VPS21_YEAST
ID VPS21_YEAST Reviewed; 210 AA.
AC P36017; D6W2F0;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Vacuolar protein sorting-associated protein 21;
DE AltName: Full=GTP-binding protein YPT51;
DE AltName: Full=Vacuolar protein-targeting protein 12;
GN Name=VPS21; Synonyms=VPS12, VPT12, YPT21, YPT51; OrderedLocusNames=YOR089C;
GN ORFNames=YOR3154C;
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].
RX PubMed=8163546; DOI=10.1083/jcb.125.2.283;
RA Singer-Krueger B., Stenmark H., Duesterhoeft A., Philippsen P., Yoo J.-S.,
RA Gallwitz D., Zerial M.;
RT "Role of three rab5-like GTPases, Ypt51p, Ypt52p, and Ypt53p, in the
RT endocytic and vacuolar protein sorting pathways of yeast.";
RL J. Cell Biol. 125:283-298(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND MUTAGENESIS OF SER-21.
RX PubMed=8137814; DOI=10.1002/j.1460-2075.1994.tb06382.x;
RA Horazdovsky B.F., Busch G.R., Emr S.D.;
RT "VPS21 encodes a rab5-like GTP binding protein that is required for the
RT sorting of yeast vacuolar proteins.";
RL EMBO J. 13:1297-1309(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9200815;
RX DOI=10.1002/(sici)1097-0061(19970615)13:7<655::aid-yea120>3.0.co;2-i;
RA Voss H., Benes V., Andrade M.A., Valencia A., Rechmann S., Teodoru C.,
RA Schwager C., Paces V., Sander C., Ansorge W.;
RT "DNA sequencing and analysis of 130 kb from yeast chromosome XV.";
RL Yeast 13:655-672(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169874;
RA Dujon B., Albermann K., Aldea M., Alexandraki D., Ansorge W., Arino J.,
RA Benes V., Bohn C., Bolotin-Fukuhara M., Bordonne R., Boyer J., Camasses A.,
RA Casamayor A., Casas C., Cheret G., Cziepluch C., Daignan-Fornier B.,
RA Dang V.-D., de Haan M., Delius H., Durand P., Fairhead C., Feldmann H.,
RA Gaillon L., Galisson F., Gamo F.-J., Gancedo C., Goffeau A., Goulding S.E.,
RA Grivell L.A., Habbig B., Hand N.J., Hani J., Hattenhorst U., Hebling U.,
RA Hernando Y., Herrero E., Heumann K., Hiesel R., Hilger F., Hofmann B.,
RA Hollenberg C.P., Hughes B., Jauniaux J.-C., Kalogeropoulos A.,
RA Katsoulou C., Kordes E., Lafuente M.J., Landt O., Louis E.J., Maarse A.C.,
RA Madania A., Mannhaupt G., Marck C., Martin R.P., Mewes H.-W., Michaux G.,
RA Paces V., Parle-McDermott A.G., Pearson B.M., Perrin A., Pettersson B.,
RA Poch O., Pohl T.M., Poirey R., Portetelle D., Pujol A., Purnelle B.,
RA Ramezani Rad M., Rechmann S., Schwager C., Schweizer M., Sor F., Sterky F.,
RA Tarassov I.A., Teodoru C., Tettelin H., Thierry A., Tobiasch E.,
RA Tzermia M., Uhlen M., Unseld M., Valens M., Vandenbol M., Vetter I.,
RA Vlcek C., Voet M., Volckaert G., Voss H., Wambutt R., Wedler H.,
RA Wiemann S., Winsor B., Wolfe K.H., Zollner A., Zumstein E., Kleine K.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XV.";
RL Nature 387:98-102(1997).
RN [5]
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 [6]
RP PROTEIN SEQUENCE OF 10-20; 27-97; 112-131 AND 146-186, AND IDENTIFICATION
RP BY MASS SPECTROMETRY.
RA Bienvenut W.V., Peters C.;
RL Submitted (MAY-2005) to UniProtKB.
