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Protein

Alkaline ceramidase 2

Gene

ACER2

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. Unsaturated long-chain ceramides are the best substrates, saturated long-chain ceramides and unsaturated very long-chain ceramides are good substrates, whereas saturated very long-chain ceramides and short-chain ceramides were poor substrates. The substrate preference is D-erythro-C(18:1)-, C(20:1)-, C(20:4)-ceramide > D-erythro-C(16:0)-, C(18:0), C(20:0)-ceramide > D-erythro-C(24:1)-ceramide > D-erythro-C(12:0)-ceramide, D-erythro-C(14:0)-ceramides > D-erythro-C(24:0)-ceramide > D-erythro-C(6:0)-ceramide. Inhibits the maturation of protein glycosylation in the Golgi complex, including that of integrin beta-1 (ITGB1) and of LAMP1, by increasing the levels of sphingosine. Inhibits cell adhesion by reducing the level of ITGB1 in the cell surface. May have a role in cell proliferation and apoptosis that seems to depend on the balance between sphingosine and sphingosine-1-phosphate.3 Publications

Catalytic activityi

N-acylsphingosine + H2O = a carboxylate + sphingosine.

Enzyme regulationi

Specifically activated by lumenal, but not cytosolic Ca2+. Inhibited by Zn2+ or Cu2+. Mg2+ or Mn2+ have no effect on ceramidase activity.1 Publication

Kineticsi

  1. KM=81 µM for D-erythro-C(24:1)-ceramide (at 37 degrees Celsius and pH 9.0)1 Publication
  1. Vmax=27 pmol/min/mg enzyme with D-erythro-C(24:1)-ceramide as substrate1 Publication

pH dependencei

Optimum pH is 7.5-9.0.1 Publication

GO - Molecular functioni

  • ceramidase activity Source: UniProtKB
  • dihydroceramidase activity Source: BHF-UCL

GO - Biological processi

  • activation of cysteine-type endopeptidase activity involved in apoptotic process Source: BHF-UCL
  • cellular response to drug Source: BHF-UCL
  • ceramide metabolic process Source: InterPro
  • negative regulation of cell adhesion mediated by integrin Source: UniProtKB
  • negative regulation of cell-matrix adhesion Source: UniProtKB
  • negative regulation of protein glycosylation in Golgi Source: UniProtKB
  • positive regulation of cell death Source: BHF-UCL
  • positive regulation of cell proliferation Source: UniProtKB
  • response to retinoic acid Source: UniProtKB
  • sphingolipid biosynthetic process Source: Reactome
  • sphingosine biosynthetic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Lipid metabolism

Enzyme and pathway databases

BioCyciZFISH:HS16784-MONOMER.
BRENDAi3.5.1.23. 2681.
ReactomeiR-HSA-1660661. Sphingolipid de novo biosynthesis.
SABIO-RKQ5QJU3.

Chemistry databases

SwissLipidsiSLP:000000164.

Names & Taxonomyi

Protein namesi
Recommended name:
Alkaline ceramidase 2 (EC:3.5.1.23)
Short name:
AlkCDase 2
Short name:
Alkaline CDase 2
Short name:
haCER2
Alternative name(s):
Acylsphingosine deacylase 3-like
N-acylsphingosine amidohydrolase 3-like
Gene namesi
Name:ACER2
Synonyms:ASAH3L
ORF Names:PP11646
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:23675. ACER2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 32LumenalSequence analysisAdd BLAST32
Transmembranei33 – 53HelicalSequence analysisAdd BLAST21
Topological domaini54 – 62CytoplasmicSequence analysis9
Transmembranei63 – 83HelicalSequence analysisAdd BLAST21
Topological domaini84 – 86LumenalSequence analysis3
Transmembranei87 – 107HelicalSequence analysisAdd BLAST21
Topological domaini108 – 124CytoplasmicSequence analysisAdd BLAST17
Transmembranei125 – 142HelicalSequence analysisAdd BLAST18
Topological domaini143LumenalSequence analysis1
Transmembranei144 – 164HelicalSequence analysisAdd BLAST21
Topological domaini165 – 173CytoplasmicSequence analysis9
Transmembranei174 – 194HelicalSequence analysisAdd BLAST21
Topological domaini195 – 211LumenalSequence analysisAdd BLAST17
Transmembranei212 – 232HelicalSequence analysisAdd BLAST21
Topological domaini233 – 275CytoplasmicSequence analysisAdd BLAST43

GO - Cellular componenti

  • Golgi apparatus Source: UniProtKB
  • Golgi membrane Source: Reactome
  • integral component of Golgi membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Golgi apparatus, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi340485.
OpenTargetsiENSG00000177076.
PharmGKBiPA164714853.

Chemistry databases

ChEMBLiCHEMBL2331067.

Polymorphism and mutation databases

BioMutaiACER2.
DMDMi110832756.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002477481 – 275Alkaline ceramidase 2Add BLAST275

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi23N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ5QJU3.
PRIDEiQ5QJU3.

Expressioni

Tissue specificityi

Highly expressed in placenta.1 Publication

Gene expression databases

BgeeiENSG00000177076.
CleanExiHS_ACER2.

Organism-specific databases

HPAiHPA014092.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000342609.

Chemistry databases

BindingDBiQ5QJU3.

Structurei

3D structure databases

ProteinModelPortaliQ5QJU3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 13Essential for localization in the Golgi apparatus and for activityAdd BLAST13

Sequence similaritiesi

Belongs to the alkaline ceramidase family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2329. Eukaryota.
ENOG4111RPN. LUCA.
GeneTreeiENSGT00730000110920.
HOGENOMiHOG000220878.
InParanoidiQ5QJU3.
KOiK01441.
OMAiKFWPSER.
OrthoDBiEOG091G0HT1.
PhylomeDBiQ5QJU3.
TreeFamiTF313019.

Family and domain databases

InterProiIPR008901. Ceramidase.
[Graphical view]
PfamiPF05875. Ceramidase. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q5QJU3-1) [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
MGAPHWWDQL QAGSSEVDWC EDNYTIVPAI AEFYNTISNV LFFILPPICM
60 70 80 90 100
CLFRQYATCF NSGIYLIWTL LVVVGIGSVY FHATLSFLGQ MLDELAVLWV
110 120 130 140 150
LMCALAMWFP RRYLPKIFRN DRGRFKVVVS VLSAVTTCLA FVKPAINNIS
160 170 180 190 200
LMTLGVPCTA LLIAELKRCD NMRVFKLGLF SGLWWTLALF CWISDRAFCE
210 220 230 240 250
LLSSFNFPYL HCMWHILICL AAYLGCVCFA YFDAASEIPE QGPVIKFWPN
260 270
EKWAFIGVPY VSLLCANKKS SVKIT
Length:275
Mass (Da):31,309
Last modified:July 25, 2006 - v2
Checksum:i56FD619B53C296B1
GO
Isoform 2 (identifier: Q5QJU3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-49: Missing.

Show »
Length:226
Mass (Da):25,724
Checksum:i49441E790CBAD583
GO
Isoform 3 (identifier: Q5QJU3-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-49: Missing.
     169-189: CDNMRVFKLGLFSGLWWTLAL → HERNQRRRHRKGGQQGGGDKV
     190-275: Missing.

