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O14494

- LPP1_HUMAN

UniProt

O14494 - LPP1_HUMAN

Protein

Lipid phosphate phosphohydrolase 1

Gene

PPAP2A

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 126 (01 Oct 2014)
      Sequence version 1 (01 Jan 1998)
      Previous versions | rss
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    Functioni

    Broad-specificity phosphohydrolase that dephosphorylates exogenous bioactive glycerolipids and sphingolipids. Catalyzes the conversion of phosphatidic acid (PA) to diacylglycerol (DG). Pivotal regulator of lysophosphatidic acid (LPA) signaling in the cardiovascular system. Major enzyme responsible of dephosphorylating LPA in platelets, which terminates signaling actions of LPA. May control circulating, and possibly also regulate localized, LPA levels resulting from platelet activation. It has little activity towards ceramide-1-phosphate (C-1-P) and sphingosine-1-phosphate (S-1-P). The relative catalytic efficiency is LPA > PA > S-1-P > C-1-P. It's down-regulation may contribute to the development of colon adenocarcinoma.1 Publication

    Catalytic activityi

    A 1,2-diacylglycerol 3-phosphate + H2O = a 1,2-diacyl-sn-glycerol + phosphate.

    Enzyme regulationi

    Inhibited by sphingosine, zinc ions and propanolol. Not inhibited by N-ethylmaleimide treatment.

    GO - Molecular functioni

    1. phosphatidate phosphatase activity Source: UniProtKB

    GO - Biological processi

    1. androgen receptor signaling pathway Source: UniProtKB
    2. germ cell migration Source: ProtInc
    3. intracellular steroid hormone receptor signaling pathway Source: UniProtKB
    4. lipid metabolic process Source: ProtInc
    5. negative regulation of cell proliferation Source: UniProtKB
    6. phospholipid dephosphorylation Source: UniProtKB
    7. protein dephosphorylation Source: Ensembl
    8. protein kinase C-activating G-protein coupled receptor signaling pathway Source: UniProtKB
    9. regulation of lipid metabolic process Source: UniProtKB
    10. small molecule metabolic process Source: Reactome
    11. sphingolipid biosynthetic process Source: Reactome
    12. sphingolipid metabolic process Source: Reactome

    Keywords - Molecular functioni

    Hydrolase

    Enzyme and pathway databases

    ReactomeiREACT_115810. Sphingolipid de novo biosynthesis.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Lipid phosphate phosphohydrolase 1 (EC:3.1.3.4)
    Alternative name(s):
    PAP2-alpha
    Phosphatidate phosphohydrolase type 2a
    Phosphatidic acid phosphatase 2a
    Short name:
    PAP-2a
    Short name:
    PAP2a
    Gene namesi
    Name:PPAP2A
    Synonyms:LPP1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 5

    Organism-specific databases

    HGNCiHGNC:9228. PPAP2A.

    Subcellular locationi

    GO - Cellular componenti

    1. extracellular vesicular exosome Source: UniProt
    2. integral component of plasma membrane Source: UniProtKB
    3. membrane Source: UniProtKB
    4. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA33552.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 284284Lipid phosphate phosphohydrolase 1PRO_0000220905Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi142 – 1421N-linked (GlcNAc...)Sequence Analysis

    Post-translational modificationi

    N-glycosylated. Contains high-mannose oligosaccharides.

    Keywords - PTMi

    Glycoprotein

    Proteomic databases

    MaxQBiO14494.
    PaxDbiO14494.
    PRIDEiO14494.

    PTM databases

    PhosphoSiteiO14494.

    Expressioni

    Tissue specificityi

    Ubiquitously expressed with highest expression found in prostate. Isoform 1 is predominant in kidney, lung, placenta and liver. Isoform 2 is predominant in heart and pancreas. Found to be down-regulated in colon adenocarcinomas.

    Inductioni

    By androgens.

    Gene expression databases

    ArrayExpressiO14494.
    BgeeiO14494.
    CleanExiHS_PPAP2A.
    GenevestigatoriO14494.

    Organism-specific databases

    HPAiCAB033331.
    HPA047815.

    Interactioni

    Subunit structurei

    Homodimer.By similarity

    Protein-protein interaction databases

    BioGridi114169. 4 interactions.
    IntActiO14494. 3 interactions.
    STRINGi9606.ENSP00000264775.

    Structurei

    3D structure databases

    ProteinModelPortaliO14494.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 66CytoplasmicSequence Analysis
    Topological domaini28 – 5326ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini75 – 9420CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini116 – 16449ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini186 – 19914CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini221 – 2299ExtracellularSequence Analysis
    Topological domaini251 – 28434CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei7 – 2721HelicalSequence AnalysisAdd
    BLAST
    Transmembranei54 – 7421HelicalSequence AnalysisAdd
    BLAST
    Transmembranei95 – 11521HelicalSequence AnalysisAdd
    BLAST
    Transmembranei165 – 18521HelicalSequence AnalysisAdd
    BLAST
    Transmembranei200 – 22021HelicalSequence AnalysisAdd
    BLAST
    Transmembranei230 – 25021HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0671.
    HOGENOMiHOG000041307.
    HOVERGENiHBG002048.
    KOiK01080.
    OMAiRVASKHK.
    OrthoDBiEOG7C5M9Q.
    PhylomeDBiO14494.
    TreeFamiTF316040.

