ID   PHLA3_DANRE             Reviewed;         127 AA.
AC   Q8AW35;
DT   14-APR-2009, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   03-AUG-2022, entry version 109.
DE   RecName: Full=Pleckstrin homology-like domain family A member 3;
DE   AltName: Full=TDAG51/Ipl homolog 1;
GN   Name=phlda3; Synonyms=tih1; ORFNames=si:dZ182N13.5, zgc:92333;
OS   Danio rerio (Zebrafish) (Brachydanio rerio).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC   Danionidae; Danioninae; Danio.
OX   NCBI_TaxID=7955;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Tuebingen;
RX   PubMed=23594743; DOI=10.1038/nature12111;
RA   Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA   Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA   Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA   White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA   Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA   Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA   Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA   Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA   Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA   Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA   Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA   Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA   Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA   Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA   Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA   McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA   Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA   Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA   Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA   Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA   Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA   Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA   Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA   Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA   Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA   Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA   Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA   Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA   de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA   Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT   "The zebrafish reference genome sequence and its relationship to the human
RT   genome.";
RL   Nature 496:498-503(2013).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG   NIH - Zebrafish Gene Collection (ZGC) project;
RL   Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
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:0000250}. Membrane {ECO:0000250};
CC       Peripheral membrane protein {ECO:0000250}.
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   -!- SIMILARITY: Belongs to the PHLDA3 family. {ECO:0000305}.
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DR   EMBL; AL662880; CAD59121.1; -; Genomic_DNA.
DR   EMBL; BC076016; AAH76016.1; -; mRNA.
DR   RefSeq; NP_001002455.1; NM_001002455.1.
DR   AlphaFoldDB; Q8AW35; -.
DR   SMR; Q8AW35; -.
DR   STRING; 7955.ENSDARP00000055086; -.
DR   PaxDb; Q8AW35; -.
DR   DNASU; 368779; -.
DR   Ensembl; ENSDART00000055087; ENSDARP00000055086; ENSDARG00000037804.
DR   GeneID; 368779; -.
DR   KEGG; dre:368779; -.
DR   CTD; 23612; -.
DR   ZFIN; ZDB-GENE-030616-267; phlda3.
DR   eggNOG; ENOG502S2UN; Eukaryota.
DR   GeneTree; ENSGT00440000039564; -.
DR   HOGENOM; CLU_062639_1_0_1; -.
DR   InParanoid; Q8AW35; -.
DR   OMA; TLWNAEI; -.
DR   OrthoDB; 1412115at2759; -.
DR   PhylomeDB; Q8AW35; -.
DR   TreeFam; TF332320; -.
DR   PRO; PR:Q8AW35; -.
DR   Proteomes; UP000000437; Genome assembly.
DR   Proteomes; UP000814640; Chromosome 23.
DR   Bgee; ENSDARG00000037804; Expressed in spleen and 27 other tissues.
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   2: Evidence at transcript level;
KW   Apoptosis; Cytoplasm; Membrane; Reference proteome; Tumor suppressor.
FT   CHAIN           1..127
FT                   /note="Pleckstrin homology-like domain family A member 3"
FT                   /id="PRO_0000369391"
FT   DOMAIN          5..108
FT                   /note="PH"
SQ   SEQUENCE   127 AA;  14529 MW;  0B970E0EED51CE6A CRC64;
     MNQCKVMNDG YLEKRSNGLL QLWKKKRCVL SDEGLRLYGC KGDSGKEMRF EQMTTLDCVE
     YKRGLVYFTI VMNDGKEVDF RCQQEGTAWN AEIALALVRF KNRVAVQTGR NRHLSHLGSC
     GEGDVEL