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Reviewed, UniProtKB/Swiss-Prot O14494 (LPP1_HUMAN)

Last modified June 16, 2009. Version 75. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Lipid phosphate phosphohydrolase 1
    EC=3.1.3.4
Alternative name(s):
    Phosphatidic acid phosphatase 2a
    PAP2-alpha
      Short name=PAP-2a
      Short name=PAP2a
    Phosphatidate phosphohydrolase type 2a
Gene names
Name: PPAP2A
Synonyms: LPP1
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length284 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

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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.6

Catalytic activity

A 3-sn-phosphatidate + 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.

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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...LVGVGLPVSS

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 284284Lipid phosphate phosphohydrolase 1
PRO_0000220905

Regions

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

Amino acid modifications

Glycosylation1421N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence21 – 7050GLPFA…FSIIV → SMPMAVLKLGQIYPFQRGFF CKDNSINYPYHDSTAASTVL ILVGVGLPVSS in isoform 2.
VSP_009651

Experimental info

Sequence conflict271L → FTSRHI Ref.4
Sequence conflict911R → S in AAC16033. Ref.2

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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).

Checksum: 00DA12C685625A09
Show »

FASTA28532,078

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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: 9305923] [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: 9570154] [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: 9468526] [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: 9705349] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION.
[5]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[6]"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: 12909631] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

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Cross-references

Sequence databases

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.
BC039847 mRNA. Translation: AAH39847.1.
BC117133 mRNA. Translation: AAI17134.1.
IPIIPI00297037.
IPI00409585.
RefSeqNP_003702.2.
NP_795714.1.
UniGeneHs.696231

3D structure databases

ModBaseSearch...

PTM databases

PhosphoSiteO14494.

Proteomic databases

PRIDEO14494.

Genome annotation databases

EnsemblENSG00000067113. Homo sapiens. [Contig view]
GeneID8611.
KEGGhsa:8611.
NMPDRfig|9606.3.peg.25252.

Organism-specific databases

GeneCardsGC05M054756.
H-InvDBHIX0024776.
HGNCHGNC:9228. PPAP2A.
MIM607124. gene.
PharmGKBPA33552.
GenAtlasSearch...

Phylogenomic databases

HOVERGENO14494.

Enzyme and pathway databases

BRENDA3.1.3.4. 247.
Pathway_Interaction_DBfcer1pathway. Fc-epsilon receptor I signaling in mast cells.
ReactomeREACT_602. Lipid and lipoprotein metabolism.

Gene expression databases

ArrayExpressO14494.
BgeeO14494.
CleanExHS_PPAP2A.
GermOnlineENSG00000067113. Homo sapiens.

Family and domain databases

InterProIPR000326. P_Acid_Pase_2/haloperoxidase.
[Graphical view]
PfamPF01569. PAP2. 1 hit.
[Graphical view]
SMARTSM00014. acidPPc. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio32263.
SOURCESearch...

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Entry information

Entry nameLPP1_HUMAN
AccessionPrimary (citable) accession number: O14494
Secondary accession number(s): O60457, O60463, Q17RZ4
Entry history
Integrated into UniProtKB/Swiss-Prot: March 15, 2004
Last sequence update: January 1, 1998
Last modified: June 16, 2009
This is version 75 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 5

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

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents