 1 interaction.
MINTiMINT-4111698.
STRINGi10090.ENSMUSP00000093830.

Structurei

3D structure databases

ProteinModelPortaliQ9JHE3.
SMRiQ9JHE3. Positions 75-755.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni746 – 75611Required for correct folding and localizationBy similarityAdd
BLAST

Sequence similaritiesi

Belongs to the neutral ceramidase family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2232. Eukaryota.
ENOG410XQWE. LUCA.
GeneTreeiENSGT00390000015792.
HOGENOMiHOG000209915.
HOVERGENiHBG080870.
InParanoidiQ9JHE3.
KOiK12349.
OMAiNTQKNNA.
OrthoDBiEOG7WQ7RQ.
PhylomeDBiQ9JHE3.
TreeFamiTF300786.

Family and domain databases

InterProiIPR006823. Ceramidase_alk.
IPR031331. NEUT/ALK_ceramidase_C.
IPR031329. NEUT/ALK_ceramidase_N.
[Graphical view]
PANTHERiPTHR12670. PTHR12670. 2 hits.
PfamiPF04734. Ceramidase_alk. 1 hit.
PF17048. Ceramidse_alk_C. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9JHE3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAKRTFSTLE AFLIFLLVIM TVITVALLTL LFVTSGTIEN HKDSGNHWFS
60 70 80 90 100
TTLGSTTTQP PPITQTPNFP SFRNFSGYYI GVGRADCTGQ VSDINLMGYG
110 120 130 140 150
KNGQNARGLL TRLFSRAFIL ADPDGSNRMA FVSVELCMIS QRLRLEVLKR
160 170 180 190 200
LESKYGSLYR RDNVILSAIH THSGPAGFFQ YTLYILASEG FSNRTFQYIV
210 220 230 240 250
SGIMKSIDIA HTNLKPGKIF INKGNVANVQ INRSPSSYLL NPQSERARYS
260 270 280 290 300
SNTDKEMLVL KLVDLNGEDL GLISWFAIHP VSMNNSNHFV NSDNMGYAAY
310 320 330 340 350
LFEQEKNKGY LPGQGPFVAG FASSNLGDVS PNILGPHCVN TGESCDNDKS
360 370 380 390 400
TCPNGGPSMC MASGPGQDMF ESTHIIGRII YQKAKELYAS ASQEVTGPVL
410 420 430 440 450
AAHQWVNMTD VSVQLNATHT VKTCKPALGY SFAAGTIDGV SGLNITQGTT
460 470 480 490 500
EGDPFWDTLR DQLLGKPSEE IVECQKPKPI LLHSGELTIP HPWQPDIVDV
510 520 530 540 550
QIVTVGSLAI AAIPGELTTM SGRRFREAIK KEFALYGMKD MTVVIAGLSN
560 570 580 590 600
VYTHYITTYE EYQAQRYEAA STIYGPHTLS AYIQLFRDLA KAIATDTVAN
610 620 630 640 650
MSSGPEPPFF KNLIASLIPN IADRAPIGKH FGDVLQPAKP EYRVGEVVEV
660 670 680 690 700
IFVGANPKNS AENQTHQTFL TVEKYEDSVA DWQIMYNDAS WETRFYWHKG
710 720 730 740 750
ILGLSNATIY WHIPDTAYPG IYRIRYFGHN RKQELLKPAV ILAFEGISSP

FEVVTT
Length:756
Mass (Da):83,509
Last modified:October 1, 2000 - v1
Checksum:iFFD514E51280D4BE
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti543 – 5431V → I in BAC38089 (PubMed:16141072).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB037111 mRNA. Translation: BAA94545.1.
AB037181 mRNA. Translation: BAA94546.1.
AK047692 mRNA. Translation: BAC33126.1.
AK080951 mRNA. Translation: BAC38089.1.
AK136189 mRNA. Translation: BAE22865.1.
AK166100 mRNA. Translation: BAE38571.1.
BC022604 mRNA. Translation: AAH22604.1.
CCDSiCCDS29749.1.
RefSeqiNP_061300.1. NM_018830.1.
XP_011245585.1. XM_011247283.1.
XP_011245586.1. XM_011247284.1.
XP_011245587.1. XM_011247285.1.
XP_011245588.1. XM_011247286.1.
XP_011245589.1. XM_011247287.1.
XP_011245590.1. XM_011247288.1.
XP_011245591.1. XM_011247289.1.
XP_011245592.1. XM_011247290.1.
UniGeneiMm.491229.

Genome annotation databases

EnsembliENSMUST00000096119; ENSMUSP00000093830; ENSMUSG00000024887.
GeneIDi54447.
KEGGimmu:54447.
UCSCiuc008hew.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB037111 mRNA. Translation: BAA94545.1.
AB037181 mRNA. Translation: BAA94546.1.
AK047692 mRNA. Translation: BAC33126.1.
AK080951 mRNA. Translation: BAC38089.1.
AK136189 mRNA. Translation: BAE22865.1.
AK166100 mRNA. Translation: BAE38571.1.
BC022604 mRNA. Translation: AAH22604.1.
CCDSiCCDS29749.1.
RefSeqiNP_061300.1. NM_018830.1.
XP_011245585.1. XM_011247283.1.
XP_011245586.1. XM_011247284.1.
XP_011245587.1. XM_011247285.1.
XP_011245588.1. XM_011247286.1.
XP_011245589.1. XM_011247287.1.
XP_011245590.1. XM_011247288.1.
XP_011245591.1. XM_011247289.1.
XP_011245592.1. XM_011247290.1.
UniGeneiMm.491229.

