O43633 (CHM2A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	222 AA.
Sequence status	Complete.
Protein existence	Evidence 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.16 Ref.18 Ref.19 Ref.20
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.16 Ref.17
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.
Miscellaneous	Its overexpression strongly inhibits HIV-1 release.
Sequence similarities	Belongs to the SNF7 family.

Ontologies

Keywords
Biological process	Protein transport Transport
Cellular component	Endosome Membrane
Domain	Coiled coil
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	cellular membrane organization Traceable author statement. Source: Reactome endosome transport Traceable author statement. Source: Reactome protein transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Traceable author statement. Source: Reactome late endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein domain specific binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 222	222	Charged multivesicular body protein 2a		PRO_0000211462
Regions
	Region	56 – 222	167	Interaction with VPS4B
	Region	217 – 222	6	Interaction with VTA1
	Coiled coil	12 – 53	42	Potential
	Coiled coil	195 – 222	28	Potential
	Motif	210 – 220	11	MIT-interacting motif
Amino acid modifications
	Modified residue	1	1	N-acetylmethionine Ref.9
	Modified residue	203	1	Phosphoserine Ref.15
Experimental info
	Mutagenesis	169 – 170	2	DE → AA: Diminishes interaction with VPS4B.
	Mutagenesis	181 – 222	42	Missing: Membrane association; releases autoinhibition. Ref.18
	Mutagenesis	216	1	L → A: Diminishes interaction with VTA1. Ref.19
	Mutagenesis	217 – 222	6	Missing: Abolishes interaction with VTA1. Ref.19

Sequences

	Sequence		Length	Mass (Da)
	O43633 [UniParc]. Last modified June 1, 1998. Version 1. Checksum: F2B86C623829E32E	FASTA	222	25,104
	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

References

	« Hide 'large scale' referencesShow '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: 16533400] [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. , 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: 14702039] [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. , 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: 15489334] [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: 12665801] [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: 11559748] [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: 14505570] [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: 14519844] [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]	"Phosphoproteome analysis of the human mitotic spindle." Nousiainen M., Sillje H.H.W., Sauer G., Nigg E.A., Koerner R. Proc. Natl. Acad. Sci. U.S.A. 103:5391-5396(2006) [PubMed: 16565220] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203, MASS SPECTROMETRY. Tissue: Cervix adenocarcinoma.
[16]	"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: 16730941] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH MITD1.
[17]	"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: 17853893] [Abstract] Cited for: SUBCELLULAR LOCATION.
[18]	"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: 17547705] [Abstract] Cited for: AUTOINHIBITORY MECHANISM, INTERACTION WITH VPS4B, MUTAGENESIS OF 181-ASN--ASP-222.
[19]	"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: 18385515] [Abstract] Cited for: INTERACTION WITH VTA1, MUTAGENESIS OF 169-ASP-GLU-170; LEU-216 AND 217-LYS--ASP-222.
[20]	"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: 18687924] [Abstract] Cited for: POLYMERIZATION WITH CHMP3, ELECTRON MICROSCOPY.
[21]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	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.
IPI	IPI00004416.
RefSeq	NP_055268.1. NM_014453.2. NP_940818.1. NM_198426.1.
UniGene	Hs.12107.
3D structure databases
ProteinModelPortal	O43633.
SMR	O43633. Positions 4-183.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-48533N.
IntAct	O43633. 3 interactions.
MINT	MINT-5005843.
STRING	O43633.
PTM databases
PhosphoSite	O43633.
2D gel databases
OGP	O43633.
Proteomic databases
PeptideAtlas	O43633.
PRIDE	O43633.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000312547; ENSP00000310440; ENSG00000130724. ENST00000391693; ENSP00000375575; ENSG00000130724.
GeneID	27243.
KEGG	hsa:27243.
UCSC	uc002qti.1. human.
Organism-specific databases
CTD	27243.
GeneCards	GC19M059062.
H-InvDB	HIX0015541.
HGNC	HGNC:30216. CHMP2A.
HPA	HPA041153. HPA042031.
MIM	610893. gene.
neXtProt	NX_O43633.
PharmGKB	PA142672111.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG16982.
GeneTree	ENSGT00550000074737.
HOGENOM	HBG464741.
HOVERGEN	HBG107298.
InParanoid	O43633.
OMA	VKKFIMM.
OrthoDB	EOG4HMJBJ.
PhylomeDB	O43633.
Enzyme and pathway databases
Reactome	REACT_11123. Membrane Trafficking.
Gene expression databases
ArrayExpress	O43633.
Bgee	O43633.
CleanEx	HS_CHMP2A.
Genevestigator	O43633.
GermOnline	ENSG00000130724. Homo sapiens.
Family and domain databases
InterPro	IPR005024. Snf7. [Graphical view]
KO	K12191.
Pfam	PF03357. Snf7. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	50143.
SOURCE	Search...

Entry information

Entry name

CHM2A_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 94 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.