Note: No experimental confirmation available.
Show »
Length:140
Mass (Da):15,864
Checksum:i7888DB0189A6DF42
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti274I → T in AAQ85132 (PubMed:16940153).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_027150134A → V.Corresponds to variant rs10964136dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0200331 – 49Missing in isoform 2 and isoform 3. 2 PublicationsAdd BLAST49
Alternative sequenceiVSP_020034169 – 189CDNMR…WTLAL → HERNQRRRHRKGGQQGGGDK V in isoform 3. 1 PublicationAdd BLAST21
Alternative sequenceiVSP_020035190 – 275Missing in isoform 3. 1 PublicationAdd BLAST86

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY312516 mRNA. Translation: AAQ85132.1.
AF370405 mRNA. Translation: AAQ15241.1.
AL158206, AL391834 Genomic DNA. Translation: CAH73022.1.
AL391834, AL158206 Genomic DNA. Translation: CAM21146.1.
BC092487 mRNA. Translation: AAH92487.1.
CCDSiCCDS34992.1. [Q5QJU3-1]
RefSeqiNP_001010887.2. NM_001010887.2. [Q5QJU3-1]
XP_005251505.1. XM_005251448.3. [Q5QJU3-2]
XP_016870183.1. XM_017014694.1. [Q5QJU3-2]
UniGeneiHs.41379.
Hs.99785.

Genome annotation databases

EnsembliENST00000340967; ENSP00000342609; ENSG00000177076. [Q5QJU3-1]
GeneIDi340485.
KEGGihsa:340485.
UCSCiuc003zny.2. human. [Q5QJU3-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY312516 mRNA. Translation: AAQ85132.1.
AF370405 mRNA. Translation: AAQ15241.1.
AL158206, AL391834 Genomic DNA. Translation: CAH73022.1.
AL391834, AL158206 Genomic DNA. Translation: CAM21146.1.
BC092487 mRNA. Translation: AAH92487.1.
CCDSiCCDS34992.1. [Q5QJU3-1]
RefSeqiNP_001010887.2. NM_001010887.2. [Q5QJU3-1]
XP_005251505.1. XM_005251448.3. [Q5QJU3-2]
XP_016870183.1. XM_017014694.1. [Q5QJU3-2]
UniGeneiHs.41379.
Hs.99785.

3D structure databases

ProteinModelPortaliQ5QJU3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000342609.

Chemistry databases

BindingDBiQ5QJU3.
ChEMBLiCHEMBL2331067.
SwissLipidsiSLP:000000164.

Polymorphism and mutation databases

BioMutaiACER2.
DMDMi110832756.

Proteomic databases

PaxDbiQ5QJU3.
PRIDEiQ5QJU3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000340967; ENSP00000342609; ENSG00000177076. [Q5QJU3-1]
GeneIDi340485.
KEGGihsa:340485.
UCSCiuc003zny.2. human. [Q5QJU3-1]

Organism-specific databases

CTDi340485.
DisGeNETi340485.
GeneCardsiACER2.
H-InvDBHIX0025758.
HGNCiHGNC:23675. ACER2.
HPAiHPA014092.
MIMi613492. gene.
neXtProtiNX_Q5QJU3.
OpenTargetsiENSG00000177076.
PharmGKBiPA164714853.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2329. Eukaryota.
ENOG4111RPN. LUCA.
GeneTreeiENSGT00730000110920.
HOGENOMiHOG000220878.
InParanoidiQ5QJU3.
KOiK01441.
OMAiKFWPSER.
OrthoDBiEOG091G0HT1.
PhylomeDBiQ5QJU3.
TreeFamiTF313019.

Enzyme and pathway databases

BioCyciZFISH:HS16784-MONOMER.
BRENDAi3.5.1.23. 2681.
ReactomeiR-HSA-1660661. Sphingolipid de novo biosynthesis.
SABIO-RKQ5QJU3.

Miscellaneous databases

ChiTaRSiACER2. human.
GeneWikiiACER2.
GenomeRNAii340485.
PROiQ5QJU3.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000177076.
CleanExiHS_ACER2.

Family and domain databases

InterProiIPR008901. Ceramidase.
[Graphical view]
PfamiPF05875. Ceramidase. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiACER2_HUMAN
AccessioniPrimary (citable) accession number: Q5QJU3
Secondary accession number(s): A2A3R8
, Q569G5, Q5VZR7, Q71RD2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 25, 2006
Last sequence update: July 25, 2006
Last modified: November 2, 2016
This is version 93 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: 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. 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.