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Q5QJU3

- ACER2_HUMAN

UniProt

Q5QJU3 - ACER2_HUMAN

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Protein

Alkaline ceramidase 2

Gene

ACER2

Organism
Homo sapiens (Human)
Status
Reviewed - 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

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

  1. ceramidase activity Source: UniProtKB
  2. dihydroceramidase activity Source: BHF-UCL

GO - Biological processi

  1. activation of cysteine-type endopeptidase activity involved in apoptotic process Source: BHF-UCL
  2. cellular response to drug Source: BHF-UCL
  3. ceramide metabolic process Source: InterPro
  4. negative regulation of cell adhesion mediated by integrin Source: UniProtKB
  5. negative regulation of cell-matrix adhesion Source: UniProtKB
  6. negative regulation of protein glycosylation in Golgi Source: UniProtKB
  7. positive regulation of cell death Source: BHF-UCL
  8. positive regulation of cell proliferation Source: UniProtKB
  9. response to retinoic acid Source: UniProtKB
  10. small molecule metabolic process Source: Reactome
  11. sphingolipid biosynthetic process Source: Reactome
  12. sphingolipid metabolic process Source: Reactome
  13. sphingosine biosynthetic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Lipid metabolism

Enzyme and pathway databases

BRENDAi3.5.1.23. 2681.
ReactomeiREACT_115810. Sphingolipid de novo biosynthesis.

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
ProteomesiUP000005640: Chromosome 9

Organism-specific databases

HGNCiHGNC:23675. ACER2.

Subcellular locationi

Golgi apparatus membrane 2 Publications; Multi-pass membrane protein 2 Publications

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3232LumenalSequence AnalysisAdd
BLAST
Transmembranei33 – 5321HelicalSequence AnalysisAdd
BLAST
Topological domaini54 – 629CytoplasmicSequence Analysis
Transmembranei63 – 8321HelicalSequence AnalysisAdd
BLAST
Topological domaini84 – 863LumenalSequence Analysis
Transmembranei87 – 10721HelicalSequence AnalysisAdd
BLAST
Topological domaini108 – 12417CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei125 – 14218HelicalSequence AnalysisAdd
BLAST
Topological domaini143 – 1431LumenalSequence Analysis
Transmembranei144 – 16421HelicalSequence AnalysisAdd
BLAST
Topological domaini165 – 1739CytoplasmicSequence Analysis
Transmembranei174 – 19421HelicalSequence AnalysisAdd
BLAST
Topological domaini195 – 21117LumenalSequence AnalysisAdd
BLAST
Transmembranei212 – 23221HelicalSequence AnalysisAdd
BLAST
Topological domaini233 – 27543CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. Golgi apparatus Source: UniProtKB
  2. Golgi membrane Source: Reactome
  3. integral component of Golgi membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Golgi apparatus, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA164714853.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 275275Alkaline ceramidase 2PRO_0000247748Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi23 – 231N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ5QJU3.
PRIDEiQ5QJU3.

Expressioni

Tissue specificityi

Highly expressed in placenta.1 Publication

Gene expression databases

BgeeiQ5QJU3.
CleanExiHS_ACER2.
GenevestigatoriQ5QJU3.

Organism-specific databases

HPAiHPA014092.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000342609.

Structurei

3D structure databases

ProteinModelPortaliQ5QJU3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 1313Essential for localization in the Golgi apparatus and for activityAdd
BLAST

Sequence similaritiesi

Belongs to the alkaline ceramidase family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG323012.
GeneTreeiENSGT00730000110920.
HOGENOMiHOG000220878.
InParanoidiQ5QJU3.
KOiK01441.
OMAiEVEMQVF.
OrthoDBiEOG7F5127.
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. Align

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti274 – 2741I → T in AAQ85132. (PubMed:16940153)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti134 – 1341A → V.
Corresponds to variant rs10964136 [ dbSNP | Ensembl ].
VAR_027150

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 4949Missing in isoform 2 and isoform 3. 2 PublicationsVSP_020033Add
BLAST
Alternative sequencei169 – 18921CDNMR…WTLAL → HERNQRRRHRKGGQQGGGDK V in isoform 3. 1 PublicationVSP_020034Add
BLAST
Alternative sequencei190 – 27586Missing in isoform 3. 1 PublicationVSP_020035Add
BLAST

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_005251448.1. [Q5QJU3-2]
UniGeneiHs.41379.

Genome annotation databases

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

Polymorphism databases

DMDMi110832756.

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 .
CCDSi CCDS34992.1. [Q5QJU3-1 ]
RefSeqi NP_001010887.2. NM_001010887.2. [Q5QJU3-1 ]
XP_005251505.1. XM_005251448.1. [Q5QJU3-2 ]
UniGenei Hs.41379.

3D structure databases

ProteinModelPortali Q5QJU3.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9606.ENSP00000342609.

Chemistry

BindingDBi Q5QJU3.
ChEMBLi CHEMBL2331067.

Polymorphism databases

DMDMi 110832756.

Proteomic databases

PaxDbi Q5QJU3.
PRIDEi Q5QJU3.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000340967 ; ENSP00000342609 ; ENSG00000177076 . [Q5QJU3-1 ]
GeneIDi 340485.
KEGGi hsa:340485.
UCSCi uc003zny.1. human. [Q5QJU3-1 ]

Organism-specific databases

CTDi 340485.
GeneCardsi GC09P019408.
H-InvDB HIX0025758.
HGNCi HGNC:23675. ACER2.
HPAi HPA014092.
MIMi 613492. gene.
neXtProti NX_Q5QJU3.
PharmGKBi PA164714853.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG323012.
GeneTreei ENSGT00730000110920.
HOGENOMi HOG000220878.
InParanoidi Q5QJU3.
KOi K01441.
OMAi EVEMQVF.
OrthoDBi EOG7F5127.
PhylomeDBi Q5QJU3.
TreeFami TF313019.

Enzyme and pathway databases

BRENDAi 3.5.1.23. 2681.
Reactomei REACT_115810. Sphingolipid de novo biosynthesis.

Miscellaneous databases

ChiTaRSi ACER2. human.
GeneWikii ACER2.
GenomeRNAii 340485.
NextBioi 97878.
PROi Q5QJU3.
SOURCEi Search...

Gene expression databases

Bgeei Q5QJU3.
CleanExi HS_ACER2.
Genevestigatori Q5QJU3.

Family and domain databases

InterProi IPR008901. Ceramidase.
[Graphical view ]
Pfami PF05875. Ceramidase. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.
    , 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.

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 26, 2014
This is version 80 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

External Data

Dasty 3