ID   GPN1_YEAST              Reviewed;         385 AA.
AC   P47122; D6VWP2;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1996, sequence version 1.
DT   27-MAR-2024, entry version 176.
DE   RecName: Full=GPN-loop GTPase 1 {ECO:0000303|PubMed:21532343};
DE            EC=3.6.5.- {ECO:0000305|PubMed:21844196};
DE   AltName: Full=Essential PCL1-interacting ATPase 1 {ECO:0000303|PubMed:15082539};
DE   AltName: Full=GPN-loop GTPase NPA3 {ECO:0000305};
DE   AltName: Full=Nucleolar preribosomal-associated protein 3 {ECO:0000303|PubMed:15226434};
GN   Name=NPA3 {ECO:0000303|PubMed:15226434};
GN   Synonyms=EPA1 {ECO:0000303|PubMed:15082539}, GPN1
GN   {ECO:0000303|PubMed:21532343};
GN   OrderedLocusNames=YJR072C {ECO:0000312|SGD:S000003833};
GN   ORFNames=J1821;
OS   Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX   NCBI_TaxID=559292;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=8840504;
RX   DOI=10.1002/(sici)1097-0061(199607)12:9<869::aid-yea964>3.0.co;2-1;
RA   Huang M.-E., Manus V., Chuat J.-C., Galibert F.;
RT   "Analysis of a 62 kb DNA sequence of chromosome X reveals 36 open reading
RT   frames and a gene cluster with a counterpart on chromosome XI.";
RL   Yeast 12:869-875(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=8641269; DOI=10.1002/j.1460-2075.1996.tb00557.x;
RA   Galibert F., Alexandraki D., Baur A., Boles E., Chalwatzis N., Chuat J.-C.,
RA   Coster F., Cziepluch C., de Haan M., Domdey H., Durand P., Entian K.-D.,
RA   Gatius M., Goffeau A., Grivell L.A., Hennemann A., Herbert C.J.,
RA   Heumann K., Hilger F., Hollenberg C.P., Huang M.-E., Jacq C.,
RA   Jauniaux J.-C., Katsoulou C., Kirchrath L., Kleine K., Kordes E.,
RA   Koetter P., Liebl S., Louis E.J., Manus V., Mewes H.-W., Miosga T.,
RA   Obermaier B., Perea J., Pohl T.M., Portetelle D., Pujol A., Purnelle B.,
RA   Ramezani Rad M., Rasmussen S.W., Rose M., Rossau R.,
RA   Schaaff-Gerstenschlaeger I., Smits P.H.M., Scarcez T., Soriano N.,
RA   To Van D., Tzermia M., Van Broekhoven A., Vandenbol M., Wedler H.,
RA   von Wettstein D., Wambutt R., Zagulski M., Zollner A., Karpfinger-Hartl L.;
RT   "Complete nucleotide sequence of Saccharomyces cerevisiae chromosome X.";
RL   EMBO J. 15:2031-2049(1996).
RN   [3]
RP   GENOME REANNOTATION.
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=24374639; DOI=10.1534/g3.113.008995;
RA   Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA   Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA   Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT   "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL   G3 (Bethesda) 4:389-398(2014).
RN   [4]
RP   SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX   PubMed=14562095; DOI=10.1038/nature02026;
RA   Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA   Weissman J.S., O'Shea E.K.;
RT   "Global analysis of protein localization in budding yeast.";
RL   Nature 425:686-691(2003).
RN   [5]
RP   LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX   PubMed=14562106; DOI=10.1038/nature02046;
RA   Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA   O'Shea E.K., Weissman J.S.;
RT   "Global analysis of protein expression in yeast.";
RL   Nature 425:737-741(2003).
RN   [6]
RP   FUNCTION, PHOSPHORYLATION, AND INTERACTION WITH PCL1.
RX   PubMed=15082539; DOI=10.1534/genetics.166.3.1177;
RA   Keniry M.E., Kemp H.A., Rivers D.M., Sprague G.F. Jr.;
RT   "The identification of Pcl1-interacting proteins that genetically interact
RT   with Cla4 may indicate a link between G1 progression and mitotic exit.";
RL   Genetics 166:1177-1186(2004).
RN   [7]
RP   IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION.
RX   PubMed=15226434; DOI=10.1128/mcb.24.14.6324-6337.2004;
RA   Dez C., Froment C., Noaillac-Depeyre J., Monsarrat B.,
RA   Caizergues-Ferrer M., Henry Y.;
RT   "Npa1p, a component of very early pre-60S ribosomal particles, associates
RT   with a subset of small nucleolar RNPs required for peptidyl transferase
RT   center modification.";
RL   Mol. Cell. Biol. 24:6324-6337(2004).
RN   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-313 AND SER-352, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA   Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT   "A multidimensional chromatography technology for in-depth phosphoproteome
RT   analysis.";
RL   Mol. Cell. Proteomics 7:1389-1396(2008).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-304; SER-308; SER-313 AND
RP   SER-352, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19779198; DOI=10.1126/science.1172867;
RA   Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT   "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT   into evolution.";
RL   Science 325:1682-1686(2009).
RN   [10]
RP   FUNCTION, AND BINDING TO RNA POLYMERASE II.
RX   PubMed=20855544; DOI=10.1074/mcp.m110.003616;
RA   Forget D., Lacombe A.A., Cloutier P., Al-Khoury R., Bouchard A.,
RA   Lavallee-Adam M., Faubert D., Jeronimo C., Blanchette M., Coulombe B.;
RT   "The protein interaction network of the human transcription machinery
RT   reveals a role for the conserved GTPase RPAP4/GPN1 and microtubule assembly
RT   in nuclear import and biogenesis of RNA polymerase II.";
RL   Mol. Cell. Proteomics 9:2827-2839(2010).
RN   [11]
RP   FUNCTION.
RX   PubMed=21532343; DOI=10.4161/cc.10.11.15763;
RA   Alonso B., Chaussinand G., Armengaud J., Godon C.;
RT   "A role for GPN-loop GTPase yGPN1 in sister chromatid cohesion.";
RL   Cell Cycle 10:1828-1837(2011).
RN   [12]
RP   FUNCTION, BINDING TO RNA POLYMERASE II, INTERACTION WITH NUP133 AND CRM1,
RP   AND MUTAGENESIS OF ASP-106 AND GLN-110.
RX   PubMed=21844196; DOI=10.1074/jbc.m111.286161;
RA   Staresincic L., Walker J., Dirac-Svejstrup A.B., Mitter R., Svejstrup J.Q.;
RT   "GTP-dependent binding and nuclear transport of RNA polymerase II by Npa3
RT   protein.";
RL   J. Biol. Chem. 286:35553-35561(2011).
RN   [13]
RP   UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-369, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22106047; DOI=10.1002/pmic.201100166;
RA   Starita L.M., Lo R.S., Eng J.K., von Haller P.D., Fields S.;
RT   "Sites of ubiquitin attachment in Saccharomyces cerevisiae.";
RL   Proteomics 12:236-240(2012).
RN   [14]
RP   INTERACTION WITH GPN2 AND GPN3, AND MUTAGENESIS OF GLU-112.
RX   PubMed=23324351; DOI=10.4161/cc.23367;
RA   Alonso B., Beraud C., Meguellati S., Chen S.W., Pellequer J.L.,
RA   Armengaud J., Godon C.;
RT   "Eukaryotic GPN-loop GTPases paralogs use a dimeric assembly reminiscent of
RT   archeal GPN.";
RL   Cell Cycle 12:463-472(2013).
RN   [15]
RP   INTERACTION WITH GPN2.
RX   PubMed=23267056; DOI=10.1534/genetics.112.148726;
RA   Minaker S.W., Filiatrault M.C., Ben-Aroya S., Hieter P., Stirling P.C.;
RT   "Biogenesis of RNA polymerases II and III requires the conserved GPN small
RT   GTPases in Saccharomyces cerevisiae.";
RL   Genetics 193:853-864(2013).
CC   -!- FUNCTION: Small GTPase required for proper nuclear import of RNA
CC       polymerase II (RNAPII) (PubMed:20855544, PubMed:21844196). May act at
CC       an RNAP assembly step prior to nuclear import (PubMed:23267056).
CC       Promotes sister chromatid separation during anaphase (PubMed:21532343).
CC       {ECO:0000269|PubMed:15082539, ECO:0000269|PubMed:20855544,
CC       ECO:0000269|PubMed:21532343, ECO:0000269|PubMed:21844196,
CC       ECO:0000305|PubMed:23267056}.
CC   -!- SUBUNIT: Heterodimers with GPN2 or GPN3 (PubMed:23324351,
CC       PubMed:23267056). Binds to RNA polymerase II (RNAPII) in a GTP-
CC       dependent manner (PubMed:20855544, PubMed:21844196). Interacts with
CC       nuclear pore protein NUP133 and nuclear export factor CRM1
CC       (PubMed:21844196). Interacts with PCL1 (PubMed:15082539).
CC       {ECO:0000269|PubMed:15082539, ECO:0000269|PubMed:20855544,
CC       ECO:0000269|PubMed:21844196, ECO:0000269|PubMed:23267056,
CC       ECO:0000269|PubMed:23324351}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095,
CC       ECO:0000269|PubMed:15226434}.
CC   -!- PTM: Phosphorylated by the cyclin-CDK PCL1-PHO85.
CC       {ECO:0000269|PubMed:15082539}.
CC   -!- MISCELLANEOUS: Present with 15200 molecules/cell in log phase SD
CC       medium. {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the GPN-loop GTPase family. {ECO:0000305}.
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DR   EMBL; Z49572; CAA89600.1; -; Genomic_DNA.
DR   EMBL; L47993; AAB39297.1; -; Genomic_DNA.
DR   EMBL; BK006943; DAA08858.1; -; Genomic_DNA.
DR   PIR; S57091; S57091.
DR   RefSeq; NP_012606.3; NM_001181730.3.
DR   PDB; 5HCI; X-ray; 2.30 A; A/B/C/D/E/F=2-264.
DR   PDB; 5HCN; X-ray; 2.20 A; A=2-264.
DR   PDBsum; 5HCI; -.
DR   PDBsum; 5HCN; -.
DR   AlphaFoldDB; P47122; -.
DR   SMR; P47122; -.
DR   BioGRID; 33828; 127.
DR   DIP; DIP-1676N; -.
DR   IntAct; P47122; 75.
DR   MINT; P47122; -.
DR   STRING; 4932.YJR072C; -.
DR   iPTMnet; P47122; -.
DR   MaxQB; P47122; -.
DR   PaxDb; 4932-YJR072C; -.
DR   PeptideAtlas; P47122; -.
DR   EnsemblFungi; YJR072C_mRNA; YJR072C; YJR072C.
DR   GeneID; 853535; -.
DR   KEGG; sce:YJR072C; -.
DR   AGR; SGD:S000003833; -.
DR   SGD; S000003833; NPA3.
DR   VEuPathDB; FungiDB:YJR072C; -.
DR   eggNOG; KOG1532; Eukaryota.
DR   GeneTree; ENSGT00950000183172; -.
DR   HOGENOM; CLU_037460_1_2_1; -.
DR   InParanoid; P47122; -.
DR   OMA; MIIVFNK; -.
DR   OrthoDB; 5475185at2759; -.
DR   BioCyc; YEAST:G3O-31704-MONOMER; -.
DR   BioGRID-ORCS; 853535; 8 hits in 10 CRISPR screens.
DR   PRO; PR:P47122; -.
DR   Proteomes; UP000002311; Chromosome X.
DR   RNAct; P47122; Protein.
DR   GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR   GO; GO:0005829; C:cytosol; HDA:SGD.
DR   GO; GO:0016887; F:ATP hydrolysis activity; IDA:SGD.
DR   GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR   GO; GO:0003924; F:GTPase activity; IDA:SGD.
DR   GO; GO:0007064; P:mitotic sister chromatid cohesion; IMP:SGD.
DR   GO; GO:0006913; P:nucleocytoplasmic transport; IDA:SGD.
DR   GO; GO:0006606; P:protein import into nucleus; IMP:SGD.
DR   CDD; cd17870; GPN1; 1.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1.
DR   InterPro; IPR004130; Gpn.
DR   InterPro; IPR030230; Gpn1/Npa3/XAB1.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   PANTHER; PTHR21231:SF8; GPN-LOOP GTPASE 1; 1.
DR   PANTHER; PTHR21231; XPA-BINDING PROTEIN 1-RELATED; 1.
DR   Pfam; PF03029; ATP_bind_1; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Cytoplasm; GTP-binding; Hydrolase; Isopeptide bond;
KW   Nucleotide-binding; Phosphoprotein; Reference proteome; Ubl conjugation.
FT   CHAIN           1..385
FT                   /note="GPN-loop GTPase 1"
FT                   /id="PRO_0000203101"
FT   REGION          317..356
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           70..72
FT                   /note="Gly-Pro-Asn (GPN)-loop; involved in dimer interface"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UYR9"
FT   COMPBIAS        327..349
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         13..18
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UYR9"
FT   BINDING         173..176
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UYR9"
FT   SITE            72
FT                   /note="Stabilizes the phosphate intermediate; shared with
FT                   dimeric partner"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UYR9"
FT   MOD_RES         304
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19779198"
FT   MOD_RES         308
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19779198"
FT   MOD_RES         313
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18407956,
FT                   ECO:0007744|PubMed:19779198"
FT   MOD_RES         352
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18407956,
FT                   ECO:0007744|PubMed:19779198"
FT   CROSSLNK        369
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0007744|PubMed:22106047"
FT   MUTAGEN         106
FT                   /note="D->A: Impairs nuclear localization of RNAPII.
FT                   Completely abolishes RNAPII binding."
FT                   /evidence="ECO:0000269|PubMed:21844196"
FT   MUTAGEN         110
FT                   /note="Q->L: Impairs nuclear localization of RNAPII, but
FT                   does not impair RNAPII binding."
FT                   /evidence="ECO:0000269|PubMed:21844196"
FT   MUTAGEN         112
FT                   /note="E->K: Impairs heterodimer formation with GPN2 and
FT                   GPN3."
FT                   /evidence="ECO:0000269|PubMed:23324351"
FT   STRAND          4..9
FT                   /evidence="ECO:0007829|PDB:5HCN"
FT   HELIX           16..29
FT                   /evidence="ECO:0007829|PDB:5HCN"
FT   STRAND          35..38
FT                   /evidence="ECO:0007829|PDB:5HCN"
FT   STRAND          51..54
FT                   /evidence="ECO:0007829|PDB:5HCN"
FT   TURN            55..57
FT                   /evidence="ECO:0007829|PDB:5HCN"
FT   HELIX           60..67
FT                   /evidence="ECO:0007829|PDB:5HCI"
FT   HELIX           73..84
FT                   /evidence="ECO:0007829|PDB:5HCN"
FT   HELIX           86..95
FT                   /evidence="ECO:0007829|PDB:5HCN"
FT   TURN            96..99
FT                   /evidence="ECO:0007829|PDB:5HCN"
FT   STRAND          101..106
FT                   /evidence="ECO:0007829|PDB:5HCN"
FT   HELIX           112..115
FT                   /evidence="ECO:0007829|PDB:5HCN"
FT   HELIX           118..128
FT                   /evidence="ECO:0007829|PDB:5HCN"
FT   STRAND          133..139
FT                   /evidence="ECO:0007829|PDB:5HCN"
FT   HELIX           141..143
FT                   /evidence="ECO:0007829|PDB:5HCN"
FT   HELIX           147..164
FT                   /evidence="ECO:0007829|PDB:5HCN"
FT   STRAND          168..172
FT                   /evidence="ECO:0007829|PDB:5HCN"
FT   HELIX           175..177
FT                   /evidence="ECO:0007829|PDB:5HCN"
FT   HELIX           182..197
FT                   /evidence="ECO:0007829|PDB:5HCN"
FT   HELIX           216..231
FT                   /evidence="ECO:0007829|PDB:5HCN"
FT   STRAND          232..236
FT                   /evidence="ECO:0007829|PDB:5HCN"
FT   TURN            239..241
FT                   /evidence="ECO:0007829|PDB:5HCN"
FT   HELIX           245..262
FT                   /evidence="ECO:0007829|PDB:5HCN"
SQ   SEQUENCE   385 AA;  43195 MW;  EA271D14EA1FFAEF CRC64;
     MSLSTIICIG MAGSGKTTFM QRLNSHLRAE KTPPYVINLD PAVLRVPYGA NIDIRDSIKY
     KKVMENYQLG PNGAIVTSLN LFSTKIDQVI RLVEQKKDKF QNCIIDTPGQ IECFVWSASG
     AIITESFASS FPTVIAYIVD TPRNSSPTTF MSNMLYACSI LYKTKLPMIV VFNKTDVCKA
     DFAKEWMTDF ESFQAAIKED QDLNGDNGLG SGYMSSLVNS MSLMLEEFYS QLDVVGVSSF
     TGDGFDEFMQ CVDKKVDEYD QYYKQEREKA LNLKKKKEEM RKQKSLNGLM KDLGLNEKSS
     AAASDNDSID AISDLEEDAN DGLVDRDEDE GVEREYTFPG EERTKGEVNE NSAPDLQRRY
     QEAMQQVGKT ASSETAENIA KYIRN
//