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Protein

Charged multivesicular body protein 4c

Gene

CHMP4C

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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). Key component of the cytokinesis checkpoint, a process required to delay abscission to prevent both premature resolution of intercellular chromosome bridges and accumulation of DNA damage: upon phosphorylation by AURKB, together with ZFYVE19/ANCHR, retains abscission-competent VPS4 (VPS4A and/or VPS4B) at the midbody ring until abscission checkpoint signaling is terminated at late cytokinesis. Deactivation of AURKB results in dephosphorylation of CHMP4C followed by its dissociation from ANCHR and VPS4 and subsequent abscission (PubMed:22422861, PubMed:24814515). 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. CHMP4A/B/C are required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413).6 Publications

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB

GO - Biological processi

  • abscission Source: UniProtKB
  • autophagy Source: ParkinsonsUK-UCL
  • cell separation after cytokinesis Source: UniProtKB
  • endosomal transport Source: Reactome
  • mitotic metaphase plate congression Source: UniProtKB
  • multivesicular body assembly Source: ParkinsonsUK-UCL
  • negative regulation of cytokinesis Source: UniProtKB
  • nucleus organization Source: UniProtKB
  • positive regulation of viral release from host cell Source: UniProtKB
  • protein transport Source: UniProtKB-KW
  • regulation of centrosome duplication Source: UniProtKB
  • regulation of mitotic spindle assembly Source: UniProtKB
  • regulation of viral process Source: UniProtKB
  • ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway Source: UniProtKB
  • viral budding via host ESCRT complex Source: ParkinsonsUK-UCL
  • viral life cycle Source: Reactome
Complete GO annotation...

Keywords - Biological processi

Protein transport, Transport

Enzyme and pathway databases

ReactomeiR-HSA-162588. Budding and maturation of HIV virion.
R-HSA-1632852. Macroautophagy.
R-HSA-917729. Endosomal Sorting Complex Required For Transport (ESCRT).
SIGNORiQ96CF2.

Names & Taxonomyi

Protein namesi
Recommended name:
Charged multivesicular body protein 4c
Alternative name(s):
Chromatin-modifying protein 4c
Short name:
CHMP4c
SNF7 homolog associated with Alix 3
SNF7-3
Short name:
hSnf7-3
Vacuolar protein sorting-associated protein 32-3
Short name:
Vps32-3
Short name:
hVps32-3
Gene namesi
Name:CHMP4C
Synonyms:SHAX3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:30599. CHMP4C.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: Reactome
  • ESCRT III complex Source: ParkinsonsUK-UCL
  • extracellular exosome Source: UniProtKB
  • Flemming body Source: UniProtKB
  • late endosome membrane Source: UniProtKB-SubCell
  • midbody Source: FlyBase
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi210 – 2101S → A: Abolishes localization to the Flemming body and ability to delay abscission. 1 Publication

Organism-specific databases

PharmGKBiPA142672113.

Polymorphism and mutation databases

BioMutaiCHMP4C.
DMDMi73917755.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 233233Charged multivesicular body protein 4cPRO_0000211495Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei210 – 2101Phosphoserine; by AURKB1 Publication

Post-translational modificationi

Phosphorylated at Ser-210 by AURKB during cytokinesis: together with ZFYVE19/ANCHR, phosphorylated CHMP4C retains abscission-competent VPS4 (VPS4A and/or VPS4B) at the midbody ring until abscission checkpoint signaling is terminated at late cytokinesis.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ96CF2.
MaxQBiQ96CF2.
PaxDbiQ96CF2.
PRIDEiQ96CF2.

PTM databases

iPTMnetiQ96CF2.
PhosphoSiteiQ96CF2.

Expressioni

Tissue specificityi

Expressed in heart, spleen and kidney.2 Publications

Gene expression databases

BgeeiQ96CF2.
CleanExiHS_CHMP4C.
GenevisibleiQ96CF2. HS.

Organism-specific databases

HPAiHPA023799.

Interactioni

Subunit structurei

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. Self-associates. Interacts with CHMP2A. Interacts with CHMP4A. Interacts with CHMP4B. Interacts with CHMP6. Interacts with VPS4A. Interacts with PDCD6IP; the interaction is direct.6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
USP8P408182EBI-1221015,EBI-1050865

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi124946. 14 interactions.
DIPiDIP-38342N.
IntActiQ96CF2. 10 interactions.
MINTiMINT-6942276.
STRINGi9606.ENSP00000297265.

Structurei

Secondary structure

1
233
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi222 – 23110Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3C3RX-ray2.02B221-233[»]
ProteinModelPortaliQ96CF2.
SMRiQ96CF2. Positions 23-97.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96CF2.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 153153Intramolecular interaction with C-terminusBy similarityAdd
BLAST
Regioni154 – 23380Intramolecular interaction with N-terminusBy similarityAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili125 – 18359Sequence analysisAdd
BLAST

Domaini

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 (By similarity).By similarity

Sequence similaritiesi

Belongs to the SNF7 family.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG1656. Eukaryota.
ENOG410YE9I. LUCA.
GeneTreeiENSGT00390000005006.
HOGENOMiHOG000209959.
HOVERGENiHBG050928.
InParanoidiQ96CF2.
KOiK12194.
OMAiSYTNTEV.
OrthoDBiEOG7PGDSH.
PhylomeDBiQ96CF2.
TreeFamiTF314269.

Family and domain databases

InterProiIPR005024. Snf7_fam.
[Graphical view]
PfamiPF03357. Snf7. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q96CF2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSKLGKFFKG GGSSKSRAAP SPQEALVRLR ETEEMLGKKQ EYLENRIQRE
60 70 80 90 100
IALAKKHGTQ NKRAALQALK RKKRFEKQLT QIDGTLSTIE FQREALENSH
110 120 130 140 150
TNTEVLRNMG FAAKAMKSVH ENMDLNKIDD LMQEITEQQD IAQEISEAFS
160 170 180 190 200
QRVGFGDDFD EDELMAELEE LEQEELNKKM TNIRLPNVPS SSLPAQPNRK
210 220 230
PGMSSTARRS RAASSQRAEE EDDDIKQLAA WAT
Length:233
Mass (Da):26,411
Last modified:December 1, 2001 - v1
Checksum:iC18050F0A6C4C899
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti232 – 2321A → T.
Corresponds to variant rs35094336 [ dbSNP | Ensembl ].
VAR_052028

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB120734 mRNA. Translation: BAC87888.1.
AY329086 mRNA. Translation: AAQ91195.1.
AK314873 mRNA. Translation: BAG37388.1.
CH471068 Genomic DNA. Translation: EAW87107.1.
BC014321 mRNA. Translation: AAH14321.1.
CCDSiCCDS6233.1.
RefSeqiNP_689497.1. NM_152284.3.
UniGeneiHs.183861.

Genome annotation databases

EnsembliENST00000297265; ENSP00000297265; ENSG00000164695.
GeneIDi92421.
KEGGihsa:92421.
UCSCiuc003ycl.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB120734 mRNA. Translation: BAC87888.1.
AY329086 mRNA. Translation: AAQ91195.1.
AK314873 mRNA. Translation: BAG37388.1.
CH471068 Genomic DNA. Translation: EAW87107.1.
BC014321 mRNA. Translation: AAH14321.1.
CCDSiCCDS6233.1.
RefSeqiNP_689497.1. NM_152284.3.
UniGeneiHs.183861.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3C3RX-ray2.02B221-233[»]
ProteinModelPortaliQ96CF2.
SMRiQ96CF2. Positions 23-97.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124946. 14 interactions.
DIPiDIP-38342N.
IntActiQ96CF2. 10 interactions.
MINTiMINT-6942276.
STRINGi9606.ENSP00000297265.

PTM databases

iPTMnetiQ96CF2.
PhosphoSiteiQ96CF2.

Polymorphism and mutation databases

BioMutaiCHMP4C.
DMDMi73917755.

Proteomic databases

EPDiQ96CF2.
MaxQBiQ96CF2.
PaxDbiQ96CF2.
PRIDEiQ96CF2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000297265; ENSP00000297265; ENSG00000164695.
GeneIDi92421.
KEGGihsa:92421.
UCSCiuc003ycl.4. human.

Organism-specific databases

CTDi92421.
GeneCardsiCHMP4C.
HGNCiHGNC:30599. CHMP4C.
HPAiHPA023799.
MIMi610899. gene.
neXtProtiNX_Q96CF2.
PharmGKBiPA142672113.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1656. Eukaryota.
ENOG410YE9I. LUCA.
GeneTreeiENSGT00390000005006.
HOGENOMiHOG000209959.
HOVERGENiHBG050928.
InParanoidiQ96CF2.
KOiK12194.
OMAiSYTNTEV.
OrthoDBiEOG7PGDSH.
PhylomeDBiQ96CF2.
TreeFamiTF314269.

Enzyme and pathway databases

ReactomeiR-HSA-162588. Budding and maturation of HIV virion.
R-HSA-1632852. Macroautophagy.
R-HSA-917729. Endosomal Sorting Complex Required For Transport (ESCRT).
SIGNORiQ96CF2.

Miscellaneous databases

EvolutionaryTraceiQ96CF2.
GeneWikiiCHMP4C.
GenomeRNAii92421.
PROiQ96CF2.
SOURCEiSearch...

Gene expression databases

BgeeiQ96CF2.
CleanExiHS_CHMP4C.
GenevisibleiQ96CF2. HS.

Family and domain databases

InterProiIPR005024. Snf7_fam.
[Graphical view]
PfamiPF03357. Snf7. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "CHMP4b is a major binding partner of the ALG-2-interacting protein Alix among the three CHMP4 isoforms."
    Katoh K., Shibata H., Hatta K., Maki M.
    Arch. Biochem. Biophys. 421:159-165(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INTERACTION WITH PDCD6IP.
  2. "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, TISSUE SPECIFICITY, INTERACTION WITH PDCD6IP.
  3. "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: Small intestine.
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  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: Kidney.
  6. "AIP1/ALIX is a binding partner for HIV-1 p6 and EIAV p9 functioning in virus budding."
    Strack B., Calistri A., Craig S., Popova E., Goettlinger H.G.
    Cell 114:689-699(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN HIV-1 BUDDING, INTERACTION WITH PDCD6IP.
  7. Cited for: FUNCTION IN HIV-1 BUDDING, SELF-ASSOCIATION, INTERACTION WITH CHMPC4A; CHMPC4B; VPS4A AND PDCD6IP.
  8. "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, SELF-ASSOCIATION, INTERACTION WITH CHMP2A; CHMP4A; CHMP4B; CHMP6 AND PDCD6IP.
  9. Erratum
    Martin-Serrano J., Yarovoy A., Perez-Caballero D., Bieniasz P.D.
    Proc. Natl. Acad. Sci. U.S.A. 100:152845-152845(2003)
  10. Cited for: FUNCTION.
  11. "ESCRT-III governs the Aurora B-mediated abscission checkpoint through CHMP4C."
    Carlton J.G., Caballe A., Agromayor M., Kloc M., Martin-Serrano J.
    Science 336:220-225(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-210, MUTAGENESIS OF SER-210.
  12. "ANCHR mediates Aurora-B-dependent abscission checkpoint control through retention of VPS4."
    Thoresen S.B., Campsteijn C., Vietri M., Schink K.O., Liestoel K., Andersen J.S., Raiborg C., Stenmark H.
    Nat. Cell Biol. 16:550-560(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  13. Cited for: X-RAY CRYSTALLOGRAPHY (2.02 ANGSTROMS) OF 221-233 IN COMPLEX WITH PDCD6IP.

Entry informationi

Entry nameiCHM4C_HUMAN
AccessioniPrimary (citable) accession number: Q96CF2
Secondary accession number(s): B2RBZ1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: December 1, 2001
Last modified: June 8, 2016
This is version 125 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Miscellaneous

Its overexpression strongly inhibits HIV-1 release.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.