PHLA3_MOUSE
ID PHLA3_MOUSE Reviewed; 125 AA.
AC Q9WV95;
DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Pleckstrin homology-like domain family A member 3;
DE AltName: Full=TDAG51/Ipl homolog 1;
GN Name=Phlda3; Synonyms=Tih1;
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 [MRNA], 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 [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [4]
RP PHOSPHOINOSITIDE-BINDING, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-27
RP AND ARG-28.
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 [5]
RP DISRUPTION PHENOTYPE.
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: p53/TP53-regulated repressor of Akt/AKT1 signaling. Represses
CC AKT1 by preventing AKT1-binding to membrane lipids, thereby inhibiting
CC AKT1 translocation to the cellular membrane and activation. Contributes
CC to p53/TP53-dependent apoptosis by repressing AKT1 activity. Its direct
CC transcription regulation by p53/TP53 may explain how p53/TP53 can
CC negatively regulate AKT1. May act as a tumor suppressor (By
CC similarity). {ECO:0000250}.
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: Widely expressed in fetal tissues, with the
CC exception of liver. Strongly expressed in adult skeletal muscle and
CC lung. Widely expressed at lower levels in other adult tissues, with
CC weakest expression in liver and spleen. {ECO:0000269|PubMed:10594239}.
CC -!- DEVELOPMENTAL STAGE: Expressed in extraembryonic tissues and placenta
CC at 11.5 and 18.5 dpc (at protein level). Expression continues
CC throughout gestation and is strong in adult lung (at protein level).
CC {ECO:0000269|PubMed:10594239}.
CC -!- DOMAIN: The PH domain binds phosphoinositides with a broad specificity.
CC It competes with the PH domain of AKT1 and directly interferes with
CC AKT1 binding to phosphatidylinositol 4,5-bisphosphate (PIP2) and
CC phosphatidylinositol 3,4,5-trisphosphate (PIP3), preventing AKT1
CC association to membrane lipids and subsequent activation of AKT1
CC signaling (By similarity). {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable and fertile, and show normal
CC placenta and embryonic weights. {ECO:0000269|PubMed:12032310}.
CC -!- SIMILARITY: Belongs to the PHLDA3 family. {ECO:0000305}.
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DR EMBL; AF151099; AAD42080.1; -; Genomic_DNA.
DR EMBL; AK003767; BAB22985.1; -; mRNA.
DR EMBL; BC023408; AAH23408.1; -; mRNA.
DR CCDS; CCDS35722.1; -.
DR RefSeq; NP_038778.1; NM_013750.2.
DR AlphaFoldDB; Q9WV95; -.
DR SMR; Q9WV95; -.
DR IntAct; Q9WV95; 1.
DR MINT; Q9WV95; -.
DR STRING; 10090.ENSMUSP00000040614; -.
DR iPTMnet; Q9WV95; -.
DR PhosphoSitePlus; Q9WV95; -.
DR EPD; Q9WV95; -.
DR MaxQB; Q9WV95; -.
DR PaxDb; Q9WV95; -.
DR PeptideAtlas; Q9WV95; -.
DR PRIDE; Q9WV95; -.
DR ProteomicsDB; 287933; -.
DR Antibodypedia; 34503; 163 antibodies from 31 providers.
DR DNASU; 27280; -.
DR Ensembl; ENSMUST00000038945; ENSMUSP00000040614; ENSMUSG00000041801.
DR GeneID; 27280; -.
DR KEGG; mmu:27280; -.
DR UCSC; uc007ctq.2; mouse.
DR CTD; 23612; -.
DR MGI; MGI:1351485; Phlda3.
DR VEuPathDB; HostDB:ENSMUSG00000041801; -.
DR eggNOG; ENOG502S2UN; Eukaryota.
DR GeneTree; ENSGT00440000039564; -.
DR HOGENOM; CLU_062639_1_0_1; -.
DR InParanoid; Q9WV95; -.
DR OMA; TLWNAEI; -.
DR OrthoDB; 1412115at2759; -.
DR PhylomeDB; Q9WV95; -.
DR TreeFam; TF332320; -.
DR BioGRID-ORCS; 27280; 0 hits in 72 CRISPR screens.
DR PRO; PR:Q9WV95; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q9WV95; protein.
DR Bgee; ENSMUSG00000041801; Expressed in temporalis muscle and 230 other tissues.
DR Genevisible; Q9WV95; MM.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; ISS:UniProtKB.
DR GO; GO:0043325; F:phosphatidylinositol-3,4-bisphosphate binding; ISS:UniProtKB.
DR GO; GO:0080025; F:phosphatidylinositol-3,5-bisphosphate binding; ISS:UniProtKB.
DR GO; GO:0032266; F:phosphatidylinositol-3-phosphate binding; ISS:UniProtKB.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; ISS:UniProtKB.
DR GO; GO:0010314; F:phosphatidylinositol-5-phosphate binding; ISS:UniProtKB.
DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; ISS:UniProtKB.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
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 Apoptosis; Cytoplasm; Membrane; Reference proteome; Tumor suppressor.
FT CHAIN 1..125
FT /note="Pleckstrin homology-like domain family A member 3"
FT /id="PRO_0000053903"
FT DOMAIN 6..125
FT /note="PH"
FT MUTAGEN 27
FT /note="K->A: Impairs the ability to resucue growth in
FT cdc25ts mutant yeasts."
FT /evidence="ECO:0000269|PubMed:12374806"
FT MUTAGEN 28
FT /note="R->A: Impairs the ability to resucue growth in
FT cdc25ts mutant yeasts."
FT /evidence="ECO:0000269|PubMed:12374806"
SQ SEQUENCE 125 AA; 13719 MW; 53E44E6A29C036A4 CRC64;
MTAAATVLKE GVLEKRSGGL LQLWKRKRCV LTERGLQLFE AKGTGGRPKE LSFARIKAVE
CVESTGRHIY FTLVTEGGGE IDFRCPLEDP GWNAQITLGL VKFKNQQAIQ TVRARQSLGT
GTLVS
