O14494 (LPP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	284 AA.
Sequence status	Complete.
Protein existence	Evidence 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 component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	Transmembrane Transmembrane helix
Molecular function	Hydrolase
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	androgen receptor signaling pathway Non-traceable author statement Ref.3. Source: UniProtKB germ cell migration Traceable author statement Ref.1. Source: ProtInc negative regulation of cell proliferation Non-traceable author statement Ref.3. Source: UniProtKB phospholipid dephosphorylation Traceable author statement Ref.3. Source: UniProtKB phospholipid metabolic process Traceable author statement. Source: Reactome 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
Cellular_component	integral to plasma membrane Non-traceable author statement Ref.4. Source: UniProtKB
Molecular_function	phosphatidate 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 284	284	Lipid phosphate phosphohydrolase 1		PRO_0000220905
Regions
	Topological domain	1 – 6	6	Cytoplasmic Potential
	Transmembrane	7 – 27	21	Helical; Potential
	Topological domain	28 – 53	26	Extracellular Potential
	Transmembrane	54 – 74	21	Helical; Potential
	Topological domain	75 – 94	20	Cytoplasmic Potential
	Transmembrane	95 – 115	21	Helical; Potential
	Topological domain	116 – 164	49	Extracellular Potential
	Transmembrane	165 – 185	21	Helical; Potential
	Topological domain	186 – 199	14	Cytoplasmic Potential
	Transmembrane	200 – 220	21	Helical; Potential
	Topological domain	221 – 229	9	Extracellular Potential
	Transmembrane	230 – 250	21	Helical; Potential
	Topological domain	251 – 284	34	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	142	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	21 – 70	50	GLPFA…FSIIV → SMPMAVLKLGQIYPFQRGFF CKDNSINYPYHDSTVTSTVL ILVGVGLPISS in isoform 2.		VSP_009651
Experimental info
	Sequence conflict	27	1	L → FTSRHI in AAC32041. Ref.4
	Sequence conflict	91	1	R → S in AAC16033. Ref.2
Isoform 2:
	Sequence conflict	55	1	V → A in AAC16033. Ref.2
	Sequence conflict	56	1	T → A in AAC16033. Ref.2
	Sequence conflict	69	1	I → V in AAC16033. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Alpha-1) (hLPP1) (PAP2-a1) [UniParc]. Last modified January 1, 1998. Version 1. Checksum: FC2F00617EE07EB3	FASTA	284	32,156
	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
	Isoform 2 (Alpha-2) (hLPP1-a) (PAP2-a2) [UniParc]. Checksum: 7209608A420380CE	FASTA	285	32,150
	10 20 30 40 50 60 MFDKTRLPYV ALDVLCVLLA SMPMAVLKLG QIYPFQRGFF CKDNSINYPY HDSTVTSTVL 70 80 90 100 110 120 ILVGVGLPIS SIILGETLSV YCNLLHSNSF IRNNYIATIY KAIGTFLFGA AASQSLTDIA 130 140 150 160 170 180 KYSIGRLRPH FLDVCDPDWS KINCSDGYIE YYICRGNAER VKEGRLSFYS GHSSFSMYCM 190 200 210 220 230 240 LFVALYLQAR MKGDWARLLR PTLQFGLVAV SIYVGLSRVS DYKHHWSDVL TGLIQGALVA 250 260 270 280 ILVAVYVSDF FKERTSFKER KEEDSHTTLH ETPTTGNHYP SNHQP

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] (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. , 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. , 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.
IPI	IPI00297037. IPI00409585.
RefSeq	NP_003702.2. NM_003711.2. NP_795714.1. NM_176895.1.
UniGene	Hs.696231.
3D structure databases
ProteinModelPortal	O14494.
SMR	O14494. Positions 114-241.
ModBase	Search...
Protein-protein interaction databases
IntAct	O14494. 2 interactions.
STRING	9606.ENSP00000264775.
PTM databases
PhosphoSite	O14494.
Proteomic databases
PaxDb	O14494.
PRIDE	O14494.
Protocols and materials databases
DNASU	8611.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000264775; ENSP00000264775; ENSG00000067113. ENST00000307259; ENSP00000302229; ENSG00000067113.
GeneID	8611.
KEGG	hsa:8611.
UCSC	uc003jpz.3. human. uc003jqa.3. human.
Organism-specific databases
CTD	8611.
GeneCards	GC05M054756.
HGNC	HGNC:9228. PPAP2A.
HPA	CAB033331.
MIM	607124. gene.
neXtProt	NX_O14494.
PharmGKB	PA33552.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0671.
HOGENOM	HOG000041307.
HOVERGEN	HBG002048.
KO	K01080.
OMA	CNDNSIK.
OrthoDB	EOG4RR6J5.
Enzyme and pathway databases
Pathway_Interaction_DB	fcer1pathway. Fc-epsilon receptor I signaling in mast cells.
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	O14494.
Bgee	O14494.
CleanEx	HS_PPAP2A.
Genevestigator	O14494.
GermOnline	ENSG00000067113. 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
GenomeRNAi	8611.
NextBio	32263.
SOURCE	Search...

Entry information

Entry name

LPP1_HUMAN

Accession

Primary (citable) accession number: O14494
Secondary accession number(s): B7ZKN8 , G3XA95, O60457, O60463, Q17RZ4

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2004
Last sequence update:	January 1, 1998
Last modified:	April 3, 2013
This is version 112 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.