3D structure databases

ProteinModelPortaliQ9JHE3.
SMRiQ9JHE3. Positions 75-755.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9JHE3. 1 interaction.
MINTiMINT-4111698.
STRINGi10090.ENSMUSP00000093830.

Chemistry

ChEMBLiCHEMBL2146344.
SwissLipidsiSLP:000000216.

PTM databases

iPTMnetiQ9JHE3.
PhosphoSiteiQ9JHE3.

Proteomic databases

MaxQBiQ9JHE3.
PaxDbiQ9JHE3.
PRIDEiQ9JHE3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000096119; ENSMUSP00000093830; ENSMUSG00000024887.
GeneIDi54447.
KEGGimmu:54447.
UCSCiuc008hew.1. mouse.

Organism-specific databases

CTDi56624.
MGIiMGI:1859310. Asah2.

Phylogenomic databases

eggNOGiKOG2232. Eukaryota.
ENOG410XQWE. LUCA.
GeneTreeiENSGT00390000015792.
HOGENOMiHOG000209915.
HOVERGENiHBG080870.
InParanoidiQ9JHE3.
KOiK12349.
OMAiNTQKNNA.
OrthoDBiEOG7WQ7RQ.
PhylomeDBiQ9JHE3.
TreeFamiTF300786.

Enzyme and pathway databases

BRENDAi3.5.1.23. 3474.
ReactomeiR-MMU-1660662. Glycosphingolipid metabolism.
SABIO-RKQ9JHE3.

Miscellaneous databases

ChiTaRSiAsah2. mouse.
PROiQ9JHE3.
SOURCEiSearch...

Gene expression databases

BgeeiQ9JHE3.
CleanExiMM_ASAH2.
ExpressionAtlasiQ9JHE3. baseline and differential.
GenevisibleiQ9JHE3. MM.

Family and domain databases

InterProiIPR006823. Ceramidase_alk.
IPR031331. NEUT/ALK_ceramidase_C.
IPR031329. NEUT/ALK_ceramidase_N.
[Graphical view]
PANTHERiPTHR12670. PTHR12670. 2 hits.
PfamiPF04734. Ceramidase_alk. 1 hit.
PF17048. Ceramidse_alk_C. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning of the full-length cDNA encoding mouse neutral ceramidase. A novel but highly conserved gene family of neutral/alkaline ceramidases."
    Tani M., Okino N., Mori K., Tanigawa T., Izu H., Ito M.
    J. Biol. Chem. 275:11229-11234(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], ENZYME ACTIVITY, TISSUE SPECIFICITY, GLYCOSYLATION.
    Tissue: Brain and Liver.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Adipose tissue, Corpus striatum, Egg and Lung.
  3. "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 261-756.
    Strain: FVB/N.
    Tissue: Liver.
  4. "Purification and characterization of a neutral ceramidase from mouse liver. A single protein catalyzes the reversible reaction in which ceramide is both hydrolyzed and synthesized."
    Tani M., Okino N., Mitsutake S., Tanigawa T., Izu H., Ito M.
    J. Biol. Chem. 275:3462-3468(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 309-343 AND 592-603, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME ACTIVITY, GLYCOSYLATION.
    Tissue: Liver.
  5. "Localization of neutral ceramidase in caveolin-enriched light membranes of murine endothelial cells."
    Romiti E., Meacci E., Tanzi G., Becciolini L., Mitsutake S., Farnararo M., Ito M., Bruni P.
    FEBS Lett. 506:163-168(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  6. "Neutral ceramidase secreted by endothelial cells is released in part associated with caveolin-1."
    Romiti E., Meacci E., Donati C., Formigli L., Zecchi-Orlandini S., Farnararo M., Ito M., Bruni P.
    Arch. Biochem. Biophys. 417:27-33(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  7. "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: FUNCTION, ENZYME REGULATION.
  8. "Involvement of neutral ceramidase in ceramide metabolism at the plasma membrane and in extracellular milieu."
    Tani M., Igarashi Y., Ito M.
    J. Biol. Chem. 280:36592-36600(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. "Neutral ceramidase encoded by the Asah2 gene is essential for the intestinal degradation of sphingolipids."
    Kono M., Dreier J.L., Ellis J.M., Allende M.L., Kalkofen D.N., Sanders K.M., Bielawski J., Bielawska A., Hannun Y.A., Proia R.L.
    J. Biol. Chem. 281:7324-7331(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.

Entry informationi

Entry nameiASAH2_MOUSE
AccessioniPrimary (citable) accession number: Q9JHE3
Secondary accession number(s): Q3UWP9
, Q8BNP0, Q8BQN7, Q8R236
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 25, 2006
Last sequence update: October 1, 2000
Last modified: June 8, 2016
This is version 103 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.