Reviewed, UniProtKB/Swiss-Prot Q9JHE3 (ASAH2_MOUSE)

Names and origin

Protein names

Recommended name:
    Neutral ceramidase
      Short name=N-CDase
      Short name=NCDase
    EC=3.5.1.23
Alternative name(s):
    Acylsphingosine deacylase 2
    N-acylsphingosine amidohydrolase 2
Cleaved into the following chain:
    1- Recommended name:
            Neutral ceramidase soluble form

Gene names

Name:

Asah2

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	756 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.7 Ref.8 Ref.9
Catalytic activity	N-acylsphingosine + H2O = a carboxylate + sphingosine. Ref.1 Ref.4
Enzyme regulation	Inhibited by dithiothreitol (DTT), D-erythro-MAPP and 2-mercaptoethanol. Ref.7
Subcellular location	Cell membrane; Single-pass type II membrane protein. Note: The neutral ceramidase soluble form is a secreted protein. Ref.5 Ref.6
Tissue specificity	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. Ref.9 Ref.1
Post-translational modification	N-glycosylated. Required for enzyme activity. Ref.1 Ref.4 O-glycosylated. Required to retain it as a type II membrane protein at the cell surface By similarity. 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.
Disruption phenotype	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. Ref.9
Sequence similarities	Belongs to the neutral ceramidase family.
Biophysicochemical properties	Kinetic parameters: KM=22.3 mM for C12-4-nitrobenzo-2-oxa-1,3-diazole-ceramide KM=72.4 mM for C16-(14)C-ceramide Vmax=29.1 µmol/min/mg enzyme with C12-4-nitrobenzo-2-oxa-1,3-diazole-ceramide as substrate Vmax=3.6 µmol/min/mg enzyme with C16-(14)C-ceramide as substrate pH dependence: Optimum pH is 7.5.

