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Protein

Charged multivesicular body protein 4c

Gene

CHMP4C

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Miscellaneous

Its overexpression strongly inhibits HIV-1 release.

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB

GO - Biological processi

Keywordsi

Biological processProtein 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
SNF7-31 Publication
Short name:
hSnf7-31 Publication
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

EuPathDBiHostDB:ENSG00000164695.4
HGNCiHGNC:30599 CHMP4C
MIMi610899 gene
neXtProtiNX_Q96CF2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi210S → A: Abolishes localization to the Flemming body and ability to delay abscission. 1 Publication1

Organism-specific databases

DisGeNETi92421
OpenTargetsiENSG00000164695
PharmGKBiPA142672113

Polymorphism and mutation databases

BioMutaiCHMP4C
DMDMi73917755

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002114951 – 233Charged multivesicular body protein 4cAdd BLAST233

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei210Phosphoserine; by AURKB1 Publication1

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
PeptideAtlasiQ96CF2
PRIDEiQ96CF2
ProteomicsDBi76183

PTM databases

iPTMnetiQ96CF2
PhosphoSitePlusiQ96CF2

Expressioni

Tissue specificityi

Expressed in heart, spleen and kidney.2 Publications

Gene expression databases

BgeeiENSG00000164695 Expressed in 144 organ(s), highest expression level in amniotic fluid
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 sequentially. 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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi124946, 14 interactors
ComplexPortaliCPX-329 ESCRT-III complex
CORUMiQ96CF2
DIPiDIP-38342N
IntActiQ96CF2, 13 interactors
MINTiQ96CF2
STRINGi9606.ENSP00000297265

Structurei

Secondary structure

1233
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ96CF2
SMRiQ96CF2
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96CF2

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 153Intramolecular interaction with C-terminusBy similarityAdd BLAST153
Regioni154 – 233Intramolecular interaction with N-terminusBy similarityAdd BLAST80

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili125 – 183Sequence analysisAdd BLAST59

Domaini

The acidic C-terminus and the basic N-terminus 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
OMAiGYAAQAM
OrthoDBiEOG091G0V7X
PhylomeDBiQ96CF2
TreeFamiTF314269

Family and domain databases

InterProiView protein in InterPro
IPR005024 Snf7_fam
PfamiView protein in Pfam
PF03357 Snf7, 1 hit

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)DescriptionActionsGraphical viewLength
Natural variantiVAR_052028232A → T. Corresponds to variant dbSNP:rs35094336Ensembl.1

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

Similar proteinsi

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
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3C3RX-ray2.02B221-233[»]
5MK3X-ray2.00E/F/G/H216-233[»]
5V3RX-ray1.91B216-233[»]
5WA1X-ray1.87B216-233[»]
ProteinModelPortaliQ96CF2
SMRiQ96CF2
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124946, 14 interactors
ComplexPortaliCPX-329 ESCRT-III complex
CORUMiQ96CF2
DIPiDIP-38342N
IntActiQ96CF2, 13 interactors
MINTiQ96CF2
STRINGi9606.ENSP00000297265

PTM databases

iPTMnetiQ96CF2
PhosphoSitePlusiQ96CF2

Polymorphism and mutation databases

BioMutaiCHMP4C
DMDMi73917755

Proteomic databases

EPDiQ96CF2
MaxQBiQ96CF2
PaxDbiQ96CF2
PeptideAtlasiQ96CF2
PRIDEiQ96CF2
ProteomicsDBi76183

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi92421
DisGeNETi92421
EuPathDBiHostDB:ENSG00000164695.4
GeneCardsiCHMP4C
HGNCiHGNC:30599 CHMP4C
HPAiHPA023799
MIMi610899 gene
neXtProtiNX_Q96CF2
OpenTargetsiENSG00000164695
PharmGKBiPA142672113
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1656 Eukaryota
ENOG410YE9I LUCA
GeneTreeiENSGT00390000005006
HOGENOMiHOG000209959
HOVERGENiHBG050928
InParanoidiQ96CF2
KOiK12194
OMAiGYAAQAM
OrthoDBiEOG091G0V7X
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
PROiPR:Q96CF2
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000164695 Expressed in 144 organ(s), highest expression level in amniotic fluid
CleanExiHS_CHMP4C
GenevisibleiQ96CF2 HS

Family and domain databases

InterProiView protein in InterPro
IPR005024 Snf7_fam
PfamiView protein in Pfam
PF03357 Snf7, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCHM4C_HUMAN
AccessioniPrimary (citable) accession number: Q96CF2
Secondary accession number(s): B2RBZ1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: December 1, 2001
Last modified: November 7, 2018
This is version 143 of the entry and version 1 of the sequence. See 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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