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Protein

Phospholipid phosphatase 1

Gene

PLPP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Caution

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

Catalytic activityi

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

Activity regulationi

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

GO - Molecular functioni

  • lipid phosphatase activity Source: UniProtKB
  • phosphatase activity Source: GO_Central
  • phosphatidate phosphatase activity Source: UniProtKB
  • sphingosine-1-phosphate phosphatase activity Source: Reactome

GO - Biological processi

Keywordsi

Molecular functionHydrolase

Enzyme and pathway databases

ReactomeiR-HSA-1660661 Sphingolipid de novo biosynthesis

Chemistry databases

SwissLipidsiSLP:000000160

Names & Taxonomyi

Protein namesi
Recommended name:
Phospholipid phosphatase 1Imported (EC:3.1.3.4)
Alternative name(s):
Lipid phosphate phosphohydrolase 1
PAP2-alpha
Phosphatidate phosphohydrolase type 2a
Phosphatidic acid phosphatase 2a
Short name:
PAP-2a
Short name:
PAP2a
Gene namesi
Name:PLPP1Imported
Synonyms:LPP1, PPAP2A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000067113.16
HGNCiHGNC:9228 PLPP1
MIMi607124 gene
neXtProtiNX_O14494

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 6CytoplasmicSequence analysis6
Transmembranei7 – 27HelicalSequence analysisAdd BLAST21
Topological domaini28 – 53ExtracellularSequence analysisAdd BLAST26
Transmembranei54 – 74HelicalSequence analysisAdd BLAST21
Topological domaini75 – 94CytoplasmicSequence analysisAdd BLAST20
Transmembranei95 – 115HelicalSequence analysisAdd BLAST21
Topological domaini116 – 164ExtracellularSequence analysisAdd BLAST49
Transmembranei165 – 185HelicalSequence analysisAdd BLAST21
Topological domaini186 – 199CytoplasmicSequence analysisAdd BLAST14
Transmembranei200 – 220HelicalSequence analysisAdd BLAST21
Topological domaini221 – 229ExtracellularSequence analysis9
Transmembranei230 – 250HelicalSequence analysisAdd BLAST21
Topological domaini251 – 284CytoplasmicSequence analysisAdd BLAST34

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi8611
OpenTargetsiENSG00000067113
PharmGKBiPA33552

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002209051 – 284Phospholipid phosphatase 1Add BLAST284

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi142N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

N-glycosylated. Contains high-mannose oligosaccharides.

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiO14494
MaxQBiO14494
PeptideAtlasiO14494
PRIDEiO14494
ProteomicsDBi48037
48038 [O14494-2]

PTM databases

DEPODiO14494
iPTMnetiO14494
PhosphoSitePlusiO14494

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

BgeeiENSG00000067113 Expressed in 232 organ(s), highest expression level in prostate gland
CleanExiHS_PPAP2A
ExpressionAtlasiO14494 baseline and differential
GenevisibleiO14494 HS

Organism-specific databases

HPAiCAB033331
HPA047815

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

BioGridi114169, 9 interactors
IntActiO14494, 5 interactors
MINTiO14494

Structurei

3D structure databases

ProteinModelPortaliO14494
SMRiO14494
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

GeneTreeiENSGT00620000087654
HOGENOMiHOG000041307
HOVERGENiHBG002048
InParanoidiO14494
KOiK01080
OMAiNLGQIYP
PhylomeDBiO14494
TreeFamiTF316040

Family and domain databases

InterProiView protein in InterPro
IPR028670 LPP1
IPR036938 P_Acid_Pase_2/haloperoxi_sf
IPR000326 P_Acid_Pase_2/haloperoxidase
PANTHERiPTHR10165:SF26 PTHR10165:SF26, 1 hit
PfamiView protein in Pfam
PF01569 PAP2, 1 hit
SMARTiView protein in SMART
SM00014 acidPPc, 1 hit
SUPFAMiSSF48317 SSF48317, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Note: Additional isoforms seem to exist.

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D6REC3D6REC3_HUMAN
Phospholipid phosphatase 1
PLPP1
110Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti27L → FTSRHI in AAC32041 (PubMed:9705349).Curated1
Sequence conflicti91R → S in AAC16033 (PubMed:9570154).Curated1
Isoform 2 (identifier: O14494-2)
Sequence conflicti55V → A in AAC16033 (PubMed:9570154).Curated1
Sequence conflicti56T → A in AAC16033 (PubMed:9570154).Curated1
Sequence conflicti69I → V in AAC16033 (PubMed:9570154).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00965121 – 70GLPFA…FSIIV → SMPMAVLKLGQIYPFQRGFF CKDNSINYPYHDSTVTSTVL ILVGVGLPISS in isoform 2. 1 PublicationAdd BLAST50

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.5 human [O14494-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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

3D structure databases

ProteinModelPortaliO14494
SMRiO14494
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114169, 9 interactors
IntActiO14494, 5 interactors
MINTiO14494

Chemistry databases

SwissLipidsiSLP:000000160

PTM databases

DEPODiO14494
iPTMnetiO14494
PhosphoSitePlusiO14494

Proteomic databases

EPDiO14494
MaxQBiO14494
PeptideAtlasiO14494
PRIDEiO14494
ProteomicsDBi48037
48038 [O14494-2]

Protocols and materials databases

DNASUi8611
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264775; ENSP00000264775; ENSG00000067113 [O14494-2]
ENST00000307259; ENSP00000302229; ENSG00000067113 [O14494-1]
GeneIDi8611
KEGGihsa:8611
UCSCiuc003jpz.5 human [O14494-1]

Organism-specific databases

CTDi8611
DisGeNETi8611
EuPathDBiHostDB:ENSG00000067113.16
GeneCardsiPLPP1
HGNCiHGNC:9228 PLPP1
HPAiCAB033331
HPA047815
MIMi607124 gene
neXtProtiNX_O14494
OpenTargetsiENSG00000067113
PharmGKBiPA33552
GenAtlasiSearch...

Phylogenomic databases

GeneTreeiENSGT00620000087654
HOGENOMiHOG000041307
HOVERGENiHBG002048
InParanoidiO14494
KOiK01080
OMAiNLGQIYP
PhylomeDBiO14494
TreeFamiTF316040

Enzyme and pathway databases

ReactomeiR-HSA-1660661 Sphingolipid de novo biosynthesis

Miscellaneous databases

ChiTaRSiPLPP1 human
GeneWikiiPPAP2A
GenomeRNAii8611
PROiPR:O14494
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000067113 Expressed in 232 organ(s), highest expression level in prostate gland
CleanExiHS_PPAP2A
ExpressionAtlasiO14494 baseline and differential
GenevisibleiO14494 HS

Family and domain databases

InterProiView protein in InterPro
IPR028670 LPP1
IPR036938 P_Acid_Pase_2/haloperoxi_sf
IPR000326 P_Acid_Pase_2/haloperoxidase
PANTHERiPTHR10165:SF26 PTHR10165:SF26, 1 hit
PfamiView protein in Pfam
PF01569 PAP2, 1 hit
SMARTiView protein in SMART
SM00014 acidPPc, 1 hit
SUPFAMiSSF48317 SSF48317, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPLPP1_HUMAN
AccessioniPrimary (citable) accession number: O14494
Secondary accession number(s): B7ZKN8
, G3XA95, O60457, O60463, Q17RZ4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 15, 2004
Last sequence update: January 1, 1998
Last modified: November 7, 2018
This is version 160 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
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