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Protein

Neutral ceramidase

Gene

Asah2

Organism
Rattus norvegicus (Rat)
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.1 Publication

Catalytic activityi

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

Enzyme regulationi

Inhibited by dithiothreitol (DTT), 2-mercaptoethanol, Zn2+ and Cu2+.

Kineticsi

  1. KM=71.4 µM for octanoyl-sphingosine3 Publications
  2. KM=66 µM for palmitoyl-sphingosine3 Publications
  3. KM=1.29 M for C16-ceramide3 Publications
  4. KM=3.84 M for dihydroceramide3 Publications
  1. Vmax=160 µmol/min/mg enzyme with octanoyl-sphingosine as substrate3 Publications
  2. Vmax=16 µmol/min/mg enzyme with palmitoyl-sphingosine as substrate3 Publications
  3. Vmax=4.4 µmol/min/mg enzyme with C16-ceramide as substrate3 Publications
  4. Vmax=1.2 µmol/min/mg enzyme with dihydroceramide as substrate3 Publications

pH dependencei

Optimum pH is 7-10.3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei335NucleophileBy similarity1

GO - Molecular functioni

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • response to organic substance Source: RGD
  • sphingolipid metabolic process Source: UniProtKB-KW

Keywordsi

Molecular functionHydrolase
Biological processApoptosis, Lipid metabolism, Sphingolipid metabolism

Enzyme and pathway databases

BRENDAi3.5.1.23 5301
ReactomeiR-RNO-1660662 Glycosphingolipid metabolism
SABIO-RKQ91XT9

Chemistry databases

SwissLipidsiSLP:000000682

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi69410 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 – 761LumenalSequence analysisAdd BLAST729

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi44S → A: Abolishes O-glycosylation and localization at the cell surface; when associated with A-50; A-51; A-52; A-56; A-57; A-58; A-60; A-61; A-62; A-63; A-65; A-76; A-68; A-69; A-71 and A-77. 1 Publication1
Mutagenesisi50 – 71STTQG…PTTQT → AAAQGPAAAQAAPAAQAPAA QA: Abolishes O-glycosylation and localization at the cell surface; when associated with A-44 and A-77. 1 PublicationAdd BLAST22
Mutagenesisi77S → A: Abolishes O-glycosylation and localization at the cell surface; when associated with A-44; A-50; A-51; A-52; A-56; A-57; A-58; A-60; A-61; A-62; A-63; A-65; A-76; A-68; A-69 and A-71. 1 Publication1
Mutagenesisi756F → I: No effect. 1 Publication1
Mutagenesisi756F → R or D: Loss of function. 1 Publication1
Mutagenesisi757E → R: No effect. 1 Publication1
Mutagenesisi758I → F: Impairs enzyme activity. 1 Publication1
Mutagenesisi758I → R or D: Loss of function. 1 Publication1
Mutagenesisi758I → V: No effect. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002471031 – 761Neutral ceramidaseAdd BLAST761
ChainiPRO_000024710480 – 761Neutral ceramidase soluble formAdd BLAST682

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi51O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi52O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi56O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi57O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi58O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi60O-linked (GalNAc...) serineSequence analysis1
Glycosylationi61O-linked (GalNAc...) serineSequence analysis1
Glycosylationi63O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi64O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi66O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi68O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi69O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi71O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi198N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi412N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi449N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

N-glycosylated. Required for enzyme activity.
O-glycosylated. Required to retain it as a type II membrane protein at the cell surface.
Phosphorylated. May prevent ubiquitination and subsequent degradation.2 Publications
Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is triggered by nitric oxid.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ91XT9
PRIDEiQ91XT9

Expressioni

Tissue specificityi

Widely expressed. Highly expressed in brain, kidney and heart. Expressed at lower level in other tissues such as liver. Localizes in the epithelia of the jejunum and ileum.2 Publications

Inductioni

By interleukin-1-beta in renal mesengial cells.1 Publication

Gene expression databases

BgeeiENSRNOG00000012196
GenevisibleiQ91XT9 RN

Interactioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000016688

Structurei

3D structure databases

SMRiQ91XT9
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni751 – 761Required for correct folding and localizationAdd 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
InParanoidiQ91XT9
KOiK12349
OMAiGAWCDDG
OrthoDBiEOG091G06OC
PhylomeDBiQ91XT9

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.

