PURA_HUMAN
ID PURA_HUMAN Reviewed; 322 AA.
AC Q00577;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 2.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Transcriptional activator protein Pur-alpha;
DE AltName: Full=Purine-rich single-stranded DNA-binding protein alpha;
GN Name=PURA; Synonyms=PUR1;
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].
RC TISSUE=Fetal liver;
RX PubMed=1448097; DOI=10.1128/mcb.12.12.5673-5682.1992;
RA Bergemann A.D., Ma Z.-W., Johnson E.M.;
RT "Sequence of cDNA comprising the human pur gene and sequence-specific
RT single-stranded-DNA-binding properties of the encoded protein.";
RL Mol. Cell. Biol. 12:5673-5682(1992).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [4]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
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 ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-182, 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 [8]
RP INVOLVEMENT IN NEDRIHF, AND VARIANTS NEDRIHF 88-ILE-ALA-89 DELINS THR;
RP PRO-89; GLU-97; PRO-100; LYS-157; PRO-199 AND PHE-271 DEL.
RX PubMed=25439098; DOI=10.1016/j.ajhg.2014.09.014;
RA Lalani S.R., Zhang J., Schaaf C.P., Brown C.W., Magoulas P., Tsai A.C.,
RA El-Gharbawy A., Wierenga K.J., Bartholomew D., Fong C.T.,
RA Barbaro-Dieber T., Kukolich M.K., Burrage L.C., Austin E., Keller K.,
RA Pastore M., Fernandez F., Lotze T., Wilfong A., Purcarin G., Zhu W.,
RA Craigen W.J., McGuire M., Jain M., Cooney E., Azamian M., Bainbridge M.N.,
RA Muzny D.M., Boerwinkle E., Person R.E., Niu Z., Eng C.M., Lupski J.R.,
RA Gibbs R.A., Beaudet A.L., Yang Y., Wang M.C., Xia F.;
RT "Mutations in PURA cause profound neonatal hypotonia, seizures, and
RT encephalopathy in 5q31.3 microdeletion syndrome.";
RL Am. J. Hum. Genet. 95:579-583(2014).
RN [9]
RP IDENTIFICATION BY 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).
RN [10]
RP VARIANTS NEDRIHF PHE-206 AND PHE-233 DEL.
RX PubMed=25342064; DOI=10.1136/jmedgenet-2014-102798;
RG DDD study;
RA Hunt D., Leventer R.J., Simons C., Taft R., Swoboda K.J., Gawne-Cain M.,
RA Magee A.C., Turnpenny P.D., Baralle D.;
RT "Whole exome sequencing in family trios reveals de novo mutations in PURA
RT as a cause of severe neurodevelopmental delay and learning disability.";
RL J. Med. Genet. 51:806-813(2014).
CC -!- FUNCTION: This is a probable transcription activator that specifically
CC binds the purine-rich single strand of the PUR element located upstream
CC of the MYC gene. May play a role in the initiation of DNA replication
CC and in recombination.
CC -!- SUBUNIT: Homodimer, heterodimer with PURB and heterotrimer with PURB
CC and YBX1/Y-box protein 1. Interacts with FMR1; this interaction occurs
CC in association with polyribosome. {ECO:0000250|UniProtKB:P42669}.
CC -!- INTERACTION:
CC Q00577; P06400: RB1; NbExp=6; IntAct=EBI-1045860, EBI-491274;
CC Q00577; P03070; Xeno; NbExp=2; IntAct=EBI-1045860, EBI-617698;
CC Q00577; P03072; Xeno; NbExp=4; IntAct=EBI-1045860, EBI-8658901;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- DISEASE: Neurodevelopmental disorder with neonatal respiratory
CC insufficiency, hypotonia, and feeding difficulties (NEDRIHF)
CC [MIM:616158]: An autosomal dominant disorder characterized by severe
CC neonatal hypotonia, respiratory and feeding difficulties,
CC encephalopathy, and severe developmental delay. Additional common
CC features may include seizures, exaggerated startle reflex, abnormal
CC movements, and dysmorphic facial features.
CC {ECO:0000269|PubMed:25342064, ECO:0000269|PubMed:25439098}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the PUR DNA-binding protein family.
CC {ECO:0000305}.
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DR EMBL; M96684; AAA60229.1; -; mRNA.
DR EMBL; U02098; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS4220.1; -.
DR PIR; A45036; A45036.
DR RefSeq; NP_005850.1; NM_005859.4.
DR AlphaFoldDB; Q00577; -.
DR SMR; Q00577; -.
DR BioGRID; 111772; 395.
DR IntAct; Q00577; 44.
DR MINT; Q00577; -.
DR STRING; 9606.ENSP00000332706; -.
DR GlyGen; Q00577; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q00577; -.
DR PhosphoSitePlus; Q00577; -.
DR SwissPalm; Q00577; -.
DR BioMuta; PURA; -.
DR DMDM; 1346918; -.
DR EPD; Q00577; -.
DR jPOST; Q00577; -.
DR MassIVE; Q00577; -.
DR MaxQB; Q00577; -.
DR PaxDb; Q00577; -.
DR PeptideAtlas; Q00577; -.
DR PRIDE; Q00577; -.
DR ProteomicsDB; 57857; -.
DR Antibodypedia; 26834; 277 antibodies from 28 providers.
DR DNASU; 5813; -.
DR Ensembl; ENST00000331327.5; ENSP00000332706.3; ENSG00000185129.8.
DR Ensembl; ENST00000651386.1; ENSP00000499133.1; ENSG00000185129.8.
DR GeneID; 5813; -.
DR KEGG; hsa:5813; -.
DR MANE-Select; ENST00000331327.5; ENSP00000332706.3; NM_005859.5; NP_005850.1.
DR UCSC; uc003lfa.4; human.
DR CTD; 5813; -.
DR DisGeNET; 5813; -.
DR GeneCards; PURA; -.
DR GeneReviews; PURA; -.
DR HGNC; HGNC:9701; PURA.
DR HPA; ENSG00000185129; Tissue enhanced (brain).
DR MalaCards; PURA; -.
DR MIM; 600473; gene.
DR MIM; 616158; phenotype.
DR neXtProt; NX_Q00577; -.
DR OpenTargets; ENSG00000185129; -.
DR Orphanet; 438216; PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome due to a point mutation.
DR Orphanet; 314655; Severe neonatal hypotonia-seizures-encephalopathy syndrome due to 5q31.3 microdeletion.
DR PharmGKB; PA34045; -.
DR VEuPathDB; HostDB:ENSG00000185129; -.
DR eggNOG; KOG3074; Eukaryota.
DR GeneTree; ENSGT00950000183162; -.
DR HOGENOM; CLU_057873_1_1_1; -.
DR InParanoid; Q00577; -.
DR OMA; WAKFGST; -.
DR OrthoDB; 1248813at2759; -.
DR PhylomeDB; Q00577; -.
DR TreeFam; TF313701; -.
DR PathwayCommons; Q00577; -.
DR SignaLink; Q00577; -.
DR SIGNOR; Q00577; -.
DR BioGRID-ORCS; 5813; 16 hits in 1083 CRISPR screens.
DR ChiTaRS; PURA; human.
DR GeneWiki; PURA; -.
DR GenomeRNAi; 5813; -.
DR Pharos; Q00577; Tbio.
DR PRO; PR:Q00577; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q00577; protein.
DR Bgee; ENSG00000185129; Expressed in Brodmann (1909) area 23 and 209 other tissues.
DR ExpressionAtlas; Q00577; baseline and differential.
DR Genevisible; Q00577; HS.
DR GO; GO:0000781; C:chromosome, telomeric region; IC:UniProtKB.
DR GO; GO:0032839; C:dendrite cytoplasm; IEA:GOC.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0098794; C:postsynapse; IEA:Ensembl.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISS:UniProtKB.
DR GO; GO:0003691; F:double-stranded telomeric DNA binding; IDA:UniProtKB.
DR GO; GO:0000900; F:mRNA regulatory element binding translation repressor activity; IEA:Ensembl.
