PSF1_HUMAN
ID PSF1_HUMAN Reviewed; 196 AA.
AC Q14691; Q9NQE2; Q9NQI7;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=DNA replication complex GINS protein PSF1;
DE AltName: Full=GINS complex subunit 1;
GN Name=GINS1; Synonyms=KIAA0186, PSF1;
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 [LARGE SCALE MRNA].
RC TISSUE=Bone marrow;
RX PubMed=8724849; DOI=10.1093/dnares/3.1.17;
RA Nagase T., Seki N., Ishikawa K., Tanaka A., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. V. The
RT coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of
RT cDNA clones from human cell line KG-1.";
RL DNA Res. 3:17-24(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ILE-97.
RC TISSUE=Skin;
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 INDUCTION.
RX PubMed=17611626; DOI=10.1371/journal.pone.0000594;
RA Ryu B., Kim D.S., Deluca A.M., Alani R.M.;
RT "Comprehensive expression profiling of tumor cell lines identifies
RT molecular signatures of melanoma progression.";
RL PLoS ONE 2:E594-E594(2007).
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 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).
RN [7]
RP FUNCTION, INTERACTION WITH GINS3 AND GINS4, INVOLVEMENT IN IMD55, VARIANTS
RP IMD55 CYS-83 AND TYR-152, AND CHARACTERIZATION OF VARIANTS IMD55 CYS-83 AND
RP TYR-152.
RX PubMed=28414293; DOI=10.1172/jci90727;
RA Cottineau J., Kottemann M.C., Lach F.P., Kang Y.H., Vely F., Deenick E.K.,
RA Lazarov T., Gineau L., Wang Y., Farina A., Chansel M., Lorenzo L.,
RA Piperoglou C., Ma C.S., Nitschke P., Belkadi A., Itan Y., Boisson B.,
RA Jabot-Hanin F., Picard C., Bustamante J., Eidenschenk C., Boucherit S.,
RA Aladjidi N., Lacombe D., Barat P., Qasim W., Hurst J.A., Pollard A.J.,
RA Uhlig H.H., Fieschi C., Michon J., Bermudez V.P., Abel L.,
RA de Villartay J.P., Geissmann F., Tangye S.G., Hurwitz J., Vivier E.,
RA Casanova J.L., Smogorzewska A., Jouanguy E.;
RT "Inherited GINS1 deficiency underlies growth retardation along with
RT neutropenia and NK cell deficiency.";
RL J. Clin. Invest. 127:1991-2006(2017).
RN [8]
RP STRUCTURE BY ELECTRON MICROSCOPY (33 ANGSTROMS) IN COMPLEX WITH GINS2;
RP GINS3 AND GINS4, SUBUNIT, AND MASS SPECTROMETRY OF GINS COMPLEX.
RX PubMed=17557111; DOI=10.1038/sj.embor.7401002;
RA Boskovic J., Coloma J., Aparicio T., Zhou M., Robinson C.V., Mendez J.,
RA Montoya G.;
RT "Molecular architecture of the human GINS complex.";
RL EMBO Rep. 8:678-684(2007).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 1-151 IN COMPLEX WITH GINS2; GINS3
RP AND GINS4, AND SUBUNIT.
RX PubMed=17545466; DOI=10.1101/gad.1548107;
RA Choi J.M., Lim H.S., Kim J.J., Song O.K., Cho Y.;
RT "Crystal structure of the human GINS complex.";
RL Genes Dev. 21:1316-1321(2007).
RN [10]
RP FUNCTION, X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-149 IN COMPLEX WITH
RP GINS2; GINS3 AND GINS4, AND SUBUNIT.
RX PubMed=17417653; DOI=10.1038/nsmb1231;
RA Kamada K., Kubota Y., Arata T., Shindo Y., Hanaoka F.;
RT "Structure of the human GINS complex and its assembly and functional
RT interface in replication initiation.";
RL Nat. Struct. Mol. Biol. 14:388-396(2007).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.36 ANGSTROMS) IN COMPLEX WITH GINS2; GINS3 AND
RP GINS4, SUBUNIT, AND REGION.
RX PubMed=17652513; DOI=10.1073/pnas.0705558104;
RA Chang Y.P., Wang G., Bermudez V., Hurwitz J., Chen X.S.;
RT "Crystal structure of the GINS complex and functional insights into its
RT role in DNA replication.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:12685-12690(2007).
CC -!- FUNCTION: Required for correct functioning of the GINS complex, a
CC complex that plays an essential role in the initiation of DNA
CC replication, and progression of DNA replication forks. GINS complex
CC seems to bind preferentially to single-stranded DNA.
CC {ECO:0000269|PubMed:17417653, ECO:0000269|PubMed:28414293}.
