Reviewed, UniProtKB/Swiss-Prot Q9Y3E7 (CHMP3_HUMAN)

Names and origin

Protein names

Recommended name:
Charged multivesicular body protein 3

Alternative name(s):
Chromatin-modifying protein 3
Vacuolar protein sorting-associated protein 24
Short name=hVps24
Neuroendocrine differentiation factor

Gene names

Name:	VPS24
Synonyms:	CHMP3, NEDF
ORF Names:	CGI-149

Organism

Homo sapiens (Human) [Complete proteome]

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.
Sequence processing	The displayed sequence is further processed into a mature form.
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. Selectively binds to phosphatidylinositol 3,5-bisphosphate PtdIns(3,5)P2 and PtdIns(3,4)P2 in preference to other phosphoinositides tested. Involved in late stages of cytokinesis. Required for sorting/trafficking of EGF receptor By similarity. Ref.5 Ref.8 Ref.18 Ref.22
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. Forms a metastable monomer in solution; its core structure (without part of the putative autoinhibitory C-terminal acidic region) oligomerizes into a flat lattice via two different dimerization interfaces. In vitro, heteromerizes with CHMP2A (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. May interact with IGFBP7; the relevance of such interaction however remains unclear. Interacts with CHMP2A. Interacts with CHMP4A; the interaction requires the release of CHMP4A autoinhibition. Interacts with VPS4A. Interacts with STAMBP; the interaction appears to relieve the autoinhibition of CHMP3. Ref.5 Ref.22 Ref.1 Ref.6 Ref.11 Ref.12 Ref.13 Ref.16 Ref.17 Ref.19
Subcellular location	Cytoplasm › cytosol. Membrane; Lipid-anchor. Endosome. Late endosome membrane Probable. Note: Localizes to the midbody of dividing cells. Ref.8 Ref.18 Ref.11
Tissue specificity	Widely expressed. Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Ref.9
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	Cell cycle Cell division Protein transport Transport
Cellular component	Cytoplasm Endosome Membrane
Domain	Coiled coil
PTM	Isopeptide bond Lipoprotein Myristate Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW cell division Inferred from electronic annotation. Source: UniProtKB-KW protein transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Inferred from electronic annotation. Source: UniProtKB-SubCell late endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
STAMBP	O95630	2	EBI-2118119,EBI-396676

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Potential

Chain

2 – 222

221

Charged multivesicular body protein 3

PRO_0000211479

Regions

Region

2 – 113

112

Intramolecular interaction with C-terminus

Region

151 – 222

72

Interaction with VPS4A

Region

151 – 220

70

Intramolecular interaction with N-terminus

Region

196 – 222

27

Interaction with STAMBP

Coiled coil

22 – 54

33

Potential

Coiled coil

141 – 222

82

Potential

Motif

201 – 211

11

MIT-interacting motif

Amino acid modifications

Modified residue

116

1

Phosphoserine By similarity

Modified residue

126

1

Phosphothreonine By similarity

Modified residue

200

1

Phosphoserine Ref.10 Ref.15 Ref.21

Lipidation

2

1

N-myristoyl glycine Potential

Cross-link

179

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.14

Experimental info

Mutagenesis

24 – 25

2

RK → SA: Impairs HIV-1 release; when associated with S-28. Ref.12

Mutagenesis

28

1

R → S: Impairs HIV-1 relase; when associated with 24-S-A-25. Ref.22 Ref.12

Mutagenesis

54

1

K → S: Abolishes dimerization; when associated with N-56; E-59 and 62-D-E-63. Ref.22 Ref.12

Mutagenesis

56

1

Q → N: Abolishes dimerization; when associated with S-54; E-59 and 62-D-E-63. Ref.22 Ref.12

Mutagenesis

59

1

V → E: Abolishes dimerization; when associated with S-54; N-56 and 62-D-E-63. Ref.22 Ref.12

Mutagenesis

62 – 63

2

VL → DE: Abolishes dimerization; when associated with S-54; N-56 and E-59. Ref.12

Mutagenesis

78 – 79

2

YA → AE: Abolishes dimerization. Ref.12

Mutagenesis

179 – 222

44

Missing: Membrane association; releases autoinhibition. Ref.12 Ref.13

Mutagenesis

221 – 222

2

RS → AA: Abolishes interaction with VPS4A and STAMBP. Ref.12

Mutagenesis

221 – 222

2

Missing: Abolishes interaction with VPS4A and STAMBP. Ref.12

Sequence conflict

208

1

E → D in AAF26737. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

222

Helix Strand Turn

Details...

Helix

15 – 53

39

Helix

57 – 100

44

Helix

109 – 112

4

Turn

113 – 115

3

Beta strand

120 – 122

3

Helix

125 – 137

13

Helix

164 – 167

4

Sequences

	Sequence		Length	Mass (Da)
	Q9Y3E7-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 7B1ACE5EA453E8C0	FASTA	222	25,073
	10 20 30 40 50 60 MGLFGKTQEK PPKELVNEWS LKIRKEMRVV DRQIRDIQRE EEKVKRSVKD AAKKGQKDVC 70 80 90 100 110 120 IVLAKEMIRS RKAVSKLYAS KAHMNSVLMG MKNQLAVLRV AGSLQKSTEV MKAMQSLVKI 130 140 150 160 170 180 PEIQATMREL SKEMMKAGII EEMLEDTFES MDDQEEMEEE AEMEIDRILF EITAGALGKA 190 200 210 220 PSKVTDALPE PEPPGAMAAS EDEEEEEEAL EAMQSRLATL RS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Interaction of IGF-binding protein-related protein 1 with a novel protein, neuroendocrine differentiation factor, results in neuroendocrine differentiation of prostate cancer cells." Wilson E.M., Oh Y., Hwa V., Rosenfeld R.G. J. Clin. Endocrinol. Metab. 86:4504-4511(2001) [PubMed: 11549700] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], POSSIBLE INTERACTION WITH IGFBP7.
[2]	"Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics." Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C. Genome Res. 10:703-713(2000) [PubMed: 10810093] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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: Uterus.
[5]	"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 CHMP4A.
[6]	"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: INTERACTION WITH CHMP2A AND VPS4A.
[7]	Erratum Martin-Serrano J., Yarovoy A., Perez-Caballero D., Bieniasz P.D. Proc. Natl. Acad. Sci. U.S.A. 100:152845-152845(2003)
[8]	"mVps24p functions in EGF receptor sorting/trafficking from the early endosome." Yan Q., Hunt P.R., Frelin L., Vida T.A., Pevsner J., Bean A.J. Exp. Cell Res. 304:265-273(2005) [PubMed: 15707591] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[9]	"Interaction of the mammalian endosomal sorting complex required for transport (ESCRT) III protein hSnf7-1 with itself, membranes, and the AAA+ ATPase SKD1." Lin Y., Kimpler L.A., Naismith T.V., Lauer J.M., Hanson P.I. J. Biol. Chem. 280:12799-12809(2005) [PubMed: 15632132] [Abstract] Cited for: TISSUE SPECIFICITY.
[10]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-200, MASS SPECTROMETRY. Tissue: Epithelium.
[11]	"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 STAMBP.
[12]	"Release of autoinhibition converts ESCRT-III components into potent inhibitors of HIV-1 budding." Zamborlini A., Usami Y., Radoshitzky S.R., Popova E., Palu G., Goettlinger H. Proc. Natl. Acad. Sci. U.S.A. 103:19140-19145(2006) [PubMed: 17146056] [Abstract] Cited for: AUTOINHIBITORY MECHANISM, INTRAMOLECULAR INTERACTION, INTERACTION WITH STAMBP AND VPS4A, MUTAGENESIS OF 221-ARG-SER-222.
[13]	"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 CHMP4A, MUTAGENESIS OF 179-LYS--SER-222.
[14]	"Quantitative analysis of global ubiquitination in HeLa cells by mass spectrometry." Meierhofer D., Wang X., Huang L., Kaiser P. J. Proteome Res. 7:4566-4576(2008) [PubMed: 18781797] [Abstract] Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-179, MASS SPECTROMETRY.
[15]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-200, MASS SPECTROMETRY.
[16]	"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 CHMP2A, ELECTRON MICROSCOPY.
[17]	"Targeting of AMSH to endosomes is required for epidermal growth factor receptor degradation." Ma Y.M., Boucrot E., Villen J., Affar el B., Gygi S.P., Goettlinger H.G., Kirchhausen T. J. Biol. Chem. 282:9805-9812(2007) [PubMed: 17261583] [Abstract] Cited for: INTERACTION WITH STAMBP, MASS SPECTROMETRY.
[18]	"A dominant-negative ESCRT-III protein perturbs cytokinesis and trafficking to lysosomes." Dukes J.D., Richardson J.D., Simmons R., Whitley P. Biochem. J. 411:233-239(2008) [PubMed: 18076377] [Abstract] Cited for: FUNCTION IN CYTOKINESIS, SUBCELLULAR LOCATION.
[19]	"Structural basis for autoinhibition of ESCRT-III CHMP3." Lata S., Roessle M., Solomons J., Jamin M., Goettlinger H.G., Svergun D.I., Weissenhorn W. J. Mol. Biol. 378:818-827(2008) [PubMed: 18395747] [Abstract] Cited for: AUTOINHIBITORY MECHANISM, INTERACTION WITH STAMBP.
[20]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[21]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-200, MASS SPECTROMETRY. Tissue: T-cell.
[22]	"Structural basis for budding by the ESCRT-III factor CHMP3." Muziol T., Pineda-Molina E., Ravelli R.B., Zamborlini A., Usami Y., Goettlinger H., Weissenhorn W. Dev. Cell 10:821-830(2006) [PubMed: 16740483] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 5-183, SUBUNIT, FUNCTION IN HIV-1 BUDDING, MUTAGENESIS OF 24-ARG-LYS-25; ARG-28; LYS-54; GLN-56; VAL-59; 62-VAL-LEU-63 AND 78-TYR-ALA-79.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF219226 mRNA. Translation: AAF26737.1.
AF151907 mRNA. Translation: AAD34144.1.
AC015971 Genomic DNA. Translation: AAX93078.1.
AC068288 Genomic DNA. Translation: AAY24211.1.
BC004419 mRNA. Translation: AAH04419.1.

IPI

IPI00100673.

RefSeq

NP_001005753.1.
NP_057163.1.

UniGene

Hs.591582

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2GD5	X-ray	2.80	A/B/C/D	9-183	[»]
3FRT	X-ray	4.00	A/B	8-222	[»]
3FRV	X-ray	3.70	A	1-150	[»]

SMR

Q9Y3E7. Positions 5-180.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9Y3E7. 1 interaction.

STRING

Q9Y3E7.

PTM databases

PhosphoSite

Q9Y3E7.

Proteomic databases

PRIDE

Q9Y3E7.

Genome annotation databases

Ensembl

ENST00000263856; ENSP00000263856; ENSG00000115561; Homo sapiens. [Genome view]

GeneID

51652.

KEGG

hsa:51652.

UCSC

uc002srj.1. human.

Organism-specific databases

CTD

51652.

GeneCards

GC02M086642.

H-InvDB

HIX0002239.

HGNC

HGNC:29865. VPS24.

HPA

HPA015673.

MIM

610052. gene.

PharmGKB

PA134920495.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

HBG107031.

PhylomeDB

Q9Y3E7.

Gene expression databases

ArrayExpress

Q9Y3E7.

Bgee

Q9Y3E7.

CleanEx

HS_VPS24.

Genevestigator

Q9Y3E7.

GermOnline

ENSG00000115561. Homo sapiens.

Family and domain databases

InterPro

IPR005024. Snf7.
[Graphical view]

Pfam

PF03357. Snf7. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

55614.

SOURCE

Search...

Entry information

Entry name

CHMP3_HUMAN

Accession

Primary (citable) accession number: Q9Y3E7
Secondary accession number(s): Q53S71, Q53SU5, Q9NZ51

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 30, 2005
Last sequence update:	January 23, 2007
Last modified:	March 2, 2010
This is version 69 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.