CHMP4C

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
Inferred from physical interactionⁱ
- 14505570
- 14519844

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

abscission
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 22422861
- 24814515
endosomal transport Source: Reactome
macroautophagy
Source: ParkinsonsUK-UCL
Traceable author statementⁱ
- 20588296
midbody abscission
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 20616062
mitotic cytokinesis checkpoint
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 22422861
- 24814515
mitotic metaphase plate congression
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 20616062
multivesicular body assembly
Source: ParkinsonsUK-UCL
Traceable author statementⁱ
- 20588296
negative regulation of cytokinesis
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 22422861
- 24814515
nucleus organization
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 20616062
positive regulation of viral release from host cell
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 14505570
protein transport Source: UniProtKB-KW
regulation of centrosome duplication
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 20616062
regulation of mitotic spindle assembly
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 20616062
regulation of viral process
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 14505570
ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 22547407
vacuolar transport Source: InterPro
viral budding via host ESCRT complex
Source: ParkinsonsUK-UCL
Traceable author statementⁱ
- 20588296
viral life cycle Source: Reactome

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Biological process	Protein transport, Transport

Biological process

Protein transport, Transport

Enzyme and pathway databases

Reactomeⁱ	R-HSA-162588 Budding and maturation of HIV virion R-HSA-1632852 Macroautophagy R-HSA-917729 Endosomal Sorting Complex Required For Transport (ESCRT)
SIGNORⁱ	Q96CF2

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
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 8

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000164695.4
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:30599 CHMP4C
MIMⁱ	610899 gene
neXtProtⁱ	NX_Q96CF2

Keywords - Cellular componentⁱ

Cytoplasm, Endosome, Membrane

Pathology & 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

DisGeNET More...DisGeNETⁱ	92421
Open Targets More...OpenTargetsⁱ	ENSG00000164695
PharmGKBⁱ	PA142672113

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

Phosphoprotein

Proteomic databases

EPDⁱ	Q96CF2
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	Q96CF2
PaxDbⁱ	Q96CF2
PeptideAtlas More...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 144 organ(s), highest expression level in amniotic fluid
CleanExⁱ	HS_CHMP4C
Genevisibleⁱ	Q96CF2 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	HPA023799

HPAⁱ

HPA023799

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

With	Entry	#Exp.	IntAct	Notes
PDCD6IP	Q8WUM4	3	EBI-1221015,EBI-310624
USP8	P40818	2	EBI-1221015,EBI-1050865

GO - Molecular functionⁱ

protein homodimerization activity
Source: UniProtKB
Inferred from physical interactionⁱ
- 14505570
- 14519844

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridⁱ	124946, 14 interactors
ComplexPortalⁱ	CPX-329 ESCRT-III complex
CORUMⁱ	Q96CF2
Database of interacting proteins More...DIPⁱ	DIP-38342N
IntActⁱ	Q96CF2, 13 interactors
Molecular INTeraction database More...MINTⁱ	Q96CF2
STRINGⁱ	9606.ENSP00000297265

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Helixⁱ	224 – 232	Combined sources		9

Show more details

3D structure databases

ProteinModelPortalⁱ	Q96CF2
SMRⁱ	Q96CF2
ModBaseⁱ	Search...
MobiDBⁱ	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 coil

Phylogenomic databases

eggNOGⁱ	KOG1656 Eukaryota ENOG410YE9I LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00390000005006
HOGENOMⁱ	HOG000209959
HOVERGENⁱ	HBG050928
InParanoidⁱ	Q96CF2
KEGG Orthology (KO) More...KOⁱ	K12194
OMAⁱ	GYAAQAM
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0V7X
PhylomeDBⁱ	Q96CF2
TreeFamⁱ	TF314269

Family and domain databases

InterProⁱ	View protein in InterPro IPR005024 Snf7_fam
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF03357 Snf7, 1 hit

Sequenceⁱ

Sequence statusⁱ: Complete.

Q96CF2-1 [UniParc]FASTA Add 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 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
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS6233.1
NCBI Reference Sequences More...RefSeqⁱ	NP_689497.1, NM_152284.3
UniGeneⁱ	Hs.183861

Genome annotation databases

Ensemblⁱ	ENST00000297265; ENSP00000297265; ENSG00000164695
GeneIDⁱ	92421
KEGGⁱ	hsa:92421
UCSC genome browser More...UCSCⁱ	uc003ycl.4 human

Keywords - Coding sequence diversityⁱ

Polymorphism

Similar proteinsⁱ

90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q96CF2	charged multivesicular body protein 4c		URSMA		237	UniRef90_Q96CF2
charged multivesicular body protein 4c		Enhydra lutris kenyoni		237
charged multivesicular body protein 4c		LEPWE		237
charged multivesicular body protein 4c		NEOSC		237
Uncharacterized protein		MUSPF		237
+40

Protein	Similar proteins		Species	Score	Length	Source
Q96CF2	Charged multivesicular body protein 4b		XENLA		222	UniRef50_Q96CF2
charged multivesicular body protein 4c		URSMA		237
charged multivesicular body protein 4c		LEPWE		237
charged multivesicular body protein 4c		NEOSC		237
charged multivesicular body protein 4c		Enhydra lutris kenyoni		237
+93

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
UniGeneⁱ	Hs.183861

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...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	[»]
ProteinModelPortalⁱ	Q96CF2
SMRⁱ	Q96CF2
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	124946, 14 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
MaxQBⁱ	Q96CF2
PaxDbⁱ	Q96CF2
PeptideAtlasⁱ	Q96CF2
PRIDEⁱ	Q96CF2
ProteomicsDBⁱ	76183

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

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	HPA023799
MIMⁱ	610899 gene
neXtProtⁱ	NX_Q96CF2
OpenTargetsⁱ	ENSG00000164695
PharmGKBⁱ	PA142672113
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG1656 Eukaryota ENOG410YE9I LUCA
GeneTreeⁱ	ENSGT00390000005006
HOGENOMⁱ	HOG000209959
HOVERGENⁱ	HBG050928
InParanoidⁱ	Q96CF2
KOⁱ	K12194
OMAⁱ	GYAAQAM
OrthoDBⁱ	EOG091G0V7X
PhylomeDBⁱ	Q96CF2
TreeFamⁱ	TF314269

Enzyme and pathway databases

Reactomeⁱ	R-HSA-162588 Budding and maturation of HIV virion R-HSA-1632852 Macroautophagy R-HSA-917729 Endosomal Sorting Complex Required For Transport (ESCRT)
SIGNORⁱ	Q96CF2

Miscellaneous databases

EvolutionaryTraceⁱ	Q96CF2
GeneWikiⁱ	CHMP4C
GenomeRNAiⁱ	92421
Protein Ontology More...PROⁱ	PR:Q96CF2
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000164695 Expressed in 144 organ(s), highest expression level in amniotic fluid
CleanExⁱ	HS_CHMP4C
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...

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:	November 7, 2018
	This is version 143 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, Complete proteome, Reference proteome

Documents

SIMILARITY comments
Index of protein domains and families
Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations
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
Human chromosome 8
Human chromosome 8: entries, gene names and cross-references to MIM

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UniRef

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Supporting data

UniProtKB - Q96CF2 (CHM4C_HUMAN)

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Charged multivesicular body protein 4c

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Miscellaneous

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Endosome

Cytosol

Other locations

Cytosol

Endosome

Other locations

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Organism-specific databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

GO - Molecular functioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Region

Coiled coil

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Keywords - Domaini

Phylogenomic databases

Family and domain databases

Natural variant

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Documents

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