CHMP3_HUMAN
ID CHMP3_HUMAN Reviewed; 222 AA.
AC Q9Y3E7; A8K3W0; B4DG34; B8ZZM0; B8ZZX5; Q3ZTS9; Q53S71; Q53SU5; Q9NZ51;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Charged multivesicular body protein 3;
DE AltName: Full=Chromatin-modifying protein 3;
DE AltName: Full=Neuroendocrine differentiation factor;
DE AltName: Full=Vacuolar protein sorting-associated protein 24;
DE Short=hVps24;
GN Name=CHMP3; Synonyms=CGI149, NEDF, VPS24; ORFNames=CGI-149;
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 [MRNA] (ISOFORM 1), AND POSSIBLE INTERACTION WITH
RP IGFBP7.
RX PubMed=11549700; DOI=10.1210/jcem.86.9.7845;
RA Wilson E.M., Oh Y., Hwa V., Rosenfeld R.G.;
RT "Interaction of IGF-binding protein-related protein 1 with a novel protein,
RT neuroendocrine differentiation factor, results in neuroendocrine
RT differentiation of prostate cancer cells.";
RL J. Clin. Endocrinol. Metab. 86:4504-4511(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Heart;
RX PubMed=15707591; DOI=10.1016/j.yexcr.2004.11.003;
RA Yan Q., Hunt P.R., Frelin L., Vida T.A., Pevsner J., Bean A.J.;
RT "mVps24p functions in EGF receptor sorting/trafficking from the early
RT endosome.";
RL Exp. Cell Res. 304:265-273(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=16533400; DOI=10.1186/1471-2164-7-48;
RA Kemmer D., Podowski R.M., Arenillas D., Lim J., Hodges E., Roth P.,
RA Sonnhammer E.L.L., Hoeoeg C., Wasserman W.W.;
RT "NovelFam3000 -- uncharacterized human protein domains conserved across
RT model organisms.";
RL BMC Genomics 7:48-48(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND FUNCTION.
RC TISSUE=Heart;
RX PubMed=17331679; DOI=10.1016/j.gene.2006.12.039;
RA Khoury C.M., Yang Z., Ismail S., Greenwood M.T.;
RT "Characterization of a novel alternatively spliced human transcript
RT encoding an N-terminally truncated Vps24 protein that suppresses the
RT effects of Bax in an ESCRT independent manner in yeast.";
RL Gene 391:233-241(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=10810093; DOI=10.1101/gr.10.5.703;
RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.;
RT "Identification of novel human genes evolutionarily conserved in
RT Caenorhabditis elegans by comparative proteomics.";
RL Genome Res. 10:703-713(2000).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Amygdala, Pericardium, and Synovial cell;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Uterus;
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 [10]
RP FUNCTION IN HIV-1 BUDDING, AND INTERACTION WITH CHMP4A.
RX PubMed=14505570; DOI=10.1016/s0092-8674(03)00714-1;
RA von Schwedler U.K., Stuchell M., Mueller B., Ward D.M., Chung H.-Y.,
RA Morita E., Wang H.E., Davis T., He G.P., Cimbora D.M., Scott A.,
RA Kraeusslich H.-G., Kaplan J., Morham S.G., Sundquist W.I.;
RT "The protein network of HIV budding.";
RL Cell 114:701-713(2003).
RN [11]
RP INTERACTION WITH CHMP2A AND VPS4A.
RX PubMed=14519844; DOI=10.1073/pnas.2133846100;
RA Martin-Serrano J., Yarovoy A., Perez-Caballero D., Bieniasz P.D.;
RT "Divergent retroviral late-budding domains recruit vacuolar protein sorting
RT factors by using alternative adaptor proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:12414-12419(2003).
RN [12]
RP ERRATUM OF PUBMED:14519844.
RA Martin-Serrano J., Yarovoy A., Perez-Caballero D., Bieniasz P.D.;
RL Proc. Natl. Acad. Sci. U.S.A. 100:152845-152845(2003).
RN [13]
RP TISSUE SPECIFICITY.
RX PubMed=15632132; DOI=10.1074/jbc.m413968200;
RA Lin Y., Kimpler L.A., Naismith T.V., Lauer J.M., Hanson P.I.;
RT "Interaction of the mammalian endosomal sorting complex required for
RT transport (ESCRT) III protein hSnf7-1 with itself, membranes, and the AAA+
RT ATPase SKD1.";
RL J. Biol. Chem. 280:12799-12809(2005).
RN [14]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH STAMBP.
RX PubMed=16730941; DOI=10.1016/j.ygeno.2006.04.003;
RA Tsang H.T.H., Connell J.W., Brown S.E., Thompson A., Reid E.,
RA Sanderson C.M.;
RT "A systematic analysis of human CHMP protein interactions: additional MIT
RT domain-containing proteins bind to multiple components of the human ESCRT
RT III complex.";
RL Genomics 88:333-346(2006).
RN [15]
RP AUTOINHIBITORY MECHANISM, INTRAMOLECULAR INTERACTION, INTERACTION WITH
RP STAMBP AND VPS4A, AND MUTAGENESIS OF 216-ARG-LEU-217; 221-ARG-SER-222 AND
RP SER-222.
RX PubMed=17146056; DOI=10.1073/pnas.0603788103;
RA Zamborlini A., Usami Y., Radoshitzky S.R., Popova E., Palu G.,
RA Goettlinger H.;
RT "Release of autoinhibition converts ESCRT-III components into potent
RT inhibitors of HIV-1 budding.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:19140-19145(2006).
RN [16]
RP INTERACTION WITH STAMBP, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=17261583; DOI=10.1074/jbc.m611635200;
RA Ma Y.M., Boucrot E., Villen J., Affar el B., Gygi S.P., Goettlinger H.G.,
RA Kirchhausen T.;
RT "Targeting of AMSH to endosomes is required for epidermal growth factor
RT receptor degradation.";
RL J. Biol. Chem. 282:9805-9812(2007).
RN [17]
RP AUTOINHIBITORY MECHANISM, INTERACTION WITH CHMP4A, AND MUTAGENESIS OF
RP 179-LYS--SER-222.
RX PubMed=17547705; DOI=10.1111/j.1600-0854.2007.00584.x;
RA Shim S., Kimpler L.A., Hanson P.I.;
RT "Structure/function analysis of four core ESCRT-III proteins reveals common
RT regulatory role for extreme C-terminal domain.";
RL Traffic 8:1068-1079(2007).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-200, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [19]
RP POLYMERIZATION WITH CHMP2A, AND ELECTRON MICROSCOPY.
RX PubMed=18687924; DOI=10.1126/science.1161070;
RA Lata S., Schoehn G., Jain A., Pires R., Piehler J., Goettlinger H.G.,
RA Weissenhorn W.;
RT "Helical structures of ESCRT-III are disassembled by VPS4.";
RL Science 321:1354-1357(2008).
RN [20]
RP FUNCTION IN CYTOKINESIS, AND SUBCELLULAR LOCATION.
RX PubMed=18076377; DOI=10.1042/bj20071296;
RA Dukes J.D., Richardson J.D., Simmons R., Whitley P.;
RT "A dominant-negative ESCRT-III protein perturbs cytokinesis and trafficking
RT to lysosomes.";
RL Biochem. J. 411:233-239(2008).
RN [21]
RP AUTOINHIBITORY MECHANISM, AND INTERACTION WITH STAMBP.
RX PubMed=18395747; DOI=10.1016/j.jmb.2008.03.030;
RA Lata S., Roessle M., Solomons J., Jamin M., Goettlinger H.G., Svergun D.I.,
RA Weissenhorn W.;
RT "Structural basis for autoinhibition of ESCRT-III CHMP3.";
RL J. Mol. Biol. 378:818-827(2008).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-200, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-200, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [24]
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 [25]
RP INTERACTION WITH VTA1 AND VPS4A.
RX PubMed=21543490; DOI=10.1128/jvi.02610-10;
RA Kuang Z., Seo E.J., Leis J.;
RT "Mechanism of inhibition of retrovirus release from cells by interferon-
RT induced gene ISG15.";
RL J. Virol. 85:7153-7161(2011).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-200, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-200, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 5-183, SUBUNIT, FUNCTION IN HIV-1
RP BUDDING, AND MUTAGENESIS OF 24-ARG-LYS-25; ARG-28; LYS-54; GLN-56; VAL-59;
RP 62-VAL-LEU-63 AND 78-TYR-ALA-79.
RX PubMed=16740483; DOI=10.1016/j.devcel.2006.03.013;
RA Muziol T., Pineda-Molina E., Ravelli R.B., Zamborlini A., Usami Y.,
RA Goettlinger H., Weissenhorn W.;
RT "Structural basis for budding by the ESCRT-III factor CHMP3.";
RL Dev. Cell 10:821-830(2006).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (3.70 ANGSTROMS) OF 1-222, INTERACTION WITH CHMP2A,
RP AND MUTAGENESIS OF VAL-48; VAL-59; VAL-62; ALA-64 AND 168-ILE-LEU-169.
RX PubMed=19525971; DOI=10.1038/nsmb.1621;
RA Bajorek M., Schubert H.L., McCullough J., Langelier C., Eckert D.M.,
RA Stubblefield W.M., Uter N.T., Myszka D.G., Hill C.P., Sundquist W.I.;
RT "Structural basis for ESCRT-III protein autoinhibition.";
RL Nat. Struct. Mol. Biol. 16:754-762(2009).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 183-222 IN COMPLEX WITH STAMBP
RP FRAGMENT.
RX PubMed=21827950; DOI=10.1016/j.str.2011.05.011;
RA Solomons J., Sabin C., Poudevigne E., Usami Y., Hulsik D.L., Macheboeuf P.,
RA Hartlieb B., Gottlinger H., Weissenhorn W.;
RT "Structural basis for Escrt-III Chmp3 recruitment of Amsh.";
RL Structure 19:1149-1159(2011).
CC -!- FUNCTION: Probable core component of the endosomal sorting required for
CC transport complex III (ESCRT-III) which is involved in multivesicular
CC bodies (MVBs) formation and sorting of endosomal cargo proteins into
CC MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by
CC invagination and scission from the limiting membrane of the endosome
CC and mostly are delivered to lysosomes enabling degradation of membrane
CC proteins, such as stimulated growth factor receptors, lysosomal enzymes
CC and lipids. The MVB pathway appears to require the sequential function
CC of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly
CC dissociate from the invaginating membrane before the ILV is released.
CC The ESCRT machinery also functions in topologically equivalent membrane
CC fission events, such as the terminal stages of cytokinesis and the
CC budding of enveloped viruses (HIV-1 and other lentiviruses). ESCRT-III
CC proteins are believed to mediate the necessary vesicle extrusion and/or
CC membrane fission activities, possibly in conjunction with the AAA
CC ATPase VPS4. Selectively binds to phosphatidylinositol 3,5-bisphosphate
CC PtdIns(3,5)P2 and PtdIns(3,4)P2 in preference to other
CC phosphoinositides tested. Involved in late stages of cytokinesis. Plays
CC a role in endosomal sorting/trafficking of EGF receptor. Isoform 2
CC prevents stress-mediated cell death and accumulation of reactive oxygen
CC species when expressed in yeast cells. {ECO:0000269|PubMed:14505570,
CC ECO:0000269|PubMed:15707591, ECO:0000269|PubMed:16740483,
CC ECO:0000269|PubMed:17331679, ECO:0000269|PubMed:18076377}.
CC -!- SUBUNIT: Probable core component of the endosomal sorting required for
CC transport complex III (ESCRT-III). ESCRT-III components are thought to
CC multimerize to form a flat lattice on the perimeter membrane of the
CC endosome. Several assembly forms of ESCRT-III may exist that interact
CC and act sequentially. Forms a metastable monomer in solution; its core
CC structure (without part of the putative autoinhibitory C-terminal
CC acidic region) oligomerizes into a flat lattice via two different
CC dimerization interfaces. In vitro, heteromerizes with CHMP2A (but not
CC CHMP4) to form helical tubular structures that expose membrane-
CC interacting sites on the outside whereas VPS4B can associate on the
CC inside of the tubule. May interact with IGFBP7; the relevance of such
CC interaction however remains unclear. Interacts with CHMP2A. Interacts
CC with CHMP4A; the interaction requires the release of CHMP4A
CC autoinhibition. Interacts with VPS4A. Interacts with STAMBP; the
CC interaction appears to relieve the autoinhibition of CHMP3. Interacts
CC with VTA1. {ECO:0000269|PubMed:14505570, ECO:0000269|PubMed:14519844,
CC ECO:0000269|PubMed:16730941, ECO:0000269|PubMed:16740483,
CC ECO:0000269|PubMed:17146056, ECO:0000269|PubMed:17261583,
CC ECO:0000269|PubMed:17547705, ECO:0000269|PubMed:18395747,
CC ECO:0000269|PubMed:19525971, ECO:0000269|PubMed:21543490,
CC ECO:0000269|PubMed:21827950}.
CC -!- INTERACTION:
CC Q9Y3E7; O43633: CHMP2A; NbExp=3; IntAct=EBI-2118119, EBI-2692789;
CC Q9Y3E7; Q9UQN3: CHMP2B; NbExp=2; IntAct=EBI-2118119, EBI-718324;
CC Q9Y3E7; Q9H444: CHMP4B; NbExp=5; IntAct=EBI-2118119, EBI-749627;
CC Q9Y3E7; O95630: STAMBP; NbExp=26; IntAct=EBI-2118119, EBI-396676;
CC Q9Y3E7-1; O43633: CHMP2A; NbExp=2; IntAct=EBI-15613847, EBI-2692789;
CC Q9Y3E7-1; Q9Y3E7-1: CHMP3; NbExp=3; IntAct=EBI-15613847, EBI-15613847;
CC Q9Y3E7-1; O95630: STAMBP; NbExp=6; IntAct=EBI-15613847, EBI-396676;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol. Membrane; Lipid-anchor.
CC Endosome. Late endosome membrane {ECO:0000305}. Note=Localizes to the
CC midbody of dividing cells.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=Vps24alpha;
CC IsoId=Q9Y3E7-1; Sequence=Displayed;
CC Name=2; Synonyms=Vps24beta;
CC IsoId=Q9Y3E7-2; Sequence=VSP_041076;
CC Name=3;
CC IsoId=Q9Y3E7-3; Sequence=VSP_042124;
CC Name=4;
CC IsoId=Q9Y3E7-4; Sequence=VSP_042125;
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in heart, brain,
CC placenta, lung, liver, skeletal muscle, kidney and pancreas.
CC {ECO:0000269|PubMed:15632132}.
CC -!- DOMAIN: The acidic C-terminus and the basic N-termminus are thought to
CC render the protein in a closed, soluble and inactive conformation
CC through an autoinhibitory intramolecular interaction. The open and
CC active conformation, which enables membrane binding and
CC oligomerization, is achieved by interaction with other cellular binding
CC partners, probably including other ESCRT components.
CC -!- MISCELLANEOUS: Its overexpression strongly inhibits HIV-1 release.
CC -!- SIMILARITY: Belongs to the SNF7 family. {ECO:0000305}.
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DR EMBL; AF219226; AAF26737.1; -; mRNA.
DR EMBL; AY364249; AAQ76808.1; -; mRNA.
DR EMBL; AF151907; AAD34144.1; -; mRNA.
DR EMBL; AK290725; BAF83414.1; -; mRNA.
DR EMBL; AK294389; BAG57645.1; -; mRNA.
DR EMBL; AK312353; BAG35273.1; -; mRNA.
DR EMBL; AK315835; BAF98726.1; -; mRNA.
DR EMBL; AC015971; AAX93078.1; -; Genomic_DNA.
DR EMBL; AC064848; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC068288; AAY24211.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99448.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99449.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99450.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99451.1; -; Genomic_DNA.
DR EMBL; BC004419; AAH04419.1; -; mRNA.
DR CCDS; CCDS33236.1; -. [Q9Y3E7-1]
DR CCDS; CCDS42707.1; -. [Q9Y3E7-2]
DR CCDS; CCDS54375.1; -. [Q9Y3E7-4]
DR RefSeq; NP_001005753.1; NM_001005753.2. [Q9Y3E7-2]
DR RefSeq; NP_001180446.1; NM_001193517.1. [Q9Y3E7-4]
DR RefSeq; NP_001185883.1; NM_001198954.1. [Q9Y3E7-3]
DR RefSeq; NP_057163.1; NM_016079.3. [Q9Y3E7-1]
DR PDB; 2GD5; X-ray; 2.80 A; A/B/C/D=9-183.
DR PDB; 2XZE; X-ray; 1.75 A; Q/R=183-222.
DR PDB; 3FRT; X-ray; 4.00 A; A/B=8-222.
DR PDB; 3FRV; X-ray; 3.70 A; A=1-150.
DR PDBsum; 2GD5; -.
DR PDBsum; 2XZE; -.
DR PDBsum; 3FRT; -.
DR PDBsum; 3FRV; -.
DR AlphaFoldDB; Q9Y3E7; -.
DR SMR; Q9Y3E7; -.
DR BioGRID; 119660; 62.
DR BioGRID; 1529307; 2.
DR ComplexPortal; CPX-329; ESCRT-III complex.
DR CORUM; Q9Y3E7; -.
DR DIP; DIP-48532N; -.
DR IntAct; Q9Y3E7; 32.
DR MINT; Q9Y3E7; -.
DR STRING; 9606.ENSP00000405575; -.
DR iPTMnet; Q9Y3E7; -.
DR MetOSite; Q9Y3E7; -.
DR PhosphoSitePlus; Q9Y3E7; -.
DR BioMuta; CHMP3; -.
DR DMDM; 73917763; -.
DR EPD; Q9Y3E7; -.
DR jPOST; Q9Y3E7; -.
DR MassIVE; Q9Y3E7; -.
DR MaxQB; Q9Y3E7; -.
DR PaxDb; Q9Y3E7; -.
DR PeptideAtlas; Q9Y3E7; -.
DR PRIDE; Q9Y3E7; -.
DR ProteomicsDB; 86031; -. [Q9Y3E7-1]
DR ProteomicsDB; 86032; -. [Q9Y3E7-2]
DR ProteomicsDB; 86033; -. [Q9Y3E7-3]
DR ProteomicsDB; 86034; -. [Q9Y3E7-4]
DR Antibodypedia; 17073; 102 antibodies from 23 providers.
DR DNASU; 51652; -.
DR Ensembl; ENST00000263856.9; ENSP00000263856.4; ENSG00000115561.16. [Q9Y3E7-1]
DR Ensembl; ENST00000409225.2; ENSP00000386590.2; ENSG00000115561.16. [Q9Y3E7-2]
DR Ensembl; ENST00000409727.5; ENSP00000387045.1; ENSG00000115561.16. [Q9Y3E7-4]
DR GeneID; 100526767; -.
DR GeneID; 51652; -.
DR KEGG; hsa:100526767; -.
DR KEGG; hsa:51652; -.
DR MANE-Select; ENST00000263856.9; ENSP00000263856.4; NM_016079.4; NP_057163.1.
DR UCSC; uc002srj.4; human. [Q9Y3E7-1]
DR CTD; 100526767; -.
DR CTD; 51652; -.
DR DisGeNET; 100526767; -.
DR DisGeNET; 51652; -.
DR GeneCards; CHMP3; -.
DR HGNC; HGNC:29865; CHMP3.
DR HPA; ENSG00000115561; Low tissue specificity.
DR MIM; 610052; gene.
DR neXtProt; NX_Q9Y3E7; -.
DR OpenTargets; ENSG00000115561; -.
DR OpenTargets; ENSG00000249884; -.
DR PharmGKB; PA134920495; -.
DR VEuPathDB; HostDB:ENSG00000115561; -.
DR eggNOG; KOG0800; Eukaryota.
DR eggNOG; KOG3229; Eukaryota.
DR GeneTree; ENSGT00950000182832; -.
DR HOGENOM; CLU_069208_0_1_1; -.
DR InParanoid; Q9Y3E7; -.
DR OMA; RICHFAT; -.
DR OrthoDB; 1418709at2759; -.
DR PhylomeDB; Q9Y3E7; -.
