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Q5QJU3

- ACER2_HUMAN

UniProt

Q5QJU3 - ACER2_HUMAN

Protein

Alkaline ceramidase 2

Gene

ACER2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 78 (01 Oct 2014)
      Sequence version 2 (25 Jul 2006)
      Previous versions | rss
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    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

    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

    GO - Cellular componenti

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

    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...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 3232LumenalSequence AnalysisAdd
    BLAST
    Topological domaini54 – 629CytoplasmicSequence Analysis
    Topological domaini84 – 863LumenalSequence Analysis
    Topological domaini108 – 12417CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini143 – 1431LumenalSequence Analysis
    Topological domaini165 – 1739CytoplasmicSequence Analysis
    Topological domaini195 – 21117LumenalSequence AnalysisAdd
    BLAST
    Topological domaini233 – 27543CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei33 – 5321HelicalSequence AnalysisAdd
    BLAST
    Transmembranei63 – 8321HelicalSequence AnalysisAdd
    BLAST
    Transmembranei87 – 10721HelicalSequence AnalysisAdd
    BLAST
    Transmembranei125 – 14218HelicalSequence AnalysisAdd
    BLAST
    Transmembranei144 – 16421HelicalSequence AnalysisAdd
    BLAST
    Transmembranei174 – 19421HelicalSequence AnalysisAdd
    BLAST
    Transmembranei212 – 23221HelicalSequence AnalysisAdd
    BLAST

    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.
    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

    MGAPHWWDQL QAGSSEVDWC EDNYTIVPAI AEFYNTISNV LFFILPPICM    50
    CLFRQYATCF NSGIYLIWTL LVVVGIGSVY FHATLSFLGQ MLDELAVLWV 100
    LMCALAMWFP RRYLPKIFRN DRGRFKVVVS VLSAVTTCLA FVKPAINNIS 150
    LMTLGVPCTA LLIAELKRCD NMRVFKLGLF SGLWWTLALF CWISDRAFCE 200
    LLSSFNFPYL HCMWHILICL AAYLGCVCFA YFDAASEIPE QGPVIKFWPN 250
    EKWAFIGVPY VSLLCANKKS SVKIT 275
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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

    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.
    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

    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

    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: October 1, 2014
    This is version 78 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