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Protein

Neutral ceramidase

Gene

ASAH2

Organism
Homo sapiens (Human)
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.2 Publications

Catalytic activityi

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

Enzyme regulationi

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

Kineticsi

  1. KM=71.4 µM for octanoyl-sphingosine2 Publications
  2. KM=66 µM for palmitoyl-sphingosine2 Publications
  3. KM=60.1 µM for D-erythro-C12-NBD-ceramide2 Publications
  1. Vmax=160 µmol/min/mg enzyme with octanoyl-sphingosine as substrate2 Publications
  2. Vmax=16 µmol/min/mg enzyme with palmitoyl-sphingosine as substrate2 Publications
  3. Vmax=0.68 nmol/min/mg enzyme with D-erythro-C12-NBD-ceramide as substrate2 Publications

pH dependencei

Optimum pH is 7.5-9.5.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei354Nucleophile1 Publication1

GO - Molecular functioni

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • ceramide metabolic process Source: ProtInc
  • signal transduction Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Apoptosis, Lipid metabolism, Sphingolipid metabolism

Enzyme and pathway databases

BioCyciZFISH:G66-33393-MONOMER.
BRENDAi3.5.1.23. 2681.
ReactomeiR-HSA-1660662. Glycosphingolipid metabolism.
SABIO-RKQ9NR71.

Chemistry databases

SwissLipidsiSLP:000000163.

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
BCDase
LCDase
Short name:
hCD
N-acylsphingosine amidohydrolase 2
Non-lysosomal ceramidase
Cleaved into the following chain:
Gene namesi
Name:ASAH2
Synonyms:HNAC1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:18860. ASAH2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 12CytoplasmicSequence analysisAdd BLAST12
Transmembranei13 – 33Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini34 – 780LumenalSequence analysisAdd BLAST747

GO - Cellular componenti

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

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi258S → A: Impairs enzyme activity. 1 Publication1
Mutagenesisi352D → A: Abolishes enzyme activity. 1 Publication1
Mutagenesisi354S → A: Abolishes enzyme activity. 1 Publication1
Mutagenesisi362C → A: Abolishes enzyme activity. 1 Publication1
Mutagenesisi374S → A: Impairs enzyme activity. 1 Publication1
Mutagenesisi396S → A: No effect. 1 Publication1
Mutagenesisi595S → A: Impairs enzyme activity. 1 Publication1
Mutagenesisi729S → A: Impairs enzyme activity. 1 Publication1

Organism-specific databases

DisGeNETi56624.
OpenTargetsiENSG00000188611.
PharmGKBiPA134977109.

Chemistry databases

ChEMBLiCHEMBL2021754.

Polymorphism and mutation databases

BioMutaiASAH2.
DMDMi110832757.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002470991 – 780Neutral ceramidaseAdd BLAST780
ChainiPRO_000024710099 – 780Neutral ceramidase soluble formBy similarityAdd BLAST682

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi62O-linked (GalNAc...)Sequence analysis1
Glycosylationi67O-linked (GalNAc...)Sequence analysis1
Glycosylationi68O-linked (GalNAc...)Sequence analysis1
Glycosylationi70O-linked (GalNAc...)Sequence analysis1
Glycosylationi73O-linked (GalNAc...)Sequence analysis1
Glycosylationi74O-linked (GalNAc...)Sequence analysis1
Glycosylationi76O-linked (GalNAc...)Sequence analysis1
Glycosylationi78O-linked (GalNAc...)Sequence analysis1
Glycosylationi79O-linked (GalNAc...)Sequence analysis1
Glycosylationi80O-linked (GalNAc...)Sequence analysis1
Glycosylationi82O-linked (GalNAc...)Sequence analysis1
Glycosylationi84O-linked (GalNAc...)Sequence analysis1
Glycosylationi98N-linked (GlcNAc...)Sequence analysis1
Glycosylationi151N-linked (GlcNAc...)Sequence analysis1
Glycosylationi217N-linked (GlcNAc...)Sequence analysis1
Glycosylationi468N-linked (GlcNAc...)Sequence analysis1
Glycosylationi564N-linked (GlcNAc...)Sequence analysis1
Glycosylationi730N-linked (GlcNAc...)Sequence analysis1
Glycosylationi779O-linked (GalNAc...)Sequence analysis1

Post-translational modificationi

N-glycosylated. Required for enzyme activity (By similarity).By similarity
O-glycosylated. Required to retain it as a type II membrane protein at the cell surface.1 Publication
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

MaxQBiQ9NR71.
PaxDbiQ9NR71.
PeptideAtlasiQ9NR71.
PRIDEiQ9NR71.

PTM databases

iPTMnetiQ9NR71.
PhosphoSitePlusiQ9NR71.

Expressioni

Tissue specificityi

Primarily expressed in the intestine (PubMed:17334805). Ubiquitously expressed with higher levels in kidney, skeletal muscle and heart (PubMed:10781606). According to PubMed:17334805, ubiquitous expression attributed to ASAH2 may be actually that of the paralog ASAH2B.2 Publications

Gene expression databases

BgeeiENSG00000188611.
CleanExiHS_ASAH2.
ExpressionAtlasiQ9NR71. baseline and differential.
GenevisibleiQ9NR71. HS.

Organism-specific databases

HPAiHPA061171.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000378897.

Chemistry databases

BindingDBiQ9NR71.

Structurei

Secondary structure

1780
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi102 – 110Combined sources9
Beta strandi115 – 123Combined sources9
Beta strandi129 – 135Combined sources7
Beta strandi138 – 145Combined sources8
Beta strandi153 – 161Combined sources9
Helixi165 – 179Combined sources15
Beta strandi185 – 192Combined sources8
Beta strandi196 – 199Combined sources4
Helixi206 – 212Combined sources7
Helixi217 – 235Combined sources19
Beta strandi239 – 249Combined sources11
Beta strandi255 – 257Combined sources3
Helixi259 – 262Combined sources4
Helixi267 – 270Combined sources4
Beta strandi280 – 288Combined sources9
Beta strandi293 – 299Combined sources7
Helixi317 – 330Combined sources14
Beta strandi342 – 346Combined sources5
Beta strandi353 – 355Combined sources3
Beta strandi360 – 362Combined sources3
Turni363 – 365Combined sources3
Turni377 – 379Combined sources3
Helixi380 – 383Combined sources4
Beta strandi384 – 386Combined sources3
Beta strandi389 – 392Combined sources4
Helixi393 – 413Combined sources21
Beta strandi417 – 419Combined sources3
Beta strandi423 – 431Combined sources9
Beta strandi436 – 442Combined sources7
Beta strandi444 – 446Combined sources3
Helixi454 – 458Combined sources5
Helixi478 – 487Combined sources10
Helixi493 – 499Combined sources7
Beta strandi504 – 506Combined sources3
Helixi508 – 510Combined sources3
Beta strandi513 – 515Combined sources3
Beta strandi520 – 529Combined sources10
Beta strandi532 – 536Combined sources5
Beta strandi538 – 541Combined sources4
Helixi543 – 559Combined sources17
Beta strandi566 – 570Combined sources5
Beta strandi572 – 575Combined sources4
Beta strandi578 – 580Combined sources3
Helixi583 – 588Combined sources6
Helixi591 – 594Combined sources4
Helixi602 – 618Combined sources17
Helixi622 – 624Combined sources3
Beta strandi658 – 660Combined sources3
Beta strandi664 – 667Combined sources4
Beta strandi670 – 677Combined sources8
Helixi681 – 684Combined sources4
Beta strandi693 – 700Combined sources8
Turni701 – 704Combined sources4
Beta strandi705 – 711Combined sources7
Beta strandi717 – 723Combined sources7
Beta strandi729 – 736Combined sources8
Beta strandi744 – 756Combined sources13
Beta strandi764 – 771Combined sources8
Beta strandi775 – 779Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4WGKX-ray2.58A/B99-780[»]
ProteinModelPortaliQ9NR71.
SMRiQ9NR71.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni770 – 780Required 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.
HOVERGENiHBG080870.
InParanoidiQ9NR71.
KOiK12349.
OMAiMGSFDIT.
OrthoDBiEOG091G06OC.
PhylomeDBiQ9NR71.
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]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NR71-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAKRTFSNLE TFLIFLLVMM SAITVALLSL LFITSGTIEN HKDLGGHFFS
60 70 80 90 100
TTQSPPATQG STAAQRSTAT QHSTATQSST ATQTSPVPLT PESPLFQNFS
110 120 130 140 150
GYHIGVGRAD CTGQVADINL MGYGKSGQNA QGILTRLYSR AFIMAEPDGS
160 170 180 190 200
NRTVFVSIDI GMVSQRLRLE VLNRLQSKYG SLYRRDNVIL SGTHTHSGPA
210 220 230 240 250
GYFQYTVFVI ASEGFSNQTF QHMVTGILKS IDIAHTNMKP GKIFINKGNV
260 270 280 290 300
DGVQINRSPY SYLQNPQSER ARYSSNTDKE MIVLKMVDLN GDDLGLISWF
310 320 330 340 350
AIHPVSMNNS NHLVNSDNVG YASYLLEQEK NKGYLPGQGP FVAAFASSNL
360 370 380 390 400
GDVSPNILGP RCINTGESCD NANSTCPIGG PSMCIAKGPG QDMFDSTQII
410 420 430 440 450
GRAMYQRAKE LYASASQEVT GPLASAHQWV DMTDVTVWLN STHASKTCKP
460 470 480 490 500
ALGYSFAAGT IDGVGGLNFT QGKTEGDPFW DTIRDQILGK PSEEIKECHK
510 520 530 540 550
PKPILLHTGE LSKPHPWHPD IVDVQIITLG SLAITAIPGE FTTMSGRRLR
560 570 580 590 600
EAVQAEFASH GMQNMTVVIS GLCNVYTHYI TTYEEYQAQR YEAASTIYGP
610 620 630 640 650
HTLSAYIQLF RNLAKAIATD TVANLSRGPE PPFFKQLIVP LIPSIVDRAP
660 670 680 690 700
KGRTFGDVLQ PAKPEYRVGE VAEVIFVGAN PKNSVQNQTH QTFLTVEKYE
710 720 730 740 750
ATSTSWQIVC NDASWETRFY WHKGLLGLSN ATVEWHIPDT AQPGIYRIRY
760 770 780
FGHNRKQDIL KPAVILSFEG TSPAFEVVTI
Length:780
Mass (Da):85,516
Last modified:July 25, 2006 - v2
Checksum:iD2BD7947B022A619
GO
Isoform 2 (identifier: Q9NR71-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     410-444: Missing.

Note: No experimental confirmation available.
Show »
Length:745
Mass (Da):81,718
Checksum:iB4577FFD1C6397EA
GO

Sequence cautioni

The sequence AAL06061 differs from that shown. Reason: Erroneous initiation.Curated
The sequence CAI15870 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti274S → P in AAL06061 (PubMed:14557071).Curated1
Sequence conflicti274S → P in AAF86240 (PubMed:10781606).Curated1
Sequence conflicti602T → A in AAL06061 (PubMed:14557071).Curated1
Sequence conflicti602T → A in AAF86240 (PubMed:10781606).Curated1
Sequence conflicti689T → N in CAI17190 (PubMed:15164054).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02706451T → A.Corresponds to variant rs7067625dbSNPEnsembl.1
Natural variantiVAR_027065346A → S.Corresponds to variant rs993869dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_019928410 – 444Missing in isoform 2. 1 PublicationAdd BLAST35

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS44398.1. [Q9NR71-2]
CCDS7239.2. [Q9NR71-1]
RefSeqiNP_001137446.1. NM_001143974.1. [Q9NR71-2]
NP_063946.2. NM_019893.2. [Q9NR71-1]
XP_011538272.1. XM_011539970.2. [Q9NR71-1]
UniGeneiHs.512645.

Genome annotation databases

EnsembliENST00000395526; ENSP00000378897; ENSG00000188611. [Q9NR71-1]
ENST00000447815; ENSP00000388206; ENSG00000188611. [Q9NR71-2]
GeneIDi56624.
KEGGihsa:56624.
UCSCiuc001jjd.4. human. [Q9NR71-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS44398.1. [Q9NR71-2]
CCDS7239.2. [Q9NR71-1]
RefSeqiNP_001137446.1. NM_001143974.1. [Q9NR71-2]
NP_063946.2. NM_019893.2. [Q9NR71-1]
XP_011538272.1. XM_011539970.2. [Q9NR71-1]
UniGeneiHs.512645.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4WGKX-ray2.58A/B99-780[»]
ProteinModelPortaliQ9NR71.
SMRiQ9NR71.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000378897.

Chemistry databases

BindingDBiQ9NR71.
ChEMBLiCHEMBL2021754.
SwissLipidsiSLP:000000163.

PTM databases

iPTMnetiQ9NR71.
PhosphoSitePlusiQ9NR71.

Polymorphism and mutation databases

BioMutaiASAH2.
DMDMi110832757.

Proteomic databases

MaxQBiQ9NR71.
PaxDbiQ9NR71.
PeptideAtlasiQ9NR71.
PRIDEiQ9NR71.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000395526; ENSP00000378897; ENSG00000188611. [Q9NR71-1]
ENST00000447815; ENSP00000388206; ENSG00000188611. [Q9NR71-2]
GeneIDi56624.
KEGGihsa:56624.
UCSCiuc001jjd.4. human. [Q9NR71-1]

Organism-specific databases

CTDi56624.
DisGeNETi56624.
GeneCardsiASAH2.
H-InvDBHIX0058802.
HGNCiHGNC:18860. ASAH2.
HPAiHPA061171.
MIMi611202. gene.
neXtProtiNX_Q9NR71.
OpenTargetsiENSG00000188611.
PharmGKBiPA134977109.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2232. Eukaryota.
ENOG410XQWE. LUCA.
GeneTreeiENSGT00390000015792.
HOVERGENiHBG080870.
InParanoidiQ9NR71.
KOiK12349.
OMAiMGSFDIT.
OrthoDBiEOG091G06OC.
PhylomeDBiQ9NR71.
TreeFamiTF300786.

Enzyme and pathway databases

BioCyciZFISH:G66-33393-MONOMER.
BRENDAi3.5.1.23. 2681.
ReactomeiR-HSA-1660662. Glycosphingolipid metabolism.
SABIO-RKQ9NR71.

Miscellaneous databases

GeneWikiiASAH2.
GenomeRNAii56624.
PROiQ9NR71.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000188611.
CleanExiHS_ASAH2.
ExpressionAtlasiQ9NR71. baseline and differential.
GenevisibleiQ9NR71. HS.

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...

Entry informationi

Entry nameiASAH2_HUMAN
AccessioniPrimary (citable) accession number: Q9NR71
Secondary accession number(s): Q3KNU1
, Q5SNT7, Q5SZP6, Q5SZP7, Q5T1D5, Q71ME6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 25, 2006
Last sequence update: July 25, 2006
Last modified: November 2, 2016
This is version 120 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.