PHLA1_HUMAN
ID PHLA1_HUMAN Reviewed; 401 AA.
AC Q8WV24; A1A4G9; Q15184; Q2TAN2; Q9NZ17;
DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 4.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Pleckstrin homology-like domain family A member 1;
DE AltName: Full=Apoptosis-associated nuclear protein;
DE AltName: Full=Proline- and glutamine-rich protein;
DE Short=PQ-rich protein;
DE Short=PQR protein;
DE AltName: Full=Proline- and histidine-rich protein;
DE AltName: Full=T-cell death-associated gene 51 protein;
GN Name=PHLDA1; Synonyms=PHRIP, TDAG51;
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 [GENOMIC DNA].
RX PubMed=10894922; DOI=10.1159/000015575;
RA Kuske M.D., Johnson J.P.;
RT "Assignment of the human PHLDA1 gene to chromosome 12q15 by radiation
RT hybrid mapping.";
RL Cytogenet. Cell Genet. 89:1-1(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Fetal liver;
RA Wagner F.F., Flegel W.A.;
RT "A cDNA, which predicts a protein with PQ-rich repeats, isolated from a
RT phage library of human fetal liver tissue.";
RL Submitted (JUL-1995) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 53-401.
RC TISSUE=Brain, 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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 350-401, AND TISSUE SPECIFICITY.
RX PubMed=12384558;
RA Neef R., Kuske M.A., Proels E., Johnson J.P.;
RT "Identification of the human PHLDA1/TDAG51 gene: down-regulation in
RT metastatic melanoma contributes to apoptosis resistance and growth
RT deregulation.";
RL Cancer Res. 62:5920-5929(2002).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH RPL14; EIF3S7 AND
RP PABPC4.
RX PubMed=11369516; DOI=10.1016/s0898-6568(01)00141-3;
RA Hinz T., Flindt S., Marx A., Janssen O., Kabelitz D.;
RT "Inhibition of protein synthesis by the T cell receptor-inducible human
RT TDAG51 gene product.";
RL Cell. Signal. 13:345-352(2001).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=12738777; DOI=10.1074/jbc.m212897200;
RA Hossain G.S., van Thienen J.V., Werstuck G.H., Zhou J., Sood S.K.,
RA Dickhout J.G., de Koning A.B., Tang D., Wu D., Falk E., Poddar R.,
RA Jacobsen D.W., Zhang K., Kaufman R.J., Austin R.C.;
RT "TDAG51 is induced by homocysteine, promotes detachment-mediated programmed
RT cell death, and contributes to the development of atherosclerosis in
RT hyperhomocysteinemia.";
RL J. Biol. Chem. 278:30317-30327(2003).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: Seems to be involved in regulation of apoptosis. May be
CC involved in detachment-mediated programmed cell death. May mediate
CC apoptosis during neuronal development. May be involved in regulation of
CC anti-apoptotic effects of IGF1. May be involved in translational
CC regulation. {ECO:0000269|PubMed:11369516, ECO:0000269|PubMed:12738777}.
CC -!- SUBUNIT: Interacts with RPL14, EIF3S7 and PABPC4.
CC {ECO:0000269|PubMed:11369516}.
CC -!- INTERACTION:
CC Q8WV24; O15371: EIF3D; NbExp=2; IntAct=EBI-738731, EBI-353818;
CC Q8WV24; Q99750: MDFI; NbExp=3; IntAct=EBI-738731, EBI-724076;
CC Q8WV24; Q13310: PABPC4; NbExp=2; IntAct=EBI-738731, EBI-372844;
CC Q8WV24; P50914: RPL14; NbExp=2; IntAct=EBI-738731, EBI-356746;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11369516}.
CC Cytoplasmic vesicle {ECO:0000269|PubMed:12738777}. Nucleus, nucleolus
CC {ECO:0000269|PubMed:11369516}. Note=Colocalizes with intracellular
CC vesicles. {ECO:0000269|PubMed:12738777}.
CC -!- TISSUE SPECIFICITY: Widely expressed with highest levels in pancreas.
CC Strongly expressed by benign melanocytic nevi, and progressively
CC reduced expressed in primary and metastatic melanomas (at protein
CC level). {ECO:0000269|PubMed:12384558, ECO:0000269|PubMed:12738777}.
CC -!- INDUCTION: Induced by homocysteine and other endoplasmic reticulum
CC stress-inducing reagents. Induced by phorbol ester (TPA)/ionomycin, and
CC stimulation of the T-cell receptor (TCR) complex in T-cells.
CC {ECO:0000269|PubMed:12738777}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH18929.3; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAI10821.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAI26426.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF239986; AAF64165.1; -; Genomic_DNA.
DR EMBL; Z50194; CAA90576.1; -; mRNA.
DR EMBL; BC018929; AAH18929.3; ALT_INIT; mRNA.
DR EMBL; BC110820; AAI10821.1; ALT_INIT; mRNA.
DR EMBL; BC126425; AAI26426.2; ALT_INIT; mRNA.
DR EMBL; AF220656; AAF36387.1; -; mRNA.
DR CCDS; CCDS31861.1; -.