Q91XT9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAKRTFSSLE AFLIFLLVMM TAITVALLTL LFVTSGTIEN HKDSGNHWVS
60 70 80 90 100
TTQGPTTTQS SPTTQTPTTQ TPDLPPSQNF SGYYIGVGRA DCTGQVSDIN
110 120 130 140 150
LMGYGKNGQN AQGLLTRLFS RAFILADPDG SNRMAFVSVE LCMISQRLRL
160 170 180 190 200
EVLKRLQSKY GSLYRRDNVI LSATHTHSGP AGFFQYTLYI LASEGFSNRT
210 220 230 240 250
FQYIVSGIVK SIDIAHTNLK PGKVLINKGN VANVQINRSP SSYLQNPPSE
260 270 280 290 300
RARYSSDTDK EMVVLKLVDL NGEDLGLISW FAVHPVSMNN SNHLVNSDNM
310 320 330 340 350
GYAAYLFEQE KNRGYLPGQG PFVAGFASSN LGDVSPNILG PHCVNTGESC
360 370 380 390 400
DNDKSTCPSG GPSMCMASGP GQDMFESTHI IGRVIYQKAK ELHASASQEV
410 420 430 440 450
TGPVLTAHQW VNMTDVSVQL NATHTVKTCK AALGYSFAAG TIDGVSGLNI
460 470 480 490 500
TQGTTEGNLF WDTLRDQLLG KPSEEIIECQ KPKPILIHTG ELTKPHPWQP
510 520 530 540 550
DIVDIQIVTL GSLAIAAIPG EFTTMSGRRL REAVKKEFAL YGMKDMTVVI
560 570 580 590 600
AGLSNVYTHY ITTYEEYQAQ RYEAASTIYG PHTLSAYIQL FRALAKAIAT
610 620 630 640 650
DTVANMSSGP EPPFFKNLIG SLIPNIADRA PIGKQFGDVL QPAKPEYRVG
660 670 680 690 700
EVVEVVFVGA NPKNSAENQT HQTFLTVEKY EDSVANWQIM HNDASWETRF
710 720 730 740 750
YWHKGVLGLS NATIHWHIPD TALPGVYRIR YFGHNRKQEL LKPAVILAFE
760
GISSPFEIVT T
Length:761
Mass (Da):83,488
Last modified:December 1, 2001 - v1
Checksum:i68B91BC78AEB6324
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti325G → N AA sequence (PubMed:10781606).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB057433 mRNA Translation: BAB62033.1
RefSeqiNP_446098.1, NM_053646.2
XP_006231325.1, XM_006231263.1
XP_006231330.1, XM_006231268.3
XP_006231332.1, XM_006231270.1
XP_008758542.1, XM_008760320.2
XP_017444135.1, XM_017588646.1
XP_017444136.1, XM_017588647.1
XP_017444137.1, XM_017588648.1
XP_017444138.1, XM_017588649.1
XP_017444139.1, XM_017588650.1
XP_017444140.1, XM_017588651.1
UniGeneiRn.156958

Genome annotation databases

EnsembliENSRNOT00000016688; ENSRNOP00000016688; ENSRNOG00000012196
ENSRNOT00000077135; ENSRNOP00000073116; ENSRNOG00000012196
GeneIDi114104
KEGGirno:114104
UCSCiRGD:69410 rat

Similar proteinsi

Entry informationi

Entry nameiASAH2_RAT
AccessioniPrimary (citable) accession number: Q91XT9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 25, 2006
Last sequence update: December 1, 2001
Last modified: May 23, 2018
This is version 99 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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