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Protein

Neutral ceramidase

Gene

Asah2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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)DescriptionActionsGraphical viewLength
Active sitei330NucleophileBy similarity1

GO - Molecular functioni

  • ceramidase activity Source: UniProtKB-EC
  • N-acylsphingosine amidohydrolase 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

Keywordsi

Molecular functionHydrolase
Biological processApoptosis, Lipid metabolism, Sphingolipid metabolism

Enzyme and pathway databases

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

Chemistry databases

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:1859310 Asah2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 11CytoplasmicSequence analysisAdd BLAST11
Transmembranei12 – 32Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini33 – 756LumenalSequence analysisAdd BLAST724

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 databases

ChEMBLiCHEMBL2146344

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002471011 – 756Neutral ceramidaseAdd BLAST756
ChainiPRO_000024710275 – 756Neutral ceramidase soluble formBy similarityAdd BLAST682

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi56O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi57O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi58O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi64O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi193N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi407N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi444N-linked (GlcNAc...) asparagineSequence analysis1

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
PhosphoSitePlusiQ9JHE3

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

BgeeiENSMUSG00000024887
CleanExiMM_ASAH2
ExpressionAtlasiQ9JHE3 baseline and differential
GenevisibleiQ9JHE3 MM

Interactioni

Protein-protein interaction databases

IntActiQ9JHE3, 1 interactor
MINTiQ9JHE3
STRINGi10090.ENSMUSP00000093830

Structurei

3D structure databases

ProteinModelPortaliQ9JHE3
SMRiQ9JHE3
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni746 – 756Required for correct folding and localizationBy similarityAdd BLAST11

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
OMAiGAWCDDG
OrthoDBiEOG091G06OC
PhylomeDBiQ9JHE3
TreeFamiTF300786

Family and domain databases

Gene3Di2.60.40.2300, 1 hit
InterProiView protein in InterPro
IPR006823 Ceramidase_alk
IPR038445 NCDase_C_sf
IPR031331 NEUT/ALK_ceramidase_C
IPR031329 NEUT/ALK_ceramidase_N
PANTHERiPTHR12670 PTHR12670, 1 hit
PfamiView protein in Pfam
PF04734 Ceramidase_alk, 1 hit
PF17048 Ceramidse_alk_C, 1 hit

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)DescriptionActionsGraphical viewLength
Sequence conflicti543V → I in BAC38089 (PubMed:16141072).Curated1

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_011247283.2
XP_011245586.1, XM_011247284.2
XP_011245587.1, XM_011247285.2
XP_011245588.1, XM_011247286.2
XP_011245589.1, XM_011247287.2
XP_011245591.1, XM_011247289.1
XP_011245592.1, XM_011247290.2
UniGeneiMm.491229

Genome annotation databases

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

Similar proteinsi

Entry informationi

Entry nameiASAH2_MOUSE
AccessioniPrimary (citable) accession number: Q9JHE3
Secondary accession number(s): Q3UWP9
, Q8BNP0, Q8BQN7, Q8R236
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 25, 2006
Last sequence update: October 1, 2000
Last modified: May 23, 2018
This is version 114 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

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