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Description:
Splicing factor, proline- and glutamine-rich (Polypyrimidine tract-binding protein-associated splicing factor) (PTB-associated splicingfactor) (PSF) (DNA-binding p52/p100 complex, 100 kDa subunit) (100-kDaDNA-pairing protein) (hPOMp100).
Molecular weight: 76149
View which proteins in this organism that is involved with DNA Repair;
classified after biological processes (using data from the GOA project):
DNA repair( GO:0006281 )
Important dates:
01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
01-OCT-1996, sequence version 2.
07-MAR-2006, entry version 64.
Phylogenetic order:
Eukaryota Metazoa Chordata Craniata Vertebrata Euteleostomi Mammalia Eutheria Euarchontoglires Primates Catarrhini Hominidae Homo.
To calculate the pI (Isoelectric point - the pH where a protein has a neutral charge),
go to this page and enter the protein ID (e.g 3MG_ECOLI): http://us.expasy.org/tools/pi_tool.html
Links to references in other databases for protein SFPQ_HUMAN:
| Database | Pointer | Add. info#1 | Add. info#2 |
| EMBL | X70944 | CAA50283.1 | - |
| EMBL | X16850 | CAA34747.1 | - |
| PIR | A46302 | A46302. | |
| PIR | S29770 | S29770. | |
| HSSP | O08583 | 1NO8 | |
| IntAct | P23246 | -.1 | |
| SWISS-2DPAGE | P23246 | HUMAN. | |
| Ensembl | ENSG00000116560 | Homo sapiens.1 | |
| HGNC | HGNC:10774 | SFPQ.1 | |
| MIM | 605199 | gene. | |
| GO | GO:0005515 | F:protein binding | IPI. |
| GO | GO:0006397 | P:mRNA processing | TAS. |
| GO | GO:0008380 | P:RNA splicing | TAS. |
| InterPro | IPR012677 | a_b_plait_nuc_bd. | |
| InterPro | IPR012975 | NOPS. | |
| InterPro | IPR000504 | RNP1_RNA_bd. | |
| Pfam | PF08075 | NOPS | 1. |
| Pfam | PF00076 | RRM_1 | 2. |
| SMART | SM00360 | RRM | 2. |
| PROSITE | PS50102 | RRM | 2. |
Keywords:
Activator; Alternative splicing; Chromosomal translocation; Direct protein sequencing; DNA damage; DNA recombination; DNA repair; DNA-binding; mRNA processing; mRNA splicing; Nuclear protein; Phosphorylation; Repeat; Repressor; RNA-binding; Transcription; Transcription regulation.
References:
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, ALTERNATIVE
RP SPLICING, AND FUNCTION.
RC TISSUE=Fetal brain;
RX MEDLINE=93194059; PubMed=8449401;
RA Patton J.G., Porro E.B., Galceran J., Tempst P., Nadal-Ginard B.;
RT "Cloning and characterization of PSF, a novel pre-mRNA splicing
RT factor.";
RL Genes Dev. 7:393-406(1993).
RN [2]
RP PROTEIN SEQUENCE OF 48-68 AND 213-246, BLOCKAGE OF THE N-TERMINUS,
RP DNA-BINDING, AND SUBUNIT.
RX MEDLINE=93176127; PubMed=8439294;
RA Zhang W.-W., Zhang L.-X., Busch R.K., Farres J., Busch H.;
RT "Purification and characterization of a DNA-binding heterodimer of 52
RT and 100 kDa from HeLa cells.";
RL Biochem. J. 290:267-272(1993).
RN [3]
RP PROTEIN SEQUENCE OF 292-311; 415-421 AND 503-510, AND IDENTIFICATION
RP IN U5/4/6 SNRNP COMPLEXES.
RX MEDLINE=98072280; PubMed=9409622;
RA Teigelkamp S., Mundt C., Achsel T., Will C.L., Luehrmann R.;
RT "The human U5 snRNP-specific 100-kD protein is an RS domain-
RT containing, putative RNA helicase with significant homology to the
RT yeast splicing factor Prp28p.";
RL RNA 3:1313-1326(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 312-707.
RC TISSUE=Fetal skeletal muscle;
RX MEDLINE=90091812; PubMed=2480877;
RA Gower H.J., Moore S.E., Dickson G., Elsom V.L., Nayak R., Walsh F.S.;
RT "Cloning and characterization of a myoblast cell surface antigen
RT defined by 24.1D5 monoclonal antibody.";
RL Development 105:723-731(1989).
RN [5]
RP PROTEIN SEQUENCE OF 414-421 AND 427-448, SUBCELLULAR LOCATION,
RP INTERACTION WITH SNRPA, AND IDENTIFICATION IN A SNRNP-FREE COMPLEX
RP WITH SNRPA.
RX MEDLINE=99063394; PubMed=9848648; DOI=10.1017/S1355838298981183;
RA Lutz C.S., Cooke C., O'Connor J.P., Kobayashi R., Alwine J.C.;
RT "The snRNP-free U1A (SF-A) complex(es): identification of the largest
RT subunit as PSF, the polypyrimidine-tract binding protein-associated
RT splicing factor.";
RL RNA 4:1493-1499(1998).
RN [6]
RP PROTEIN SEQUENCE OF 600-606 AND 667-677, INTERACTION WITH PTBP1, AND
RP SUBCELLULAR LOCATION.
RX DOI=10.1002/(SICI)1097-4644(20000315)76:4<559::AID-JCB4>3.0.CO;2-U;
RA Meissner M., Dechat T., Gerner C., Grimm R., Foisner R., Sauermann G.;
RT "Differential nuclear localization and nuclear matrix association of
RT the splicing factors PSF and PTB.";
RL J. Cell. Biochem. 76:559-566(2000).
RN [7]
RP FUNCTION, INTERACTION WITH PRE-MRNA, AND IDENTIFICATION IN SPLICEOSOME
RP COMPLEX.
RA Gozani O., Patton J.G., Reed R.;
RT "A novel set of spliceosome-associated proteins and the essential
RT splicing factor PSF bind stably to pre-mRNA prior to catalytic step II
RT of the splicing reaction.";
RL EMBO J. 13:3356-3367(1994).
RN [8]
RP CHROMOSOMAL TRANSLOCATION WITH TFE3.
RX MEDLINE=98054131; PubMed=9393982; DOI=10.1038/sj.onc.1201394;
RA Clark J., Lu Y.-J., Sidhar S.K., Parker C., Gill S., Smedley D.,
RA Hamoudi R., Linehan W.M., Shipley J., Cooper C.S.;
RT "Fusion of splicing factor genes PSF and NonO (p54nrb) to the TFE3
RT gene in papillary renal cell carcinoma.";
RL Oncogene 15:2233-2239(1997).
RN [9]
RP INTERACTION WITH TOP1, AND IDENTIFICATION IN A COMPLEX WITH NONO AND
RP TOP1.
RX MEDLINE=98434520; PubMed=9756848; DOI=10.1074/jbc.273.41.26261;
RA Straub T., Grue P., Uhse A., Lisby M., Knudsen B.R., Tange T.O.,
RA Westergaard O., Boege F.;
RT "The RNA-splicing factor PSF/p54 controls DNA-topoisomerase I activity
RT by a direct interaction.";
RL J. Biol. Chem. 273:26261-26264(1998).
RN [10]
RP FUNCTION IN DNA UNWINDING.
RX PubMed=10858305; DOI=10.1021/bi992898e;
RA Straub T., Knudsen B.R., Boege F.;
RT "PSF/p54(nrb) stimulates 'jumping' of DNA topoisomerase I between
RT separate DNA helices.";
RL Biochemistry 39:7552-7558(2000).
RN [11]
RP FUNCTION IN TRANSCRIPTION REGULATION, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX MEDLINE=20304193; PubMed=10847580; DOI=10.1210/me.14.6.774;
RA Urban R.J., Bodenburg Y., Kurosky A., Wood T.G., Gasic S.;
RT "Polypyrimidine tract-binding protein-associated splicing factor is a
RT negative regulator of transcriptional activity of the porcine p450scc
RT insulin-like growth factor response element.";
RL Mol. Endocrinol. 14:774-782(2000).
RN [12]
RP FUNCTION IN HOMOLOGOUS DNA PAIRING, AND PHOSPHORYLATION.
RX MEDLINE=20392247; PubMed=10931916; DOI=10.1093/nar/28.16.3022;
RA Akhmedov A.T., Lopez B.S.;
RT "Human 100-kDa homologous DNA-pairing protein is the splicing factor
RT PSF and promotes DNA strand invasion.";
RL Nucleic Acids Res. 28:3022-3030(2000).
RN [13]
RP FUNCTION IN NUCLEAR RETENTION OF A-TO-I EDITED RNAS, AND
RP IDENTIFICATION IN A COMPLEX WITH NONO AND MATR3.
RX MEDLINE=21417141; PubMed=11525732; DOI=10.1016/S0092-8674(01)00466-4;
RA Zhang Z., Carmichael G.G.;
RT "The fate of dsRNA in the nucleus: a p54(nrb)-containing complex
RT mediates the nuclear retention of promiscuously A-to-I edited RNAs.";
RL Cell 106:465-475(2001).
RN [14]
RP INTERACTION WITH SNRP70, AND PHOSPHORYLATION.
RX MEDLINE=21406000; PubMed=11514619;
RA Shav-Tal Y., Cohen M., Lapter S., Dye B., Patton J.G.,
RA Vandekerckhove J., Zipori D.;
RT "Nuclear relocalization of the pre-mRNA splicing factor PSF during
RT apoptosis involves hyperphosphorylation, masking of antigenic
RT epitopes, and changes in protein interactions.";
RL Mol. Biol. Cell 12:2328-2340(2001).
RN [15]
RP FUNCTION IN TRANSCRIPTION REGULATION, AND INTERACTIONS WITH RXRA; THRA
RP AND SIN3A.
RX MEDLINE=21160263; PubMed=11259580;
RX DOI=10.1128/MCB.21.7.2298-2311.2001;
RA Mathur M., Tucker P.W., Samuels H.H.;
RT "PSF is a novel corepressor that mediates its effect through Sin3A and
RT the DNA binding domain of nuclear hormone receptors.";
RL Mol. Cell. Biol. 21:2298-2311(2001).
RN [16]
RP FUNCTION IN TRANSCRIPTION REGULATION, INTERACTIONS WITH NR5A1 AND
RP SIN3A, AND IDENTIFICATION IN A COMPLEX WITH NONO AND NR5A1.
RX MEDLINE=21895433; PubMed=11897684; DOI=10.1210/en.143.4.1280;
RA Sewer M.B., Nguyen V.Q., Huang C.J., Tucker P.W., Kagawa N.,
RA Waterman M.R.;
RT "Transcriptional activation of human CYP17 in H295R adrenocortical
RT cells depends on complex formation among p54(nrb)/NonO, protein-
RT associated splicing factor, and SF-1, a complex that also participates
RT in repression of transcription.";
RL Endocrinology 143:1280-1290(2002).
RN [17]
RP INTERACTIONS WITH NONO AND U5 SNRNA, AND IDENTIFICATION IN IN U5/4/6
RP SNRNP SND SPLICEOSOME COMPLEXES.
RX MEDLINE=22290639; PubMed=12403470; DOI=10.1017/S1355838202022070;
RA Peng R., Dye B.T., Perez I., Barnard D.C., Thompson A.B., Patton J.G.;
RT "PSF and p54nrb bind a conserved stem in U5 snRNA.";
RL RNA 8:1334-1347(2002).
RN [18]
RP FUNCTION IN DNA REPAIR, IDENTIFICATION BY MASS-SPECTROMETRY,
RP DNA-BINDING, AND SUBUNIT.
RX PubMed=15590677; DOI=10.1074/jbc.M412758200;
RA Bladen C.L., Udayakumar D., Takeda Y., Dynan W.S.;
RT "Identification of the polypyrimidine tract binding protein-associated
RT splicing factor.p54(nrb) complex as a candidate DNA double-strand
RT break rejoining factor.";
RL J. Biol. Chem. 280:5205-5210(2005).
