Q96FZ7 (CHMP6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Charged multivesicular body protein 6

Alternative name(s):
Chromatin-modifying protein 6
Vacuolar protein sorting-associated protein 20
Short name=Vps20
Short name=hVps20

Gene names

Name:	CHMP6
Synonyms:	VPS20

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	201 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. In the ESCRT-III complex, it probably serves as an acceptor for the ESCRT-II complex on endosomal membranes.
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. Interacts with VPS4A; the interaction is direct. Interacts with VPS4B; the interaction is direct. Interacts with CHMP4A, CHMP4B and CHMP4C. Interacts with SNF8, VPS25 and VPS36. Ref.6 Ref.7 Ref.9 Ref.10
Subcellular location	Endomembrane system. Endosome membrane; Lipid-anchor. Late endosome membrane Probable. Note: Localizes to endosomal membranes. Ref.1 Ref.9
Tissue specificity	Ubiquitously expressed. 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.
Sequence similarities	Belongs to the SNF7 family.

Ontologies

Keywords
Biological process	Protein transport Transport
Cellular component	Endosome Membrane
Coding sequence diversity	Polymorphism
Domain	Coiled coil
PTM	Lipoprotein Myristate
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular membrane organization Traceable author statement. Source: Reactome endosomal transport Traceable author statement. Source: Reactome protein transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Traceable author statement. Source: Reactome endomembrane system Inferred from electronic annotation. Source: UniProtKB-SubCell late endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 201

201

Charged multivesicular body protein 6

PRO_0000211508

Regions

Region

170 – 181

12

Interaction with VPS4A

Coiled coil

10 – 145

136

Potential

Motif

168 – 179

12

Type-2 MIT-interacting motif

Amino acid modifications

Lipidation

2

1

N-myristoyl glycine Probable

Natural variations

Natural variant

55

1

G → S.
Corresponds to variant rs61037507 [ dbSNP | Ensembl ].

VAR_061807

Experimental info

Mutagenesis

2

1

G → A: Abolishes myristoylation. Ref.9

Mutagenesis

49

1

R → E: Does not affect the subcellular location. Ref.9

Mutagenesis

168 – 201

34

Missing: Membrane association; releases autoinhibition. Ref.10

Mutagenesis

170

1

L → D: Abolishes interaction with VPS4A. Ref.12

Mutagenesis

173

1

V → D: Abolishes interaction with VPS4A. Ref.12

Mutagenesis

178

1

L → D: Reduces interaction with VPS4A. Ref.12

Sequence conflict

17

1

D → G in BAD96907. Ref.4

Sequence conflict

106

1

F → L in BAB13901. Ref.2

Secondary structure

1

.

.

.

201

Helix Strand Turn

Details...

Helix

15 – 43

29

Sequences

	Sequence		Length	Mass (Da)
	Q96FZ7 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 0D490C4DE047DC02	FASTA	201	23,485
	10 20 30 40 50 60 MGNLFGRKKQ SRVTEQDKAI LQLKQQRDKL RQYQKRIAQQ LERERALARQ LLRDGRKERA 70 80 90 100 110 120 KLLLKKKRYQ EQLLDRTENQ ISSLEAMVQS IEFTQIEMKV MEGLQFGNEC LNKMHQVMSI 130 140 150 160 170 180 EEVERILDET QEAVEYQRQI DELLAGSFTQ EDEDAILEEL SAITQEQIEL PEVPSEPLPE 190 200 KIPENVPVKA RPRQAELVAA S

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure and function of human Vps20 and Snf7 proteins." Peck J.W., Bowden E.T., Burbelo P.D. Biochem. J. 377:693-700(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION.
[2]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Embryo and Synovial cell.
[3]	"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].
[4]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Kidney proximal tubule.
[5]	"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: Uterus.
[6]	"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: INTERACTION WITH VPS25; CHMP4B; VPS4A AND VPS4B.
[7]	"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: INTERACTION WITH CHMP4A; CHMP4B; CHMP4C; VPS25; SNF8 AND VPS36.
[8]	Erratum Martin-Serrano J., Yarovoy A., Perez-Caballero D., Bieniasz P.D. Proc. Natl. Acad. Sci. U.S.A. 100:152845-152845(2003)
[9]	"Human CHMP6, a myristoylated ESCRT-III protein, interacts directly with an ESCRT-II component EAP20 and regulates endosomal cargo sorting." Yorikawa C., Shibata H., Waguri S., Hatta K., Horii M., Katoh K., Kobayashi T., Uchiyama Y., Maki M. Biochem. J. 387:17-26(2005) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MYRISTOYLATION AT GLY-2, INTERACTION WITH CHMP4B AND VPS25, MUTAGENESIS OF GLY-2 AND ARG-49.
[10]	"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, MUTAGENESIS OF 168-ILE--SER-201.
[11]	"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].
[12]	"Two distinct modes of ESCRT-III recognition are required for VPS4 functions in lysosomal protein targeting and HIV-1 budding." Kieffer C., Skalicky J.J., Morita E., De Domenico I., Ward D.M., Kaplan J., Sundquist W.I. Dev. Cell 15:62-73(2008) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 168-179 IN COMPLEX WITH VPS4A, MUTAGENESIS OF LEU-170; VAL-173 AND LEU-178.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AY329087 mRNA. Translation: AAQ91196.1.
AK021811 mRNA. Translation: BAB13901.1.
CR457284 mRNA. Translation: CAG33565.1.
AK223187 mRNA. Translation: BAD96907.1.
AK292105 mRNA. Translation: BAF84794.1.
BC010108 mRNA. Translation: AAH10108.1.

IPI

IPI00305423.

RefSeq

NP_078867.2. NM_024591.4.

UniGene

Hs.514560.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2K3W	NMR	-	B	166-181	[»]
3HTU	X-ray	2.00	B/D/F/H	11-48	[»]

ProteinModelPortal

Q96FZ7.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q96FZ7. 1 interaction.

MINT

MINT-5003442.

STRING

9606.ENSP00000317468.

PTM databases

PhosphoSite

Q96FZ7.

Polymorphism databases

DMDM

73917777.

Proteomic databases

PaxDb

Q96FZ7.

PRIDE

Q96FZ7.

Protocols and materials databases

DNASU

79643.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000325167; ENSP00000317468; ENSG00000176108.

GeneID

79643.

KEGG

hsa:79643.

UCSC

uc002jyw.4. human.

Organism-specific databases

CTD

79643.

GeneCards

GC17P078965.

HGNC

HGNC:25675. CHMP6.

HPA

HPA023001.
HPA024460.

MIM

610901. gene.

neXtProt

NX_Q96FZ7.

PharmGKB

PA142672114.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG291677.

HOGENOM

HOG000208642.

HOVERGEN

HBG080510.

InParanoid

Q96FZ7.

KO

K12195.

OMA

DAITQEQ.

OrthoDB

EOG4DBTG6.

PhylomeDB

Q96FZ7.

Enzyme and pathway databases

Reactome

REACT_11123. Membrane Trafficking.

Gene expression databases

ArrayExpress

Q96FZ7.

Bgee

Q96FZ7.

CleanEx

HS_CHMP6.

Genevestigator

Q96FZ7.

GermOnline

ENSG00000176108. Homo sapiens.

Family and domain databases

InterPro

IPR005024. Snf7.
[Graphical view]

Pfam

PF03357. Snf7. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q96FZ7.

GenomeRNAi

79643.

NextBio

68773.

SOURCE

Search...

Entry information

Entry name

CHMP6_HUMAN

Accession

Primary (citable) accession number: Q96FZ7
Secondary accession number(s): A8K7U0, Q53FU4, Q9HAE8

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 30, 2005
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 97 of the entry and version 3 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.