DR GO; GO:0032422; F:purine-rich negative regulatory element binding; IBA:GO_Central.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0003697; F:single-stranded DNA binding; ISS:UniProtKB.
DR GO; GO:0046332; F:SMAD binding; IEA:Ensembl.
DR GO; GO:0140416; F:transcription regulator inhibitor activity; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IEA:InterPro.
DR GO; GO:0098963; P:dendritic transport of messenger ribonucleoprotein complex; IEA:Ensembl.
DR GO; GO:0006270; P:DNA replication initiation; TAS:ProtInc.
DR GO; GO:0006268; P:DNA unwinding involved in DNA replication; IDA:UniProtKB.
DR GO; GO:0050673; P:epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0046651; P:lymphocyte proliferation; IEA:Ensembl.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0007399; P:nervous system development; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR InterPro; IPR006628; PUR-bd_fam.
DR InterPro; IPR030500; PURalpha.
DR PANTHER; PTHR12611; PTHR12611; 1.
DR PANTHER; PTHR12611:SF2; PTHR12611:SF2; 1.
DR Pfam; PF04845; PurA; 1.
DR SMART; SM00712; PUR; 3.
PE 1: Evidence at protein level;
KW Acetylation; Activator; Disease variant; DNA-binding;
KW Intellectual disability; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
FT CHAIN 2..322
FT /note="Transcriptional activator protein Pur-alpha"
FT /id="PRO_0000097107"
FT REGION 1..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 295..322
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 295..309
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 182
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 88..89
FT /note="IA -> T (in NEDRIHF)"
FT /evidence="ECO:0000269|PubMed:25439098"
FT /id="VAR_072698"
FT VARIANT 89
FT /note="A -> P (in NEDRIHF; dbSNP:rs587782999)"
FT /evidence="ECO:0000269|PubMed:25439098"
FT /id="VAR_072699"
FT VARIANT 97
FT /note="K -> E (in NEDRIHF; dbSNP:rs587782994)"
FT /evidence="ECO:0000269|PubMed:25439098"
FT /id="VAR_072700"
FT VARIANT 100
FT /note="L -> P (in NEDRIHF; dbSNP:rs587782995)"
FT /evidence="ECO:0000269|PubMed:25439098"
FT /id="VAR_072701"
FT VARIANT 157
FT /note="M -> K (in NEDRIHF; dbSNP:rs587782998)"
FT /evidence="ECO:0000269|PubMed:25439098"
FT /id="VAR_072702"
FT VARIANT 199
FT /note="R -> P (in NEDRIHF; dbSNP:rs587783001)"
FT /evidence="ECO:0000269|PubMed:25439098"
FT /id="VAR_072703"
FT VARIANT 206
FT /note="I -> F (in NEDRIHF; dbSNP:rs786204834)"
FT /evidence="ECO:0000269|PubMed:25342064"
FT /id="VAR_073993"
FT VARIANT 233
FT /note="Missing (in NEDRIHF)"
FT /evidence="ECO:0000269|PubMed:25342064"
FT /id="VAR_073994"
FT VARIANT 271
FT /note="Missing (in NEDRIHF)"
FT /evidence="ECO:0000269|PubMed:25439098"
FT /id="VAR_072704"
SQ SEQUENCE 322 AA; 34911 MW; 797968504D01B356 CRC64;
MADRDSGSEQ GGAALGSGGS LGHPGSGSGS GGGGGGGGGG GGSGGGGGGA PGGLQHETQE
LASKRVDIQN KRFYLDVKQN AKGRFLKIAE VGAGGNKSRL TLSMSVAVEF RDYLGDFIEH
YAQLGPSQPP DLAQAQDEPR RALKSEFLVR ENRKYYMDLK ENQRGRFLRI RQTVNRGPGL
GSTQGQTIAL PAQGLIEFRD ALAKLIDDYG VEEEPAELPE GTSLTVDNKR FFFDVGSNKY
GVFMRVSEVK PTYRNSITVP YKVWAKFGHT FCKYSEEMKK IQEKQREKRA ACEQLHQQQQ
QQQEETAAAT LLLQGEEEGE ED