DR PIR; S58222; S58222.
DR RefSeq; NP_031376.3; NM_007350.3.
DR AlphaFoldDB; Q8WV24; -.
DR BioGRID; 116498; 67.
DR IntAct; Q8WV24; 12.
DR MINT; Q8WV24; -.
DR STRING; 9606.ENSP00000266671; -.
DR iPTMnet; Q8WV24; -.
DR PhosphoSitePlus; Q8WV24; -.
DR BioMuta; PHLDA1; -.
DR DMDM; 229463035; -.
DR EPD; Q8WV24; -.
DR jPOST; Q8WV24; -.
DR MassIVE; Q8WV24; -.
DR MaxQB; Q8WV24; -.
DR PaxDb; Q8WV24; -.
DR PeptideAtlas; Q8WV24; -.
DR PRIDE; Q8WV24; -.
DR ProteomicsDB; 74739; -.
DR Antibodypedia; 4254; 243 antibodies from 31 providers.
DR DNASU; 22822; -.
DR Ensembl; ENST00000266671.10; ENSP00000266671.5; ENSG00000139289.14.
DR Ensembl; ENST00000619060.1; ENSP00000480767.1; ENSG00000139289.14.
DR GeneID; 22822; -.
DR KEGG; hsa:22822; -.
DR UCSC; uc001sxu.3; human.
DR CTD; 22822; -.
DR DisGeNET; 22822; -.
DR GeneCards; PHLDA1; -.
DR HGNC; HGNC:8933; PHLDA1.
DR HPA; ENSG00000139289; Tissue enhanced (salivary).
DR MIM; 605335; gene.
DR neXtProt; NX_Q8WV24; -.
DR OpenTargets; ENSG00000139289; -.
DR PharmGKB; PA33274; -.
DR VEuPathDB; HostDB:ENSG00000139289; -.
DR eggNOG; ENOG502RZ5Q; Eukaryota.
DR GeneTree; ENSGT00440000039564; -.
DR HOGENOM; CLU_062639_0_0_1; -.
DR InParanoid; Q8WV24; -.
DR OMA; GWGGWPI; -.
DR OrthoDB; 1412115at2759; -.
DR PhylomeDB; Q8WV24; -.
DR TreeFam; TF332320; -.
DR PathwayCommons; Q8WV24; -.
DR Reactome; R-HSA-8854521; Interaction between PHLDA1 and AURKA.
DR SignaLink; Q8WV24; -.
DR BioGRID-ORCS; 22822; 14 hits in 1070 CRISPR screens.
DR ChiTaRS; PHLDA1; human.
DR GeneWiki; PHLDA1; -.
DR GenomeRNAi; 22822; -.
DR Pharos; Q8WV24; Tbio.
DR PRO; PR:Q8WV24; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q8WV24; protein.
DR Bgee; ENSG00000139289; Expressed in ventricular zone and 103 other tissues.
DR ExpressionAtlas; Q8WV24; baseline and differential.
DR Genevisible; Q8WV24; HS.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:1901981; F:phosphatidylinositol phosphate binding; IEA:InterPro.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0045210; P:FasL biosynthetic process; IEA:Ensembl.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IBA:GO_Central.
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; 2.
DR SMART; SM00233; PH; 1.
PE 1: Evidence at protein level;
KW Apoptosis; Cytoplasm; Cytoplasmic vesicle; Nucleus; Reference proteome;
KW Repeat.
FT CHAIN 1..401
FT /note="Pleckstrin homology-like domain family A member 1"
FT /id="PRO_0000053897"
FT DOMAIN 151..283
FT /note="PH"
FT REGION 39..67
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 190..222
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 293..401
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 311..346
FT /note="15 X 2 AA repeats of P-Q"
FT REGION 352..389
FT /note="14 X 2 AA repeats of P-H"
FT COMPBIAS 39..60
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 190..210
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 293..307
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 308..353
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 354..378
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 204
FT /note="Missing (in Ref. 1; AAF64165, 2; CAA90576 and 3)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 401 AA; 45016 MW; 1E01E7F75116A517 CRC64;
MRRAPAAERL LELGFPPRCG RQEPPFPLGV TRGWGRWPIQ KRREGARPVP FSERSQEDGR
GPAARSSGTL WRIRTRLSLC RDPEPPPPLC LLRVSLLCAL RAGGRGSRWG EDGARLLLLP
PARAAGNGEA EPSGGPSYAG RMLESSGCKA LKEGVLEKRS DGLLQLWKKK CCILTEEGLL
LIPPKQLQHQ QQQQQQQQQQ QQQQPGQGPA EPSQPSGPAV ASLEPPVKLK ELHFSNMKTV
DCVERKGKYM YFTVVMAEGK EIDFRCPQDQ GWNAEITLQM VQYKNRQAIL AVKSTRQKQQ
HLVQQQPPSQ PQPQPQLQPQ PQPQPQPQPQ PQSQPQPQPQ PKPQPQQLHP YPHPHPHPHS
HPHSHPHPHP HPHPHQIPHP HPQPHSQPHG HRLLRSTSNS A
