PHLA2_MOUSE
ID PHLA2_MOUSE Reviewed; 144 AA.
AC O08969;
DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Pleckstrin homology-like domain family A member 2;
DE AltName: Full=Imprinted in placenta and liver protein;
DE AltName: Full=Protein 50C15;
GN Name=Phlda2; Synonyms=Ipl, Tssc3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9328465; DOI=10.1093/hmg/6.12.2021;
RA Qian N., Frank D., O'Keefe D., Dao D., Zhao L., Yuan L., Wang Q.,
RA Keating M., Walsh C., Tycko B.;
RT "The IPL gene on chromosome 11p15.5 is imprinted in humans and mice and is
RT similar to TDAG51, implicated in Fas expression and apoptosis.";
RL Hum. Mol. Genet. 6:2021-2029(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6 X DBA;
RA Dunwoodie S.L., Beddington R.S.P.;
RL Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=10594239; DOI=10.1007/s003359901182;
RA Frank D., Mendelsohn C.L., Ciccone E., Svensson K., Ohlsson R., Tycko B.;
RT "A novel pleckstrin homology-related gene family defined by Ipl/Tssc3,
RT TDAG51, and Tih1: tissue-specific expression, chromosomal location, and
RT parental imprinting.";
RL Mamm. Genome 10:1150-1159(1999).
RN [6]
RP PHOSPHOINOSITIDE-BINDING, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ARG-27;
RP LYS-38 AND ARG-39.
RX PubMed=12374806; DOI=10.1074/jbc.m206497200;
RA Saxena A., Morozov P., Frank D., Musalo R., Lemmon M.A., Skolnik E.Y.,
RA Tycko B.;
RT "Phosphoinositide binding by the pleckstrin homology domains of Ipl and
RT Tih1.";
RL J. Biol. Chem. 277:49935-49944(2002).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=12032310; DOI=10.1073/pnas.122039999;
RA Frank D., Fortino W., Clark L., Musalo R., Wang W., Saxena A., Li C.M.,
RA Reik W., Ludwig T., Tycko B.;
RT "Placental overgrowth in mice lacking the imprinted gene Ipl.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:7490-7495(2002).
RN [8]
RP INDUCTION, AND IMPRINTING.
RX PubMed=15327781; DOI=10.1016/j.mod.2004.05.017;
RA Salas M., John R., Saxena A., Barton S., Frank D., Fitzpatrick G.,
RA Higgins M.J., Tycko B.;
RT "Placental growth retardation due to loss of imprinting of Phlda2.";
RL Mech. Dev. 121:1199-1210(2004).
CC -!- FUNCTION: Plays a role in regulating placenta growth. May act via its
CC PH domain that competes with other PH domain-containing proteins,
CC thereby preventing their binding to membrane lipids.
CC {ECO:0000269|PubMed:12032310}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12374806}. Membrane
CC {ECO:0000269|PubMed:12374806}; Peripheral membrane protein
CC {ECO:0000269|PubMed:12374806}.
CC -!- TISSUE SPECIFICITY: Specifically expressed at high levels in
CC extraembryonic tissues in the developing conceptus (at protein level).
CC Expressed in placenta and yolc sac. Expressed at low levels in fetal
CC liver and kidney. {ECO:0000269|PubMed:10594239}.
CC -!- DEVELOPMENTAL STAGE: Expressed at high levels in the very early
CC conceptus limited to polar trophectoderm. Strongly expressed in the
CC ectoplacental cone shortly after implantation at 5.5 dpc, and the high
CC expression remains restricted to the extraembryonic tissues at later
CC stages. By 10.5 dpc expression is restricted to the labyrinthine
CC trophoblast and the endodermal component of the visceral yolk sac.
CC Between 12.5 and 14.4 dpc expression in placenta decreases, due to a
CC number of expressing cells. On day 12 of gestation, the abundant
CC expressing cells are trophoblast at the chorionic plate, and clustered
CC type II trophoblast deeper in the labyrinth. Less expressed by
CC terminally differentiated trophoblast. As early as 14.5 dpc, becomes
CC confined to a monolayer of cells at the chorionic plate and to rare
CC cells in septa that protrude into the labyrinth (at protein level).
CC {ECO:0000269|PubMed:10594239, ECO:0000269|PubMed:12032310}.
CC -!- INDUCTION: Maternal Phlda2 allele is activated, while paternal Phlda2
CC is repressed due to genomic imprinting. {ECO:0000269|PubMed:15327781}.
CC -!- DOMAIN: The PH domain binds phosphoinositides with a broad specificity.
CC It may compete with the PH domain of some other proteins, thereby
CC interfering with their binding to phosphatidylinositol 4,5-bisphosphate
CC (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3) (By
CC similarity). {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable, and show overgrowth of placentas
CC with expansion of the spongiotrophoblast. These larger placentas do not
CC confer a fetal growth advantage. {ECO:0000269|PubMed:12032310}.
CC -!- MISCELLANEOUS: The Phlda2 locus is imprinted. Loss of imprinting
CC results in overexpression, leading to placental growth retardation
CC phenotypes.
CC -!- SIMILARITY: Belongs to the PHLDA2 family. {ECO:0000305}.
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DR EMBL; AF002708; AAB86681.1; -; Genomic_DNA.
DR EMBL; Y15443; CAA75634.1; -; mRNA.
DR EMBL; AK131929; BAE20878.1; -; mRNA.
DR EMBL; BC019141; AAH19141.1; -; mRNA.
DR CCDS; CCDS22042.1; -.
DR RefSeq; NP_033460.1; NM_009434.2.
DR RefSeq; XP_006508660.1; XM_006508597.2.
DR AlphaFoldDB; O08969; -.
DR SMR; O08969; -.
DR STRING; 10090.ENSMUSP00000010904; -.
DR PhosphoSitePlus; O08969; -.
DR PaxDb; O08969; -.
DR PeptideAtlas; O08969; -.
DR PRIDE; O08969; -.
DR ProteomicsDB; 287932; -.
DR Antibodypedia; 1202; 307 antibodies from 33 providers.
DR DNASU; 22113; -.
DR Ensembl; ENSMUST00000010904; ENSMUSP00000010904; ENSMUSG00000010760.
DR GeneID; 22113; -.
DR KEGG; mmu:22113; -.
DR UCSC; uc009kpj.1; mouse.
DR CTD; 7262; -.
DR MGI; MGI:1202307; Phlda2.
DR VEuPathDB; HostDB:ENSMUSG00000010760; -.
DR eggNOG; ENOG502RXZA; Eukaryota.
DR GeneTree; ENSGT00440000039564; -.
DR HOGENOM; CLU_062639_1_0_1; -.
DR InParanoid; O08969; -.
DR OMA; DNCWNAV; -.
DR OrthoDB; 1412115at2759; -.
DR PhylomeDB; O08969; -.
DR TreeFam; TF332320; -.
DR BioGRID-ORCS; 22113; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Phlda2; mouse.
DR PRO; PR:O08969; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; O08969; protein.
DR Bgee; ENSMUSG00000010760; Expressed in yolk sac and 95 other tissues.
DR ExpressionAtlas; O08969; baseline and differential.
DR Genevisible; O08969; MM.
DR GO; GO:0005737; C:cytoplasm; TAS:MGI.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:1901981; F:phosphatidylinositol phosphate binding; IEA:InterPro.
DR GO; GO:0009887; P:animal organ morphogenesis; IMP:MGI.
DR GO; GO:0001890; P:placenta development; IDA:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:InterPro.
DR GO; GO:0030334; P:regulation of cell migration; IDA:MGI.
DR GO; GO:0045995; P:regulation of embryonic development; IDA:MGI.
DR GO; GO:0010468; P:regulation of gene expression; IDA:MGI.
DR GO; GO:0070873; P:regulation of glycogen metabolic process; IDA:MGI.
DR GO; GO:1903547; P:regulation of growth hormone activity; IMP:MGI.
DR GO; GO:0060721; P:regulation of spongiotrophoblast cell proliferation; IMP:MGI.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR042832; PHLA1/2/3.
DR PANTHER; PTHR15478; PTHR15478; 1.
DR SMART; SM00233; PH; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Membrane; Phosphoprotein; Reference proteome.
FT CHAIN 1..144
FT /note="Pleckstrin homology-like domain family A member 2"
FT /id="PRO_0000053901"
FT DOMAIN 18..111
FT /note="PH"
FT MOD_RES 140
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q53GA4"
FT MUTAGEN 27
FT /note="R->L: Impairs the ability to rescue growth in
FT cdc25ts mutant yeasts."
FT /evidence="ECO:0000269|PubMed:12374806"
FT MUTAGEN 38
FT /note="K->A: Impairs the ability to rescue growth in
FT cdc25ts mutant yeasts."
FT /evidence="ECO:0000269|PubMed:12374806"
FT MUTAGEN 39
FT /note="R->A: Impairs the ability to rescue growth in
FT cdc25ts mutant yeasts."
FT /evidence="ECO:0000269|PubMed:12374806"
SQ SEQUENCE 144 AA; 16727 MW; 9BD64B97BA22C1A9 CRC64;
MASKIVMSSK TVKTSDEILC EGELEKRSDS LFQVWKKKRC VLTADRLRLF SGKTSPAKEL
FFHSILKVDC VEHTSKYVYF TIVTNYYKEI DFRCTVESCW NAAITMALID FQNRRALQDF
PRYRYQRSES EMPSEPGEQS ALGP
