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O14494 (LPP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | 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:
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 names
Name:PPAP2A
Synonyms:LPP1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length284 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.8

Catalytic activity

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

Enzyme regulation

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

Subunit structure

Homodimer By similarity.

Subcellular location

Cell membrane; Multi-pass membrane protein.

Tissue specificity

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.

Induction

By androgens.

Post-translational modification

N-glycosylated. Contains high-mannose oligosaccharides.

Sequence similarities

Belongs to the PA-phosphatase related phosphoesterase family.

Caution

Ref.1 states that this phosphatase does not hydrolyze sphingosine 1-phosphate while Ref.4 states that it does.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
   DomainTransmembrane
Transmembrane helix
   Molecular functionHydrolase
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processandrogen receptor signaling pathway

Non-traceable author statement Ref.3. Source: UniProtKB

germ cell migration

Traceable author statement Ref.1. Source: ProtInc

intracellular steroid hormone receptor signaling pathway

Traceable author statement Ref.3. Source: UniProtKB

lipid metabolic process

Non-traceable author statement Ref.4. Source: ProtInc

negative regulation of cell proliferation

Non-traceable author statement Ref.3. Source: UniProtKB

phospholipid dephosphorylation

Traceable author statement Ref.3. Source: UniProtKB

protein dephosphorylation

Inferred from electronic annotation. Source: Ensembl

protein kinase C-activating G-protein coupled receptor signaling pathway

Traceable author statement Ref.3. Source: UniProtKB

regulation of lipid metabolic process

Non-traceable author statement Ref.3. 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

   Cellular_componentextracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

integral component of plasma membrane

Non-traceable author statement Ref.4. Source: UniProtKB

membrane

Inferred from direct assay Ref.3. Source: UniProtKB

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionphosphatidate phosphatase activity

Inferred from direct assay Ref.3. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: O14494-1)

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.
Isoform 2 (identifier: O14494-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 284284Lipid phosphate phosphohydrolase 1
PRO_0000220905

Regions

Topological domain1 – 66Cytoplasmic Potential
Transmembrane7 – 2721Helical; Potential
Topological domain28 – 5326Extracellular Potential
Transmembrane54 – 7421Helical; Potential
Topological domain75 – 9420Cytoplasmic Potential
Transmembrane95 – 11521Helical; Potential
Topological domain116 – 16449Extracellular Potential
Transmembrane165 – 18521Helical; Potential
Topological domain186 – 19914Cytoplasmic Potential
Transmembrane200 – 22021Helical; Potential
Topological domain221 – 2299Extracellular Potential
Transmembrane230 – 25021Helical; Potential
Topological domain251 – 28434Cytoplasmic Potential

Amino acid modifications

Glycosylation1421N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence21 – 7050GLPFA…FSIIV → SMPMAVLKLGQIYPFQRGFF CKDNSINYPYHDSTVTSTVL ILVGVGLPISS in isoform 2.
VSP_009651

Experimental info

Sequence conflict271L → FTSRHI in AAC32041. Ref.4
Sequence conflict911R → S in AAC16033. Ref.2
Isoform 2:
Sequence conflict551V → A in AAC16033. Ref.2
Sequence conflict561T → A in AAC16033. Ref.2
Sequence conflict691I → V in AAC16033. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Alpha-1) (hLPP1) (PAP2-a1) [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: FC2F00617EE07EB3

FASTA28432,156
        10         20         30         40         50         60 
MFDKTRLPYV ALDVLCVLLA GLPFAILTSR HTPFQRGVFC NDESIKYPYK EDTIPYALLG 

        70         80         90        100        110        120 
GIIIPFSIIV IILGETLSVY CNLLHSNSFI RNNYIATIYK AIGTFLFGAA ASQSLTDIAK 

       130        140        150        160        170        180 
YSIGRLRPHF LDVCDPDWSK INCSDGYIEY YICRGNAERV KEGRLSFYSG HSSFSMYCML 

       190        200        210        220        230        240 
FVALYLQARM KGDWARLLRP TLQFGLVAVS IYVGLSRVSD YKHHWSDVLT GLIQGALVAI 

       250        260        270        280 
LVAVYVSDFF KERTSFKERK EEDSHTTLHE TPTTGNHYPS NHQP 

« Hide

Isoform 2 (Alpha-2) (hLPP1-a) (PAP2-a2) [UniParc].

Checksum: 7209608A420380CE
Show »

FASTA28532,150

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_003702.2. NM_003711.3.
NP_795714.1. NM_176895.2.
UniGeneHs.696231.

3D structure databases

ProteinModelPortalO14494.
SMRO14494. Positions 114-240.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114169. 4 interactions.
IntActO14494. 3 interactions.
STRING9606.ENSP00000264775.

PTM databases

PhosphoSiteO14494.

Proteomic databases

PaxDbO14494.
PRIDEO14494.

Protocols and materials databases

DNASU8611.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264775; ENSP00000264775; ENSG00000067113. [O14494-2]
ENST00000307259; ENSP00000302229; ENSG00000067113. [O14494-1]
GeneID8611.
KEGGhsa:8611.
UCSCuc003jpz.4. human.
uc003jqa.4. human. [O14494-1]

Organism-specific databases

CTD8611.
GeneCardsGC05M054756.
HGNCHGNC:9228. PPAP2A.
HPACAB033331.
HPA047815.
MIM607124. gene.
neXtProtNX_O14494.
PharmGKBPA33552.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0671.
HOGENOMHOG000041307.
HOVERGENHBG002048.
KOK01080.
OMASKINCSA.
OrthoDBEOG7C5M9Q.
PhylomeDBO14494.
TreeFamTF316040.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressO14494.
BgeeO14494.
CleanExHS_PPAP2A.
GenevestigatorO14494.

Family and domain databases

Gene3D1.20.144.10. 1 hit.
InterProIPR028670. LPP1.
IPR000326. P_Acid_Pase_2/haloperoxidase.
[Graphical view]
PANTHERPTHR10165:SF26. PTHR10165:SF26. 1 hit.
PfamPF01569. PAP2. 1 hit.
[Graphical view]
SMARTSM00014. acidPPc. 1 hit.
[Graphical view]
SUPFAMSSF48317. SSF48317. 1 hit.
ProtoNetSearch...

Other

GeneWikiPPAP2A.
GenomeRNAi8611.
NextBio32263.
PROO14494.
SOURCESearch...

Entry information

Entry nameLPP1_HUMAN
AccessionPrimary (citable) accession number: O14494
Secondary accession number(s): B7ZKN8 expand/collapse secondary AC list , G3XA95, O60457, O60463, Q17RZ4
Entry history
Integrated into UniProtKB/Swiss-Prot: March 15, 2004
Last sequence update: January 1, 1998
Last modified: April 16, 2014
This is version 121 of the entry and version 1 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 chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM