PKHA4_HUMAN
ID PKHA4_HUMAN Reviewed; 779 AA.
AC Q9H4M7; Q8N4M8; Q8N658;
DT 29-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 29-MAR-2004, sequence version 2.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Pleckstrin homology domain-containing family A member 4;
DE Short=PH domain-containing family A member 4;
DE AltName: Full=Phosphoinositol 3-phosphate-binding protein 1;
DE Short=PEPP-1;
GN Name=PLEKHA4; Synonyms=PEPP1;
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 [MRNA] (ISOFORM 1), FUNCTION, AND TISSUE SPECIFICITY.
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP VAL-37.
RC TISSUE=Brain, Melanoma, and Uterus;
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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-559, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-164, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Binds specifically to phosphatidylinositol 3-phosphate
CC (PtdIns3P), but not to other phosphoinositides.
CC {ECO:0000269|PubMed:11001876}.
CC -!- INTERACTION:
CC Q9H4M7; Q5ZXN6: ankX; Xeno; NbExp=2; IntAct=EBI-716549, EBI-26359852;
CC Q9H4M7-2; Q53G59: KLHL12; NbExp=3; IntAct=EBI-12394782, EBI-740929;
CC Q9H4M7-2; A8MW99: MEI4; NbExp=3; IntAct=EBI-12394782, EBI-19944212;
CC Q9H4M7-2; Q9H4M7-2: PLEKHA4; NbExp=3; IntAct=EBI-12394782, EBI-12394782;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. Membrane {ECO:0000305};
CC Peripheral membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H4M7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H4M7-2; Sequence=VSP_009770, VSP_009771, VSP_009772;
CC -!- TISSUE SPECIFICITY: Highly expressed in melanoma. Detected at low
CC levels in heart, skeletal muscle, kidney, liver and small intestine.
CC {ECO:0000269|PubMed:11001876}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH33832.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AY007233; AAG01896.1; -; mRNA.
DR EMBL; BC024157; AAH24157.1; -; mRNA.
DR EMBL; BC033832; AAH33832.1; ALT_INIT; mRNA.
DR EMBL; BC064601; AAH64601.1; -; mRNA.
DR CCDS; CCDS12737.1; -. [Q9H4M7-1]
DR CCDS; CCDS54291.1; -. [Q9H4M7-2]
DR RefSeq; NP_001154826.1; NM_001161354.1. [Q9H4M7-2]
DR RefSeq; NP_065955.2; NM_020904.2. [Q9H4M7-1]
DR PDB; 1UPQ; X-ray; 1.48 A; A=45-167.
DR PDB; 1UPR; X-ray; 2.27 A; A=45-167.
DR PDBsum; 1UPQ; -.
DR PDBsum; 1UPR; -.
DR AlphaFoldDB; Q9H4M7; -.
DR SMR; Q9H4M7; -.
DR BioGRID; 121697; 2969.
DR IntAct; Q9H4M7; 13.
DR MINT; Q9H4M7; -.
DR STRING; 9606.ENSP00000263265; -.
DR DrugBank; DB01863; Inositol 1,3,4,5-Tetrakisphosphate.
DR iPTMnet; Q9H4M7; -.
DR PhosphoSitePlus; Q9H4M7; -.
DR BioMuta; PLEKHA4; -.
DR DMDM; 48474644; -.
DR EPD; Q9H4M7; -.
DR jPOST; Q9H4M7; -.
DR MassIVE; Q9H4M7; -.
DR MaxQB; Q9H4M7; -.
DR PaxDb; Q9H4M7; -.
DR PeptideAtlas; Q9H4M7; -.
DR PRIDE; Q9H4M7; -.
DR ProteomicsDB; 80865; -. [Q9H4M7-1]
DR ProteomicsDB; 80866; -. [Q9H4M7-2]
DR Antibodypedia; 31820; 112 antibodies from 18 providers.
DR DNASU; 57664; -.
DR Ensembl; ENST00000263265.11; ENSP00000263265.5; ENSG00000105559.12. [Q9H4M7-1]
DR Ensembl; ENST00000355496.9; ENSP00000347683.4; ENSG00000105559.12. [Q9H4M7-2]
DR GeneID; 57664; -.
DR KEGG; hsa:57664; -.
DR MANE-Select; ENST00000263265.11; ENSP00000263265.5; NM_020904.3; NP_065955.2.
DR UCSC; uc002pkx.4; human. [Q9H4M7-1]
DR CTD; 57664; -.
DR DisGeNET; 57664; -.
DR GeneCards; PLEKHA4; -.
DR HGNC; HGNC:14339; PLEKHA4.
DR HPA; ENSG00000105559; Low tissue specificity.
DR MIM; 607769; gene.
DR neXtProt; NX_Q9H4M7; -.
DR OpenTargets; ENSG00000105559; -.
DR PharmGKB; PA33404; -.
DR VEuPathDB; HostDB:ENSG00000105559; -.
DR eggNOG; ENOG502RI1J; Eukaryota.
DR GeneTree; ENSGT00940000161121; -.
DR HOGENOM; CLU_020168_0_0_1; -.
DR InParanoid; Q9H4M7; -.
DR OMA; WGPAWDA; -.
DR OrthoDB; 71844at2759; -.
DR PhylomeDB; Q9H4M7; -.
DR TreeFam; TF329090; -.
DR PathwayCommons; Q9H4M7; -.
DR Reactome; R-HSA-1660499; Synthesis of PIPs at the plasma membrane.
DR SignaLink; Q9H4M7; -.
DR BioGRID-ORCS; 57664; 13 hits in 1084 CRISPR screens.
DR ChiTaRS; PLEKHA4; human.
DR EvolutionaryTrace; Q9H4M7; -.
DR GenomeRNAi; 57664; -.
DR Pharos; Q9H4M7; Tbio.
DR PRO; PR:Q9H4M7; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9H4M7; protein.
DR Bgee; ENSG00000105559; Expressed in sural nerve and 111 other tissues.
DR ExpressionAtlas; Q9H4M7; baseline and differential.
DR Genevisible; Q9H4M7; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IDA:FlyBase.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0043325; F:phosphatidylinositol-3,4-bisphosphate binding; IDA:FlyBase.
DR GO; GO:0080025; F:phosphatidylinositol-3,5-bisphosphate binding; IDA:FlyBase.
DR GO; GO:0032266; F:phosphatidylinositol-3-phosphate binding; IDA:UniProtKB.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:FlyBase.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IMP:FlyBase.
DR GO; GO:2000096; P:positive regulation of Wnt signaling pathway, planar cell polarity pathway; IMP:FlyBase.
DR CDD; cd13248; PH_PEPP1_2_3; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR040392; PKHA4-7_PH.
DR Pfam; PF00169; PH; 1.
DR SMART; SM00233; PH; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Lipid-binding; Membrane;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..779
FT /note="Pleckstrin homology domain-containing family A
FT member 4"
FT /id="PRO_0000053880"
FT DOMAIN 54..153
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 152..352
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 492..670
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 691..764
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 186..203
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 235..266
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 316..331
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 645..665
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 703..726
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 164
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 559
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 325..349
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_009770"
FT VAR_SEQ 582..608
FT /note="APVARPRMSAQEQLERMRRNQECGRPF -> SKEHHPLLADFRRSPGAGSQP
FT LPSPGY (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_009771"
FT VAR_SEQ 609..779
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_009772"
FT VARIANT 37
FT /note="I -> V (in dbSNP:rs506425)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_056667"
FT VARIANT 597
FT /note="R -> Q (in dbSNP:rs12460394)"
FT /id="VAR_056668"
FT VARIANT 714
FT /note="T -> A (in dbSNP:rs34460869)"
FT /id="VAR_056669"
FT VARIANT 742
FT /note="G -> V (in dbSNP:rs35965411)"
FT /id="VAR_056670"
FT CONFLICT 590
FT /note="S -> N (in Ref. 1; AAG01896)"
FT /evidence="ECO:0000305"
FT CONFLICT 779
FT /note="F -> L (in Ref. 1; AAG01896)"
FT /evidence="ECO:0000305"
FT STRAND 55..64
FT /evidence="ECO:0007829|PDB:1UPQ"
FT STRAND 66..69
FT /evidence="ECO:0007829|PDB:1UPQ"
FT STRAND 72..80
FT /evidence="ECO:0007829|PDB:1UPQ"
FT STRAND 83..89
FT /evidence="ECO:0007829|PDB:1UPQ"
FT STRAND 97..100
FT /evidence="ECO:0007829|PDB:1UPQ"
FT HELIX 101..103
FT /evidence="ECO:0007829|PDB:1UPQ"
FT STRAND 105..108
FT /evidence="ECO:0007829|PDB:1UPQ"
FT STRAND 116..124
FT /evidence="ECO:0007829|PDB:1UPQ"
FT STRAND 131..134
FT /evidence="ECO:0007829|PDB:1UPQ"
FT HELIX 138..152
FT /evidence="ECO:0007829|PDB:1UPQ"
SQ SEQUENCE 779 AA; 85401 MW; 35866CAE2F2C262F CRC64;
MEGSRPRSSL SLASSASTIS SLSSLSPKKP TRAVNKIHAF GKRGNALRRD PNLPVHIRGW
LHKQDSSGLR LWKRRWFVLS GHCLFYYKDS REESVLGSVL LPSYNIRPDG PGAPRGRRFT
FTAEHPGMRT YVLAADTLED LRGWLRALGR ASRAEGDDYG QPRSPARPQP GEGPGGPGGP
PEVSRGEEGR ISESPEVTRL SRGRGRPRLL TPSPTTDLHS GLQMRRARSP DLFTPLSRPP
SPLSLPRPRS APARRPPAPS GDTAPPARPH TPLSRIDVRP PLDWGPQRQT LSRPPTPRRG
PPSEAGGGKP PRSPQHWSQE PRTQAHSGSP TYLQLPPRPP GTRASMVLLP GPPLESTFHQ
SLETDTLLTK LCGQDRLLRR LQEEIDQKQE EKEQLEAALE LTRQQLGQAT REAGAPGRAW
GRQRLLQDRL VSVRATLCHL TQERERVWDT YSGLEQELGT LRETLEYLLH LGSPQDRVSA
QQQLWMVEDT LAGLGGPQKP PPHTEPDSPS PVLQGEESSE RESLPESLEL SSPRSPETDW
GRPPGGDKDL ASPHLGLGSP RVSRASSPEG RHLPSPQLGT KAPVARPRMS AQEQLERMRR
NQECGRPFPR PTSPRLLTLG RTLSPARRQP DVEQRPVVGH SGAQKWLRSS GSWSSPRNTT
PYLPTSEGHR ERVLSLSQAL ATEASQWHRM MTGGNLDSQG DPLPGVPLPP SDPTRQETPP
PRSPPVANSG STGFSRRGSG RGGGPTPWGP AWDAGIAPPV LPQDEGAWPL RVTLLQSSF