    Family and domain databases

    Gene3Di1.20.144.10. 1 hit.
    InterProiIPR028670. LPP1.
    IPR000326. P_Acid_Pase_2/haloperoxidase.
    [Graphical view]
    PANTHERiPTHR10165:SF26. PTHR10165:SF26. 1 hit.
    PfamiPF01569. PAP2. 1 hit.
    [Graphical view]
    SMARTiSM00014. acidPPc. 1 hit.
    [Graphical view]
    SUPFAMiSSF48317. SSF48317. 1 hit.

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Note: Additional isoforms seem to exist.

    Isoform 1 (identifier: O14494-1) [UniParc]FASTAAdd to Basket

    Also known as: Alpha-1, hLPP1, PAP2-a1

    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

    MFDKTRLPYV ALDVLCVLLA GLPFAILTSR HTPFQRGVFC NDESIKYPYK    50
    EDTIPYALLG GIIIPFSIIV IILGETLSVY CNLLHSNSFI RNNYIATIYK 100
    AIGTFLFGAA ASQSLTDIAK YSIGRLRPHF LDVCDPDWSK INCSDGYIEY 150
    YICRGNAERV KEGRLSFYSG HSSFSMYCML FVALYLQARM KGDWARLLRP 200
    TLQFGLVAVS IYVGLSRVSD YKHHWSDVLT GLIQGALVAI LVAVYVSDFF 250
    KERTSFKERK EEDSHTTLHE TPTTGNHYPS NHQP 284
    Length:284
    Mass (Da):32,156
    Last modified:January 1, 1998 - v1
    Checksum:iFC2F00617EE07EB3
    GO
    Isoform 2 (identifier: O14494-2) [UniParc]FASTAAdd to Basket

    Also known as: Alpha-2, hLPP1-a, PAP2-a2

    The sequence of this isoform differs from the canonical sequence as follows:
         21-70: GLPFAILTSR...GIIIPFSIIV → SMPMAVLKLG...LVGVGLPISS

    Show »
    Length:285
    Mass (Da):32,150
    Checksum:i7209608A420380CE
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti27 – 271L → FTSRHI in AAC32041. (PubMed:9705349)Curated
    Sequence conflicti91 – 911R → S in AAC16033. (PubMed:9570154)Curated
    Isoform 2 (identifier: O14494-2)
    Sequence conflicti55 – 551V → A in AAC16033. (PubMed:9570154)Curated
    Sequence conflicti56 – 561T → A in AAC16033. (PubMed:9570154)Curated
    Sequence conflicti69 – 691I → V in AAC16033. (PubMed:9570154)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei21 – 7050GLPFA…FSIIV → SMPMAVLKLGQIYPFQRGFF CKDNSINYPYHDSTVTSTVL ILVGVGLPISS in isoform 2. 1 PublicationVSP_009651Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB000888 mRNA. Translation: BAA22593.1.
    AF014402 mRNA. Translation: AAC16032.1.
    AF014403 mRNA. Translation: AAC16033.1.
    Y14436 mRNA. Translation: CAC14588.1.
    AF017116 mRNA. Translation: AAC32041.1.
    AC010480 Genomic DNA. No translation available.
    AC025777 Genomic DNA. No translation available.
    CH471123 Genomic DNA. Translation: EAW54920.1.
    CH471123 Genomic DNA. Translation: EAW54922.1.
    BC039847 mRNA. Translation: AAH39847.1.
    BC117133 mRNA. Translation: AAI17134.1.
    BC143281 mRNA. Translation: AAI43282.1.
    CCDSiCCDS34159.1. [O14494-1]
    CCDS34160.1. [O14494-2]
    RefSeqiNP_003702.2. NM_003711.3. [O14494-1]
    NP_795714.1. NM_176895.2. [O14494-2]
    UniGeneiHs.696231.

    Genome annotation databases

    EnsembliENST00000264775; ENSP00000264775; ENSG00000067113. [O14494-2]
    ENST00000307259; ENSP00000302229; ENSG00000067113. [O14494-1]
    GeneIDi8611.
    KEGGihsa:8611.
    UCSCiuc003jpz.4. human.
    uc003jqa.4. human. [O14494-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB000888 mRNA. Translation: BAA22593.1 .
    AF014402 mRNA. Translation: AAC16032.1 .
    AF014403 mRNA. Translation: AAC16033.1 .
    Y14436 mRNA. Translation: CAC14588.1 .
    AF017116 mRNA. Translation: AAC32041.1 .
    AC010480 Genomic DNA. No translation available.
    AC025777 Genomic DNA. No translation available.
    CH471123 Genomic DNA. Translation: EAW54920.1 .
    CH471123 Genomic DNA. Translation: EAW54922.1 .
    BC039847 mRNA. Translation: AAH39847.1 .
    BC117133 mRNA. Translation: AAI17134.1 .
    BC143281 mRNA. Translation: AAI43282.1 .
    CCDSi CCDS34159.1. [O14494-1 ]
    CCDS34160.1. [O14494-2 ]
    RefSeqi NP_003702.2. NM_003711.3. [O14494-1 ]
    NP_795714.1. NM_176895.2. [O14494-2 ]
    UniGenei Hs.696231.

