O14495 (LPP3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Lipid phosphate phosphohydrolase 3
EC=3.1.3.4

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

Gene names

Name:	PPAP2B
Synonyms:	LPP3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	311 AA.
Sequence status	Complete.
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 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. This complex seems not to be involved in substrate recognition, it may confer only structural or functional stability. Ref.9
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 EGF, VEGF, FGF2 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 Transmembrane helix
Molecular function	Hydrolase
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	blood vessel development Inferred from electronic annotation. Source: Compara canonical Wnt receptor signaling pathway involved in positive regulation of cell-cell adhesion Inferred from mutant phenotype PubMed 20123964. Source: BHF-UCL canonical Wnt receptor signaling pathway involved in positive regulation of endothelial cell migration Inferred from mutant phenotype PubMed 20123964. Source: BHF-UCL canonical Wnt receptor signaling pathway involved in positive regulation of wound healing Inferred from mutant phenotype PubMed 20123964. Source: BHF-UCL gastrulation with mouth forming second Inferred from electronic annotation. Source: Compara germ cell migration Traceable author statement Ref.1. Source: ProtInc homotypic cell-cell adhesion Inferred from direct assay PubMed 20123964. Source: BHF-UCL negative regulation of protein phosphorylation Inferred from direct assay PubMed 20123964. Source: BHF-UCL phospholipid metabolic process Inferred from electronic annotation. Source: Compara positive regulation of peptidyl-tyrosine phosphorylation Inferred from electronic annotation. Source: Compara positive regulation of sequence-specific DNA binding transcription factor activity Inferred from direct assay PubMed 20123964. Source: BHF-UCL protein stabilization Inferred from direct assay PubMed 20123964. Source: BHF-UCL regulation of Wnt receptor signaling pathway Inferred from electronic annotation. Source: Compara small molecule metabolic process Traceable author statement. Source: Reactome sphingolipid biosynthetic process Traceable author statement. Source: Reactome
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-SubCell adherens junction Traceable author statement PubMed 20123964. Source: BHF-UCL integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Molecular_function	lipid phosphatase activity Inferred from electronic annotation. Source: Compara phosphatidate phosphatase activity Inferred from electronic annotation. Source: EC phosphoprotein phosphatase activity Traceable author statement Ref.2. 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	Helical; Potential
	Topological domain	55 – 85	31	Lumenal Potential
	Transmembrane	86 – 106	21	Helical; Potential
	Topological domain	107 – 122	16	Cytoplasmic Potential
	Transmembrane	123 – 143	21	Helical; Potential
	Topological domain	144 – 193	50	Lumenal Potential
	Transmembrane	194 – 214	21	Helical; Potential
	Topological domain	215 – 227	13	Cytoplasmic Potential
	Transmembrane	228 – 248	21	Helical; Potential
	Topological domain	249 – 257	9	Lumenal Potential
	Transmembrane	258 – 278	21	Helical; Potential
	Topological domain	279 – 311	33	Cytoplasmic Potential
Amino acid modifications
	Modified residue	19	1	Phosphoserine Ref.10 Ref.12
	Modified residue	297	1	Phosphoserine Ref.10
	Glycosylation	170	1	N-linked (GlcNAc...) Potential
Experimental info
	Sequence conflict	282	1	T → M in AAH09196. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	O14495 [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[6]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[7]	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. , 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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]. Tissue: Placenta.
[9]	"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] [Europe PMC] [Abstract] Cited for: SUBUNIT.
[10]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19 AND SER-297, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[12]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19, MASS SPECTROMETRY.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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. AK312439 mRNA. Translation: BAG35348.1. CH471059 Genomic DNA. Translation: EAX06651.1. CH471059 Genomic DNA. Translation: EAX06652.1. CH471059 Genomic DNA. Translation: EAX06653.1. BC009196 mRNA. Translation: AAH09196.1.
IPI	IPI00021453.
RefSeq	NP_003704.3. NM_003713.4.
UniGene	Hs.405156. Hs.619002.
3D structure databases
ProteinModelPortal	O14495.
SMR	O14495. Positions 141-270.
ModBase	Search...
Protein-protein interaction databases
IntAct	O14495. 1 interaction.
MINT	MINT-4648964.
STRING	9606.ENSP00000294390.
PTM databases
PhosphoSite	O14495.
Proteomic databases
PaxDb	O14495.
PRIDE	O14495.
Protocols and materials databases
DNASU	8613.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000371250; ENSP00000360296; ENSG00000162407.
GeneID	8613.
KEGG	hsa:8613.
UCSC	uc001cyj.2. human.
Organism-specific databases
CTD	8613.
GeneCards	GC01M056879.
HGNC	HGNC:9229. PPAP2B.
HPA	HPA028892.
MIM	607125. gene.
neXtProt	NX_O14495.
PharmGKB	PA33553.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0671.
HOGENOM	HOG000041307.
HOVERGEN	HBG002048.
InParanoid	O14495.
KO	K01080.
OMA	CSEGYIQ.
OrthoDB	EOG40CHHS.
PhylomeDB	O14495.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
SignaLink	O14495.
Gene expression databases
Bgee	O14495.
CleanEx	HS_PPAP2B.
Genevestigator	O14495.
GermOnline	ENSG00000162407. Homo sapiens.
Family and domain databases
Gene3D	1.20.144.10. 1 hit.
InterPro	IPR016118. P_Acid_Pase/Cl_peroxidase_N. IPR000326. P_Acid_Pase_2/haloperoxidase. [Graphical view]
Pfam	PF01569. PAP2. 1 hit. [Graphical view]
SMART	SM00014. acidPPc. 1 hit. [Graphical view]
SUPFAM	SSF48317. AcPase_VanPerase. 1 hit.
ProtoNet	Search...
Other
ChiTaRS	PPAP2B. human.
GenomeRNAi	8613.
NextBio	32277.
SOURCE	Search...

Entry information

Entry name

LPP3_HUMAN

Accession

Primary (citable) accession number: O14495
Secondary accession number(s): B2R651 , D3DQ52, Q96GW0, Q99782

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2004
Last sequence update:	January 1, 1998
Last modified:	May 29, 2013
This is version 113 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.