Reviewed, UniProtKB/Swiss-Prot O14495 (LPP3_HUMAN)

Names and origin

Protein names

Recommended name:
    Lipid phosphate phosphohydrolase 3
    EC=3.1.3.4
Alternative name(s):
    Phosphatidic acid phosphatase 2b
    PAP2-beta
      Short name=PAP-2b
      Short name=PAP2b
    Phosphatidate phosphohydrolase type 2b
    Vascular endothelial growth factor and type I collagen-inducible protein
      Short name=VCIP

Gene names

Name:	PPAP2B
Synonyms:	LPP3

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	311 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Catalyzes the conversion of phosphatidic acid (PA) to diacylglycerol (DG). In addition it hydrolyzes lysophosphatidic acid (LPA), ceramide-1-phosphate (C-1-P) and sphingosine-1-phosphate (S-1-P). The relative catalytic efficiency is LPA = PA > C-1-P > S-1-P. May be involved in cell adhesion and in cell-cell interactions.
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. This complex seems not to be involved in substrate recognition, it may confer only structural or functional stability. Ref.7
Subcellular location	Golgi apparatus › trans-Golgi network membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein.
Tissue specificity	Ubiquitously expressed. Highly expressed in heart and placenta.
Induction	By epidermal growth factor (EGF), vascular endothelial growrh factor (VEGF), basic fibroblast growth factor (bFGF) and phorbol myristate acetate (PMA). Ref.1
Post-translational modification	N-glycosylated. Contains high-mannose oligosaccharides.
Sequence similarities	Belongs to the PA-phosphatase related phosphoesterase family.
Sequence caution	The sequence AAB50222.1 differs from that shown. Reason: Frameshift at position 225.

Ontologies

Keywords
Cellular component	Cell membrane Golgi apparatus Membrane
Domain	Transmembrane
Molecular function	Hydrolase
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	germ cell migration Ref.1 Traceable author statement. Source: ProtInc
Cellular component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Ref.2 Inferred from Experiment. Source: Reactome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	phosphatidate phosphatase activity Ref.2 Inferred from Experiment. Source: Reactome phosphoprotein phosphatase activity Ref.2 Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 311	311	Lipid phosphate phosphohydrolase 3		PRO_0000220912
Regions
	Topological domain	1 – 33	33	Cytoplasmic Potential
	Transmembrane	34 – 54	21	Potential
	Topological domain	55 – 85	31	Lumenal Potential
	Transmembrane	86 – 106	21	Potential
	Topological domain	107 – 122	16	Cytoplasmic Potential
	Transmembrane	123 – 143	21	Potential
	Topological domain	144 – 193	50	Lumenal Potential
	Transmembrane	194 – 214	21	Potential
	Topological domain	215 – 227	13	Cytoplasmic Potential
	Transmembrane	228 – 248	21	Potential
	Topological domain	249 – 257	9	Lumenal Potential
	Transmembrane	258 – 278	21	Potential
	Topological domain	279 – 311	33	Cytoplasmic Potential
Amino acid modifications
	Modified residue	19	1	Phosphoserine Ref.9 Ref.10
	Modified residue	110	1	Phosphotyrosine Ref.8
	Modified residue	297	1	Phosphoserine Ref.9 Ref.10
	Glycosylation	170	1	N-linked (GlcNAc...) Potential
Experimental info
	Sequence conflict	282	1	T → M in AAH09196. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	O14495-1 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: CB3F60189044DA31	FASTA	311	35,116
	10 20 30 40 50 60 MQNYKYDKAI VPESKNGGSP ALNNNPRRSG SKRVLLICLD LFCLFMAGLP FLIIETSTIK 70 80 90 100 110 120 PYHRGFYCND ESIKYPLKTG ETINDAVLCA VGIVIAILAI ITGEFYRIYY LKKSRSTIQN 130 140 150 160 170 180 PYVAALYKQV GCFLFGCAIS QSFTDIAKVS IGRLRPHFLS VCNPDFSQIN CSEGYIQNYR 190 200 210 220 230 240 CRGDDSKVQE ARKSFFSGHA SFSMYTMLYL VLYLQARFTW RGARLLRPLL QFTLIMMAFY 250 260 270 280 290 300 TGLSRVSDHK HHPSDVLAGF AQGALVACCI VFFVSDLFKT KTTLSLPAPA IRKEILSPVD 310 IIDRNNHHNM M

