GET2_YEAST
ID GET2_YEAST Reviewed; 285 AA.
AC P40056; D3DLZ0;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 16-MAY-2006, sequence version 2.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Golgi to ER traffic protein 2 {ECO:0000255|HAMAP-Rule:MF_03114};
DE AltName: Full=Guided entry of tail-anchored proteins 2;
DE AltName: Full=Hydroxyurea resistance protein 2 {ECO:0000255|HAMAP-Rule:MF_03114};
DE AltName: Full=Required for meiotic nuclear division protein 7 {ECO:0000255|HAMAP-Rule:MF_03114};
GN Name=GET2 {ECO:0000255|HAMAP-Rule:MF_03114};
GN Synonyms=HUR2 {ECO:0000255|HAMAP-Rule:MF_03114},
GN RMD7 {ECO:0000255|HAMAP-Rule:MF_03114}; OrderedLocusNames=YER083C;
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169868;
RA Dietrich F.S., Mulligan J.T., Hennessy K.M., Yelton M.A., Allen E.,
RA Araujo R., Aviles E., Berno A., Brennan T., Carpenter J., Chen E.,
RA Cherry J.M., Chung E., Duncan M., Guzman E., Hartzell G., Hunicke-Smith S.,
RA Hyman R.W., Kayser A., Komp C., Lashkari D., Lew H., Lin D., Mosedale D.,
RA Nakahara K., Namath A., Norgren R., Oefner P., Oh C., Petel F.X.,
RA Roberts D., Sehl P., Schramm S., Shogren T., Smith V., Taylor P., Wei Y.,
RA Botstein D., Davis R.W.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome V.";
RL Nature 387:78-81(1997).
RN [2]
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 [3]
RP FUNCTION.
RX PubMed=10929718; DOI=10.1016/s0092-8674(00)00015-5;
RA Hughes T.R., Marton M.J., Jones A.R., Roberts C.J., Stoughton R.,
RA Armour C.D., Bennett H.A., Coffey E., Dai H., He Y.D., Kidd M.J.,
RA King A.M., Meyer M.R., Slade D., Lum P.Y., Stepaniants S.B.,
RA Shoemaker D.D., Gachotte D., Chakraburtty K., Simon J., Bard M.,
RA Friend S.H.;
RT "Functional discovery via a compendium of expression profiles.";
RL Cell 102:109-126(2000).
RN [4]
RP IDENTIFICATION IN GET COMPLEX, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=11805837; DOI=10.1038/415180a;
RA Ho Y., Gruhler A., Heilbut A., Bader G.D., Moore L., Adams S.-L.,
RA Millar A., Taylor P., Bennett K., Boutilier K., Yang L., Wolting C.,
RA Donaldson I., Schandorff S., Shewnarane J., Vo M., Taggart J.,
RA Goudreault M., Muskat B., Alfarano C., Dewar D., Lin Z., Michalickova K.,
RA Willems A.R., Sassi H., Nielsen P.A., Rasmussen K.J., Andersen J.R.,
RA Johansen L.E., Hansen L.H., Jespersen H., Podtelejnikov A., Nielsen E.,
RA Crawford J., Poulsen V., Soerensen B.D., Matthiesen J., Hendrickson R.C.,
RA Gleeson F., Pawson T., Moran M.F., Durocher D., Mann M., Hogue C.W.V.,
RA Figeys D., Tyers M.;
RT "Systematic identification of protein complexes in Saccharomyces cerevisiae
RT by mass spectrometry.";
RL Nature 415:180-183(2002).
RN [5]
RP FUNCTION.
RX PubMed=12586695; DOI=10.1093/genetics/163.1.47;
RA Enyenihi A.H., Saunders W.S.;
RT "Large-scale functional genomic analysis of sporulation and meiosis in
RT Saccharomyces cerevisiae.";
RL Genetics 163:47-54(2003).
RN [6]
RP IDENTIFICATION OF PROBABLE INITIATION SITE.
RX PubMed=12748633; DOI=10.1038/nature01644;
RA Kellis M., Patterson N., Endrizzi M., Birren B.W., Lander E.S.;
RT "Sequencing and comparison of yeast species to identify genes and
RT regulatory elements.";
RL Nature 423:241-254(2003).
RN [7]
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 [8]
RP FUNCTION.
RX PubMed=12615994; DOI=10.1073/pnas.0530118100;
RA Zewail A., Xie M.W., Xing Y., Lin L., Zhang P.F., Zou W., Saxe J.P.,
RA Huang J.;
RT "Novel functions of the phosphatidylinositol metabolic pathway discovered
RT by a chemical genomics screen with wortmannin.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:3345-3350(2003).
RN [9]
RP FUNCTION, IDENTIFICATION IN GET COMPLEX, AND SUBCELLULAR LOCATION.
RX PubMed=16269340; DOI=10.1016/j.cell.2005.08.031;
RA Schuldiner M., Collins S.R., Thompson N.J., Denic V., Bhamidipati A.,
RA Punna T., Ihmels J., Andrews B., Boone C., Greenblatt J.F., Weissman J.S.,
RA Krogan N.J.;
RT "Exploration of the function and organization of the yeast early secretory
RT pathway through an epistatic miniarray profile.";
RL Cell 123:507-519(2005).
RN [10]
RP INTERACTION WITH GET3.
RX PubMed=16816426; DOI=10.1534/genetics.106.058362;
RA Auld K.L., Hitchcock A.L., Doherty H.K., Frietze S., Huang L.S.,
RA Silver P.A.;
RT "The conserved ATPase Get3/Arr4 modulates the activity of membrane-
RT associated proteins in Saccharomyces cerevisiae.";
RL Genetics 174:215-227(2006).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-45, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ADR376;
RX PubMed=17330950; DOI=10.1021/pr060559j;
RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA Elias J.E., Gygi S.P.;
RT "Large-scale phosphorylation analysis of alpha-factor-arrested
RT Saccharomyces cerevisiae.";
RL J. Proteome Res. 6:1190-1197(2007).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=17287358; DOI=10.1073/pnas.0607084104;
RA Chi A., Huttenhower C., Geer L.Y., Coon J.J., Syka J.E.P., Bai D.L.,
RA Shabanowitz J., Burke D.J., Troyanskaya O.G., Hunt D.F.;
RT "Analysis of phosphorylation sites on proteins from Saccharomyces
RT cerevisiae by electron transfer dissociation (ETD) mass spectrometry.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:2193-2198(2007).
RN [13]
RP FUNCTION.
RX PubMed=18724936; DOI=10.1016/j.cell.2008.06.025;
RA Schuldiner M., Metz J., Schmid V., Denic V., Rakwalska M., Schmitt H.D.,
RA Schwappach B., Weissman J.S.;
RT "The GET complex mediates insertion of tail-anchored proteins into the ER
RT membrane.";
RL Cell 134:634-645(2008).
RN [14]
RP 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 [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [16]
RP FUNCTION.
RX PubMed=24392163; DOI=10.1371/journal.pone.0085033;
RA Vilardi F., Stephan M., Clancy A., Janshoff A., Schwappach B.;
RT "WRB and CAML are necessary and sufficient to mediate tail-anchored protein
RT targeting to the ER membrane.";
RL PLoS ONE 9:e85033-e85033(2014).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1-38 IN COMPLEX WITH GET3,
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=21835666; DOI=10.1016/j.molcel.2011.07.020;
RA Wang F., Whynot A., Tung M., Denic V.;
RT "The mechanism of tail-anchored protein insertion into the ER membrane.";
RL Mol. Cell 43:738-750(2011).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (4.6 ANGSTROMS) OF 2-35 IN COMPLEX WITH GET3,
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=21719644; DOI=10.1126/science.1207125;
RA Stefer S., Reitz S., Wang F., Wild K., Pang Y.Y., Schwarz D., Bomke J.,
RA Hein C., Lohr F., Bernhard F., Denic V., Dotsch V., Sinning I.;
RT "Structural basis for tail-anchored membrane protein biogenesis by the
RT Get3-receptor complex.";
RL Science 333:758-762(2011).
RN [19]
RP STRUCTURE BY ELECTRON MICROSCOPY (14 ANGSTROMS) OF THE GET COMPLEX, AND
RP MUTAGENESIS OF LYS-150 AND LYS-157.
RX PubMed=32910895; DOI=10.1016/j.molcel.2020.08.012;
RA McDowell M.A., Heimes M., Fiorentino F., Mehmood S., Farkas A.,
RA Coy-Vergara J., Wu D., Bolla J.R., Schmid V., Heinze R., Wild K.,
RA Flemming D., Pfeffer S., Schwappach B., Robinson C.V., Sinning I.;
RT "Structural Basis of Tail-Anchored Membrane Protein Biogenesis by the GET
RT Insertase Complex.";
RL Mol. Cell 80:72-86(2020).
CC -!- FUNCTION: Required for the post-translational delivery of tail-anchored
CC (TA) proteins to the endoplasmic reticulum. Together with GET1, acts as
CC a membrane receptor for soluble GET3, which recognizes and selectively
CC binds the transmembrane domain of TA proteins in the cytosol. The GET
CC complex cooperates with the HDEL receptor ERD2 to mediate the ATP-
CC dependent retrieval of resident ER proteins that contain a C-terminal
CC H-D-E-L retention signal from the Golgi to the ER. Involved in DNA
CC replication and DNA damage response and also in cell wall function.
CC {ECO:0000255|HAMAP-Rule:MF_03114, ECO:0000269|PubMed:10929718,
CC ECO:0000269|PubMed:12586695, ECO:0000269|PubMed:12615994,
CC ECO:0000269|PubMed:16269340, ECO:0000269|PubMed:18724936,
CC ECO:0000269|PubMed:21719644, ECO:0000269|PubMed:21835666,
CC ECO:0000269|PubMed:24392163}.
CC -!- SUBUNIT: Component of the Golgi to ER traffic (GET) complex, which is
CC composed of GET1, GET2 and GET3. Within the complex, GET1 and GET2 form
CC a heterotetramer which is stabilized by phosphatidylinositol binding
CC and which binds to the GET3 homodimer (PubMed:32910895).
CC {ECO:0000255|HAMAP-Rule:MF_03114, ECO:0000269|PubMed:11805837,
CC ECO:0000269|PubMed:16269340, ECO:0000269|PubMed:21719644,
CC ECO:0000269|PubMed:21835666, ECO:0000269|PubMed:32910895}.
CC -!- INTERACTION:
CC P40056; P53192: GET1; NbExp=3; IntAct=EBI-22604, EBI-23722;
CC P40056; Q12154: GET3; NbExp=9; IntAct=EBI-22604, EBI-2989;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass
CC membrane protein. Golgi apparatus membrane; Multi-pass membrane
CC protein.
CC -!- SIMILARITY: Belongs to the GET2 family. {ECO:0000255|HAMAP-
CC Rule:MF_03114}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB64638.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; U18839; AAB64638.1; ALT_INIT; Genomic_DNA.
DR EMBL; BK006939; DAA07744.1; -; Genomic_DNA.
DR PIR; S50586; S50586.
DR RefSeq; NP_011006.2; NM_001178974.1.
DR PDB; 3SJD; X-ray; 4.60 A; D/E=2-35.
DR PDB; 3ZS9; X-ray; 2.10 A; C/D=1-38.
DR PDBsum; 3SJD; -.
DR PDBsum; 3ZS9; -.
DR AlphaFoldDB; P40056; -.
DR SMR; P40056; -.
DR BioGRID; 36828; 974.
DR ComplexPortal; CPX-956; GET complex.
DR DIP; DIP-4508N; -.
DR IntAct; P40056; 10.
DR MINT; P40056; -.
DR STRING; 4932.YER083C; -.
DR TCDB; 3.A.21.1.1; the c-terminal tail-anchored membrane protein biogenesis/ insertion complex (tamp-b) family.
DR iPTMnet; P40056; -.
DR MaxQB; P40056; -.
DR PaxDb; P40056; -.
DR PRIDE; P40056; -.
DR TopDownProteomics; P40056; -.
DR EnsemblFungi; YER083C_mRNA; YER083C; YER083C.
DR GeneID; 856817; -.
DR KEGG; sce:YER083C; -.
DR SGD; S000000885; GET2.
DR VEuPathDB; FungiDB:YER083C; -.
DR eggNOG; ENOG502QW0H; Eukaryota.
DR HOGENOM; CLU_066477_0_0_1; -.
DR InParanoid; P40056; -.
DR OMA; ALQYWDV; -.
DR BioCyc; YEAST:G3O-30253-MON; -.
DR EvolutionaryTrace; P40056; -.
DR PRO; PR:P40056; -.
DR Proteomes; UP000002311; Chromosome V.
DR RNAct; P40056; protein.
DR GO; GO:0005783; C:endoplasmic reticulum; HDA:SGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0043529; C:GET complex; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043495; F:protein-membrane adaptor activity; IGI:SGD.
DR GO; GO:0000423; P:mitophagy; IMP:SGD.
DR GO; GO:0045048; P:protein insertion into ER membrane; IDA:ComplexPortal.
DR GO; GO:0006890; P:retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum; IDA:SGD.
DR HAMAP; MF_03114; Get2; 1.
DR InterPro; IPR014802; GET2.
DR InterPro; IPR028143; Get2/sif1.
DR PANTHER; PTHR28263; PTHR28263; 1.
DR Pfam; PF08690; GET2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Endoplasmic reticulum; ER-Golgi transport;
KW Glycoprotein; Golgi apparatus; Membrane; Phosphoprotein;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..285
FT /note="Golgi to ER traffic protein 2"
FT /id="PRO_0000097362"
FT TOPO_DOM 2..148
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03114"
FT TRANSMEM 149..169
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03114"
FT TOPO_DOM 170..196
FT /note="Lumenal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03114"
FT TRANSMEM 197..216
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03114"
FT TOPO_DOM 217..263
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03114"
FT TRANSMEM 264..284
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03114"
FT TOPO_DOM 285
FT /note="Lumenal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03114"
FT REGION 1..72
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 87..106
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..22
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 23..45
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 88..106
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 45
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17330950"
FT CARBOHYD 173
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03114"
FT CARBOHYD 196
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03114"
FT MUTAGEN 150
FT /note="K->A: Impaired tail-anchored protein insertion,
FT impaired GET3 localization and loss of the GET1-GET2
FT heterotetramer; when associated with A-157."
FT /evidence="ECO:0000269|PubMed:32910895"
FT MUTAGEN 157
FT /note="K->A: Impaired tail-anchored protein insertion and
FT impaired GET3 localization and loss of the GET1-GET2
FT heterotetramer; when associated with A-150."
FT /evidence="ECO:0000269|PubMed:32910895"
FT HELIX 6..21
FT /evidence="ECO:0007829|PDB:3ZS9"
FT TURN 22..24
FT /evidence="ECO:0007829|PDB:3ZS9"
FT HELIX 25..33
FT /evidence="ECO:0007829|PDB:3ZS9"
SQ SEQUENCE 285 AA; 31493 MW; 1667E7C879CFB6EA CRC64;
MSELTEAEKR RLLRERRQKK FSNGGASSRL NKITGQASSH LNAESPLDAP SAAKTTPPAS
VHSATPDIKE DSNVAPQLDL LKQLAAMQGQ GTGKSTPQDS STPDLLSLLS SMNTGMPSAE
GTPSFGQAAP AAPINQAALD YHDYLLNRLK AWTILVKWVF FLLPYLYLIT RPNSSVWPAY
AFTQSAWFAP LRNPSNFTRI FATFEFLSIS IYYQLLKNVE HKSKIKNLQD TNKLVKLVSL
VPEGVIPVAN LKGKLITLLQ YWDLLSMLIT DISFVLIVLG LLTYL
