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   24-JAN-2024, entry version 188.
DE   RecName: Full=DNA replication complex GINS protein PSF1;
DE   AltName: Full=GINS complex subunit 1;
GN   Name=GINS1 {ECO:0000312|HGNC:HGNC:28980}; 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   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=35585232; DOI=10.1038/s41586-022-04759-1;
RA   Baris Y., Taylor M.R.G., Aria V., Yeeles J.T.P.;
RT   "Fast and efficient DNA replication with purified human proteins.";
RL   Nature 606:204-210(2022).
RN   [9]
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   [10]
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   [11]
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   [12]
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).
RN   [13] {ECO:0007744|PDB:6XTX, ECO:0007744|PDB:6XTY}
RP   STRUCTURE BY ELECTRON MICROSCOPY (3.29 ANGSTROMS) IN CMG COMPLEX, SUBUNIT,
RP   AND FUNCTION.
RX   PubMed=32453425; DOI=10.1093/nar/gkaa429;
RA   Rzechorzek N.J., Hardwick S.W., Jatikusumo V.A., Chirgadze D.Y.,
RA   Pellegrini L.;
RT   "CryoEM structures of human CMG-ATPgammaS-DNA and CMG-AND-1 complexes.";
RL   Nucleic Acids Res. 48:6980-6995(2020).
RN   [14] {ECO:0007744|PDB:7PFO}
RP   STRUCTURE BY ELECTRON MICROSCOPY (3.20 ANGSTROMS) IN REPLISOME, SUBUNIT,
RP   AND FUNCTION.
RX   PubMed=34694004; DOI=10.15252/embj.2021108819;
RA   Jones M.L., Baris Y., Taylor M.R.G., Yeeles J.T.P.;
RT   "Structure of a human replisome shows the organisation and interactions of
RT   a DNA replication machine.";
RL   EMBO J. 40:e108819-e108819(2021).
RN   [15] {ECO:0007744|PDB:7PLO}
RP   STRUCTURE BY ELECTRON MICROSCOPY (2.80 ANGSTROMS) IN REPLISOME, SUBUNIT,
RP   AND FUNCTION.
RX   PubMed=34700328; DOI=10.1038/s41586-021-04145-3;
RA   Jenkyn-Bedford M., Jones M.L., Baris Y., Labib K.P.M., Cannone G.,
RA   Yeeles J.T.P., Deegan T.D.;
RT   "A conserved mechanism for regulating replisome disassembly in
RT   eukaryotes.";
RL   Nature 600:743-747(2021).
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 (PubMed:17417653,
CC       PubMed:28414293). GINS complex is a core component of CDC45-MCM-GINS
CC       (CMG) helicase, the molecular machine that unwinds template DNA during
CC       replication, and around which the replisome is built (PubMed:32453425,
CC       PubMed:34694004, PubMed:34700328, PubMed:35585232).
CC       {ECO:0000269|PubMed:17417653, ECO:0000269|PubMed:28414293,
CC       ECO:0000269|PubMed:32453425, ECO:0000269|PubMed:34694004,
CC       ECO:0000269|PubMed:34700328, ECO:0000269|PubMed:35585232}.
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, a hexameric ring of related
CC       MCM2-7 subunits stabilized by CDC45 and the tetrameric GINS complex
CC       (PubMed:34700328, PubMed:34694004, PubMed:32453425).
CC       {ECO:0000269|PubMed:17545466, ECO:0000269|PubMed:17557111,
CC       ECO:0000269|PubMed:17652513, ECO:0000269|PubMed:28414293,
CC       ECO:0000269|PubMed:32453425, ECO:0000269|PubMed:34694004,
CC       ECO:0000269|PubMed:34700328}.
CC   -!- INTERACTION:
CC       Q14691; Q9NYP3: DONSON; NbExp=7; IntAct=EBI-9019496, EBI-32724208;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305|PubMed:35585232}. Chromosome
CC       {ECO:0000305|PubMed:35585232}. Note=Associates with chromatin.
CC       {ECO:0000305|PubMed:35585232}.
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; Note=Extended N-terminus.; 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   PDB; 8B9D; EM; 3.40 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   PDBsum; 8B9D; -.
DR   AlphaFoldDB; Q14691; -.
DR   EMDB; EMD-10619; -.
DR   EMDB; EMD-10621; -.
DR   EMDB; EMD-13375; -.
DR   EMDB; EMD-13494; -.
DR   SMR; Q14691; -.
DR   BioGRID; 115174; 33.
DR   ComplexPortal; CPX-787; GINS complex.
DR   CORUM; Q14691; -.
DR   DIP; DIP-29331N; -.
DR   IntAct; Q14691; 16.
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; 9606-ENSP00000262460; -.
DR   PeptideAtlas; Q14691; -.
DR   ProteomicsDB; 60129; -.
DR   Pumba; Q14691; -.
DR   Antibodypedia; 10061; 211 antibodies from 27 providers.
DR   DNASU; 9837; -.
DR   Ensembl; ENST00000262460.5; ENSP00000262460.4; ENSG00000101003.12.
DR   Ensembl; ENST00000696874.1; ENSP00000512943.1; ENSG00000101003.12.
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   AGR; HGNC:28980; -.
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; 166901at2759; -.
DR   PhylomeDB; Q14691; -.
DR   TreeFam; TF312848; -.
DR   PathwayCommons; Q14691; -.
DR   Reactome; R-HSA-176974; Unwinding of DNA.
DR   SignaLink; Q14691; -.
DR   BioGRID-ORCS; 9837; 826 hits in 1175 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 157 other cell types or tissues.
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   CDD; cd11710; GINS_A_psf1; 1.
DR   CDD; cd21696; GINS_B_Psf1; 1.
DR   Gene3D; 1.20.58.1030; -; 1.
DR   InterPro; IPR021151; GINS_A.
DR   InterPro; IPR036224; GINS_bundle-like_dom_sf.
DR   InterPro; IPR005339; GINS_Psf1.
DR   PANTHER; PTHR12914:SF2; DNA REPLICATION COMPLEX GINS PROTEIN PSF1; 1.
DR   PANTHER; PTHR12914; PARTNER OF SLD5; 1.
DR   Pfam; PF05916; Sld5; 1.
DR   SUPFAM; SSF158573; GINS helical bundle-like; 1.
DR   Genevisible; Q14691; HS.
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
//