DR TreeFam; TF105848; -.
DR PathwayCommons; Q9Y3E7; -.
DR Reactome; R-HSA-162588; Budding and maturation of HIV virion.
DR Reactome; R-HSA-1632852; Macroautophagy.
DR Reactome; R-HSA-5620971; Pyroptosis.
DR Reactome; R-HSA-917729; Endosomal Sorting Complex Required For Transport (ESCRT).
DR Reactome; R-HSA-9610379; HCMV Late Events.
DR Reactome; R-HSA-9615710; Late endosomal microautophagy.
DR Reactome; R-HSA-9668328; Sealing of the nuclear envelope (NE) by ESCRT-III.
DR Reactome; R-HSA-9679504; Translation of Replicase and Assembly of the Replication Transcription Complex.
DR Reactome; R-HSA-9694676; Translation of Replicase and Assembly of the Replication Transcription Complex.
DR SignaLink; Q9Y3E7; -.
DR SIGNOR; Q9Y3E7; -.
DR BioGRID-ORCS; 100526767; 167 hits in 571 CRISPR screens.
DR BioGRID-ORCS; 51652; 497 hits in 1065 CRISPR screens.
DR EvolutionaryTrace; Q9Y3E7; -.
DR GeneWiki; VPS24; -.
DR Pharos; Q9Y3E7; Tbio.
DR PRO; PR:Q9Y3E7; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9Y3E7; protein.
DR Bgee; ENSG00000115561; Expressed in calcaneal tendon and 207 other tissues.
DR Genevisible; Q9Y3E7; HS.
DR GO; GO:1904930; C:amphisome membrane; IDA:ComplexPortal.
DR GO; GO:0000421; C:autophagosome membrane; IDA:ComplexPortal.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005769; C:early endosome; IEA:Ensembl.
DR GO; GO:0000815; C:ESCRT III complex; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0000776; C:kinetochore; IDA:ComplexPortal.
DR GO; GO:0005828; C:kinetochore microtubule; IDA:ComplexPortal.
DR GO; GO:0005770; C:late endosome; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005765; C:lysosomal membrane; IDA:ComplexPortal.
DR GO; GO:0030496; C:midbody; IDA:ComplexPortal.
DR GO; GO:0005771; C:multivesicular body; IBA:GO_Central.
DR GO; GO:0032585; C:multivesicular body membrane; IDA:ComplexPortal.
DR GO; GO:0005643; C:nuclear pore; IDA:ComplexPortal.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0031210; F:phosphatidylcholine binding; IMP:UniProtKB.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IEA:Ensembl.
DR GO; GO:1990381; F:ubiquitin-specific protease binding; IPI:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0097352; P:autophagosome maturation; IMP:ComplexPortal.
DR GO; GO:0006914; P:autophagy; IMP:ComplexPortal.
DR GO; GO:0032509; P:endosome transport via multivesicular body sorting pathway; IBA:GO_Central.
DR GO; GO:1902774; P:late endosome to lysosome transport; IMP:ComplexPortal.
DR GO; GO:0045324; P:late endosome to vacuole transport; IBA:GO_Central.
DR GO; GO:0016236; P:macroautophagy; TAS:ParkinsonsUK-UCL.
DR GO; GO:0090148; P:membrane fission; IC:ComplexPortal.
DR GO; GO:0061952; P:midbody abscission; IMP:UniProtKB.
DR GO; GO:0007080; P:mitotic metaphase plate congression; IMP:ComplexPortal.
DR GO; GO:0036258; P:multivesicular body assembly; TAS:ParkinsonsUK-UCL.
DR GO; GO:0071985; P:multivesicular body sorting pathway; IDA:ComplexPortal.
DR GO; GO:0061763; P:multivesicular body-lysosome fusion; IMP:ParkinsonsUK-UCL.
DR GO; GO:0060548; P:negative regulation of cell death; IMP:ComplexPortal.
DR GO; GO:0031468; P:nuclear membrane reassembly; IMP:ComplexPortal.
DR GO; GO:0006997; P:nucleus organization; IMP:ComplexPortal.
DR GO; GO:0001778; P:plasma membrane repair; IDA:ComplexPortal.
DR GO; GO:0032467; P:positive regulation of cytokinesis; IEA:Ensembl.
DR GO; GO:0051258; P:protein polymerization; IDA:UniProtKB.
DR GO; GO:0015031; P:protein transport; IBA:GO_Central.
DR GO; GO:0010824; P:regulation of centrosome duplication; IMP:UniProtKB.
DR GO; GO:2000641; P:regulation of early endosome to late endosome transport; IMP:ParkinsonsUK-UCL.
DR GO; GO:0051036; P:regulation of endosome size; IEA:Ensembl.
DR GO; GO:1901673; P:regulation of mitotic spindle assembly; IMP:ComplexPortal.
DR GO; GO:0044790; P:suppression of viral release by host; IMP:UniProtKB.
DR GO; GO:0043162; P:ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway; IDA:ComplexPortal.
DR GO; GO:0051469; P:vesicle fusion with vacuole; IC:ComplexPortal.
DR GO; GO:0046761; P:viral budding from plasma membrane; IDA:ComplexPortal.
DR GO; GO:0039702; P:viral budding via host ESCRT complex; IDA:UniProtKB.
DR GO; GO:0019076; P:viral release from host cell; IMP:UniProtKB.
DR DisProt; DP01283; -.
DR IDEAL; IID00230; -.
DR InterPro; IPR005024; Snf7_fam.
DR PANTHER; PTHR10476; PTHR10476; 1.
DR Pfam; PF03357; Snf7; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; Cell cycle; Cell division;
KW Coiled coil; Cytoplasm; Endosome; Isopeptide bond; Lipoprotein; Membrane;
KW Myristate; Phosphoprotein; Protein transport; Reference proteome;
KW Transport; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000255"
FT CHAIN 2..222
FT /note="Charged multivesicular body protein 3"
FT /id="PRO_0000211479"
FT REGION 2..113
FT /note="Intramolecular interaction with C-terminus"
FT REGION 59..64
FT /note="Important for autoinhibitory function"
FT REGION 151..222
FT /note="Interaction with VPS4A"
FT REGION 151..220
FT /note="Intramolecular interaction with N-terminus"
FT REGION 168..169
FT /note="Important for autoinhibitory function"
FT REGION 180..222
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 203..207
FT /note="Interaction with STAMBP"
FT REGION 221..222
FT /note="Interaction with STAMBP"
FT COILED 22..54
FT /evidence="ECO:0000255"
FT COILED 141..222
FT /evidence="ECO:0000255"
FT MOTIF 201..211
FT /note="MIT-interacting motif"
FT SITE 48
FT /note="Important for autoinhibitory function"
FT SITE 216
FT /note="Interaction with STAMBP"
FT MOD_RES 200
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000255"
FT CROSSLNK 179
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT VAR_SEQ 1..66
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:17331679"
FT /id="VSP_041076"
FT VAR_SEQ 1..15
FT /note="MGLFGKTQEKPPKEL -> MEGELYSALKEEEASESVSSTNFSGEMHFYELV
FT EDTKDGIWLVQ (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042124"
FT VAR_SEQ 74..113
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_042125"
FT MUTAGEN 24..25
FT /note="RK->SA: Impairs HIV-1 release; when associated with
FT S-28."
FT /evidence="ECO:0000269|PubMed:16740483"
FT MUTAGEN 28
FT /note="R->S: Impairs HIV-1 release; when associated with
FT 24-S-A-25."
FT /evidence="ECO:0000269|PubMed:16740483"
FT MUTAGEN 48
FT /note="V->D: Induces assembly with CHMP2A into helical
FT tubes in vitro; when associated with D-64. Enhances
FT inhibition of HIV-1 budding in vivo; when associated with
FT D-168 and D-169."
FT /evidence="ECO:0000269|PubMed:19525971"
FT MUTAGEN 54
FT /note="K->S: Abolishes dimerization; when associated with
FT N-56; E-59 and 62-D-E-63."
FT /evidence="ECO:0000269|PubMed:16740483"
FT MUTAGEN 56
FT /note="Q->N: Abolishes dimerization; when associated with
FT S-54; E-59 and 62-D-E-63."
FT /evidence="ECO:0000269|PubMed:16740483"
FT MUTAGEN 59
FT /note="V->D: Abolishes interaction with CHMP2A and assembly
FT into helical tubes in vitro; when associated with D-62; D-
FT 168 and D-169."
FT /evidence="ECO:0000269|PubMed:16740483,
FT ECO:0000269|PubMed:19525971"
FT MUTAGEN 59
FT /note="V->E: Abolishes dimerization; when associated with
FT S-54; N-56 and 62-D-E-63."
FT /evidence="ECO:0000269|PubMed:16740483,
FT ECO:0000269|PubMed:19525971"
FT MUTAGEN 62..63
FT /note="VL->DE: Abolishes dimerization; when associated with
FT S-54; N-56 and E-59."
FT /evidence="ECO:0000269|PubMed:16740483"
FT MUTAGEN 62
FT /note="V->D: Abolishes interaction with CHMP2A and assembly
FT into helical tubes in vitro; when associated with D-59; D-
FT 168 and D-169."
FT /evidence="ECO:0000269|PubMed:19525971"
FT MUTAGEN 64
FT /note="A->D: Induces assembly with CHMP2A into helical
FT tubes in vitro; when associated with D-48."
FT /evidence="ECO:0000269|PubMed:19525971"
FT MUTAGEN 78..79
FT /note="YA->AE: Abolishes dimerization."
FT /evidence="ECO:0000269|PubMed:16740483"
FT MUTAGEN 168..169
FT /note="IL->DD: Induces assembly with CHMP2A into helical
FT tubes in vitro and slightly enhances inhibition of HIV-1
FT budding in vivo. Abolishes interaction with CHMP2A and
FT assembly into helical tubes in vitro; when associated with
FT D-59 and D-62."
FT /evidence="ECO:0000269|PubMed:19525971"
FT MUTAGEN 179..222
FT /note="Missing: Membrane association; releases
FT autoinhibition."
FT /evidence="ECO:0000269|PubMed:17547705"
FT MUTAGEN 216..217
FT /note="RL->AA: Abolishes interaction with VPS4A and
FT STAMBP."
FT /evidence="ECO:0000269|PubMed:17146056"
FT MUTAGEN 221..222
FT /note="Missing: Abolishes interaction with VPS4A and
FT STAMBP."
FT /evidence="ECO:0000269|PubMed:17146056"
FT MUTAGEN 222
FT /note="Missing: Impairs interaction with VPS4A and STAMBP."
FT /evidence="ECO:0000269|PubMed:17146056"
FT CONFLICT 208
FT /note="E -> D (in Ref. 1; AAF26737)"
FT /evidence="ECO:0000305"
FT HELIX 15..53
FT /evidence="ECO:0007829|PDB:2GD5"
FT HELIX 57..100
FT /evidence="ECO:0007829|PDB:2GD5"
FT HELIX 109..112
FT /evidence="ECO:0007829|PDB:2GD5"
FT TURN 113..115
FT /evidence="ECO:0007829|PDB:2GD5"
FT STRAND 120..122
FT /evidence="ECO:0007829|PDB:2GD5"
FT HELIX 125..137
FT /evidence="ECO:0007829|PDB:2GD5"
FT HELIX 164..167
FT /evidence="ECO:0007829|PDB:2GD5"
FT STRAND 175..177
FT /evidence="ECO:0007829|PDB:2GD5"
FT HELIX 201..220
FT /evidence="ECO:0007829|PDB:2XZE"
SQ SEQUENCE 222 AA; 25073 MW; 7B1ACE5EA453E8C0 CRC64;
MGLFGKTQEK PPKELVNEWS LKIRKEMRVV DRQIRDIQRE EEKVKRSVKD AAKKGQKDVC
IVLAKEMIRS RKAVSKLYAS KAHMNSVLMG MKNQLAVLRV AGSLQKSTEV MKAMQSLVKI
PEIQATMREL SKEMMKAGII EEMLEDTFES MDDQEEMEEE AEMEIDRILF EITAGALGKA
PSKVTDALPE PEPPGAMAAS EDEEEEEEAL EAMQSRLATL RS