Feature:
CHAIN 1 707 Splicing factor, proline- and glutamine-
rich.
/FTId=PRO_0000081909.
REPEAT 9 11 1.
REPEAT 19 21 2.
REPEAT 25 27 3.
DOMAIN 297 369 RRM 1.
DOMAIN 371 452 RRM 2.
REGION 9 27 3 X 3 AA repeats of R-G-G.
COMPBIAS 10 266 Gln/Glu/Pro-rich.
COMPBIAS 10 15 Poly-Gly.
COMPBIAS 20 27 Poly-Gly.
COMPBIAS 56 65 Poly-Pro.
COMPBIAS 67 71 Poly-Gln.
COMPBIAS 95 98 Poly-Gln.
COMPBIAS 99 103 Poly-Pro.
COMPBIAS 184 188 Poly-Pro.
COMPBIAS 571 574 Poly-Arg.
COMPBIAS 613 616 Poly-Gly.
COMPBIAS 635 641 Poly-Gly.
SITE 662 663 Breakpoint for translocation to form
SFPQ-TFE3.
VARSPLIC 663 707 RTERFGQGGAGPVGGQGPRGMGPGTPAGYGRGREEYEGPNK
KPRF -> VRMIDVG (in isoform Short).
/FTId=VSP_005855.
CONFLICT 243 243 G -> R (in Ref. 2).
Comments:
-!- FUNCTION: DNA- and RNA binding protein, involved in several
nuclear processes. Essential pre-mRNA splicing factor required
early in spliceosome formation and for splicing catalytic step II,
probably as an heteromer with NONO. Binds to pre-mRNA in
spliceosome C complex, and specifically binds to intronic
polypyrimidine tracts. Interacts with U5 snRNA, probably by
binding to a purine-rich sequence located on the 3' side of U5
snRNA stem 1b. May be involved in a pre-mRNA coupled splicing and
polyadenylation process as component of a snRNP-free complex with
SNRPA/U1A. The SFPQ-NONO heteromer associated with MATR3 may play
a role in nuclear retention of defective RNAs. SFPQ may be
involved in homologous DNA pairing; in vitro, promotes the
invasion of ssDNA between a duplex DNA and produces a D-loop
formation. The SFPQ-NONO heteromer may be involved in DNA
unwinding by modulating the function of topoisomerase I/TOP1; in
vitro, stimulates dissociation of TOP1 from DNA after cleavage and
enhances its jumping between separate DNA helices. The SFPQ-NONO
heteromer may be involved in DNA nonhomologous end joining (NHEJ)
required for double-strand break repair and V(D)J recombination
and may stabilize paired DNA ends; in vitro, the complex strongly
stimulates DNA end joining, binds directly to the DNA substrates
and cooperates with the Ku70/G22P1-Ku80/XRCC5 (Ku) dimer to
establish a functional preligation complex. SFPQ is involved in
transcriptional regulation. Transcriptional repression is probably
mediated by an interaction of SFPQ with SIN3A and subsequent
recruitment of histone deacatylases (HDACs). The SFPQ-NONO/SF-1
complex binds to the CYP17 promoter and regulates basal and cAMP-
dependent transcriptional avtivity. SFPQ isoform Long binds to the
DNA binding domains (DBD) of nuclear hormone receptors, like RXRA
and probably THRA, and acts as transcriptional corepressor in
absence of hormone ligands. Binds the DNA sequence 5'-CTGAGTC-3'
in the insulin-like growth factor response element (IGFRE) and
inhibits IGF-I-stimulated transcriptional activity.
-!- SUBUNIT: Monomer and component of the SFPQ-NONO complex, which is
probably a heterotetramer of two 52 kDa (NONO) and two 100 kDa
(SFPQ) subunits. SFPQ is a component of spliceosome and U5.4/6
snRNP complexes. Interacts with SNRPA/U1A. Component of a snRNP-
free complex with SNRPA/U1A. Part of complex consisiting of SFPQ,
NONO and MATR3. Interacts with polypyrimidine tract-binding
protein 1/PTB. Part of a complex consisting of SFPQ, NONO and
NR5A1/SF-1. Interacts with RXRA, probably THRA, and SIN3A.