Ontologies

Keywords
Biological process	Apoptosis Lipid metabolism Sphingolipid metabolism
Cellular component	Cell membrane Membrane
Domain	Signal-anchor Transmembrane
Molecular function	Hydrolase
PTM	Glycoprotein Phosphoprotein Ubl conjugation
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	apoptosis Inferred from electronic annotation. Source: UniProtKB-KW cell proliferation Ref.1 Traceable author statement. Source: MGI sphingolipid metabolic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell membrane fraction Ref.1 Inferred from direct assay. Source: MGI mitochondrion Inferred from direct assay. Source: MGI plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	ceramidase activity Ref.1 Inferred from direct assay. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 756	756	Neutral ceramidase		PRO_0000247101
	Chain	75 – 756	682	Neutral ceramidase soluble form By similarity		PRO_0000247102
Regions
	Topological domain	1 – 11	11	Cytoplasmic Potential
	Transmembrane	12 – 32	21	Signal-anchor for type II membrane protein Potential
	Topological domain	33 – 756	724	Lumenal Potential
	Region	746 – 756	11	Required for correct folding and localization By similarity
Sites
	Active site	330	1	Nucleophile By similarity
Amino acid modifications
	Glycosylation	56	1	O-linked (GalNAc...) Potential
	Glycosylation	57	1	O-linked (GalNAc...) Potential
	Glycosylation	58	1	O-linked (GalNAc...) Potential
	Glycosylation	64	1	O-linked (GalNAc...) Potential
	Glycosylation	193	1	N-linked (GlcNAc...) Potential
	Glycosylation	407	1	N-linked (GlcNAc...) Potential
	Glycosylation	444	1	N-linked (GlcNAc...) Potential
Experimental info
	Sequence conflict	543	1	V → I in BAC38089. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9JHE3-1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: FFD514E51280D4BE	FASTA	756	83,509
	10 20 30 40 50 60 MAKRTFSTLE AFLIFLLVIM TVITVALLTL LFVTSGTIEN HKDSGNHWFS TTLGSTTTQP 70 80 90 100 110 120 PPITQTPNFP SFRNFSGYYI GVGRADCTGQ VSDINLMGYG KNGQNARGLL TRLFSRAFIL 130 140 150 160 170 180 ADPDGSNRMA FVSVELCMIS QRLRLEVLKR LESKYGSLYR RDNVILSAIH THSGPAGFFQ 190 200 210 220 230 240 YTLYILASEG FSNRTFQYIV SGIMKSIDIA HTNLKPGKIF INKGNVANVQ INRSPSSYLL 250 260 270 280 290 300 NPQSERARYS SNTDKEMLVL KLVDLNGEDL GLISWFAIHP VSMNNSNHFV NSDNMGYAAY 310 320 330 340 350 360 LFEQEKNKGY LPGQGPFVAG FASSNLGDVS PNILGPHCVN TGESCDNDKS TCPNGGPSMC 370 380 390 400 410 420 MASGPGQDMF ESTHIIGRII YQKAKELYAS ASQEVTGPVL AAHQWVNMTD VSVQLNATHT 430 440 450 460 470 480 VKTCKPALGY SFAAGTIDGV SGLNITQGTT EGDPFWDTLR DQLLGKPSEE IVECQKPKPI 490 500 510 520 530 540 LLHSGELTIP HPWQPDIVDV QIVTVGSLAI AAIPGELTTM SGRRFREAIK KEFALYGMKD 550 560 570 580 590 600 MTVVIAGLSN VYTHYITTYE EYQAQRYEAA STIYGPHTLS AYIQLFRDLA KAIATDTVAN 610 620 630 640 650 660 MSSGPEPPFF KNLIASLIPN IADRAPIGKH FGDVLQPAKP EYRVGEVVEV IFVGANPKNS 670 680 690 700 710 720 AENQTHQTFL TVEKYEDSVA DWQIMYNDAS WETRFYWHKG ILGLSNATIY WHIPDTAYPG 730 740 750 IYRIRYFGHN RKQELLKPAV ILAFEGISSP FEVVTT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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: 10753931] [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: 16141072] [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: 15489334] [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: 10652340] [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: 11591392] [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: 12921776] [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: 14557071] [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: 16126722] [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: 16380386] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
IPI	IPI00458077.
RefSeq	NP_061300.1.
UniGene	Mm.104900
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	Q9JHE3.
Proteomic databases
PRIDE	Q9JHE3.
Genome annotation databases
Ensembl	ENSMUST00000096119; ENSMUSP00000093830; ENSMUSG00000024887; Mus musculus. [Genome view] ENSMUST00000112527; ENSMUSP00000108146; ENSMUSG00000024887; Mus musculus. [Genome view]
GeneID	54447.
KEGG	mmu:54447.
UCSC	uc008hew.1. mouse.
Organism-specific databases
CTD	54447.
MGI	MGI:1859310. Asah2.
Phylogenomic databases
HOVERGEN	Q9JHE3.
OMA	SWFAVHP.
Enzyme and pathway databases
BRENDA	3.5.1.23. 244.
Gene expression databases
ArrayExpress	Q9JHE3.
Bgee	Q9JHE3.
CleanEx	MM_ASAH2.
Genevestigator	Q9JHE3.
GermOnline	ENSMUSG00000024887. Mus musculus.
Family and domain databases
InterPro	IPR006823. Ceramidase_alk. [Graphical view]
PANTHER	PTHR12670. Ceramidase_alk. 1 hit.
Pfam	PF04734. Ceramidase_alk. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	311320.
SOURCE	Search...

Entry information

Entry name

ASAH2_MOUSE

Accession

Primary (citable) accession number: Q9JHE3
Secondary accession number(s): Q3UWP9 , Q8BNP0, Q8BQN7, Q8R236

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 25, 2006
Last sequence update:	October 1, 2000
Last modified:	November 3, 2009
This is version 50 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)