DID4_YEAST
ID DID4_YEAST Reviewed; 232 AA.
AC P36108; D6VXT5;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=DOA4-independent degradation protein 4;
DE AltName: Full=ESCRT-III complex subunit VPS2;
DE AltName: Full=Vacuolar protein-sorting-associated protein 2;
DE AltName: Full=Vacuolar protein-targeting protein 14;
GN Name=DID4; Synonyms=CHM2, GRD7, REN1, VPL2, VPS2, VPT14;
GN OrderedLocusNames=YKL002W;
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=8196765; DOI=10.1038/369371a0;
RA Dujon B., Alexandraki D., Andre B., Ansorge W., Baladron V.,
RA Ballesta J.P.G., Banrevi A., Bolle P.-A., Bolotin-Fukuhara M., Bossier P.,
RA Bou G., Boyer J., Buitrago M.J., Cheret G., Colleaux L.,
RA Daignan-Fornier B., del Rey F., Dion C., Domdey H., Duesterhoeft A.,
RA Duesterhus S., Entian K.-D., Erfle H., Esteban P.F., Feldmann H.,
RA Fernandes L., Fobo G.M., Fritz C., Fukuhara H., Gabel C., Gaillon L.,
RA Garcia-Cantalejo J.M., Garcia-Ramirez J.J., Gent M.E., Ghazvini M.,
RA Goffeau A., Gonzalez A., Grothues D., Guerreiro P., Hegemann J.H.,
RA Hewitt N., Hilger F., Hollenberg C.P., Horaitis O., Indge K.J.,
RA Jacquier A., James C.M., Jauniaux J.-C., Jimenez A., Keuchel H.,
RA Kirchrath L., Kleine K., Koetter P., Legrain P., Liebl S., Louis E.J.,
RA Maia e Silva A., Marck C., Monnier A.-L., Moestl D., Mueller S.,
RA Obermaier B., Oliver S.G., Pallier C., Pascolo S., Pfeiffer F.,
RA Philippsen P., Planta R.J., Pohl F.M., Pohl T.M., Poehlmann R.,
RA Portetelle D., Purnelle B., Puzos V., Ramezani Rad M., Rasmussen S.W.,
RA Remacha M.A., Revuelta J.L., Richard G.-F., Rieger M.,
RA Rodrigues-Pousada C., Rose M., Rupp T., Santos M.A., Schwager C.,
RA Sensen C., Skala J., Soares H., Sor F., Stegemann J., Tettelin H.,
RA Thierry A., Tzermia M., Urrestarazu L.A., van Dyck L.,
RA van Vliet-Reedijk J.C., Valens M., Vandenbol M., Vilela C., Vissers S.,
RA von Wettstein D., Voss H., Wiemann S., Xu G., Zimmermann J., Haasemann M.,
RA Becker I., Mewes H.-W.;
RT "Complete DNA sequence of yeast chromosome XI.";
RL Nature 369:371-378(1994).
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 IDENTIFICATION OF INTRON.
RX PubMed=10734188; DOI=10.1093/nar/28.8.1700;
RA Davis C.A., Grate L., Spingola M., Ares M. Jr.;
RT "Test of intron predictions reveals novel splice sites, alternatively
RT spliced mRNAs and new introns in meiotically regulated genes of yeast.";
RL Nucleic Acids Res. 28:1700-1706(2000).
RN [4]
RP FUNCTION.
RX PubMed=11559748; DOI=10.1242/jcs.114.13.2395;
RA Howard T.L., Stauffer D.R., Degnin C.R., Hollenberg S.M.;
RT "CHMP1 functions as a member of a newly defined family of vesicle
RT trafficking proteins.";
RL J. Cell Sci. 114:2395-2404(2001).
RN [5]
RP FUNCTION, IDENTIFICATION IN THE ESCRT-III COMPLEX, INTERACTION WITH VPS24,
RP AND SUBCELLULAR LOCATION.
RX PubMed=12194857; DOI=10.1016/s1534-5807(02)00220-4;
RA Babst M., Katzmann D.J., Estepa-Sabal E.J., Meerloo T., Emr S.D.;
RT "Escrt-III: an endosome-associated heterooligomeric protein complex
RT required for mvb sorting.";
RL Dev. Cell 3:271-282(2002).
RN [6]
RP INTERACTION WITH VPS4.
RX PubMed=17949747; DOI=10.1016/j.jmb.2007.09.067;
RA Xiao J., Xia H., Yoshino-Koh K., Zhou J., Xu Z.;
RT "Structural characterization of the ATPase reaction cycle of endosomal AAA
RT protein Vps4.";
RL J. Mol. Biol. 374:655-670(2007).
RN [7]
RP FUNCTION.
RX PubMed=18194652; DOI=10.1016/j.devcel.2007.10.021;
RA Azmi I.F., Davies B.A., Xiao J., Babst M., Xu Z., Katzmann D.J.;
RT "ESCRT-III family members stimulate Vps4 ATPase activity directly or via
RT Vta1.";
RL Dev. Cell 14:50-61(2008).
RN [8]
RP ASSEMBLY OF THE ESCRT-III COMPLEX.
RX PubMed=18854142; DOI=10.1016/j.devcel.2008.08.013;
RA Teis D., Saksena S., Emr S.D.;
RT "Ordered assembly of the ESCRT-III complex on endosomes is required to
RT sequester cargo during MVB formation.";
RL Dev. Cell 15:578-589(2008).
RN [9]
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 [10]
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 [11]
RP X-RAY CRYSTALLOGRAPHY (1.98 ANGSTROMS) OF 183-232 IN COMPLEX WITH VPS4, AND
RP MUTAGENESIS OF LEU-221; ARG-224; LEU-225; LEU-228 AND LYS-229.
RX PubMed=17928861; DOI=10.1038/nature06171;
RA Obita T., Saksena S., Ghazi-Tabatabai S., Gill D.J., Perisic O., Emr S.D.,
RA Williams R.L.;
RT "Structural basis for selective recognition of ESCRT-III by the AAA ATPase
RT Vps4.";
RL Nature 449:735-739(2007).
CC -!- FUNCTION: Required for the sorting and concentration of proteins
CC resulting in the entry of these proteins into the invaginating vesicles
CC of the multivesicular body (MVB). Acts a component of the ESCRT-III
CC complex, which appears to be critical for late steps in MVB sorting,
CC such as membrane invagination and final cargo sorting and recruitment
CC of late-acting components of the sorting machinery. The MVB pathway
CC requires the sequential function of ESCRT-O, -I,-II and -III complex
CC assemblies. Can directly stimulate VPS4 ATPase activity. The DID4/VPS2-
CC VPS24 subcomplex is required for the VPS4-dependent dissociation of
CC ESCRT-III. {ECO:0000269|PubMed:11559748, ECO:0000269|PubMed:12194857,
CC ECO:0000269|PubMed:18194652}.
CC -!- SUBUNIT: Core component of the ESCRT-III complex (endosomal sorting
CC required for transport complex III). ESCRT-III appears to be
CC sequentially assembled as a flat lattice on the endosome membrane and
CC forms a transient 450 kDa complex that contains DID4, oligomerized
CC SNF7, VPS20 and VPS24. SNF7 oligomerization into a membrane-associated
CC filament is nucleated by association of SNF7 with VPS20; the process is
CC terminated through association of VPS24, possibly by capping the SNF7
CC filament. VPS24 subsequently associates with DID4/VPS2.
CC {ECO:0000269|PubMed:12194857, ECO:0000269|PubMed:17928861}.
CC -!- INTERACTION:
CC P36108; P39929: SNF7; NbExp=4; IntAct=EBI-26574, EBI-17554;
CC P36108; P52917: VPS4; NbExp=4; IntAct=EBI-26574, EBI-20475;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12194857}. Endosome
CC membrane {ECO:0000269|PubMed:12194857}; Peripheral membrane protein
CC {ECO:0000269|PubMed:12194857}.
CC -!- SIMILARITY: Belongs to the SNF7 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA81834.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; Z28002; CAA81834.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BK006944; DAA09155.1; -; Genomic_DNA.
DR PIR; S37812; S37812.
DR RefSeq; NP_012924.2; NM_001179568.1.
DR PDB; 2V6X; X-ray; 1.98 A; B=183-232.
DR PDB; 6AP1; EM; 3.20 A; G=165-172.
DR PDB; 6BMF; EM; 3.20 A; G=165-172.
DR PDBsum; 2V6X; -.
DR PDBsum; 6AP1; -.
DR PDBsum; 6BMF; -.
DR AlphaFoldDB; P36108; -.
DR SMR; P36108; -.
DR BioGRID; 34131; 229.
DR ComplexPortal; CPX-1624; ESCRT-III complex.
DR DIP; DIP-1916N; -.
DR IntAct; P36108; 14.
DR MINT; P36108; -.
DR STRING; 4932.YKL002W; -.
DR TCDB; 3.A.31.1.1; the endosomal sorting complexes required for transport iii (escrt-iii) family.
DR iPTMnet; P36108; -.
DR MaxQB; P36108; -.
DR PaxDb; P36108; -.
DR PRIDE; P36108; -.
DR DNASU; 853868; -.
DR EnsemblFungi; YKL002W_mRNA; YKL002W; YKL002W.
DR GeneID; 853868; -.
DR KEGG; sce:YKL002W; -.
DR SGD; S000001485; DID4.
DR VEuPathDB; FungiDB:YKL002W; -.
DR eggNOG; KOG3230; Eukaryota.
DR GeneTree; ENSGT00950000182832; -.
DR HOGENOM; CLU_069208_1_0_1; -.
DR InParanoid; P36108; -.
DR OMA; RYAKKFM; -.
DR BioCyc; YEAST:G3O-31813-MON; -.
DR Reactome; R-SCE-1632852; Macroautophagy.
DR Reactome; R-SCE-917729; Endosomal Sorting Complex Required For Transport (ESCRT).
DR Reactome; R-SCE-9668328; Sealing of the nuclear envelope (NE) by ESCRT-III.
DR EvolutionaryTrace; P36108; -.
DR PRO; PR:P36108; -.
DR Proteomes; UP000002311; Chromosome XI.
DR RNAct; P36108; protein.
DR GO; GO:0005737; C:cytoplasm; IDA:SGD.
DR GO; GO:0000815; C:ESCRT III complex; IDA:SGD.
DR GO; GO:0005771; C:multivesicular body; IBA:GO_Central.
DR GO; GO:1904669; P:ATP export; IMP:SGD.
DR GO; GO:0032509; P:endosome transport via multivesicular body sorting pathway; IBA:GO_Central.
DR GO; GO:0070676; P:intralumenal vesicle formation; IMP:SGD.
DR GO; GO:0045324; P:late endosome to vacuole transport; IDA:SGD.
DR GO; GO:0045053; P:protein retention in Golgi apparatus; IMP:SGD.
DR GO; GO:0015031; P:protein transport; IBA:GO_Central.
DR GO; GO:0043162; P:ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway; IDA:ComplexPortal.
DR InterPro; IPR005024; Snf7_fam.
DR PANTHER; PTHR10476; PTHR10476; 1.
DR Pfam; PF03357; Snf7; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Coiled coil; Cytoplasm; Endosome; Membrane;
KW Protein transport; Reference proteome; Transport.
FT CHAIN 1..232
FT /note="DOA4-independent degradation protein 4"
FT /id="PRO_0000211477"
FT REGION 183..232
FT /note="Interaction with VPS4"
FT /evidence="ECO:0000269|PubMed:17949747"
FT REGION 203..232
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 14..97
FT /evidence="ECO:0000255"
FT MOTIF 219..229
FT /note="MIT-interacting motif"
FT MUTAGEN 221
FT /note="L->D: Abolishes interaction with VPS4."
FT /evidence="ECO:0000269|PubMed:17928861"
FT MUTAGEN 224
FT /note="R->D: Abolishes interaction with VPS4. Impairs
FT sorting."
FT /evidence="ECO:0000269|PubMed:17928861"
FT MUTAGEN 225
FT /note="L->D: Abolishes interaction with VPS4."
FT /evidence="ECO:0000269|PubMed:17928861"
FT MUTAGEN 228..229
FT /note="LK->DD: Greatly impairs sorting."
FT MUTAGEN 228
FT /note="L->D: Abolishes interaction with VPS4."
FT /evidence="ECO:0000269|PubMed:17928861"
FT MUTAGEN 229
FT /note="K->D: Abolishes interaction with VPS4."
FT /evidence="ECO:0000269|PubMed:17928861"
FT HELIX 188..191
FT /evidence="ECO:0007829|PDB:2V6X"
FT HELIX 197..200
FT /evidence="ECO:0007829|PDB:2V6X"
FT STRAND 201..204
FT /evidence="ECO:0007829|PDB:2V6X"
FT HELIX 219..229
FT /evidence="ECO:0007829|PDB:2V6X"
SQ SEQUENCE 232 AA; 26291 MW; 200D07DB4C45DCBC CRC64;
MSLFEWVFGK NVTPQERLKK NQRALERTQR ELEREKRKLE LQDKKLVSEI KKSAKNGQVA
AAKVQAKDLV RTRNYIQKFD NMKAQLQAIS LRIQAVRSSD QMTRSMSEAT GLLAGMNRTM
NLPQLQRISM EFEKQSDLMG QRQEFMDEAI DNVMGDEVDE DEEADEIVNK VLDEIGVDLN
SQLQSTPQNL VSNAPIAETA MGIPEPIGAG SEFHGNPDDD LQARLNTLKK QT