References

	« Hide 'large scale' referencesShow '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], CHARACTERIZATION, INDUCTION.
[2]	"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], CHARACTERIZATION.
[3]	"Regulation of cell-cell interactions by phosphatidic acid phosphatase 2b/VCIP." Humtsoe J.O., Feng S., Thakker G.D., Yang J., Hong J., Wary K.K. EMBO J. 22:1539-1554(2003) [PubMed: 12660161] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Molecular cloning of and expression of an isoform of human phosphatidic acid phosphatase cDNA." Leung D.W., Tompkins C.K. Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"Large-scale concatenation cDNA sequencing." Yu W., Andersson B., Worley K.C., Muzny D.M., Ding Y., Liu W., Ricafrente J.Y., Wentland M.A., Lennon G., Gibbs R.A. Genome Res. 7:353-358(1997) [PubMed: 9110174] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[6]	"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]. Tissue: Placenta.
[7]	"Lipid phosphate phosphatases dimerise, but this interaction is not required for in vivo activity." Burnett C., Makridou P., Hewlett L., Howard K. BMC Biochem. 5:2-2(2004) [PubMed: 14725715] [Abstract] Cited for: SUBUNIT.
[8]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-110, MASS SPECTROMETRY. Tissue: Epithelium.
[9]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19 AND SER-297, MASS SPECTROMETRY.
[10]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19 AND SER-297, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB000889 mRNA. Translation: BAA22594.1. AF017786 mRNA. Translation: AAC63433.1. AF480883 mRNA. Translation: AAO84481.1. AF043329 mRNA. Translation: AAD02271.1. U79294 mRNA. Translation: AAB50222.1. Frameshift. BC009196 mRNA. Translation: AAH09196.1.
IPI	IPI00021453.
RefSeq	NP_003704.3. NP_803133.1.
UniGene	Hs.405156 Hs.708050
3D structure databases
ModBase	Search...
PTM databases
PhosphoSite	O14495.
Proteomic databases
PRIDE	O14495.
Genome annotation databases
Ensembl	ENSG00000162407. Homo sapiens. [Contig view]
GeneID	8613.
KEGG	hsa:8613.
UCSC	uc001cyj.1. human.
Organism-specific databases
GeneCards	GC01M056671.
H-InvDB	HIX0000628.
HGNC	HGNC:9229. PPAP2B.
MIM	607125. gene.
PharmGKB	PA33553.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O14495.
HOVERGEN	O14495.
OMA	O14495. YIQNYRC.
Enzyme and pathway databases
BRENDA	3.1.3.4. 247.
Reactome	REACT_602. Metabolism of lipids and lipoproteins.
Gene expression databases
ArrayExpress	O14495.
Bgee	O14495.
CleanEx	HS_PPAP2B.
GermOnline	ENSG00000162407. Homo sapiens.
Family and domain databases
InterPro	IPR016118. P_Acid_Pase/Cl_peroxidase_N. IPR000326. P_Acid_Pase_2/haloperoxidase. [Graphical view]
Gene3D	G3DSA:1.20.144.10. P_Acid_Pase/Cl_peroxidase_N. 1 hit.
Pfam	PF01569. PAP2. 1 hit. [Graphical view]
SMART	SM00014. acidPPc. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	32277.
SOURCE	Search...

Entry information

Entry name

LPP3_HUMAN

Accession

Primary (citable) accession number: O14495
Secondary accession number(s): Q96GW0, Q99782

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2004
Last sequence update:	January 1, 1998
Last modified:	July 7, 2009
This is version 74 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)