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O14494

- LPP1_HUMAN

UniProt

O14494 - LPP1_HUMAN

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Protein

Lipid phosphate phosphohydrolase 1

Gene

PPAP2A

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

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
Complete GO annotation...

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: UniProtKB
  2. integral component of plasma membrane Source: UniProtKB
  3. membrane Source: UniProtKB
  4. plasma membrane Source: Reactome
Complete GO annotation...

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

BgeeiO14494.
CleanExiHS_PPAP2A.
ExpressionAtlasiO14494. baseline and differential.
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.
GeneTreeiENSGT00620000087654.
HOGENOMiHOG000041307.
HOVERGENiHBG002048.
InParanoidiO14494.
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

        10         20         30         40         50
MFDKTRLPYV ALDVLCVLLA GLPFAILTSR HTPFQRGVFC NDESIKYPYK
60 70 80 90 100
EDTIPYALLG GIIIPFSIIV IILGETLSVY CNLLHSNSFI RNNYIATIYK
110 120 130 140 150
AIGTFLFGAA ASQSLTDIAK YSIGRLRPHF LDVCDPDWSK INCSDGYIEY
160 170 180 190 200
YICRGNAERV KEGRLSFYSG HSSFSMYCML FVALYLQARM KGDWARLLRP
210 220 230 240 250
TLQFGLVAVS IYVGLSRVSD YKHHWSDVLT GLIQGALVAI LVAVYVSDFF
260 270 280
KERTSFKERK EEDSHTTLHE TPTTGNHYPS NHQP
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 GC05M054721.
HGNCi HGNC:9228. PPAP2A.
HPAi CAB033331.
HPA047815.
MIMi 607124. gene.
neXtProti NX_O14494.
PharmGKBi PA33552.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0671.
GeneTreei ENSGT00620000087654.
HOGENOMi HOG000041307.
HOVERGENi HBG002048.
InParanoidi O14494.
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

Bgeei O14494.
CleanExi HS_PPAP2A.
ExpressionAtlasi O14494. baseline and differential.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 127 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