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Q5QJU3 (ACER2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 74. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Alkaline ceramidase 2

Short name=AlkCDase 2
Short name=Alkaline CDase 2
Short name=haCER2
EC=3.5.1.23
Alternative name(s):
Acylsphingosine deacylase 3-like
N-acylsphingosine amidohydrolase 3-like
Gene names
Name:ACER2
Synonyms:ASAH3L
ORF Names:PP11646
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length275 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.5 Ref.6

Catalytic activity

N-acylsphingosine + H2O = a carboxylate + sphingosine.

Enzyme regulation

Specifically activated by lumenal, but not cytosolic Ca2+. Inhibited by Zn2+ or Cu2+. Mg2+ or Mn2+ have no effect on ceramidase activity. Ref.6

Subcellular location

Golgi apparatus membrane; Multi-pass membrane protein Ref.1 Ref.6.

Tissue specificity

Highly expressed in placenta. Ref.1

Sequence similarities

Belongs to the alkaline ceramidase family.

Biophysicochemical properties

Kinetic parameters:

KM=81 µM for D-erythro-C(24:1)-ceramide (at 37 degrees Celsius and pH 9.0) Ref.6

Vmax=27 pmol/min/mg enzyme with D-erythro-C(24:1)-ceramide as substrate

pH dependence:

Optimum pH is 7.5-9.0.

Ontologies

Keywords
   Biological processLipid metabolism
   Cellular componentGolgi apparatus
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransmembrane
Transmembrane helix
   Molecular functionHydrolase
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from mutant phenotype PubMed 20628055. Source: BHF-UCL

cellular response to drug

Inferred from expression pattern PubMed 20628055. Source: BHF-UCL

ceramide metabolic process

Inferred from electronic annotation. Source: InterPro

negative regulation of cell adhesion mediated by integrin

Inferred from direct assay Ref.5. Source: UniProtKB

negative regulation of cell-matrix adhesion

Inferred from direct assay Ref.5. Source: UniProtKB

negative regulation of protein glycosylation in Golgi

Inferred from mutant phenotype Ref.6. Source: UniProtKB

positive regulation of cell death

Inferred from mutant phenotype PubMed 20628055. Source: BHF-UCL

positive regulation of cell proliferation

Inferred from direct assay Ref.1. Source: UniProtKB

response to retinoic acid

Inferred from direct assay Ref.5. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

sphingolipid biosynthetic process

Traceable author statement. Source: Reactome

sphingolipid metabolic process

Traceable author statement. Source: Reactome

sphingosine biosynthetic process

Inferred from direct assay Ref.1Ref.6. Source: UniProtKB

   Cellular_componentGolgi apparatus

Inferred from direct assay Ref.1. Source: UniProtKB

Golgi membrane

Traceable author statement. Source: Reactome

integral component of Golgi membrane

Inferred from direct assay Ref.6. Source: UniProtKB

   Molecular_functionceramidase activity

Inferred from direct assay Ref.1Ref.6. Source: UniProtKB

dihydroceramidase activity

Inferred from direct assay PubMed 20628055. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q5QJU3-1)

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.
Isoform 2 (identifier: Q5QJU3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-49: Missing.
Isoform 3 (identifier: Q5QJU3-3)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 275275Alkaline ceramidase 2
PRO_0000247748

Regions

Topological domain1 – 3232Lumenal Potential
Transmembrane33 – 5321Helical; Potential
Topological domain54 – 629Cytoplasmic Potential
Transmembrane63 – 8321Helical; Potential
Topological domain84 – 863Lumenal Potential
Transmembrane87 – 10721Helical; Potential
Topological domain108 – 12417Cytoplasmic Potential
Transmembrane125 – 14218Helical; Potential
Topological domain1431Lumenal Potential
Transmembrane144 – 16421Helical; Potential
Topological domain165 – 1739Cytoplasmic Potential
Transmembrane174 – 19421Helical; Potential
Topological domain195 – 21117Lumenal Potential
Transmembrane212 – 23221Helical; Potential
Topological domain233 – 27543Cytoplasmic Potential
Region1 – 1313Essential for localization in the Golgi apparatus and for activity

Amino acid modifications

Glycosylation231N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 4949Missing in isoform 2 and isoform 3.
VSP_020033
Alternative sequence169 – 18921CDNMR…WTLAL → HERNQRRRHRKGGQQGGGDK V in isoform 3.
VSP_020034
Alternative sequence190 – 27586Missing in isoform 3.
VSP_020035
Natural variant1341A → V.
Corresponds to variant rs10964136 [ dbSNP | Ensembl ].
VAR_027150

Experimental info

Sequence conflict2741I → T in AAQ85132. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 25, 2006. Version 2.
Checksum: 56FD619B53C296B1

FASTA27531,309
        10         20         30         40         50         60 
MGAPHWWDQL QAGSSEVDWC EDNYTIVPAI AEFYNTISNV LFFILPPICM CLFRQYATCF 

        70         80         90        100        110        120 
NSGIYLIWTL LVVVGIGSVY FHATLSFLGQ MLDELAVLWV LMCALAMWFP RRYLPKIFRN 

       130        140        150        160        170        180 
DRGRFKVVVS VLSAVTTCLA FVKPAINNIS LMTLGVPCTA LLIAELKRCD NMRVFKLGLF 

       190        200        210        220        230        240 
SGLWWTLALF CWISDRAFCE LLSSFNFPYL HCMWHILICL AAYLGCVCFA YFDAASEIPE 

       250        260        270 
QGPVIKFWPN EKWAFIGVPY VSLLCANKKS SVKIT 

« Hide

Isoform 2 [UniParc].

Checksum: 49441E790CBAD583
Show »

FASTA22625,724
Isoform 3 [UniParc].

Checksum: 7888DB0189A6DF42
Show »

FASTA14015,864

References

« Hide 'large scale' references
[1]"Golgi alkaline ceramidase regulates cell proliferation and survival by controlling levels of sphingosine and S1P."
Xu R., Jin J., Hu W., Sun W., Bielawski J., Szulc Z., Taha T., Obeid L.M., Mao C.
FASEB J. 20:1813-1825(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[2]"Large-scale cDNA transfection screening for genes related to cancer development and progression."
Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X. expand/collapse author list , Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.
Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[3]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Placenta.
[5]"Alkaline ceramidase 2 regulates beta1 integrin maturation and cell adhesion."
Sun W., Hu W., Xu R., Jin J., Szulc Z.M., Zhang G., Galadari S.H., Obeid L.M., Mao C.
FASEB J. 23:656-666(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"Substrate specificity, membrane topology, and activity regulation of human alkaline ceramidase 2 (ACER2)."
Sun W., Jin J., Xu R., Hu W., Szulc Z.M., Bielawski J., Obeid L.M., Mao C.
J. Biol. Chem. 285:8995-9007(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, TOPOLOGY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001010887.2. NM_001010887.2.
XP_005251505.1. XM_005251448.1.
UniGeneHs.41379.

3D structure databases

ProteinModelPortalQ5QJU3.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000342609.

Chemistry

ChEMBLCHEMBL2331067.

Polymorphism databases

DMDM110832756.

Proteomic databases

PaxDbQ5QJU3.
PRIDEQ5QJU3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000340967; ENSP00000342609; ENSG00000177076. [Q5QJU3-1]
ENST00000380376; ENSP00000369735; ENSG00000177076. [Q5QJU3-3]
GeneID340485.
KEGGhsa:340485.
UCSCuc003zny.1. human. [Q5QJU3-1]

Organism-specific databases

CTD340485.
GeneCardsGC09P019408.
H-InvDBHIX0025758.
HGNCHGNC:23675. ACER2.
HPAHPA014092.
MIM613492. gene.
neXtProtNX_Q5QJU3.
PharmGKBPA164714853.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG323012.
HOGENOMHOG000220878.
InParanoidQ5QJU3.
KOK01441.
OMAKRCDNVR.
OrthoDBEOG7F5127.
PhylomeDBQ5QJU3.
TreeFamTF313019.

Enzyme and pathway databases

BRENDA3.5.1.23. 2681.
ReactomeREACT_111217. Metabolism.

Gene expression databases

BgeeQ5QJU3.
CleanExHS_ACER2.
GenevestigatorQ5QJU3.

Family and domain databases

InterProIPR008901. Ceramidase.
[Graphical view]
PfamPF05875. Ceramidase. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiACER2.
GenomeRNAi340485.
NextBio97878.
PROQ5QJU3.
SOURCESearch...

Entry information

Entry nameACER2_HUMAN
AccessionPrimary (citable) accession number: Q5QJU3
Secondary accession number(s): A2A3R8 expand/collapse secondary AC list , Q569G5, Q5VZR7, Q71RD2
Entry history
Integrated into UniProtKB/Swiss-Prot: July 25, 2006
Last sequence update: July 25, 2006
Last modified: April 16, 2014
This is version 74 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM