PKHA2_HUMAN
ID PKHA2_HUMAN Reviewed; 425 AA.
AC Q9HB19;
DT 29-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 20-DEC-2005, sequence version 2.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Pleckstrin homology domain-containing family A member 2;
DE Short=PH domain-containing family A member 2;
DE AltName: Full=Tandem PH domain-containing protein 2;
DE Short=TAPP-2;
GN Name=PLEKHA2; Synonyms=TAPP2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-304.
RX PubMed=11001876; DOI=10.1042/0264-6021:3510019;
RA Dowler S.J., Currie R.A., Campbell D.G., Deak M., Kular G., Downes C.P.,
RA Alessi D.R.;
RT "Identification of pleckstrin-homology-domain-containing proteins with
RT novel phosphoinositide-binding specificities.";
RL Biochem. J. 351:19-31(2000).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-349, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-184, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-184; SER-314 AND SER-349, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [7]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-141, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
CC -!- FUNCTION: Binds specifically to phosphatidylinositol 3,4-diphosphate
CC (PtdIns3,4P2), but not to other phosphoinositides. May recruit other
CC proteins to the plasma membrane (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Binds MPDZ and PTPN13. {ECO:0000250}.
CC -!- INTERACTION:
CC Q9HB19; Q9Y2V7: COG6; NbExp=3; IntAct=EBI-4401947, EBI-3866319;
CC Q9HB19; Q15700: DLG2; NbExp=3; IntAct=EBI-4401947, EBI-80426;
CC Q9HB19; Q92796: DLG3; NbExp=3; IntAct=EBI-4401947, EBI-80440;
CC Q9HB19; Q9H6Z9: EGLN3; NbExp=3; IntAct=EBI-4401947, EBI-1175354;
CC Q9HB19; Q5TD97: FHL5; NbExp=3; IntAct=EBI-4401947, EBI-750641;
CC Q9HB19; O14908: GIPC1; NbExp=3; IntAct=EBI-4401947, EBI-373132;
CC Q9HB19; Q8TF65: GIPC2; NbExp=8; IntAct=EBI-4401947, EBI-712067;
CC Q9HB19; Q8TF64: GIPC3; NbExp=3; IntAct=EBI-4401947, EBI-12372489;
CC Q9HB19; Q08379: GOLGA2; NbExp=3; IntAct=EBI-4401947, EBI-618309;
CC Q9HB19; O75031: HSF2BP; NbExp=3; IntAct=EBI-4401947, EBI-7116203;
CC Q9HB19; Q63ZY3: KANK2; NbExp=3; IntAct=EBI-4401947, EBI-2556193;
CC Q9HB19; Q8TBB1: LNX1; NbExp=5; IntAct=EBI-4401947, EBI-739832;
CC Q9HB19; Q8TC57: M1AP; NbExp=6; IntAct=EBI-4401947, EBI-748182;
CC Q9HB19; Q9NSN8: SNTG1; NbExp=3; IntAct=EBI-4401947, EBI-19763427;
CC Q9HB19; Q96N21: TEPSIN; NbExp=3; IntAct=EBI-4401947, EBI-11139477;
CC Q9HB19; P36406: TRIM23; NbExp=3; IntAct=EBI-4401947, EBI-740098;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Nucleus
CC {ECO:0000250}. Note=Locates to the plasma membrane after treatments
CC that stimulate the production of PtdIns3,4P2. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Highly expressed in heart, kidney, spleen and
CC peripheral blood leukocytes. Detected at lower levels in brain,
CC skeletal muscle, colon, thymus, liver, small intestine, placenta and
CC lung.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG15201.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AC067817; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC108863; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF286164; AAG15201.1; ALT_INIT; mRNA.
DR CCDS; CCDS75732.1; -.
DR RefSeq; NP_067636.1; NM_021623.1.
DR AlphaFoldDB; Q9HB19; -.
DR SMR; Q9HB19; -.
DR BioGRID; 121881; 89.
DR IntAct; Q9HB19; 19.
DR MINT; Q9HB19; -.
DR STRING; 9606.ENSP00000482228; -.
DR iPTMnet; Q9HB19; -.
DR MetOSite; Q9HB19; -.
DR PhosphoSitePlus; Q9HB19; -.
DR BioMuta; PLEKHA2; -.
DR DMDM; 84028237; -.
DR CPTAC; CPTAC-992; -.
DR EPD; Q9HB19; -.
DR jPOST; Q9HB19; -.
DR MassIVE; Q9HB19; -.
DR MaxQB; Q9HB19; -.
DR PaxDb; Q9HB19; -.
DR PeptideAtlas; Q9HB19; -.
DR PRIDE; Q9HB19; -.
DR ProteomicsDB; 81472; -.
DR DNASU; 59339; -.
DR GeneID; 59339; -.
DR KEGG; hsa:59339; -.
DR CTD; 59339; -.
DR DisGeNET; 59339; -.
DR GeneCards; PLEKHA2; -.
DR HGNC; HGNC:14336; PLEKHA2.
DR MIM; 607773; gene.
DR neXtProt; NX_Q9HB19; -.
DR PharmGKB; PA33402; -.
DR eggNOG; ENOG502QV0M; Eukaryota.
DR InParanoid; Q9HB19; -.
DR OrthoDB; 1513983at2759; -.
DR PhylomeDB; Q9HB19; -.
DR TreeFam; TF329516; -.
DR PathwayCommons; Q9HB19; -.
DR Reactome; R-HSA-1660499; Synthesis of PIPs at the plasma membrane.
DR SignaLink; Q9HB19; -.
DR BioGRID-ORCS; 59339; 12 hits in 289 CRISPR screens.
DR ChiTaRS; PLEKHA2; human.
DR GenomeRNAi; 59339; -.
DR Pharos; Q9HB19; Tbio.
DR PRO; PR:Q9HB19; -.
DR Proteomes; UP000005640; Unplaced.
DR RNAct; Q9HB19; protein.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0001968; F:fibronectin binding; IMP:UniProtKB.
DR GO; GO:0043236; F:laminin binding; IMP:UniProtKB.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0030165; F:PDZ domain binding; IBA:GO_Central.
DR GO; GO:0043325; F:phosphatidylinositol-3,4-bisphosphate binding; IDA:UniProtKB.
DR GO; GO:0001954; P:positive regulation of cell-matrix adhesion; IMP:UniProtKB.
DR Gene3D; 2.30.29.30; -; 2.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR Pfam; PF00169; PH; 2.
DR SMART; SM00233; PH; 2.
DR PROSITE; PS50003; PH_DOMAIN; 2.
PE 1: Evidence at protein level;
KW Cell membrane; Cytoplasm; Isopeptide bond; Lipid-binding; Membrane;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat; Ubl conjugation.
FT CHAIN 1..425
FT /note="Pleckstrin homology domain-containing family A
FT member 2"
FT /id="PRO_0000053876"
FT DOMAIN 7..113
FT /note="PH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 198..298
FT /note="PH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 312..332
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 352..425
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 312..329
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 398..425
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 184
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 314
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 349
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18220336,
FT ECO:0007744|PubMed:23186163"
FT CROSSLNK 141
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447"
FT VARIANT 186
FT /note="I -> N (in dbSNP:rs59439576)"
FT /id="VAR_061516"
FT CONFLICT 244
FT /note="L -> F (in Ref. 2; AAG15201)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 425 AA; 47255 MW; 145BBE9CE9E64B4E CRC64;
MPYVDRQNRI CGFLDIEEHE NSGKFLRRYF ILDTQANCLL WYMDNPQNLA MGAGAVGALQ
LTYISKVSIA TPKQKPKTPF CFVINALSQR YFLQANDQKD MKDWVEALNQ ASKITVPKGG
GLPMTTEVLK SLAAPPALEK KPQVAYKTEI IGGVVVHTPI SQNGGDGQEG SEPGSHTILR
RSQSYIPTSG CRASTGPPLI KSGYCVKQGN VRKSWKRRFF ALDDFTICYF KCEQDREPLR
TIFLKDVLKT HECLVKSGDL LMRDNLFEII TSSRTFYVQA DSPEDMHSWI KEIGAAVQAL
KCHPRETSFS RSISLTRPGS SSLSSGPNSI LCRGRPPLEE KKALCKAPSV ASSWQPWTPV
PQAGEKLLPP GDTSEDSLFT PRPGEGAPPG VLPSSRIRHR SEPQHPKEKP FMFNLDDENI
RTSDV