Interacts with TOP1. Part of a complex consisting of SFPQ, NONO
and TOP1. Interacts with SNRP70 in apoptotic cells.
-!- INTERACTION:
Q15233:NONO; NbExp=1; IntAct=EBI-355463, EBI-350527;
P26599:PTBP1; NbExp=1; IntAct=EBI-355453, EBI-350540;
P28700:Rxra (xeno); NbExp=3; IntAct=EBI-355463, EBI-346715;
Q96ST3:SIN3A; NbExp=2; IntAct=EBI-355453, EBI-347218;
P09012:SNRPA; NbExp=4; IntAct=EBI-355453, EBI-607085;
P04625:THRA (xeno); NbExp=2; IntAct=EBI-355463, EBI-286261;
-!- SUBCELLULAR LOCATION: Nuclear; predominantly in nuclear matrix.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Comment=Additional isoforms seem to exist;
Name=Long; Synonyms=A;
IsoId=P23246-1; Sequence=Displayed;
Name=Short; Synonyms=F;
IsoId=P23246-2; Sequence=VSP_005855;
-!- PTM: The N-terminus is blocked.
-!- PTM: Phosphorylated on multiple serine and threonoine residues
during apoptosis. In vitro phosphorylated by PKC. Phosphorylation
stimulates binding to DNA and D-loop formation, but inhibits
binding to RNA.
-!- DISEASE: A chromosomal aberration involving SFPQ may be a cause of
papillary renal cell carcinoma (PRCC). Translocation
t(X;1)(p11.2;p34) with TFE3.
-!- SIMILARITY: Contains 2 RRM (RNA recognition motif) domains.
-!- CAUTION: Was originally (Ref.2) thought to be myoblast cell
surface antigen 24.1D5 and a possible membrane-bound protein
ectokinase.
-!- DATABASE: NAME=Atlas Genet. Cytogenet. Oncol. Haematol.;
WWW="http://www.infobiogen.fr/services/chromcancer/Genes/PSFID167.html".
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Sequence length: 707
MSRDRFRSRG GGGGGFHRRG GGGGRGGLHD FRSPPPGMGL NQNRGPMGPG PGQSGPKPPI
PPPPPHQQQQ QPPPQQPPPQ QPPPHQPPPH PQPHQQQQPP PPPQDSSKPV VAQGPGPAPG
VGSAPPASSS APPATPPTSG APPGSGPGPT PTPPPAVTSA PPGAPPPTPP SSGVPTTPPQ
AGGPPPPPAA VPGPGPGPKQ GPGPGGPKGG KMPGGPKPGG GPGLSTPGGH PKPPHRGGGE
PRGGRQHHPP YHQQHHQGPP PGGPGGRSEE KISDSEGFKA NLSLLRRPGE KTYTQRCRLF
VGNLPADITE DEFKRLFAKY GEPGEVFINK GKGFGFIKLE SRALAEIAKA ELDDTPMRGR
QLRVRFATHA AALSVRNLSP YVSNELLEEA FSQFGPIERA VVIVDDRGRS TGKGIVEFAS
KPAARKAFER CSEGVFLLTT TPRPVIVEPL EQLDDEDGLP EKLAQKNPMY QKERETPPRF
AQHGTFEYEY SQRWKSLDEM EKQQREQVEK NMKDAKDKLE SEMEDAYHEH QANLLRQDLM
RRQEELRRME ELHNQEMQKR KEMQLRQEEE RRRREEEMMI RQREMEEQMR RQREESYSRM
GYMDPRERDM RMGGGGAMNM GDPYGSGGQK FPPLGGGGGI GYEANPGVPP ATMSGSMMGS
DMRTERFGQG GAGPVGGQGP RGMGPGTPAG YGRGREEYEG PNKKPRF