Full text data of PURA
PURA
(PUR1)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Transcriptional activator protein Pur-alpha (Purine-rich single-stranded DNA-binding protein alpha)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Transcriptional activator protein Pur-alpha (Purine-rich single-stranded DNA-binding protein alpha)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q00577
ID PURA_HUMAN Reviewed; 322 AA.
AC Q00577;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1996, sequence version 2.
DT 22-JAN-2014, entry version 114.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Fetal liver;
RX PubMed=1448097;
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=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 [3]
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.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: This is a probable transcription activator that
CC specifically binds the purine-rich single strand of the PUR
CC element located upstream of the MYC gene. May play a role in the
CC initiation of DNA replication and in recombination.
CC -!- SUBUNIT: Homodimer, heterodimer with PURB and heterotrimer with
CC PURB and YBX1/Y-box protein 1 (By similarity).
CC -!- INTERACTION:
CC P03070:- (xeno); NbExp=2; IntAct=EBI-1045860, EBI-617698;
CC P03072:- (xeno); NbExp=4; IntAct=EBI-1045860, EBI-8658901;
CC P06400:RB1; NbExp=6; IntAct=EBI-1045860, EBI-491274;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- SIMILARITY: Belongs to the PUR DNA-binding protein family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; M96684; AAA60229.1; -; mRNA.
DR EMBL; U02098; -; NOT_ANNOTATED_CDS; mRNA.
DR PIR; A45036; A45036.
DR RefSeq; NP_005850.1; NM_005859.4.
DR UniGene; Hs.443121; -.
DR UniGene; Hs.733524; -.
DR ProteinModelPortal; Q00577; -.
DR SMR; Q00577; 59-277.
DR IntAct; Q00577; 8.
DR MINT; MINT-112751; -.
DR STRING; 9606.ENSP00000332706; -.
DR PhosphoSite; Q00577; -.
DR DMDM; 1346918; -.
DR PaxDb; Q00577; -.
DR PeptideAtlas; Q00577; -.
DR PRIDE; Q00577; -.
DR Ensembl; ENST00000331327; ENSP00000332706; ENSG00000185129.
DR GeneID; 5813; -.
DR KEGG; hsa:5813; -.
DR UCSC; uc003lfa.3; human.
DR CTD; 5813; -.
DR GeneCards; GC05P139473; -.
DR HGNC; HGNC:9701; PURA.
DR MIM; 600473; gene.
DR neXtProt; NX_Q00577; -.
DR PharmGKB; PA34045; -.
DR eggNOG; NOG312871; -.
DR HOGENOM; HOG000232132; -.
DR HOVERGEN; HBG006888; -.
DR InParanoid; Q00577; -.
DR OMA; REKRACE; -.
DR OrthoDB; EOG78D7M4; -.
DR PhylomeDB; Q00577; -.
DR SignaLink; Q00577; -.
DR GeneWiki; PURA; -.
DR GenomeRNAi; 5813; -.
DR NextBio; 22642; -.
DR PRO; PR:Q00577; -.
DR Bgee; Q00577; -.
DR CleanEx; HS_PURA; -.
DR Genevestigator; Q00577; -.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0005662; C:DNA replication factor A complex; ISS:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0000784; C:nuclear chromosome, telomeric region; IC:UniProtKB.
DR GO; GO:0003691; F:double-stranded telomeric DNA binding; IDA:UniProtKB.
DR GO; GO:0032422; F:purine-rich negative regulatory element binding; IEA:Ensembl.
DR GO; GO:0003705; F:RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity; TAS:ProtInc.
DR GO; GO:0003697; F:single-stranded DNA binding; ISS:UniProtKB.
DR GO; GO:0008134; F:transcription factor binding; ISS:UniProtKB.
DR GO; GO:0000900; F:translation repressor activity, nucleic acid binding; 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:0045892; P:negative regulation of transcription, DNA-dependent; IEA:Ensembl.
DR GO; GO:0007399; P:nervous system development; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell proliferation; IEA:Ensembl.
DR InterPro; IPR006628; PUR_DNA_RNA-bd.
DR PANTHER; PTHR12611; PTHR12611; 1.
DR Pfam; PF04845; PurA; 1.
DR SMART; SM00712; PUR; 3.
PE 1: Evidence at protein level;
KW Activator; Complete proteome; DNA-binding; Nucleus;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1 322 Transcriptional activator protein Pur-
FT alpha.
FT /FTId=PRO_0000097107.
FT COMPBIAS 11 53 Gly-rich.
FT COMPBIAS 293 322 Gln/Glu-rich (part of the transcriptional
FT activation domain).
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
//
ID PURA_HUMAN Reviewed; 322 AA.
AC Q00577;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1996, sequence version 2.
DT 22-JAN-2014, entry version 114.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Fetal liver;
RX PubMed=1448097;
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=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 [3]
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.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: This is a probable transcription activator that
CC specifically binds the purine-rich single strand of the PUR
CC element located upstream of the MYC gene. May play a role in the
CC initiation of DNA replication and in recombination.
CC -!- SUBUNIT: Homodimer, heterodimer with PURB and heterotrimer with
CC PURB and YBX1/Y-box protein 1 (By similarity).
CC -!- INTERACTION:
CC P03070:- (xeno); NbExp=2; IntAct=EBI-1045860, EBI-617698;
CC P03072:- (xeno); NbExp=4; IntAct=EBI-1045860, EBI-8658901;
CC P06400:RB1; NbExp=6; IntAct=EBI-1045860, EBI-491274;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- SIMILARITY: Belongs to the PUR DNA-binding protein family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; M96684; AAA60229.1; -; mRNA.
DR EMBL; U02098; -; NOT_ANNOTATED_CDS; mRNA.
DR PIR; A45036; A45036.
DR RefSeq; NP_005850.1; NM_005859.4.
DR UniGene; Hs.443121; -.
DR UniGene; Hs.733524; -.
DR ProteinModelPortal; Q00577; -.
DR SMR; Q00577; 59-277.
DR IntAct; Q00577; 8.
DR MINT; MINT-112751; -.
DR STRING; 9606.ENSP00000332706; -.
DR PhosphoSite; Q00577; -.
DR DMDM; 1346918; -.
DR PaxDb; Q00577; -.
DR PeptideAtlas; Q00577; -.
DR PRIDE; Q00577; -.
DR Ensembl; ENST00000331327; ENSP00000332706; ENSG00000185129.
DR GeneID; 5813; -.
DR KEGG; hsa:5813; -.
DR UCSC; uc003lfa.3; human.
DR CTD; 5813; -.
DR GeneCards; GC05P139473; -.
DR HGNC; HGNC:9701; PURA.
DR MIM; 600473; gene.
DR neXtProt; NX_Q00577; -.
DR PharmGKB; PA34045; -.
DR eggNOG; NOG312871; -.
DR HOGENOM; HOG000232132; -.
DR HOVERGEN; HBG006888; -.
DR InParanoid; Q00577; -.
DR OMA; REKRACE; -.
DR OrthoDB; EOG78D7M4; -.
DR PhylomeDB; Q00577; -.
DR SignaLink; Q00577; -.
DR GeneWiki; PURA; -.
DR GenomeRNAi; 5813; -.
DR NextBio; 22642; -.
DR PRO; PR:Q00577; -.
DR Bgee; Q00577; -.
DR CleanEx; HS_PURA; -.
DR Genevestigator; Q00577; -.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0005662; C:DNA replication factor A complex; ISS:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0000784; C:nuclear chromosome, telomeric region; IC:UniProtKB.
DR GO; GO:0003691; F:double-stranded telomeric DNA binding; IDA:UniProtKB.
DR GO; GO:0032422; F:purine-rich negative regulatory element binding; IEA:Ensembl.
DR GO; GO:0003705; F:RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity; TAS:ProtInc.
DR GO; GO:0003697; F:single-stranded DNA binding; ISS:UniProtKB.
DR GO; GO:0008134; F:transcription factor binding; ISS:UniProtKB.
DR GO; GO:0000900; F:translation repressor activity, nucleic acid binding; 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:0045892; P:negative regulation of transcription, DNA-dependent; IEA:Ensembl.
DR GO; GO:0007399; P:nervous system development; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell proliferation; IEA:Ensembl.
DR InterPro; IPR006628; PUR_DNA_RNA-bd.
DR PANTHER; PTHR12611; PTHR12611; 1.
DR Pfam; PF04845; PurA; 1.
DR SMART; SM00712; PUR; 3.
PE 1: Evidence at protein level;
KW Activator; Complete proteome; DNA-binding; Nucleus;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1 322 Transcriptional activator protein Pur-
FT alpha.
FT /FTId=PRO_0000097107.
FT COMPBIAS 11 53 Gly-rich.
FT COMPBIAS 293 322 Gln/Glu-rich (part of the transcriptional
FT activation domain).
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
//
MIM
600473
*RECORD*
*FIELD* NO
600473
*FIELD* TI
*600473 PURINE-RICH ELEMENT-BINDING PROTEIN A; PURA
;;PUR-ALPHA
*FIELD* TX
CLONING
read more
Bergemann and Johnson (1992) characterized an approximately 28-kD
protein from HeLa cell nuclear extracts that bound specifically to a
purine-rich repeat element located at a site of DNA binding upstream of
the human c-myc gene, and at origins of replication and transcription
initiation sites in a variety of eukaryotes. Bergemann et al. (1992)
cloned and sequenced the cDNA encoding this protein, designated PURA,
from a human fetal liver cDNA library. The deduced 322-amino acid
protein contains an N-terminal glycine-rich region, 3 repeats of a
23-amino acid class I motif, 2 repeats of a 26-amino acid class II
motif, an amphipathic helix, and a C-terminal glutamine-glutamate-rich
domain. Northern blot analysis of human fetal liver, HeLa cells, lung
tumor cells, and hepatoma cells showed expression of 4 transcripts, from
2.0 to 5.0 kb, that are either multiple PURA transcripts or homologous
mRNAs. RACE-PCR suggested the presence of 3 PURA transcripts of 1.6 to
2.1 kb.
Kelm et al. (1997) cloned mouse Pura (p46) and Purb (p44) and identified
them as the 2 components of the previously designated vascular actin
single-stranded DNA-binding factor-2, which specifically bound to
purine-rich regions within an enhancer and an exon of vascular actin
(Kelm et al., 1996).
GENE FUNCTION
Bergemann et al. (1992) used gel shift assays to show that PURA binds
preferentially to single-stranded DNA containing the purine-rich
element.
Pur-alpha is a single-stranded DNA-binding protein with specific
affinity for a purine-rich element of the configuration (GGN)n present
in several initiation zones of eukaryotic DNA replication. It interacts
with large T-antigen and cellular protein YB-1 (154030) to activate JC
viral DNA transcription in human cells (Chen et al., 1995). The
functional activities of Pur-alpha, together with its evolutionary
conservation, suggested that it may represent an important link between
DNA replication and differential gene expression.
Gallia et al. (2000) reviewed the structure and function of PURA. The
central repeat region of PURA mediates binding to its single-stranded
DNA target sequence as well as to regulatory proteins, both of which are
modulated by RNA. In its C-terminal half, PURA contains an amphipathic
alpha-helix with limited homology to the large tumor antigen of several
polyomaviruses with a PSYC, or 'psycho,' motif. It also contains an
N-terminal glycine-rich region. PURA is implicated in the
transcriptional control of a number of cellular genes, including MBP
(159430), FE65 (APBB1; 602709), and neuronal ACHR (e.g., CHRNB2;
118507), as well as viral promoters for JCV and HIV-1, which replicate
in the central nervous system. PURA is also involved in the control of
cell growth and interacts with the hypophosphorylated form of RB1
(614041).
Fragile X-associated tremor/ataxia syndrome (FXTAS; 300623) is a
neurodegenerative disorder caused by FMR1 premutation alleles containing
55 to 200 repeats of the trinucleotide CGG (309550.0004). Using
gel-shift assays with mouse and fly brain lysates, followed by protein
purification and mass spectroscopy, Jin et al. (2007) showed that
Pur-alpha bound (CGG)105. Pur-alpha bound CGG repeats in a
sequence-specific manner, and overexpression of Pur-alpha in a
Drosophila model of FXTAS suppressed CGG repeat-mediated
neurodegeneration in a dose-dependent manner. Furthermore,
immunohistochemical analysis showed that Pur-alpha was ubiquitously
expressed in wildtype fly eyes, but it was sequestered in inclusions in
fly eyes expressing (CGG)105. Human PURA was present in
ubiquitin-positive inclusions in postmortem FXTAS brain tissues. Jin et
al. (2007) hypothesized that PURA is sequestered from its normal
function by binding premutation CGG repeats, leading to pathologic
changes in FXTAS.
MAPPING
Using a 16-kb genomic probe together with hybridization of a cDNA probe
to blots of DNA from human/hamster cell lines, Ma et al. (1995) mapped
the PURA gene to 5q31. This region is frequently deleted in myelogenous
leukemias in hematologic malignancies and other cancers. Sequences with
homology to the PURA gene were also present at 6q14.
ANIMAL MODEL
Khalili et al. (2003) found that Pura -/- mice appeared normal at birth,
but at 2 weeks of age, they developed neurologic problems characterized
by severe tremor and spontaneous seizures, and they died by 4 weeks.
Regions of the hippocampus and cerebellum of Pura -/- mice showed
severely lower numbers of neurons compared with wildtype littermates,
and lamination of these regions was aberrant at time of death.
Immunohistochemical analysis of Mcm7 (600592), a marker for DNA
replication, revealed lack of proliferation of precursor cells in these
regions in Pura -/- mice. Proliferation was also low or absent in
several other tissues of Pura -/- mice, including those of myeloid
lineage, whereas those of Pura +/- mice were intermediate. Evaluation of
brain sections indicated reduced myelination and pathologic development
of oligodendrocytes and astrocytes. At postnatal day 5, a critical time
for cerebellar development, Pura and Cdk5 (123831) were both at peak
levels in bodies and dendrites of Purkinje cells of wildtype mice, but
both proteins were absent in dendrites of Pura -/- mice.
Immunohistochemical analysis revealed dramatic reduction in both
phosphorylated and nonphosphorylated neurofilaments in dendrites of the
Purkinje cell layer and of synapse formation in the hippocampus. Khalili
et al. (2003) concluded that PURA has a role in developmentally timed
DNA replication in specific cell types.
*FIELD* RF
1. Bergemann, A. D.; Johnson, E. M.: The HeLa Pur factor binds single-stranded
DNA at a specific element conserved in gene flanking regions and origins
of DNA replication. Molec. Cell. Biol. 12: 1257-1265, 1992.
2. Bergemann, A. D.; Ma, Z.-W.; Johnson, E. M.: Sequence of cDNA
comprising the human pur gene and sequence-specific single-stranded-DNA-binding
properties of the encoded protein. Molec. Cell. Biol. 12: 5673-5682,
1992.
3. Chen, N. N.; Chang, C.-F.; Gallia, G. L.; Kerr, D. A.; Johnson,
E. M.; Krachmarov, C. P.; Barr, S. M.; Frisque, R. J.; Bollag, B.;
Khalili, K.: Cooperative action of cellular proteins YB-1 and Pur-alpha
with the tumor antigen of the human JC polyomavirus determines their
interaction with the viral lytic control element. Proc. Nat. Acad.
Sci. 92: 1087-1091, 1995.
4. Gallia, G. L.; Johnson, E. M.; Khalili, K.: Pur-alpha: a multifunctional
single-stranded DNA- and RNA-binding protein. Nucleic Acids Res. 28:
3197-3205, 2000.
5. Jin, P.; Duan, R.; Qurashi, A.; Qin, Y.; Tian, D.; Rosser, T. C.;
Liu, H.; Feng, Y.; Warren, S. T.: Pur alpha binds to rCGG repeats
and modulates repeat-mediated neurodegeneration in a Drosophila model
of fragile X tremor/ataxia syndrome. Neuron 55: 556-564, 2007.
6. Kelm, R. J., Jr.; Elder, P. K.; Strauch, A. R.; Getz, M. J.: Sequence
of cDNAs encoding components of vascular actin single-stranded DNA-binding
factor 2 establish identity to Pur-alpha and Pur-beta. J. Biol. Chem. 272:
267427-26733, 1997.
7. Kelm, R. J., Jr.; Sun, S.; Strauch, A. R.; Getz, M. J.: Repression
of transcriptional enhancer factor-1 and activator protein-1-dependent
enhancer activity by vascular actin single-stranded DNA binding factor
2. J. Biol. Chem. 271: 24278-24285, 1996.
8. Khalili, K.; Del Valle, L.; Muralidharan, V.; Gault, W. J.; Darbinian,
N.; Otte, J.; Meier, E.; Johnson, E. M.; Daniel, D. C.; Kinoshita,
Y.; Amini, S.; Gordon, J.: Pur-alpha is essential for postnatal brain
development and developmentally coupled cellular proliferation as
revealed by genetic inactivation in the mouse. Molec. Cell. Biol. 23:
6857-6875, 2003.
9. Ma, Z.-W.; Pejovic, T.; Najfeld, V.; Ward, D. C.; Johnson, E. M.
: Localization of PURA, the gene encoding the sequence-specific single-stranded-DNA-binding
protein Pur-alpha, to chromosome band 5q31. Cytogenet. Cell Genet. 71:
64-67, 1995.
*FIELD* CN
Ada Hamosh - updated: 8/28/2009
Patricia A. Hartz - updated: 4/8/2009
Laura L. Baxter - updated: 8/27/2004
Paul J. Converse - updated: 10/12/2000
Victor A. McKusick - updated: 4/3/1996
*FIELD* CD
Victor A. McKusick: 3/29/1995
*FIELD* ED
carol: 06/17/2011
mgross: 9/4/2009
terry: 8/28/2009
mgross: 4/8/2009
terry: 4/8/2009
carol: 9/1/2004
terry: 8/27/2004
mcapotos: 10/19/2000
mcapotos: 10/16/2000
terry: 10/12/2000
alopez: 7/29/1998
dkim: 7/24/1998
mark: 3/5/1998
jamie: 2/12/1997
carol: 3/30/1995
carol: 3/29/1995
*RECORD*
*FIELD* NO
600473
*FIELD* TI
*600473 PURINE-RICH ELEMENT-BINDING PROTEIN A; PURA
;;PUR-ALPHA
*FIELD* TX
CLONING
read more
Bergemann and Johnson (1992) characterized an approximately 28-kD
protein from HeLa cell nuclear extracts that bound specifically to a
purine-rich repeat element located at a site of DNA binding upstream of
the human c-myc gene, and at origins of replication and transcription
initiation sites in a variety of eukaryotes. Bergemann et al. (1992)
cloned and sequenced the cDNA encoding this protein, designated PURA,
from a human fetal liver cDNA library. The deduced 322-amino acid
protein contains an N-terminal glycine-rich region, 3 repeats of a
23-amino acid class I motif, 2 repeats of a 26-amino acid class II
motif, an amphipathic helix, and a C-terminal glutamine-glutamate-rich
domain. Northern blot analysis of human fetal liver, HeLa cells, lung
tumor cells, and hepatoma cells showed expression of 4 transcripts, from
2.0 to 5.0 kb, that are either multiple PURA transcripts or homologous
mRNAs. RACE-PCR suggested the presence of 3 PURA transcripts of 1.6 to
2.1 kb.
Kelm et al. (1997) cloned mouse Pura (p46) and Purb (p44) and identified
them as the 2 components of the previously designated vascular actin
single-stranded DNA-binding factor-2, which specifically bound to
purine-rich regions within an enhancer and an exon of vascular actin
(Kelm et al., 1996).
GENE FUNCTION
Bergemann et al. (1992) used gel shift assays to show that PURA binds
preferentially to single-stranded DNA containing the purine-rich
element.
Pur-alpha is a single-stranded DNA-binding protein with specific
affinity for a purine-rich element of the configuration (GGN)n present
in several initiation zones of eukaryotic DNA replication. It interacts
with large T-antigen and cellular protein YB-1 (154030) to activate JC
viral DNA transcription in human cells (Chen et al., 1995). The
functional activities of Pur-alpha, together with its evolutionary
conservation, suggested that it may represent an important link between
DNA replication and differential gene expression.
Gallia et al. (2000) reviewed the structure and function of PURA. The
central repeat region of PURA mediates binding to its single-stranded
DNA target sequence as well as to regulatory proteins, both of which are
modulated by RNA. In its C-terminal half, PURA contains an amphipathic
alpha-helix with limited homology to the large tumor antigen of several
polyomaviruses with a PSYC, or 'psycho,' motif. It also contains an
N-terminal glycine-rich region. PURA is implicated in the
transcriptional control of a number of cellular genes, including MBP
(159430), FE65 (APBB1; 602709), and neuronal ACHR (e.g., CHRNB2;
118507), as well as viral promoters for JCV and HIV-1, which replicate
in the central nervous system. PURA is also involved in the control of
cell growth and interacts with the hypophosphorylated form of RB1
(614041).
Fragile X-associated tremor/ataxia syndrome (FXTAS; 300623) is a
neurodegenerative disorder caused by FMR1 premutation alleles containing
55 to 200 repeats of the trinucleotide CGG (309550.0004). Using
gel-shift assays with mouse and fly brain lysates, followed by protein
purification and mass spectroscopy, Jin et al. (2007) showed that
Pur-alpha bound (CGG)105. Pur-alpha bound CGG repeats in a
sequence-specific manner, and overexpression of Pur-alpha in a
Drosophila model of FXTAS suppressed CGG repeat-mediated
neurodegeneration in a dose-dependent manner. Furthermore,
immunohistochemical analysis showed that Pur-alpha was ubiquitously
expressed in wildtype fly eyes, but it was sequestered in inclusions in
fly eyes expressing (CGG)105. Human PURA was present in
ubiquitin-positive inclusions in postmortem FXTAS brain tissues. Jin et
al. (2007) hypothesized that PURA is sequestered from its normal
function by binding premutation CGG repeats, leading to pathologic
changes in FXTAS.
MAPPING
Using a 16-kb genomic probe together with hybridization of a cDNA probe
to blots of DNA from human/hamster cell lines, Ma et al. (1995) mapped
the PURA gene to 5q31. This region is frequently deleted in myelogenous
leukemias in hematologic malignancies and other cancers. Sequences with
homology to the PURA gene were also present at 6q14.
ANIMAL MODEL
Khalili et al. (2003) found that Pura -/- mice appeared normal at birth,
but at 2 weeks of age, they developed neurologic problems characterized
by severe tremor and spontaneous seizures, and they died by 4 weeks.
Regions of the hippocampus and cerebellum of Pura -/- mice showed
severely lower numbers of neurons compared with wildtype littermates,
and lamination of these regions was aberrant at time of death.
Immunohistochemical analysis of Mcm7 (600592), a marker for DNA
replication, revealed lack of proliferation of precursor cells in these
regions in Pura -/- mice. Proliferation was also low or absent in
several other tissues of Pura -/- mice, including those of myeloid
lineage, whereas those of Pura +/- mice were intermediate. Evaluation of
brain sections indicated reduced myelination and pathologic development
of oligodendrocytes and astrocytes. At postnatal day 5, a critical time
for cerebellar development, Pura and Cdk5 (123831) were both at peak
levels in bodies and dendrites of Purkinje cells of wildtype mice, but
both proteins were absent in dendrites of Pura -/- mice.
Immunohistochemical analysis revealed dramatic reduction in both
phosphorylated and nonphosphorylated neurofilaments in dendrites of the
Purkinje cell layer and of synapse formation in the hippocampus. Khalili
et al. (2003) concluded that PURA has a role in developmentally timed
DNA replication in specific cell types.
*FIELD* RF
1. Bergemann, A. D.; Johnson, E. M.: The HeLa Pur factor binds single-stranded
DNA at a specific element conserved in gene flanking regions and origins
of DNA replication. Molec. Cell. Biol. 12: 1257-1265, 1992.
2. Bergemann, A. D.; Ma, Z.-W.; Johnson, E. M.: Sequence of cDNA
comprising the human pur gene and sequence-specific single-stranded-DNA-binding
properties of the encoded protein. Molec. Cell. Biol. 12: 5673-5682,
1992.
3. Chen, N. N.; Chang, C.-F.; Gallia, G. L.; Kerr, D. A.; Johnson,
E. M.; Krachmarov, C. P.; Barr, S. M.; Frisque, R. J.; Bollag, B.;
Khalili, K.: Cooperative action of cellular proteins YB-1 and Pur-alpha
with the tumor antigen of the human JC polyomavirus determines their
interaction with the viral lytic control element. Proc. Nat. Acad.
Sci. 92: 1087-1091, 1995.
4. Gallia, G. L.; Johnson, E. M.; Khalili, K.: Pur-alpha: a multifunctional
single-stranded DNA- and RNA-binding protein. Nucleic Acids Res. 28:
3197-3205, 2000.
5. Jin, P.; Duan, R.; Qurashi, A.; Qin, Y.; Tian, D.; Rosser, T. C.;
Liu, H.; Feng, Y.; Warren, S. T.: Pur alpha binds to rCGG repeats
and modulates repeat-mediated neurodegeneration in a Drosophila model
of fragile X tremor/ataxia syndrome. Neuron 55: 556-564, 2007.
6. Kelm, R. J., Jr.; Elder, P. K.; Strauch, A. R.; Getz, M. J.: Sequence
of cDNAs encoding components of vascular actin single-stranded DNA-binding
factor 2 establish identity to Pur-alpha and Pur-beta. J. Biol. Chem. 272:
267427-26733, 1997.
7. Kelm, R. J., Jr.; Sun, S.; Strauch, A. R.; Getz, M. J.: Repression
of transcriptional enhancer factor-1 and activator protein-1-dependent
enhancer activity by vascular actin single-stranded DNA binding factor
2. J. Biol. Chem. 271: 24278-24285, 1996.
8. Khalili, K.; Del Valle, L.; Muralidharan, V.; Gault, W. J.; Darbinian,
N.; Otte, J.; Meier, E.; Johnson, E. M.; Daniel, D. C.; Kinoshita,
Y.; Amini, S.; Gordon, J.: Pur-alpha is essential for postnatal brain
development and developmentally coupled cellular proliferation as
revealed by genetic inactivation in the mouse. Molec. Cell. Biol. 23:
6857-6875, 2003.
9. Ma, Z.-W.; Pejovic, T.; Najfeld, V.; Ward, D. C.; Johnson, E. M.
: Localization of PURA, the gene encoding the sequence-specific single-stranded-DNA-binding
protein Pur-alpha, to chromosome band 5q31. Cytogenet. Cell Genet. 71:
64-67, 1995.
*FIELD* CN
Ada Hamosh - updated: 8/28/2009
Patricia A. Hartz - updated: 4/8/2009
Laura L. Baxter - updated: 8/27/2004
Paul J. Converse - updated: 10/12/2000
Victor A. McKusick - updated: 4/3/1996
*FIELD* CD
Victor A. McKusick: 3/29/1995
*FIELD* ED
carol: 06/17/2011
mgross: 9/4/2009
terry: 8/28/2009
mgross: 4/8/2009
terry: 4/8/2009
carol: 9/1/2004
terry: 8/27/2004
mcapotos: 10/19/2000
mcapotos: 10/16/2000
terry: 10/12/2000
alopez: 7/29/1998
dkim: 7/24/1998
mark: 3/5/1998
jamie: 2/12/1997
carol: 3/30/1995
carol: 3/29/1995