RN [7]
RP INTERACTION WITH PEP7, AND MUTAGENESIS OF SER-21 AND GLN-66.
RX PubMed=10021387; DOI=10.1016/s0960-9822(99)80071-2;
RA Peterson M.R., Burd C.G., Emr S.D.;
RT "Vac1p coordinates Rab and phosphatidylinositol 3-kinase signaling in
RT Vps45p-dependent vesicle docking/fusion at the endosome.";
RL Curr. Biol. 9:159-162(1999).
RN [8]
RP ACTIVITY REGULATION, AND MUTAGENESIS OF SER-21.
RX PubMed=10329739; DOI=10.1074/jbc.274.21.15284;
RA Hama H., Tall G.G., Horazdovsky B.F.;
RT "Vps9p is a guanine nucleotide exchange factor involved in vesicle-mediated
RT vacuolar protein transport.";
RL J. Biol. Chem. 274:15284-15291(1999).
RN [9]
RP ACTIVITY REGULATION.
RX PubMed=10559187; DOI=10.1074/jbc.274.47.33186;
RA Albert S., Gallwitz D.;
RT "Two new members of a family of Ypt/Rab GTPase activating proteins.
RT Promiscuity of substrate recognition.";
RL J. Biol. Chem. 274:33186-33189(1999).
RN [10]
RP INTERACTION WITH PEP7.
RX PubMed=10359603; DOI=10.1091/mbc.10.6.1873;
RA Tall G.G., Hama H., DeWald D.B., Horazdovsky B.F.;
RT "The phosphatidylinositol 3-phosphate binding protein Vac1p interacts with
RT a Rab GTPase and a Sec1p homologue to facilitate vesicle-mediated vacuolar
RT protein sorting.";
RL Mol. Biol. Cell 10:1873-1889(1999).
RN [11]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10679018; DOI=10.1091/mbc.11.2.613;
RA Gerrard S.R., Bryant N.J., Stevens T.H.;
RT "VPS21 controls entry of endocytosed and biosynthetic proteins into the
RT yeast prevacuolar compartment.";
RL Mol. Biol. Cell 11:613-626(2000).
RN [12]
RP ACTIVITY REGULATION.
RX PubMed=11359917; DOI=10.1091/mbc.12.5.1215;
RA Du L.-L., Novick P.;
RT "Yeast rab GTPase-activating protein Gyp1p localizes to the Golgi apparatus
RT and is a negative regulator of Ypt1p.";
RL Mol. Biol. Cell 12:1215-1226(2001).
RN [13]
RP SUBCELLULAR LOCATION.
RX PubMed=12589066; DOI=10.1091/mbc.e02-06-0314;
RA Misu K., Fujimura-Kamada K., Ueda T., Nakano A., Katoh H., Tanaka K.;
RT "Cdc50p, a conserved endosomal membrane protein, controls polarized growth
RT in Saccharomyces cerevisiae.";
RL Mol. Biol. Cell 14:730-747(2003).
RN [14]
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 [15]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 76625 / YPH499;
RX PubMed=14576278; DOI=10.1073/pnas.2135385100;
RA Sickmann A., Reinders J., Wagner Y., Joppich C., Zahedi R.P., Meyer H.E.,
RA Schoenfisch B., Perschil I., Chacinska A., Guiard B., Rehling P.,
RA Pfanner N., Meisinger C.;
RT "The proteome of Saccharomyces cerevisiae mitochondria.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:13207-13212(2003).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-188, AND IDENTIFICATION BY
RP 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 [17]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 1-195.
RX PubMed=10756108; DOI=10.1006/jmbi.2000.3645;
RA Esters H., Alexandrov K., Constantinescu A.-T., Goody R.S., Scheidig A.J.;
RT "High-resolution crystal structure of S. cerevisiae Ypt51(DeltaC15)-GppNHp,
RT a small GTP-binding protein involved in regulation of endocytosis.";
RL J. Mol. Biol. 298:111-121(2000).
CC -!- FUNCTION: Required for protein transport to the vacuole. Involved in
CC two vesicle trafficking steps to the prevacuolar compartment (PVC),
CC regulating the docking of endosomes and Golgi vesicles to the PVC by
CC interacting with PEP7/VAC1 on the PVC membrane and promoting SNARE
CC complex formation. {ECO:0000269|PubMed:10679018,
CC ECO:0000269|PubMed:8137814}.
CC -!- ACTIVITY REGULATION: Alternates between an inactive form bound to GDP
CC and an active form bound to GTP. Activated by the guanine nucleotide-
CC exchange factor (GEF) VPS9 and inactivated by GTPase-activating
CC proteins (GAPs) GYP1 and GYP3. {ECO:0000269|PubMed:10329739,
CC ECO:0000269|PubMed:10559187, ECO:0000269|PubMed:11359917}.
CC -!- SUBUNIT: Interacts in its active GTP-bound form with PEP7/VAC1.
CC {ECO:0000269|PubMed:10021387, ECO:0000269|PubMed:10359603}.
CC -!- INTERACTION:
CC P36017; P39958: GDI1; NbExp=4; IntAct=EBI-29399, EBI-7517;
CC P36017; P32864: MRS6; NbExp=3; IntAct=EBI-29399, EBI-14799;
CC -!- SUBCELLULAR LOCATION: Endosome membrane {ECO:0000269|PubMed:10679018,
CC ECO:0000269|PubMed:12589066}; Lipid-anchor {ECO:0000305}. Mitochondrion
CC membrane {ECO:0000269|PubMed:14576278}; Lipid-anchor {ECO:0000305}.
CC -!- MISCELLANEOUS: Present with 8759 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rab family.
CC {ECO:0000305}.
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DR EMBL; X76173; CAA53769.1; -; Genomic_DNA.
DR EMBL; Z29338; CAA82543.1; -; Genomic_DNA.
DR EMBL; X94335; CAA64010.1; -; Genomic_DNA.
DR EMBL; Z74997; CAA99285.1; -; Genomic_DNA.
DR EMBL; BK006948; DAA10866.1; -; Genomic_DNA.
DR PIR; S43399; S43399.
DR RefSeq; NP_014732.1; NM_001183508.1.
DR PDB; 1EK0; X-ray; 1.48 A; A=5-174.
DR PDBsum; 1EK0; -.
DR AlphaFoldDB; P36017; -.
DR SMR; P36017; -.
DR BioGRID; 34487; 594.
DR DIP; DIP-3801N; -.
DR IntAct; P36017; 41.
DR MINT; P36017; -.
DR STRING; 4932.YOR089C; -.
DR iPTMnet; P36017; -.
DR MaxQB; P36017; -.
DR PaxDb; P36017; -.
DR PRIDE; P36017; -.
DR EnsemblFungi; YOR089C_mRNA; YOR089C; YOR089C.
DR GeneID; 854256; -.
DR KEGG; sce:YOR089C; -.
DR SGD; S000005615; VPS21.
DR VEuPathDB; FungiDB:YOR089C; -.
DR eggNOG; KOG0092; Eukaryota.
DR GeneTree; ENSGT00940000161833; -.
DR HOGENOM; CLU_041217_10_2_1; -.
DR InParanoid; P36017; -.
DR OMA; DGIDCAE; -.
DR BioCyc; YEAST:G3O-33623-MON; -.
DR Reactome; R-SCE-6798695; Neutrophil degranulation.
DR Reactome; R-SCE-8873719; RAB geranylgeranylation.
DR EvolutionaryTrace; P36017; -.
DR PRO; PR:P36017; -.
DR Proteomes; UP000002311; Chromosome XV.
DR RNAct; P36017; protein.
DR GO; GO:0005829; C:cytosol; IEA:GOC.
DR GO; GO:0005769; C:early endosome; IDA:SGD.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005770; C:late endosome; IMP:SGD.
DR GO; GO:0005741; C:mitochondrial outer membrane; HDA:SGD.
DR GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; IDA:SGD.
DR GO; GO:0006897; P:endocytosis; IMP:SGD.
DR GO; GO:0006895; P:Golgi to endosome transport; IMP:SGD.
DR GO; GO:0006886; P:intracellular protein transport; IBA:GO_Central.
DR GO; GO:0032511; P:late endosome to vacuole transport via multivesicular body sorting pathway; IGI:SGD.
DR GO; GO:0036258; P:multivesicular body assembly; IGI:SGD.
DR GO; GO:0036010; P:protein localization to endosome; IGI:SGD.
DR GO; GO:0006623; P:protein targeting to vacuole; IMP:SGD.
DR GO; GO:0061709; P:reticulophagy; IMP:SGD.
DR GO; GO:0000011; P:vacuole inheritance; IMP:SGD.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR Pfam; PF00071; Ras; 1.
DR SMART; SM00174; RHO; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51419; RAB; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Endosome; GTP-binding;
KW Lipoprotein; Membrane; Methylation; Mitochondrion; Nucleotide-binding;
KW Phosphoprotein; Prenylation; Protein transport; Reference proteome;
KW Transport.
FT CHAIN 1..210
FT /note="Vacuolar protein sorting-associated protein 21"
FT /id="PRO_0000121325"
FT REGION 176..210
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 36..44
FT /note="Effector region"
FT /evidence="ECO:0000255"
FT BINDING 14..21
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT BINDING 62..66
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT BINDING 120..123
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT MOD_RES 188
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956"
FT MOD_RES 210
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000250"
FT LIPID 208
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 210
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250"
FT MUTAGEN 21
FT /note="S->L,N: Locks VPS21 in its GDP-bound form by
FT abolishing binding to GTP."
FT /evidence="ECO:0000269|PubMed:10021387,
FT ECO:0000269|PubMed:10329739, ECO:0000269|PubMed:8137814"
FT MUTAGEN 66
FT /note="Q->L: Abolishes GTP hydrolysis."
FT /evidence="ECO:0000269|PubMed:10021387"
FT STRAND 6..13
FT /evidence="ECO:0007829|PDB:1EK0"
FT HELIX 20..29
FT /evidence="ECO:0007829|PDB:1EK0"
FT STRAND 40..51
FT /evidence="ECO:0007829|PDB:1EK0"
FT STRAND 54..63
FT /evidence="ECO:0007829|PDB:1EK0"
FT HELIX 67..72
FT /evidence="ECO:0007829|PDB:1EK0"
FT HELIX 73..77
FT /evidence="ECO:0007829|PDB:1EK0"
FT STRAND 81..88
FT /evidence="ECO:0007829|PDB:1EK0"
FT HELIX 92..108
FT /evidence="ECO:0007829|PDB:1EK0"
FT STRAND 114..120
FT /evidence="ECO:0007829|PDB:1EK0"
FT HELIX 122..126
FT /evidence="ECO:0007829|PDB:1EK0"
FT HELIX 135..145
FT /evidence="ECO:0007829|PDB:1EK0"
FT STRAND 148..151
FT /evidence="ECO:0007829|PDB:1EK0"
FT TURN 154..156
FT /evidence="ECO:0007829|PDB:1EK0"
FT HELIX 160..168
FT /evidence="ECO:0007829|PDB:1EK0"
SQ SEQUENCE 210 AA; 23081 MW; 34D7DA0090C33F09 CRC64;
MNTSVTSIKL VLLGEAAVGK SSIVLRFVSN DFAENKEPTI GAAFLTQRVT INEHTVKFEI
WDTAGQERFA SLAPMYYRNA QAALVVYDVT KPQSFIKARH WVKELHEQAS KDIIIALVGN
KIDMLQEGGE RKVAREEGEK LAEEKGLLFF ETSAKTGENV NDVFLGIGEK IPLKTAEEQN
SASNERESNN QRVDLNAAND GTSANSACSC