    3D structure databases

    ProteinModelPortali O14494.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114169. 4 interactions.
    IntActi O14494. 3 interactions.
    STRINGi 9606.ENSP00000264775.

    PTM databases

    PhosphoSitei O14494.

    Proteomic databases

    MaxQBi O14494.
    PaxDbi O14494.
    PRIDEi O14494.

    Protocols and materials databases

    DNASUi 8611.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000264775 ; ENSP00000264775 ; ENSG00000067113 . [O14494-2 ]
    ENST00000307259 ; ENSP00000302229 ; ENSG00000067113 . [O14494-1 ]
    GeneIDi 8611.
    KEGGi hsa:8611.
    UCSCi uc003jpz.4. human.
    uc003jqa.4. human. [O14494-1 ]

    Organism-specific databases

    CTDi 8611.
    GeneCardsi GC05M054756.
    HGNCi HGNC:9228. PPAP2A.
    HPAi CAB033331.
    HPA047815.
    MIMi 607124. gene.
    neXtProti NX_O14494.
    PharmGKBi PA33552.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0671.
    HOGENOMi HOG000041307.
    HOVERGENi HBG002048.
    KOi K01080.
    OMAi RVASKHK.
    OrthoDBi EOG7C5M9Q.
    PhylomeDBi O14494.
    TreeFami TF316040.

    Enzyme and pathway databases

    Reactomei REACT_115810. Sphingolipid de novo biosynthesis.

    Miscellaneous databases

    GeneWikii PPAP2A.
    GenomeRNAii 8611.
    NextBioi 32263.
    PROi O14494.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O14494.
    Bgeei O14494.
    CleanExi HS_PPAP2A.
    Genevestigatori O14494.

    Family and domain databases

    Gene3Di 1.20.144.10. 1 hit.
    InterProi IPR028670. LPP1.
    IPR000326. P_Acid_Pase_2/haloperoxidase.
    [Graphical view ]
    PANTHERi PTHR10165:SF26. PTHR10165:SF26. 1 hit.
    Pfami PF01569. PAP2. 1 hit.
    [Graphical view ]
    SMARTi SM00014. acidPPc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF48317. SSF48317. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "Cloning and characterization of two human isozymes of Mg2+-independent phosphatidic acid phosphatase."
      Kai M., Wada I., Imai S., Sakane F., Kanoh H.
      J. Biol. Chem. 272:24572-24578(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION.
    2. "Molecular cloning of two alternatively spliced forms of human phosphatidic acid phosphatase cDNAs that are differentially expressed in normal and tumor cells."
      Leung D.W., Tompkins C.K., White T.
      DNA Cell Biol. 17:377-385(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
      Tissue: Lung.
    3. "Identification of the phosphatidic acid phosphatase type 2a isozyme as an androgen-regulated gene in the human prostatic Adenocarcinoma cell line LNCaP."
      Ulrix W.E.J., Swinnen J., Heyns W., Verhoeven G.
      J. Biol. Chem. 273:4660-4665(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Prostate.
    4. "Human type 2 phosphatidic acid phosphohydrolases. Substrate specificity of the type 2a, 2b, and 2c enzymes and cell surface activity of the 2a isoform."
      Roberts R., Sciorra V.A., Morris A.J.
      J. Biol. Chem. 273:22059-22067(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION.
    5. "The DNA sequence and comparative analysis of human chromosome 5."
      Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.
      , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
      Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    7. "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 1).
      Tissue: Brain.
    8. "Lipid phosphate phosphatases regulate lysophosphatidic acid production and signaling in platelets: studies using chemical inhibitors of lipid phosphate phosphatase activity."
      Smyth S.S., Sciorra V.A., Sigal Y.J., Pamulkar Z., Wang Z., Xu Y., Prestwich G.D., Morris A.J.
      J. Biol. Chem. 278:43214-43223(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.

    Entry informationi

    Entry nameiLPP1_HUMAN
    AccessioniPrimary (citable) accession number: O14494
    Secondary accession number(s): B7ZKN8
    , G3XA95, O60457, O60463, Q17RZ4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 15, 2004
    Last sequence update: January 1, 1998
    Last modified: October 1, 2014
    This is version 126 of the entry and version 1 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

    Caution

    PubMed:9305923 states that this phosphatase does not hydrolyze sphingosine 1-phosphate while PubMed:9705349 states that it does.Curated

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 5
      Human chromosome 5: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3