Reviewed, UniProtKB/Swiss-Prot Q61469 (LPP1_MOUSE)

Names and origin

Protein names

Recommended 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
    Hydrogen peroxide-inducible protein 53
      Short name=Hic53
    35 kDa PAP
      Short name=mPAP

Gene names

Name:	Ppap2a
Synonyms:	Hpic53, Lpp1

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	283 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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). In addition it hydrolyzes lysophosphatidic acid (LPA), diacyl glycerol pyrophosphate (DGPP), 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.
Catalytic activity	A 3-sn-phosphatidate + H2O = a 1,2-diacyl-sn-glycerol + phosphate.
Subunit structure	Homodimer. This complex seems not to be involved in substrate recognition, it may confer only structural or functional stability. Ref.6
Subcellular location	Cell membrane; Multi-pass membrane protein. Note: Found predominantly in plasma membrane.
Tissue specificity	Highly expressed in kidney and lung. Almost undetectable in brain, heart, bone, muscle or spleen.
Induction	Moderately, by hydrogen peroxide, calcium ionophore and dexamethasone. Ref.1
Post-translational modification	N-glycosylated. Contains high-mannose oligosaccharide.
Miscellaneous	Overexpression elicited a number of phenotypic alteration without affecting several aspects of LPA signaling. Phenotypic abnormalities affect primarily three organs: the liver, the skin, and the reproductive organs. There is a reduction on body size, birth weight, abnormalities in fur growth, and a severely impaired spermatogenesis.
Sequence similarities	Belongs to the PA-phosphatase related phosphoesterase family.
Sequence caution	The sequence AAA85353.1 differs from that shown. Reason: Frameshift at several positions.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	Transmembrane
Molecular function	Hydrolase
PTM	Glycoprotein
Gene Ontology (GO)
Biological process	ceramide metabolic process Traceable author statement. Source: MGI diacylglycerol biosynthetic process Ref.2 Traceable author statement. Source: MGI protein amino acid dephosphorylation Ref.2 Inferred from direct assay. Source: MGI signal transduction Ref.2 Traceable author statement. Source: MGI sphingosine metabolic process Traceable author statement. Source: MGI
Cellular component	integral to plasma membrane Traceable author statement. Source: MGI membrane fraction Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	phosphatidate phosphatase activity Ref.2 Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q61469-1)

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: Q61469-2)

The sequence of this isoform differs from the canonical sequence as follows:
     21-70: GLPFAILTSR...GIVIPFCIIV → AMPMTILKLG...ILGLGLPIFS

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 283	283	Lipid phosphate phosphohydrolase 1		PRO_0000220906
Regions
	Topological domain	1 – 6	6	Cytoplasmic Potential
	Transmembrane	7 – 27	21	Potential
	Topological domain	28 – 53	26	Extracellular Potential
	Transmembrane	54 – 74	21	Potential
	Topological domain	75 – 88	14	Cytoplasmic Potential
	Transmembrane	89 – 109	21	Potential
	Topological domain	110 – 164	55	Extracellular Potential
	Transmembrane	165 – 185	21	Potential
	Topological domain	186 – 199	14	Cytoplasmic Potential
	Transmembrane	200 – 220	21	Potential
	Topological domain	221 – 229	9	Extracellular Potential
	Transmembrane	230 – 250	21	Potential
	Topological domain	251 – 283	33	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	142	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	21 – 70	50	GLPFA…FCIIV → AMPMTILKLGKVYPFQRGFF CTDNSVKYPYHDSTIPSRIL AILGLGLPIFS in isoform 2.		VSP_009652

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 669690568E549CC6	FASTA	283	31,892
	10 20 30 40 50 60 MFDKTRLPYV ALDVICVLLA GLPFAILTSR HTPFQRGIFC NDDSIKYPYK EDTIPYALLG 70 80 90 100 110 120 GIVIPFCIIV MSIGESLSVY FNVLHSNSFV GNPYIATIYK AVGAFLFGVS ASQSLTDIAK 130 140 150 160 170 180 YTIGSLRPHF LAICNPDWSK INCSDGYIED YICQGNEEKV KEGRLSFYSG HSSFSMYCML 190 200 210 220 230 240 FVALYLQARM KGDWARLLRP MLQFGLIAFS IYVGLSRVSD YKHHWSDVTV GLIQGAAMAI 250 260 270 280 LVALYVSDFF KDTHSYKERK EEDPHTTLHE TASSRNYSTN HEP
	Isoform 2. Checksum: 72588D6301E3DD29	FASTA	284	31,996
	10 20 30 40 50 60 MFDKTRLPYV ALDVICVLLA AMPMTILKLG KVYPFQRGFF CTDNSVKYPY HDSTIPSRIL 70 80 90 100 110 120 AILGLGLPIF SMSIGESLSV YFNVLHSNSF VGNPYIATIY KAVGAFLFGV SASQSLTDIA 130 140 150 160 170 180 KYTIGSLRPH FLAICNPDWS KINCSDGYIE DYICQGNEEK VKEGRLSFYS GHSSFSMYCM 190 200 210 220 230 240 LFVALYLQAR MKGDWARLLR PMLQFGLIAF SIYVGLSRVS DYKHHWSDVT VGLIQGAAMA 250 260 270 280 ILVALYVSDF FKDTHSYKER KEEDPHTTLH ETASSRNYST NHEP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation of a novel ras-recision gene that is induced by hydrogen peroxide from a mouse osteoblastic cell line, MC3T3-E1." Egawa K., Yoshiwara M., Shibanuma M., Nose K. FEBS Lett. 372:74-77(1995) [PubMed: 7556647] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INDUCTION. Tissue: Calvaria.
[2]	"Identification and cDNA cloning of 35-kDa phosphatidic acid phosphatase (type 2) bound to plasma membranes." Kai M., Wada I., Imai S., Sakane F., Kanoh H. J. Biol. Chem. 271:18931-18938(1996) [PubMed: 8702556] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Kidney.
[3]	Yokoyama K., Tigyi G. Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). Strain: FVB/N.
[4]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Strain: C57BL/6J. Tissue: Ovary and Uterus.
[5]	"Lipid phosphate phosphohydrolase-1 degrades exogenous glycerolipid and sphingolipid phosphate esters." Jasinska R., Zhang Q.-X., Pilquil C., Singh I., Xu J., Dewald J., Dillon D.A., Berthiaume L.G., Carman G.M., Waggoner D.W., Brindley D.N. Biochem. J. 340:677-686(1999) [PubMed: 10359651] [Abstract] Cited for: CHARACTERIZATION. Tissue: Liver.
[6]	"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.
[7]	"Mice with transgenic overexpression of lipid phosphate phosphatase-1 display multiple organotypic deficits without alteration in circulating lysophosphatidate level." Yue J., Yokoyama K., Balazs L., Baker D.L., Smalley D., Pilquil C., Brindley D.N., Tigyi G. Cell. Signal. 16:385-399(2004) [PubMed: 14687668] [Abstract] Cited for: OVEREXPRESSION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	L43371 mRNA. Translation: AAA85353.1. Sequence problems. D84376 mRNA. Translation: BAA12335.1. AY247795 mRNA. Translation: AAP04434.1. AY247796 mRNA. Translation: AAP04435.1. AK077275 mRNA. Translation: BAC36724.1.
IPI	IPI00223459. IPI00407419.
PIR	S66668.
RefSeq	NP_032929.1.
UniGene	Mm.317186
3D structure databases
ModBase	Search...
PTM databases
PhosphoSite	Q61469.
Genome annotation databases
Ensembl	ENSMUSG00000021759. Mus musculus. [Contig view]
GeneID	19012.
NMPDR	fig|10090.3.peg.28430.
Organism-specific databases
MGI	MGI:108412. Ppap2a.
Phylogenomic databases
HOVERGEN	Q61469.
OMA	Q61469. LLASMPM.
Enzyme and pathway databases
BRENDA	3.1.3.4. 244.
Gene expression databases
Bgee	Q61469.
CleanEx	MM_PPAP2A.
GermOnline	ENSMUSG00000021759. Mus musculus.
Family and domain databases
InterPro	IPR000326. P_Acid_Pase_2/haloperoxidase. [Graphical view]
Pfam	PF01569. PAP2. 1 hit. [Graphical view]
SMART	SM00014. acidPPc. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	295422.
SOURCE	Search...

Entry information

Entry name

LPP1_MOUSE

Accession

Primary (citable) accession number: Q61469
Secondary accession number(s): Q61690, Q8BPB8

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2004
Last sequence update:	November 1, 1996
Last modified:	June 16, 2009
This is version 68 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)