UniProtKB - Q96CF2 (CHM4C_HUMAN)
Protein
Charged multivesicular body protein 4c
Gene
CHMP4C
Organism
Homo sapiens (Human)
Status
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
- abscission Source: UniProtKB
- endosomal transport Source: Reactome
- late endosome to vacuole transport via multivesicular body sorting pathway Source: GO_Central
- macroautophagy Source: ParkinsonsUK-UCL
- midbody abscission Source: UniProtKB
- mitotic cytokinesis checkpoint Source: UniProtKB
- 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
- vesicle budding from membrane Source: GO_Central
- viral budding via host ESCRT complex Source: ParkinsonsUK-UCL
- viral life cycle Source: Reactome
Keywordsi
Biological process | Protein transport, Transport |
Enzyme and pathway databases
PathwayCommonsi | Q96CF2 |
Reactomei | R-HSA-162588, Budding and maturation of HIV virion R-HSA-1632852, Macroautophagy R-HSA-917729, Endosomal Sorting Complex Required For Transport (ESCRT) R-HSA-9610379, HCMV Late Events R-HSA-9615710, Late endosomal microautophagy R-HSA-9668328, Sealing of the nuclear envelope (NE) by ESCRT-III R-HSA-9679504, Translation of Replicase and Assembly of the Replication Transcription Complex |
SIGNORi | Q96CF2 |
Names & Taxonomyi
Protein namesi | Recommended name: Charged multivesicular body protein 4cAlternative 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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000164695.4 |
HGNCi | HGNC:30599, CHMP4C |
MIMi | 610899, gene |
neXtProti | NX_Q96CF2 |
Subcellular locationi
Endosome
- Late endosome membrane 1 Publication; Peripheral membrane protein Curated
Cytosol
Other locations
- Midbody ring 1 Publication
Note: Localizes to the midbody during late cytokinesis. During its recruitment, localizes initially to the midbody arms, before being directed to the central region, the midbody ring, also called Flemming body. Phosphorylation at Ser-210 by AURKB triggers localization to midbody ring.1 Publication
Cytosol
- cytosol Source: Reactome
Endosome
- ESCRT III complex Source: GO_Central
- late endosome membrane Source: UniProtKB-SubCell
- multivesicular body Source: GO_Central
Plasma Membrane
- cytoplasmic side of plasma membrane Source: GO_Central
Other locations
- Flemming body Source: UniProtKB
- midbody Source: FlyBase
Keywords - Cellular componenti
Cytoplasm, Endosome, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 210 | S → A: Abolishes localization to the Flemming body and ability to delay abscission. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 92421 |
OpenTargetsi | ENSG00000164695 |
PharmGKBi | PA142672113 |
Miscellaneous databases
Pharosi | Q96CF2, Tbio |
Polymorphism and mutation databases
BioMutai | CHMP4C |
DMDMi | 73917755 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000211495 | 1 – 233 | Charged multivesicular body protein 4cAdd BLAST | 233 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 210 | Phosphoserine; by AURKB1 Publication | 1 |
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
PhosphoproteinProteomic databases
EPDi | Q96CF2 |
jPOSTi | Q96CF2 |
MassIVEi | Q96CF2 |
MaxQBi | Q96CF2 |
PaxDbi | Q96CF2 |
PeptideAtlasi | Q96CF2 |
PRIDEi | Q96CF2 |
ProteomicsDBi | 76183 |
PTM databases
iPTMneti | Q96CF2 |
PhosphoSitePlusi | Q96CF2 |
Expressioni
Tissue specificityi
Expressed in heart, spleen and kidney.2 Publications
Gene expression databases
Bgeei | ENSG00000164695, Expressed in amniotic fluid and 159 other tissues |
Genevisiblei | Q96CF2, HS |
Organism-specific databases
HPAi | ENSG00000164695, Tissue enhanced (intestine) |
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 PublicationsBinary interactionsi
Hide detailsGO - Molecular functioni
- protein homodimerization activity Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 124946, 16 interactors |
ComplexPortali | CPX-329, ESCRT-III complex |
CORUMi | Q96CF2 |
DIPi | DIP-38342N |
IntActi | Q96CF2, 13 interactors |
MINTi | Q96CF2 |
STRINGi | 9606.ENSP00000297265 |
Miscellaneous databases
RNActi | Q96CF2, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q96CF2 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q96CF2 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 153 | Intramolecular interaction with C-terminusBy similarityAdd BLAST | 153 | |
Regioni | 154 – 233 | Intramolecular interaction with N-terminusBy similarityAdd BLAST | 80 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 125 – 183 | Sequence analysisAdd BLAST | 59 |
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 coilPhylogenomic databases
eggNOGi | KOG1656, Eukaryota |
GeneTreei | ENSGT00940000159257 |
HOGENOMi | CLU_071097_0_1_1 |
InParanoidi | Q96CF2 |
OMAi | ARQHGTK |
OrthoDBi | 1490465at2759 |
PhylomeDBi | Q96CF2 |
TreeFami | TF314269 |
Family and domain databases
InterProi | View protein in InterPro IPR005024, Snf7_fam |
Pfami | View protein in Pfam PF03357, Snf7, 1 hit |
i Sequence
Sequence statusi: Complete.
Q96CF2-1 [UniParc]FASTAAdd to basket
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
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_052028 | 232 | A → 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 |
CCDSi | CCDS6233.1 |
RefSeqi | NP_689497.1, NM_152284.3 |
Genome annotation databases
Ensembli | ENST00000297265; ENSP00000297265; ENSG00000164695 |
GeneIDi | 92421 |
KEGGi | hsa:92421 |
UCSCi | uc003ycl.4, human |
Keywords - Coding sequence diversityi
PolymorphismSimilar 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 |
CCDSi | CCDS6233.1 |
RefSeqi | NP_689497.1, NM_152284.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3C3R | X-ray | 2.02 | B | 221-233 | [»] | |
5MK3 | X-ray | 2.00 | E/F/G/H | 216-233 | [»] | |
5V3R | X-ray | 1.91 | B | 216-233 | [»] | |
5WA1 | X-ray | 1.87 | B | 216-233 | [»] | |
SMRi | Q96CF2 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 124946, 16 interactors |
ComplexPortali | CPX-329, ESCRT-III complex |
CORUMi | Q96CF2 |
DIPi | DIP-38342N |
IntActi | Q96CF2, 13 interactors |
MINTi | Q96CF2 |
STRINGi | 9606.ENSP00000297265 |
PTM databases
iPTMneti | Q96CF2 |
PhosphoSitePlusi | Q96CF2 |
Polymorphism and mutation databases
BioMutai | CHMP4C |
DMDMi | 73917755 |
Proteomic databases
EPDi | Q96CF2 |
jPOSTi | Q96CF2 |
MassIVEi | Q96CF2 |
MaxQBi | Q96CF2 |
PaxDbi | Q96CF2 |
PeptideAtlasi | Q96CF2 |
PRIDEi | Q96CF2 |
ProteomicsDBi | 76183 |
Protocols and materials databases
Antibodypediai | 12567, 66 antibodies |
Genome annotation databases
Ensembli | ENST00000297265; ENSP00000297265; ENSG00000164695 |
GeneIDi | 92421 |
KEGGi | hsa:92421 |
UCSCi | uc003ycl.4, human |
Organism-specific databases
CTDi | 92421 |
DisGeNETi | 92421 |
EuPathDBi | HostDB:ENSG00000164695.4 |
GeneCardsi | CHMP4C |
HGNCi | HGNC:30599, CHMP4C |
HPAi | ENSG00000164695, Tissue enhanced (intestine) |
MIMi | 610899, gene |
neXtProti | NX_Q96CF2 |
OpenTargetsi | ENSG00000164695 |
PharmGKBi | PA142672113 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1656, Eukaryota |
GeneTreei | ENSGT00940000159257 |
HOGENOMi | CLU_071097_0_1_1 |
InParanoidi | Q96CF2 |
OMAi | ARQHGTK |
OrthoDBi | 1490465at2759 |
PhylomeDBi | Q96CF2 |
TreeFami | TF314269 |
Enzyme and pathway databases
PathwayCommonsi | Q96CF2 |
Reactomei | R-HSA-162588, Budding and maturation of HIV virion R-HSA-1632852, Macroautophagy R-HSA-917729, Endosomal Sorting Complex Required For Transport (ESCRT) R-HSA-9610379, HCMV Late Events R-HSA-9615710, Late endosomal microautophagy R-HSA-9668328, Sealing of the nuclear envelope (NE) by ESCRT-III R-HSA-9679504, Translation of Replicase and Assembly of the Replication Transcription Complex |
SIGNORi | Q96CF2 |
Miscellaneous databases
BioGRID-ORCSi | 92421, 8 hits in 842 CRISPR screens |
EvolutionaryTracei | Q96CF2 |
GeneWikii | CHMP4C |
GenomeRNAii | 92421 |
Pharosi | Q96CF2, Tbio |
PROi | PR:Q96CF2 |
RNActi | Q96CF2, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000164695, Expressed in amniotic fluid and 159 other tissues |
Genevisiblei | Q96CF2, HS |
Family and domain databases
InterProi | View protein in InterPro IPR005024, Snf7_fam |
Pfami | View protein in Pfam PF03357, Snf7, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | CHM4C_HUMAN | |
Accessioni | Q96CF2Primary (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: | December 2, 2020 | |
This is version 156 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 8
Human chromosome 8: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations