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O43633 (CHM2A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Charged multivesicular body protein 2a
Alternative name(s):
Chromatin-modifying protein 2a
Short name=CHMP2a
Putative breast adenocarcinoma marker BC-2
Vacuolar protein sorting-associated protein 2-1
Short name=Vps2-1
Short name=hVps2-1
Gene names
Name:CHMP2A
Synonyms:BC2, CHMP2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length222 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and the budding of enveloped viruses (HIV-1 and other lentiviruses). ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. Involved in HIV-1 p6- and p9-dependent virus release. Ref.12 Ref.13

Subunit structure

Probable core component of the endosomal sorting required for transport complex III (ESCRT-III). ESCRT-III components are thought to multimerize to form a flat lattice on the perimeter membrane of the endosome. Several assembly forms of ESCRT-III may exist that interact and act sequentally. In vitro, heteromerizes with CHMP3 (but not CHMP4) to form helical tubular structures that expose membrane-interacting sites on the outside whereas VPS4B can associate on the inside of the tubule. Interacts with CHMP1B, CHMP2B, CHMP3, CHMP4A, CHMP4B, CHMP4C and CHMP5. Interacts with VPS4A; the interaction is direct. Interacts with VPS4B; the interaction is direct. Interacts with MITD1. Interacts with VTA1; the interaction probably involves the open conformation of CHMP2A. Ref.11 Ref.12 Ref.13 Ref.15 Ref.17 Ref.18 Ref.19 Ref.21

Subcellular location

Late endosome membrane; Peripheral membrane protein; Cytoplasmic side. Note: Localizes to the midbody of dividing cells. Localized in two distinct rings on either side of the Fleming body. Ref.15 Ref.16

Domain

The acidic C-terminus and the basic N-termminus are thought to render the protein in a closed, soluble and inactive conformation through an autoinhibitory intramolecular interaction. The open and active conformation, which enables membrane binding and oligomerization, is achieved by interaction with other cellular binding partners, probably including other ESCRT components.

Post-translational modification

ISGylated in a CHMP5-dependent manner. Isgylation weakens and inhibits its interactions with VPS4A and VTA1 respectively. Ref.21

Miscellaneous

Its overexpression strongly inhibits HIV-1 release.

Sequence similarities

Belongs to the SNF7 family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 222222Charged multivesicular body protein 2a
PRO_0000211462

Regions

Region56 – 222167Interaction with VPS4B
Region217 – 2226Interaction with VTA1
Coiled coil12 – 5342 Potential
Coiled coil195 – 22228 Potential
Motif210 – 22011MIT-interacting motif

Amino acid modifications

Modified residue11N-acetylmethionine Ref.9

Experimental info

Mutagenesis169 – 1702DE → AA: Diminishes interaction with VPS4B.
Mutagenesis181 – 22242Missing: Membrane association; releases autoinhibition. Ref.17
Mutagenesis2161L → A: Diminishes interaction with VTA1. Ref.18
Mutagenesis217 – 2226Missing: Abolishes interaction with VTA1. Ref.18

Sequences

Sequence LengthMass (Da)Tools
O43633 [UniParc].

Last modified June 1, 1998. Version 1.
Checksum: F2B86C623829E32E

FASTA22225,104
        10         20         30         40         50         60 
MDLLFGRRKT PEELLRQNQR ALNRAMRELD RERQKLETQE KKIIADIKKM AKQGQMDAVR 

        70         80         90        100        110        120 
IMAKDLVRTR RYVRKFVLMR ANIQAVSLKI QTLKSNNSMA QAMKGVTKAM GTMNRQLKLP 

       130        140        150        160        170        180 
QIQKIMMEFE RQAEIMDMKE EMMNDAIDDA MGDEEDEEES DAVVSQVLDE LGLSLTDELS 

       190        200        210        220 
NLPSTGGSLS VAAGGKKAEA AASALADADA DLEERLKNLR RD 

« Hide

References

« Hide 'large scale' references
[1]Slater C., Thill G., Obar R.
Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Role of the BC-2 gene in breast cancer."
Koczan D., Reimer T., Rump A., Merck-Rousseau M.F., Rosenthal A., Friese K., Thiesen H.J.
Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"NovelFam3000 -- uncharacterized human protein domains conserved across model organisms."
Kemmer D., Podowski R.M., Arenillas D., Lim J., Hodges E., Roth P., Sonnhammer E.L.L., Hoeoeg C., Wasserman W.W.
BMC Genomics 7:48-48(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Skeletal muscle.
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Skin.
[9]"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides."
Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J.
Nat. Biotechnol. 21:566-569(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 1-7, ACETYLATION AT MET-1.
Tissue: Platelet.
[10]"Materials and methods for detection of breast cancer."
Keesee S.K., Obar R., Wu Y.-J.
Patent number US5914238, 05-JUN-1996
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 72-222, PROTEIN SEQUENCE OF 75-89 AND 197-205.
[11]"CHMP1 functions as a member of a newly defined family of vesicle trafficking proteins."
Howard T.L., Stauffer D.R., Degnin C.R., Hollenberg S.M.
J. Cell Sci. 114:2395-2404(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH VPS4B.
[12]"The protein network of HIV budding."
von Schwedler U.K., Stuchell M., Mueller B., Ward D.M., Chung H.-Y., Morita E., Wang H.E., Davis T., He G.P., Cimbora D.M., Scott A., Kraeusslich H.-G., Kaplan J., Morham S.G., Sundquist W.I.
Cell 114:701-713(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN HIV-1 BUDDING, INTERACTION WITH VPS4A AND VPS4B.
[13]"Divergent retroviral late-budding domains recruit vacuolar protein sorting factors by using alternative adaptor proteins."
Martin-Serrano J., Yarovoy A., Perez-Caballero D., Bieniasz P.D.
Proc. Natl. Acad. Sci. U.S.A. 100:12414-12419(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN HIV-1 BUDDING, INTERACTION WITH CHMP1B; CHMP2B; CHMP3; CHMP4A; CHMP4B; CHMP4C; CHMP5 AND VPS4A.
[14]Erratum
Martin-Serrano J., Yarovoy A., Perez-Caballero D., Bieniasz P.D.
Proc. Natl. Acad. Sci. U.S.A. 100:152845-152845(2003)
[15]"A systematic analysis of human CHMP protein interactions: additional MIT domain-containing proteins bind to multiple components of the human ESCRT III complex."
Tsang H.T.H., Connell J.W., Brown S.E., Thompson A., Reid E., Sanderson C.M.
Genomics 88:333-346(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH MITD1.
[16]"Human ESCRT and ALIX proteins interact with proteins of the midbody and function in cytokinesis."
Morita E., Sandrin V., Chung H.Y., Morham S.G., Gygi S.P., Rodesch C.K., Sundquist W.I.
EMBO J. 26:4215-4227(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[17]"Structure/function analysis of four core ESCRT-III proteins reveals common regulatory role for extreme C-terminal domain."
Shim S., Kimpler L.A., Hanson P.I.
Traffic 8:1068-1079(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: AUTOINHIBITORY MECHANISM, INTERACTION WITH VPS4B, MUTAGENESIS OF 181-ASN--ASP-222.
[18]"Novel interactions of ESCRT-III with LIP5 and VPS4 and their implications for ESCRT-III disassembly."
Shim S., Merrill S.A., Hanson P.I.
Mol. Biol. Cell 19:2661-2672(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH VTA1, MUTAGENESIS OF 169-ASP-GLU-170; LEU-216 AND 217-LYS--ASP-222.
[19]"Helical structures of ESCRT-III are disassembled by VPS4."
Lata S., Schoehn G., Jain A., Pires R., Piehler J., Goettlinger H.G., Weissenhorn W.
Science 321:1354-1357(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: POLYMERIZATION WITH CHMP3, ELECTRON MICROSCOPY.
[20]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[21]"Mechanism of inhibition of retrovirus release from cells by interferon-induced gene ISG15."
Kuang Z., Seo E.J., Leis J.
J. Virol. 85:7153-7161(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: ISGYLATION, INTERACTION WITH VTA1 AND VPS4A.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF042384 mRNA. Translation: AAC00005.1.
AJ277113 Genomic DNA. Translation: CAC14310.1.
AY364248 mRNA. Translation: AAQ76807.1.
BT007298 mRNA. Translation: AAP35962.1.
CR457002 mRNA. Translation: CAG33283.1.
AK311974 mRNA. Translation: BAG34913.1.
CH471135 Genomic DNA. Translation: EAW72609.1.
BC002502 mRNA. Translation: AAH02502.1.
CCDSCCDS12986.1.
RefSeqNP_055268.1. NM_014453.3.
NP_940818.1. NM_198426.2.
UniGeneHs.12107.

3D structure databases

ProteinModelPortalO43633.
SMRO43633. Positions 9-132.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid118091. 20 interactions.
DIPDIP-48533N.
IntActO43633. 6 interactions.
MINTMINT-5005843.
STRING9606.ENSP00000310440.

PTM databases

PhosphoSiteO43633.

2D gel databases

OGPO43633.

Proteomic databases

MaxQBO43633.
PaxDbO43633.
PeptideAtlasO43633.
PRIDEO43633.

Protocols and materials databases

DNASU27243.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000312547; ENSP00000310440; ENSG00000130724.
ENST00000600118; ENSP00000469240; ENSG00000130724.
ENST00000601220; ENSP00000472680; ENSG00000130724.
GeneID27243.
KEGGhsa:27243.
UCSCuc002qti.3. human.

Organism-specific databases

CTD27243.
GeneCardsGC19M059062.
HGNCHGNC:30216. CHMP2A.
HPAHPA041153.
HPA042031.
MIM610893. gene.
neXtProtNX_O43633.
PharmGKBPA142672111.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5491.
HOGENOMHOG000177218.
HOVERGENHBG107298.
InParanoidO43633.
KOK12191.
OMAKNGQMGA.
PhylomeDBO43633.
TreeFamTF300118.

Enzyme and pathway databases

ReactomeREACT_11123. Membrane Trafficking.
REACT_116125. Disease.

Gene expression databases

ArrayExpressO43633.
BgeeO43633.
CleanExHS_CHMP2A.
GenevestigatorO43633.

Family and domain databases

InterProIPR005024. Snf7.
[Graphical view]
PfamPF03357. Snf7. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCHMP2A. human.
GeneWikiCHMP2A.
GenomeRNAi27243.
NextBio50143.
PROO43633.
SOURCESearch...

Entry information

Entry nameCHM2A_HUMAN
AccessionPrimary (citable) accession number: O43633
Secondary accession number(s): B2R4W6, Q3ZTT0
Entry history
Integrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: June 1, 1998
Last modified: July 9, 2014
This is version 119 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM