Full text data of CHMP2A
CHMP2A
(BC2, CHMP2)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Charged multivesicular body protein 2a (Chromatin-modifying protein 2a; CHMP2a; Putative breast adenocarcinoma marker BC-2; Vacuolar protein sorting-associated protein 2-1; Vps2-1; hVps2-1)
Charged multivesicular body protein 2a (Chromatin-modifying protein 2a; CHMP2a; Putative breast adenocarcinoma marker BC-2; Vacuolar protein sorting-associated protein 2-1; Vps2-1; hVps2-1)
UniProt
O43633
ID CHM2A_HUMAN Reviewed; 222 AA.
AC O43633; B2R4W6; Q3ZTT0;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUN-1998, sequence version 1.
DT 22-JAN-2014, entry version 113.
DE RecName: Full=Charged multivesicular body protein 2a;
DE AltName: Full=Chromatin-modifying protein 2a;
DE Short=CHMP2a;
DE AltName: Full=Putative breast adenocarcinoma marker BC-2;
DE AltName: Full=Vacuolar protein sorting-associated protein 2-1;
DE Short=Vps2-1;
DE Short=hVps2-1;
GN Name=CHMP2A; Synonyms=BC2, CHMP2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Slater C., Thill G., Obar R.;
RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Koczan D., Reimer T., Rump A., Merck-Rousseau M.F., Rosenthal A.,
RA Friese K., Thiesen H.J.;
RT "Role of the BC-2 gene in breast cancer.";
RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
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
RT across model organisms.";
RL BMC Genomics 7:48-48(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skeletal muscle;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 1-7, AND ACETYLATION AT MET-1.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 72-222, AND PROTEIN SEQUENCE OF 75-89
RP AND 197-205.
RA Keesee S.K., Obar R., Wu Y.-J.;
RT "Materials and methods for detection of breast cancer.";
RL Patent number US5914238, 05-JUN-1996.
RN [11]
RP INTERACTION WITH VPS4B.
RX PubMed=11559748;
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 [12]
RP FUNCTION IN HIV-1 BUDDING, AND INTERACTION WITH VPS4A AND VPS4B.
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 [13]
RP FUNCTION IN HIV-1 BUDDING, AND INTERACTION WITH CHMP1B; CHMP2B; CHMP3;
RP CHMP4A; CHMP4B; CHMP4C; CHMP5 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
RT sorting factors by using alternative adaptor proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:12414-12419(2003).
RN [14]
RP ERRATUM.
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 [15]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH MITD1.
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
RT MIT domain-containing proteins bind to multiple components of the
RT human ESCRT III complex.";
RL Genomics 88:333-346(2006).
RN [16]
RP SUBCELLULAR LOCATION.
RX PubMed=17853893; DOI=10.1038/sj.emboj.7601850;
RA Morita E., Sandrin V., Chung H.Y., Morham S.G., Gygi S.P.,
RA Rodesch C.K., Sundquist W.I.;
RT "Human ESCRT and ALIX proteins interact with proteins of the midbody
RT and function in cytokinesis.";
RL EMBO J. 26:4215-4227(2007).
RN [17]
RP AUTOINHIBITORY MECHANISM, INTERACTION WITH VPS4B, AND MUTAGENESIS OF
RP 181-ASN--ASP-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
RT common regulatory role for extreme C-terminal domain.";
RL Traffic 8:1068-1079(2007).
RN [18]
RP INTERACTION WITH VTA1, AND MUTAGENESIS OF 169-ASP-GLU-170; LEU-216 AND
RP 217-LYS--ASP-222.
RX PubMed=18385515; DOI=10.1091/mbc.E07-12-1263;
RA Shim S., Merrill S.A., Hanson P.I.;
RT "Novel interactions of ESCRT-III with LIP5 and VPS4 and their
RT implications for ESCRT-III disassembly.";
RL Mol. Biol. Cell 19:2661-2672(2008).
RN [19]
RP POLYMERIZATION WITH CHMP3, 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 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.,
RA Buerckstuemmer T., 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 [21]
RP ISGYLATION, AND 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
RT interferon-induced gene ISG15.";
RL J. Virol. 85:7153-7161(2011).
CC -!- FUNCTION: Probable core component of the endosomal sorting
CC required for transport complex III (ESCRT-III) which is involved
CC in multivesicular bodies (MVBs) formation and sorting of endosomal
CC cargo proteins into MVBs. MVBs contain intraluminal vesicles
CC (ILVs) that are generated by invagination and scission from the
CC limiting membrane of the endosome and mostly are delivered to
CC lysosomes enabling degradation of membrane proteins, such as
CC stimulated growth factor receptors, lysosomal enzymes and lipids.
CC The MVB pathway appears to require the sequential function of
CC ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly
CC dissociate from the invaginating membrane before the ILV is
CC released. The ESCRT machinery also functions in topologically
CC equivalent membrane fission events, such as the terminal stages of
CC cytokinesis and the budding of enveloped viruses (HIV-1 and other
CC lentiviruses). ESCRT-III proteins are believed to mediate the
CC necessary vesicle extrusion and/or membrane fission activities,
CC possibly in conjunction with the AAA ATPase VPS4. Involved in HIV-
CC 1 p6- and p9-dependent virus release.
CC -!- SUBUNIT: Probable core component of the endosomal sorting required
CC for transport complex III (ESCRT-III). ESCRT-III components are
CC thought to multimerize to form a flat lattice on the perimeter
CC membrane of the endosome. Several assembly forms of ESCRT-III may
CC exist that interact and act sequentally. In vitro, heteromerizes
CC with CHMP3 (but not CHMP4) to form helical tubular structures that
CC expose membrane-interacting sites on the outside whereas VPS4B can
CC associate on the inside of the tubule. Interacts with CHMP1B,
CC CHMP2B, CHMP3, CHMP4A, CHMP4B, CHMP4C and CHMP5. Interacts with
CC VPS4A; the interaction is direct. Interacts with VPS4B; the
CC interaction is direct. Interacts with MITD1. Interacts with VTA1;
CC the interaction probably involves the open conformation of CHMP2A.
CC -!- SUBCELLULAR LOCATION: Late endosome membrane; Peripheral membrane
CC protein; Cytoplasmic side. Note=Localizes to the midbody of
CC dividing cells. Localized in two distinct rings on either side of
CC the Fleming body.
CC -!- DOMAIN: The acidic C-terminus and the basic N-termminus are
CC thought to render the protein in a closed, soluble and inactive
CC conformation through an autoinhibitory intramolecular interaction.
CC The open and active conformation, which enables membrane binding
CC and oligomerization, is achieved by interaction with other
CC cellular binding partners, probably including other ESCRT
CC components.
CC -!- PTM: ISGylated in a CHMP5-dependent manner. Isgylation weakens and
CC inhibits its interactions with VPS4A and VTA1 respectively.
CC -!- MISCELLANEOUS: Its overexpression strongly inhibits HIV-1 release.
CC -!- SIMILARITY: Belongs to the SNF7 family.
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DR EMBL; AF042384; AAC00005.1; -; mRNA.
DR EMBL; AJ277113; CAC14310.1; -; Genomic_DNA.
DR EMBL; AY364248; AAQ76807.1; -; mRNA.
DR EMBL; BT007298; AAP35962.1; -; mRNA.
DR EMBL; CR457002; CAG33283.1; -; mRNA.
DR EMBL; AK311974; BAG34913.1; -; mRNA.
DR EMBL; CH471135; EAW72609.1; -; Genomic_DNA.
DR EMBL; BC002502; AAH02502.1; -; mRNA.
DR RefSeq; NP_055268.1; NM_014453.2.
DR RefSeq; NP_940818.1; NM_198426.1.
DR UniGene; Hs.12107; -.
DR ProteinModelPortal; O43633; -.
DR SMR; O43633; 9-132.
DR DIP; DIP-48533N; -.
DR IntAct; O43633; 6.
DR MINT; MINT-5005843; -.
DR STRING; 9606.ENSP00000310440; -.
DR PhosphoSite; O43633; -.
DR OGP; O43633; -.
DR PaxDb; O43633; -.
DR PeptideAtlas; O43633; -.
DR PRIDE; O43633; -.
DR DNASU; 27243; -.
DR Ensembl; ENST00000312547; ENSP00000310440; ENSG00000130724.
DR Ensembl; ENST00000600118; ENSP00000469240; ENSG00000130724.
DR Ensembl; ENST00000601220; ENSP00000472680; ENSG00000130724.
DR GeneID; 27243; -.
DR KEGG; hsa:27243; -.
DR UCSC; uc002qti.3; human.
DR CTD; 27243; -.
DR GeneCards; GC19M059062; -.