CC -!- SUBUNIT: Component of the GINS complex which is a heterotetramer of
CC GINS1, GINS2, GINS3 and GINS4 (PubMed:17545466, PubMed:17557111,
CC PubMed:17652513, PubMed:28414293). Forms a stable subcomplex with
CC GINS4. GINS complex interacts with DNA primase in vitro
CC (PubMed:17545466, PubMed:17557111, PubMed:17652513, PubMed:28414293).
CC Component of the CMG helicase complex, composed of the MCM2-7 complex,
CC the GINS complex and CDC45 (By similarity).
CC {ECO:0000250|UniProtKB:Q7ZT47, ECO:0000269|PubMed:17545466,
CC ECO:0000269|PubMed:17557111, ECO:0000269|PubMed:17652513,
CC ECO:0000269|PubMed:28414293}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q7ZT47}.
CC Chromosome {ECO:0000250|UniProtKB:Q7ZT47}. Note=Associates with
CC chromatin. {ECO:0000250|UniProtKB:Q7ZT47}.
CC -!- INDUCTION: Significantly up-regulated in aggressive melanomas.
CC {ECO:0000269|PubMed:17611626}.
CC -!- MASS SPECTROMETRY: Mass=98373; Mass_error=13; Method=Electrospray;
CC Note=This is the measured mass for the GINS complex.;
CC Evidence={ECO:0000269|PubMed:17557111};
CC -!- DISEASE: Immunodeficiency 55 (IMD55) [MIM:617827]: An autosomal
CC recessive primary immunodeficiency characterized by chronic
CC neutropenia, natural killer cell deficiency, recurrent viral and
CC bacterial infections, and intrauterine growth retardation. Postnatal
CC growth retardation is present in most patients.
CC {ECO:0000269|PubMed:28414293}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the GINS1/PSF1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA11503.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; D80008; BAA11503.2; ALT_INIT; mRNA.
DR EMBL; AL353812; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL031672; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC012542; AAH12542.1; -; mRNA.
DR CCDS; CCDS33451.1; -.
DR RefSeq; NP_066545.3; NM_021067.4.
DR PDB; 2E9X; X-ray; 2.30 A; A/E=1-149.
DR PDB; 2EHO; X-ray; 3.00 A; B/F/J=1-151.
DR PDB; 2Q9Q; X-ray; 2.36 A; C/G=1-196.
DR PDB; 6XTX; EM; 3.29 A; A=1-196.
DR PDB; 6XTY; EM; 6.77 A; A=1-196.
DR PDB; 7PFO; EM; 3.20 A; D=1-196.
DR PDB; 7PLO; EM; 2.80 A; D=1-196.
DR PDBsum; 2E9X; -.
DR PDBsum; 2EHO; -.
DR PDBsum; 2Q9Q; -.
DR PDBsum; 6XTX; -.
DR PDBsum; 6XTY; -.
DR PDBsum; 7PFO; -.
DR PDBsum; 7PLO; -.
DR AlphaFoldDB; Q14691; -.
DR SMR; Q14691; -.
DR BioGRID; 115174; 25.
DR ComplexPortal; CPX-787; GINS complex.
DR CORUM; Q14691; -.
DR DIP; DIP-29331N; -.
DR IntAct; Q14691; 9.
DR MINT; Q14691; -.
DR STRING; 9606.ENSP00000262460; -.
DR GlyGen; Q14691; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q14691; -.
DR PhosphoSitePlus; Q14691; -.
DR BioMuta; GINS1; -.
DR DMDM; 6226339; -.
DR EPD; Q14691; -.
DR jPOST; Q14691; -.
DR MassIVE; Q14691; -.
DR MaxQB; Q14691; -.
DR PaxDb; Q14691; -.
DR PeptideAtlas; Q14691; -.
DR PRIDE; Q14691; -.
DR ProteomicsDB; 60129; -.
DR Antibodypedia; 10061; 191 antibodies from 26 providers.
DR DNASU; 9837; -.
DR Ensembl; ENST00000262460.5; ENSP00000262460.4; ENSG00000101003.10.
DR GeneID; 9837; -.
DR KEGG; hsa:9837; -.
DR MANE-Select; ENST00000262460.5; ENSP00000262460.4; NM_021067.5; NP_066545.3.
DR UCSC; uc002wuv.2; human.
DR CTD; 9837; -.
DR DisGeNET; 9837; -.
DR GeneCards; GINS1; -.
DR HGNC; HGNC:28980; GINS1.
DR HPA; ENSG00000101003; Tissue enhanced (lymphoid tissue, testis).
DR MalaCards; GINS1; -.