DR HGNC; HGNC:30216; CHMP2A.
DR HPA; HPA041153; -.
DR HPA; HPA042031; -.
DR MIM; 610893; gene.
DR neXtProt; NX_O43633; -.
DR PharmGKB; PA142672111; -.
DR eggNOG; COG5491; -.
DR HOGENOM; HOG000177218; -.
DR HOVERGEN; HBG107298; -.
DR InParanoid; O43633; -.
DR KO; K12191; -.
DR OMA; RTNEQMM; -.
DR PhylomeDB; O43633; -.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_116125; Disease.
DR ChiTaRS; CHMP2A; human.
DR GeneWiki; CHMP2A; -.
DR GenomeRNAi; 27243; -.
DR NextBio; 50143; -.
DR PRO; PR:O43633; -.
DR ArrayExpress; O43633; -.
DR Bgee; O43633; -.
DR CleanEx; HS_CHMP2A; -.
DR Genevestigator; O43633; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016197; P:endosomal transport; TAS:Reactome.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0016032; P:viral process; TAS:Reactome.
DR InterPro; IPR005024; Snf7.
DR Pfam; PF03357; Snf7; 1.
PE 1: Evidence at protein level;
KW Acetylation; Coiled coil; Complete proteome;
KW Direct protein sequencing; Endosome; Membrane; Protein transport;
KW Reference proteome; Transport; Ubl conjugation.
FT CHAIN 1 222 Charged multivesicular body protein 2a.
FT /FTId=PRO_0000211462.
FT REGION 56 222 Interaction with VPS4B.
FT REGION 217 222 Interaction with VTA1.
FT COILED 12 53 Potential.
FT COILED 195 222 Potential.
FT MOTIF 210 220 MIT-interacting motif.
FT MOD_RES 1 1 N-acetylmethionine.
FT MUTAGEN 169 170 DE->AA: Diminishes interaction with
FT VPS4B.
FT MUTAGEN 181 222 Missing: Membrane association; releases
FT autoinhibition.
FT MUTAGEN 216 216 L->A: Diminishes interaction with VTA1.
FT MUTAGEN 217 222 Missing: Abolishes interaction with VTA1.
SQ SEQUENCE 222 AA; 25104 MW; F2B86C623829E32E CRC64;
MDLLFGRRKT PEELLRQNQR ALNRAMRELD RERQKLETQE KKIIADIKKM AKQGQMDAVR
IMAKDLVRTR RYVRKFVLMR ANIQAVSLKI QTLKSNNSMA QAMKGVTKAM GTMNRQLKLP
QIQKIMMEFE RQAEIMDMKE EMMNDAIDDA MGDEEDEEES DAVVSQVLDE LGLSLTDELS
NLPSTGGSLS VAAGGKKAEA AASALADADA DLEERLKNLR RD
//
ID CHM2A_HUMAN Reviewed; 222 AA.
AC O43633; B2R4W6; Q3ZTT0;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUN-1998, sequence version 1.
DT 22-JAN-2014, entry version 113.
DE RecName: Full=Charged multivesicular body protein 2a;
DE AltName: Full=Chromatin-modifying protein 2a;
DE Short=CHMP2a;
DE AltName: Full=Putative breast adenocarcinoma marker BC-2;
DE AltName: Full=Vacuolar protein sorting-associated protein 2-1;
DE Short=Vps2-1;
DE Short=hVps2-1;
GN Name=CHMP2A; Synonyms=BC2, CHMP2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Slater C., Thill G., Obar R.;
RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Koczan D., Reimer T., Rump A., Merck-Rousseau M.F., Rosenthal A.,
RA Friese K., Thiesen H.J.;
RT "Role of the BC-2 gene in breast cancer.";
RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
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
RT across model organisms.";
RL BMC Genomics 7:48-48(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skeletal muscle;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 1-7, AND ACETYLATION AT MET-1.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 72-222, AND PROTEIN SEQUENCE OF 75-89
RP AND 197-205.
RA Keesee S.K., Obar R., Wu Y.-J.;
RT "Materials and methods for detection of breast cancer.";
RL Patent number US5914238, 05-JUN-1996.
RN [11]
RP INTERACTION WITH VPS4B.
RX PubMed=11559748;
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 [12]
RP FUNCTION IN HIV-1 BUDDING, AND INTERACTION WITH VPS4A AND VPS4B.
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 [13]
RP FUNCTION IN HIV-1 BUDDING, AND INTERACTION WITH CHMP1B; CHMP2B; CHMP3;
RP CHMP4A; CHMP4B; CHMP4C; CHMP5 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
RT sorting factors by using alternative adaptor proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:12414-12419(2003).
RN [14]
RP ERRATUM.
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 [15]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH MITD1.
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
RT MIT domain-containing proteins bind to multiple components of the
RT human ESCRT III complex.";
RL Genomics 88:333-346(2006).
RN [16]
RP SUBCELLULAR LOCATION.
RX PubMed=17853893; DOI=10.1038/sj.emboj.7601850;
RA Morita E., Sandrin V., Chung H.Y., Morham S.G., Gygi S.P.,
RA Rodesch C.K., Sundquist W.I.;
RT "Human ESCRT and ALIX proteins interact with proteins of the midbody
RT and function in cytokinesis.";
RL EMBO J. 26:4215-4227(2007).
RN [17]
RP AUTOINHIBITORY MECHANISM, INTERACTION WITH VPS4B, AND MUTAGENESIS OF
RP 181-ASN--ASP-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
RT common regulatory role for extreme C-terminal domain.";
RL Traffic 8:1068-1079(2007).
RN [18]
RP INTERACTION WITH VTA1, AND MUTAGENESIS OF 169-ASP-GLU-170; LEU-216 AND
RP 217-LYS--ASP-222.
RX PubMed=18385515; DOI=10.1091/mbc.E07-12-1263;
RA Shim S., Merrill S.A., Hanson P.I.;
RT "Novel interactions of ESCRT-III with LIP5 and VPS4 and their
RT implications for ESCRT-III disassembly.";
RL Mol. Biol. Cell 19:2661-2672(2008).
RN [19]
RP POLYMERIZATION WITH CHMP3, 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 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.,
RA Buerckstuemmer T., 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 [21]
RP ISGYLATION, AND 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
RT interferon-induced gene ISG15.";
RL J. Virol. 85:7153-7161(2011).
CC -!- FUNCTION: Probable core component of the endosomal sorting
CC required for transport complex III (ESCRT-III) which is involved
CC in multivesicular bodies (MVBs) formation and sorting of endosomal
CC cargo proteins into MVBs. MVBs contain intraluminal vesicles
CC (ILVs) that are generated by invagination and scission from the
CC limiting membrane of the endosome and mostly are delivered to
CC lysosomes enabling degradation of membrane proteins, such as
CC stimulated growth factor receptors, lysosomal enzymes and lipids.
CC The MVB pathway appears to require the sequential function of
CC ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly
CC dissociate from the invaginating membrane before the ILV is
CC released. The ESCRT machinery also functions in topologically
CC equivalent membrane fission events, such as the terminal stages of
CC cytokinesis and the budding of enveloped viruses (HIV-1 and other
CC lentiviruses). ESCRT-III proteins are believed to mediate the
CC necessary vesicle extrusion and/or membrane fission activities,
CC possibly in conjunction with the AAA ATPase VPS4. Involved in HIV-
CC 1 p6- and p9-dependent virus release.
CC -!- SUBUNIT: Probable core component of the endosomal sorting required
CC for transport complex III (ESCRT-III). ESCRT-III components are
CC thought to multimerize to form a flat lattice on the perimeter
CC membrane of the endosome. Several assembly forms of ESCRT-III may
CC exist that interact and act sequentally. In vitro, heteromerizes
CC with CHMP3 (but not CHMP4) to form helical tubular structures that
CC expose membrane-interacting sites on the outside whereas VPS4B can
CC associate on the inside of the tubule. Interacts with CHMP1B,
CC CHMP2B, CHMP3, CHMP4A, CHMP4B, CHMP4C and CHMP5. Interacts with
CC VPS4A; the interaction is direct. Interacts with VPS4B; the
CC interaction is direct. Interacts with MITD1. Interacts with VTA1;
CC the interaction probably involves the open conformation of CHMP2A.
CC -!- SUBCELLULAR LOCATION: Late endosome membrane; Peripheral membrane
CC protein; Cytoplasmic side. Note=Localizes to the midbody of
CC dividing cells. Localized in two distinct rings on either side of
CC the Fleming body.
CC -!- DOMAIN: The acidic C-terminus and the basic N-termminus are
CC thought to render the protein in a closed, soluble and inactive
CC conformation through an autoinhibitory intramolecular interaction.
CC The open and active conformation, which enables membrane binding
CC and oligomerization, is achieved by interaction with other
CC cellular binding partners, probably including other ESCRT
CC components.
CC -!- PTM: ISGylated in a CHMP5-dependent manner. Isgylation weakens and
CC inhibits its interactions with VPS4A and VTA1 respectively.
CC -!- MISCELLANEOUS: Its overexpression strongly inhibits HIV-1 release.
CC -!- SIMILARITY: Belongs to the SNF7 family.
CC -----------------------------------------------------------------------
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DR EMBL; AF042384; AAC00005.1; -; mRNA.
DR EMBL; AJ277113; CAC14310.1; -; Genomic_DNA.
DR EMBL; AY364248; AAQ76807.1; -; mRNA.
DR EMBL; BT007298; AAP35962.1; -; mRNA.
DR EMBL; CR457002; CAG33283.1; -; mRNA.
DR EMBL; AK311974; BAG34913.1; -; mRNA.
DR EMBL; CH471135; EAW72609.1; -; Genomic_DNA.
DR EMBL; BC002502; AAH02502.1; -; mRNA.
DR RefSeq; NP_055268.1; NM_014453.2.
DR RefSeq; NP_940818.1; NM_198426.1.
DR UniGene; Hs.12107; -.
DR ProteinModelPortal; O43633; -.
DR SMR; O43633; 9-132.
DR DIP; DIP-48533N; -.
DR IntAct; O43633; 6.
DR MINT; MINT-5005843; -.
DR STRING; 9606.ENSP00000310440; -.
DR PhosphoSite; O43633; -.
DR OGP; O43633; -.
DR PaxDb; O43633; -.
DR PeptideAtlas; O43633; -.
DR PRIDE; O43633; -.
DR DNASU; 27243; -.
DR Ensembl; ENST00000312547; ENSP00000310440; ENSG00000130724.
DR Ensembl; ENST00000600118; ENSP00000469240; ENSG00000130724.
DR Ensembl; ENST00000601220; ENSP00000472680; ENSG00000130724.
DR GeneID; 27243; -.
DR KEGG; hsa:27243; -.
DR UCSC; uc002qti.3; human.
DR CTD; 27243; -.
DR GeneCards; GC19M059062; -.
DR HGNC; HGNC:30216; CHMP2A.
DR HPA; HPA041153; -.
DR HPA; HPA042031; -.
DR MIM; 610893; gene.
DR neXtProt; NX_O43633; -.
DR PharmGKB; PA142672111; -.
DR eggNOG; COG5491; -.
DR HOGENOM; HOG000177218; -.
DR HOVERGEN; HBG107298; -.
DR InParanoid; O43633; -.
DR KO; K12191; -.
DR OMA; RTNEQMM; -.
DR PhylomeDB; O43633; -.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_116125; Disease.
DR ChiTaRS; CHMP2A; human.
DR GeneWiki; CHMP2A; -.
DR GenomeRNAi; 27243; -.
DR NextBio; 50143; -.
DR PRO; PR:O43633; -.
DR ArrayExpress; O43633; -.
DR Bgee; O43633; -.
DR CleanEx; HS_CHMP2A; -.
DR Genevestigator; O43633; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016197; P:endosomal transport; TAS:Reactome.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0016032; P:viral process; TAS:Reactome.
DR InterPro; IPR005024; Snf7.
DR Pfam; PF03357; Snf7; 1.
PE 1: Evidence at protein level;
KW Acetylation; Coiled coil; Complete proteome;
KW Direct protein sequencing; Endosome; Membrane; Protein transport;
KW Reference proteome; Transport; Ubl conjugation.
FT CHAIN 1 222 Charged multivesicular body protein 2a.
FT /FTId=PRO_0000211462.
FT REGION 56 222 Interaction with VPS4B.
FT REGION 217 222 Interaction with VTA1.
FT COILED 12 53 Potential.
FT COILED 195 222 Potential.
FT MOTIF 210 220 MIT-interacting motif.
FT MOD_RES 1 1 N-acetylmethionine.
FT MUTAGEN 169 170 DE->AA: Diminishes interaction with
FT VPS4B.
FT MUTAGEN 181 222 Missing: Membrane association; releases
FT autoinhibition.
FT MUTAGEN 216 216 L->A: Diminishes interaction with VTA1.
FT MUTAGEN 217 222 Missing: Abolishes interaction with VTA1.
SQ SEQUENCE 222 AA; 25104 MW; F2B86C623829E32E CRC64;
MDLLFGRRKT PEELLRQNQR ALNRAMRELD RERQKLETQE KKIIADIKKM AKQGQMDAVR
IMAKDLVRTR RYVRKFVLMR ANIQAVSLKI QTLKSNNSMA QAMKGVTKAM GTMNRQLKLP
QIQKIMMEFE RQAEIMDMKE EMMNDAIDDA MGDEEDEEES DAVVSQVLDE LGLSLTDELS
NLPSTGGSLS VAAGGKKAEA AASALADADA DLEERLKNLR RD
//
MIM
610893
*RECORD*
*FIELD* NO
610893
*FIELD* TI
*610893 CHMP FAMILY, MEMBER 2A; CHMP2A
;;CHROMATIN-MODIFYING PROTEIN 2A;;
CHARGED MULTIVESICULAR BODY PROTEIN 2A;;
read moreVACUOLAR PROTEIN SORTING 2, YEAST, HOMOLOG OF, A; VPS2A;;
VPS2;;
BC2
*FIELD* TX
DESCRIPTION
CHMP2A belongs to the chromatin-modifying protein/charged multivesicular
body protein (CHMP) family. These proteins are components of ESCRT-III
(endosomal sorting complex required for transport III), a complex
involved in degradation of surface receptor proteins and formation of
endocytic multivesicular bodies (MVBs). Some CHMPs have both nuclear and
cytoplasmic/vesicular distributions, and one such CHMP, CHMP1A (164010),
is required for both MVB formation and regulation of cell cycle
progression (Tsang et al., 2006).
CLONING
By yeast 2-hybrid screening using mouse Skd1 (VPS4B; 609983) as bait,
Fujita et al. (2004) cloned mouse Chmp2a, which they called Vps2. They
identified human CHMP2A by database analysis. The deduced 222-amino acid
mouse protein contains N- and C-terminal coiled-coil regions. Northern
blot analysis detected Chmp2a expression in most mouse tissues examined,
with highest levels in heart, brain, liver, and kidney.
Immunofluorescence microscopy localized Chmp1a mainly to the cytoplasm.
GENE FUNCTION
Fujita et al. (2004) found that deletion of the N-terminal coiled-coil
domain of mouse Chmp2a caused Chmp2a to localize mainly to the nucleus
rather than the cytoplasm. Pull-down assays showed that Chmp2a
interacted with Skd1 in transfected HeLa cells, and the interaction did
not require the N- or C-terminal coiled-coil domains of Chmp2a.
Experiments using an ATPase-negative Skd1 mutant suggested that Chmp2a
may play a role in associating Skd1 with the ESCRT-III complex.
Tsang et al. (2006) performed a systematic yeast 2-hybrid analysis of
human ESCRT-III components, including CHMP2A. CHMP2A interacted with
VPS4A (609982) and LOC129531 (MITD1). Coimmunoprecipitation assays
confirmed the interaction between CHMP2A and LOC129531, and the 2
proteins partially colocalized with M6PR (154540) on late endosomal
membranes.
The AAA ATPase Vps4 (see 609982) is central to endosomal traffic to
lysosomes, retroviral budding, and cytokinesis, and dissociates ESCRT
complexes from membranes. Obita et al. (2007) showed that, of the 6
ESCRT-III-related subunits in yeast, only Vps2 and Did2 bind the MIT
(microtubule interacting and transport) domain of Vps4, and that the
C-terminal 30 residues of the subunits are both necessary and sufficient
for interaction.
Lata et al. (2008) found that ESCRT-III proteins CHMP2A and CHMP3
(610052) could assemble in vitro into helical tubular structures that
expose their membrane-interaction sites on the outside of the tubule,
whereas the AAA-type adenosine triphosphatase VPS4 (609982) could bind
on the inside of the tubule and disassemble the tubes upon adenosine
triphosphate hydrolysis. CHMP2A and CHMP3 copolymerized in solution, and
their membrane targeting was cooperatively enhanced on planar lipid
bilayers. Lata et al. (2008) concluded that such helical CHMP structures
could thus assemble within the neck of an inwardly budding vesicle,
catalyzing late steps in budding under the control of VPS4.
BIOCHEMICAL FEATURES
- Crystal Structure
Obita et al. (2007) determined the crystal structure of the yeast Vps2 C
terminus in a complex with the MIT domain of Vps4, explaining the basis
for selective ESCRT-III recognition. MIT helices alpha-2 and alpha-3
recognize a (D/E)xxLxxRLxxL(K/R) motif, and mutations within this motif
cause sorting defects in yeast. Obita et al. (2007) concluded that their
crystal structure of the N-terminal domain of an archaeal AAA ATPase
shows that is closely related to the MIT domain of Vps4. The archaeal
ATPase interacts with an archaeal ESCRT-III-like protein even though
these organisms have no endomembrane system, suggesting that the
Vps4/ESCRT-III partnership is a relic of a function that predates the
divergence of eukaryotes and archaea.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the CHMP2A
gene to chromosome 19 (TMAP SHGC-30173).
*FIELD* RF
1. Fujita, H.; Umezuki, Y.; Imamura, K.; Ishikawa, D.; Uchimura, S.;
Nara, A.; Yoshimori, T.; Hayashizaki, Y.; Kawai, J.; Ishidoh, K.;
Tanaka, Y.; Himeno, M.: Mammalian class E Vps proteins, SBP1 and
mVps2/CHMP2A, interact with and regulate the function of an AAA-ATPase
SKD1/Vps4B. J. Cell Sci. 117: 2997-3009, 2004.
2. Lata, S.; Schoehn, G.; Jain, A.; Pires, R.; Piehler, J.; Gottlinger,
H. G.; Weissenhorn, W.: Helical structures of ESCRT-III are disassembled
by VPS4. Science 321: 1354-1357, 2008.
3. Obita, T.; Saksena, S.; Ghazi-Tabatabai, S.; Gill, D. J.; Perisic,
O.; Emr, S. D.; Williams, R. L.: Structural basis for selective recognition
of ESCRT-III by the AAA ATPase Vps4. Nature 449: 735-739, 2007.
4. Tsang, H. T. H.; Connell, J. W.; Brown, S. E.; Thompson, A.; Reid,
E.; Sanderson, C. M.: A systematic analysis of human CHMP protein
interactions: additional MIT domain-containing proteins bind to multiple
components of the human ESCRT III complex. Genomics 88: 333-346,
2006.
*FIELD* CN
Ada Hamosh - updated: 10/1/2008
Ada Hamosh - updated: 10/26/2007
*FIELD* CD
Patricia A. Hartz: 3/28/2007
*FIELD* ED
alopez: 10/03/2008
terry: 10/1/2008
alopez: 11/2/2007
terry: 10/26/2007
mgross: 3/28/2007
*RECORD*
*FIELD* NO
610893
*FIELD* TI
*610893 CHMP FAMILY, MEMBER 2A; CHMP2A
;;CHROMATIN-MODIFYING PROTEIN 2A;;
CHARGED MULTIVESICULAR BODY PROTEIN 2A;;
read moreVACUOLAR PROTEIN SORTING 2, YEAST, HOMOLOG OF, A; VPS2A;;
VPS2;;
BC2
*FIELD* TX
DESCRIPTION
CHMP2A belongs to the chromatin-modifying protein/charged multivesicular
body protein (CHMP) family. These proteins are components of ESCRT-III
(endosomal sorting complex required for transport III), a complex
involved in degradation of surface receptor proteins and formation of
endocytic multivesicular bodies (MVBs). Some CHMPs have both nuclear and
cytoplasmic/vesicular distributions, and one such CHMP, CHMP1A (164010),
is required for both MVB formation and regulation of cell cycle
progression (Tsang et al., 2006).
CLONING
By yeast 2-hybrid screening using mouse Skd1 (VPS4B; 609983) as bait,
Fujita et al. (2004) cloned mouse Chmp2a, which they called Vps2. They
identified human CHMP2A by database analysis. The deduced 222-amino acid
mouse protein contains N- and C-terminal coiled-coil regions. Northern
blot analysis detected Chmp2a expression in most mouse tissues examined,
with highest levels in heart, brain, liver, and kidney.
Immunofluorescence microscopy localized Chmp1a mainly to the cytoplasm.
GENE FUNCTION
Fujita et al. (2004) found that deletion of the N-terminal coiled-coil
domain of mouse Chmp2a caused Chmp2a to localize mainly to the nucleus
rather than the cytoplasm. Pull-down assays showed that Chmp2a
interacted with Skd1 in transfected HeLa cells, and the interaction did
not require the N- or C-terminal coiled-coil domains of Chmp2a.
Experiments using an ATPase-negative Skd1 mutant suggested that Chmp2a
may play a role in associating Skd1 with the ESCRT-III complex.
Tsang et al. (2006) performed a systematic yeast 2-hybrid analysis of
human ESCRT-III components, including CHMP2A. CHMP2A interacted with
VPS4A (609982) and LOC129531 (MITD1). Coimmunoprecipitation assays
confirmed the interaction between CHMP2A and LOC129531, and the 2
proteins partially colocalized with M6PR (154540) on late endosomal
membranes.
The AAA ATPase Vps4 (see 609982) is central to endosomal traffic to
lysosomes, retroviral budding, and cytokinesis, and dissociates ESCRT
complexes from membranes. Obita et al. (2007) showed that, of the 6
ESCRT-III-related subunits in yeast, only Vps2 and Did2 bind the MIT
(microtubule interacting and transport) domain of Vps4, and that the
C-terminal 30 residues of the subunits are both necessary and sufficient
for interaction.
Lata et al. (2008) found that ESCRT-III proteins CHMP2A and CHMP3
(610052) could assemble in vitro into helical tubular structures that
expose their membrane-interaction sites on the outside of the tubule,
whereas the AAA-type adenosine triphosphatase VPS4 (609982) could bind
on the inside of the tubule and disassemble the tubes upon adenosine
triphosphate hydrolysis. CHMP2A and CHMP3 copolymerized in solution, and
their membrane targeting was cooperatively enhanced on planar lipid
bilayers. Lata et al. (2008) concluded that such helical CHMP structures
could thus assemble within the neck of an inwardly budding vesicle,
catalyzing late steps in budding under the control of VPS4.
BIOCHEMICAL FEATURES
- Crystal Structure
Obita et al. (2007) determined the crystal structure of the yeast Vps2 C
terminus in a complex with the MIT domain of Vps4, explaining the basis
for selective ESCRT-III recognition. MIT helices alpha-2 and alpha-3
recognize a (D/E)xxLxxRLxxL(K/R) motif, and mutations within this motif
cause sorting defects in yeast. Obita et al. (2007) concluded that their
crystal structure of the N-terminal domain of an archaeal AAA ATPase
shows that is closely related to the MIT domain of Vps4. The archaeal
ATPase interacts with an archaeal ESCRT-III-like protein even though
these organisms have no endomembrane system, suggesting that the
Vps4/ESCRT-III partnership is a relic of a function that predates the
divergence of eukaryotes and archaea.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the CHMP2A
gene to chromosome 19 (TMAP SHGC-30173).
*FIELD* RF
1. Fujita, H.; Umezuki, Y.; Imamura, K.; Ishikawa, D.; Uchimura, S.;
Nara, A.; Yoshimori, T.; Hayashizaki, Y.; Kawai, J.; Ishidoh, K.;
Tanaka, Y.; Himeno, M.: Mammalian class E Vps proteins, SBP1 and
mVps2/CHMP2A, interact with and regulate the function of an AAA-ATPase
SKD1/Vps4B. J. Cell Sci. 117: 2997-3009, 2004.
2. Lata, S.; Schoehn, G.; Jain, A.; Pires, R.; Piehler, J.; Gottlinger,
H. G.; Weissenhorn, W.: Helical structures of ESCRT-III are disassembled
by VPS4. Science 321: 1354-1357, 2008.
3. Obita, T.; Saksena, S.; Ghazi-Tabatabai, S.; Gill, D. J.; Perisic,
O.; Emr, S. D.; Williams, R. L.: Structural basis for selective recognition
of ESCRT-III by the AAA ATPase Vps4. Nature 449: 735-739, 2007.
4. Tsang, H. T. H.; Connell, J. W.; Brown, S. E.; Thompson, A.; Reid,
E.; Sanderson, C. M.: A systematic analysis of human CHMP protein
interactions: additional MIT domain-containing proteins bind to multiple
components of the human ESCRT III complex. Genomics 88: 333-346,
2006.
*FIELD* CN
Ada Hamosh - updated: 10/1/2008
Ada Hamosh - updated: 10/26/2007
*FIELD* CD
Patricia A. Hartz: 3/28/2007
*FIELD* ED
alopez: 10/03/2008
terry: 10/1/2008
alopez: 11/2/2007
terry: 10/26/2007
mgross: 3/28/2007