DR MIM; 610608; gene.
DR MIM; 617827; phenotype.
DR neXtProt; NX_Q14691; -.
DR OpenTargets; ENSG00000101003; -.
DR Orphanet; 505227; Combined immunodeficiency due to GINS1 deficiency.
DR PharmGKB; PA145008291; -.
DR VEuPathDB; HostDB:ENSG00000101003; -.
DR eggNOG; KOG3303; Eukaryota.
DR GeneTree; ENSGT00390000013968; -.
DR HOGENOM; CLU_079191_1_1_1; -.
DR InParanoid; Q14691; -.
DR OMA; NHLCMRR; -.
DR OrthoDB; 1249159at2759; -.
DR PhylomeDB; Q14691; -.
DR TreeFam; TF312848; -.
DR PathwayCommons; Q14691; -.
DR Reactome; R-HSA-176974; Unwinding of DNA.
DR SignaLink; Q14691; -.
DR BioGRID-ORCS; 9837; 802 hits in 1094 CRISPR screens.
DR ChiTaRS; GINS1; human.
DR EvolutionaryTrace; Q14691; -.
DR GeneWiki; GINS1; -.
DR GenomeRNAi; 9837; -.
DR Pharos; Q14691; Tbio.
DR PRO; PR:Q14691; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q14691; protein.
DR Bgee; ENSG00000101003; Expressed in oocyte and 155 other tissues.
DR Genevisible; Q14691; HS.
DR GO; GO:0071162; C:CMG complex; IPI:ComplexPortal.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0000811; C:GINS complex; IPI:ComplexPortal.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:1902983; P:DNA strand elongation involved in mitotic DNA replication; IBA:GO_Central.
DR GO; GO:0006268; P:DNA unwinding involved in DNA replication; IDA:ComplexPortal.
DR GO; GO:0001833; P:inner cell mass cell proliferation; IEA:Ensembl.
DR GO; GO:1903934; P:positive regulation of DNA primase activity; IDA:ComplexPortal.
DR GO; GO:1900264; P:positive regulation of DNA-directed DNA polymerase activity; IDA:ComplexPortal.
DR CDD; cd11710; GINS_A_psf1; 1.
DR InterPro; IPR036224; GINS_bundle-like_dom_sf.
DR InterPro; IPR005339; GINS_Psf1.
DR PANTHER; PTHR12914; PTHR12914; 1.
DR SUPFAM; SSF158573; SSF158573; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Chromosome; Disease variant; DNA replication; Nucleus;
KW Reference proteome.
FT CHAIN 1..196
FT /note="DNA replication complex GINS protein PSF1"
FT /id="PRO_0000219035"
FT VARIANT 83
FT /note="R -> C (in IMD55; lower GINS1 protein levels and
FT defective DNA replication are observed in patient cells;
FT the mutant does not interact with GINS3 and GINS4;
FT dbSNP:rs137901350)"
FT /evidence="ECO:0000269|PubMed:28414293"
FT /id="VAR_080619"
FT VARIANT 97
FT /note="V -> I (in dbSNP:rs6076347)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_051606"
FT VARIANT 152
FT /note="C -> Y (in IMD55; lower GINS1 protein levels and
FT defective DNA replication are observed in patient cells;
FT dbSNP:rs376610445)"
FT /evidence="ECO:0000269|PubMed:28414293"
FT /id="VAR_080620"
FT HELIX 4..15
FT /evidence="ECO:0007829|PDB:2E9X"
FT STRAND 16..19
FT /evidence="ECO:0007829|PDB:2EHO"
FT HELIX 26..49
FT /evidence="ECO:0007829|PDB:2E9X"
FT HELIX 56..58
FT /evidence="ECO:0007829|PDB:2E9X"
FT HELIX 59..94
FT /evidence="ECO:0007829|PDB:2E9X"
FT HELIX 100..104
FT /evidence="ECO:0007829|PDB:2E9X"
FT HELIX 108..127
FT /evidence="ECO:0007829|PDB:2E9X"
FT STRAND 128..132
FT /evidence="ECO:0007829|PDB:2E9X"
SQ SEQUENCE 196 AA; 22988 MW; 2270B5CE6C43BFE5 CRC64;
MFCEKAMELI RELHRAPEGQ LPAFNEDGLR QVLEEMKALY EQNQSDVNEA KSGGRSDLIP
TIKFRHCSLL RNRRCTVAYL YDRLLRIRAL RWEYGSVLPN ALRFHMAAEE MEWFNNYKRS
LATYMRSLGG DEGLDITQDM KPPKSLYIEV RCLKDYGEFE VDDGTSVLLK KNSQHFLPRW
KCEQLIRQGV LEHILS
