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Protein

Charged multivesicular body protein 4a

Gene

CHMP4A

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). ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. When overexpressed, membrane-assembled circular arrays of CHMP4A filaments can promote or stabilize negative curvature and outward budding. Via its interaction with PDCD6IP 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

  • ATPase binding Source: UniProtKB
  • identical protein binding Source: UniProtKB
  • lipid binding Source: UniProtKB-KW
  • protein homodimerization activity Source: UniProtKB

GO - Biological processi

  • autophagy Source: ParkinsonsUK-UCL
  • cell separation after cytokinesis Source: UniProtKB
  • endosomal transport Source: Reactome
  • membrane budding Source: UniProtKB
  • membrane invagination Source: UniProtKB
  • membrane tubulation Source: UniProtKB
  • mitotic metaphase plate congression Source: UniProtKB
  • multivesicular body assembly Source: ParkinsonsUK-UCL
  • negative regulation of autophagosome assembly Source: UniProtKB
  • negative regulation of neuron death Source: UniProtKB
  • nucleus organization Source: UniProtKB
  • posttranslational protein targeting to membrane Source: UniProtKB
  • protein homooligomerization Source: UniProtKB
  • protein polymerization Source: UniProtKB
  • viral budding via host ESCRT complex Source: UniProtKB
  • viral life cycle Source: Reactome
Complete GO annotation...

Keywords - Biological processi

Protein transport, Transport

Keywords - Ligandi

Lipid-binding

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).
SignaLinkiQ9BY43.

Names & Taxonomyi

Protein namesi
Recommended name:
Charged multivesicular body protein 4a
Alternative name(s):
Chromatin-modifying protein 4a
Short name:
CHMP4a
SNF7 homolog associated with Alix-2
SNF7-1
Short name:
hSnf-1
Vacuolar protein sorting-associated protein 32-1
Short name:
Vps32-1
Short name:
hVps32-1
Gene namesi
Name:CHMP4A
Synonyms:C14orf123, SHAX2
ORF Names:CDA04, HSPC134
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:20274. CHMP4A.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytoplasmic side of plasma membrane Source: UniProtKB
  • cytoplasmic vesicle membrane Source: UniProtKB-SubCell
  • cytosol Source: Reactome
  • ESCRT III complex Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • late endosome membrane Source: UniProtKB-SubCell
  • membrane coat Source: UniProtKB
  • midbody Source: FlyBase
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasmic vesicle, Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi182 – 22241Missing : Membrane association; releases autoinhibition. 1 PublicationAdd
BLAST
Mutagenesisi209 – 2091E → A: Reduces interaction with PDCD6IP. 1 Publication
Mutagenesisi214 – 2141L → A: Abolishes interaction with PDCD6IP. 1 Publication
Mutagenesisi217 – 2171L → A: Abolishes interaction with PDCD6IP. 1 Publication
Mutagenesisi220 – 2201W → A: Abolishes interaction with PDCD6IP. 1 Publication

Organism-specific databases

PharmGKBiPA134888743.

Polymorphism and mutation databases

BioMutaiCHMP4A.
DMDMi90152096.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 222222Charged multivesicular body protein 4aPRO_0000211488Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei196 – 1961PhosphoserineCombined sources

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9BY43.
MaxQBiQ9BY43.
PaxDbiQ9BY43.
PeptideAtlasiQ9BY43.
PRIDEiQ9BY43.

PTM databases

iPTMnetiQ9BY43.
PhosphoSiteiQ9BY43.

Expressioni

Tissue specificityi

Widely expressed. Expressed at higher level in heart, kidney, liver and skeletal muscle. Also expressed in brain, placenta, lung and pancreas.1 Publication

Gene expression databases

BgeeiENSG00000254505.
CleanExiHS_CHMP4A.
ExpressionAtlasiQ9BY43. baseline and differential.
GenevisibleiQ9BY43. HS.

Organism-specific databases

HPAiHPA046909.
HPA066797.
HPA068473.

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; overexpression leads to the assembly of filaments that curve and associate to create circular rings. Interacts with CHMP2A. Interacts with CHMP3; the interaction requires the release of CHMP4A autoinhibition. Interacts with CHMP4B. Interacts with CHMP4C. Interacts with CHMP6. Interacts with VPS4A. Interacts with PDCD6IP; the interaction is direct.8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CHMP4BQ9H4444EBI-747981,EBI-749627
SYT17Q9BSW75EBI-747981,EBI-745392

GO - Molecular functioni

  • ATPase binding Source: UniProtKB
  • identical protein binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi118852. 38 interactions.
DIPiDIP-39082N.
IntActiQ9BY43. 17 interactions.
MINTiMINT-3063754.
STRINGi9606.ENSP00000324205.

Structurei

Secondary structure

1
222
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi212 – 2187Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3C3OX-ray2.15B210-222[»]
ProteinModelPortaliQ9BY43.
SMRiQ9BY43. Positions 20-94.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9BY43.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 150150Intramolecular interaction with C-terminusBy similarityAdd
BLAST
Regioni1 – 116116Interaction with phosphoinosidesAdd
BLAST
Regioni151 – 22272Intramolecular interaction with N-terminusBy similarityAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili20 – 10586Sequence analysisAdd
BLAST
Coiled coili155 – 18026Sequence 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

eggNOGiKOG1277. Eukaryota.
ENOG410XSVB. LUCA.
GeneTreeiENSGT00390000005006.
HOGENOMiHOG000209959.
HOVERGENiHBG050928.
InParanoidiQ9BY43.
KOiK12194.
OMAiAGPCVMR.
OrthoDBiEOG091G0V7X.
PhylomeDBiQ9BY43.

Family and domain databases

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

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9BY43-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSGLGRLFGK GKKEKGPTPE EAIQKLKETE KILIKKQEFL EQKIQQELQT
60 70 80 90 100
AKKYGTKNKR AALQALRRKK RFEQQLAQTD GTLSTLEFQR EAIENATTNA
110 120 130 140 150
EVLRTMELAA QSMKKAYQDM DIDKVDELMT DITEQQEVAQ QISDAISRPM
160 170 180 190 200
GFGDDVDEDE LLEELEELEQ EELAQELLNV GDKEEEPSVK LPSVPSTHLP
210 220
AGPAPKVDED EEALKQLAEW VS
Length:222
Mass (Da):25,098
Last modified:February 7, 2006 - v3
Checksum:i6712BA6AAA1D7CB7
GO
Isoform 2 (identifier: Q9BY43-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MSRRRPEDGLGKAGPCVMRHHPPRSKAEVWRTLRGGGGRGELAM

Note: No experimental confirmation available.
Show »
Length:265
Mass (Da):29,804
Checksum:i9F8805839882B9D1
GO

Sequence cautioni

The sequence AAH10893 differs from that shown. Reason: Erroneous initiation. Curated
The sequence AAI07700 differs from that shown. Reason: Erroneous initiation. Curated
The sequence CAD61949 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti16 – 161G → R in AAF29098 (PubMed:11042152).Curated
Sequence conflicti66 – 661L → S in AAF29098 (PubMed:11042152).Curated
Sequence conflicti152 – 1532FG → LLE in AAF29098 (PubMed:11042152).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti153 – 1531G → R.2 Publications
Corresponds to variant rs2295322 [ dbSNP | Ensembl ].
VAR_023384

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 11M → MSRRRPEDGLGKAGPCVMRH HPPRSKAEVWRTLRGGGGRG ELAM in isoform 2. 1 PublicationVSP_056264

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB100262 mRNA. Translation: BAC79376.2.
AY329084 mRNA. Translation: AAQ91193.1.
AF212243 mRNA. Translation: AAK14928.1.
AF161483 mRNA. Translation: AAF29098.1.
BX161512 mRNA. Translation: CAD61949.1. Different initiation.
AL096870 Genomic DNA. No translation available.
AL136295 Genomic DNA. No translation available.
BC010893 mRNA. Translation: AAH10893.2. Different initiation.
BC107699 mRNA. Translation: AAI07700.1. Different initiation.
BC113533 mRNA. Translation: AAI13534.1.
BC113535 mRNA. Translation: AAI13536.1.
CCDSiCCDS9619.1. [Q9BY43-2]
RefSeqiNP_054888.2. NM_014169.3. [Q9BY43-2]
UniGeneiHs.279761.

Genome annotation databases

EnsembliENST00000347519; ENSP00000324205; ENSG00000254505. [Q9BY43-2]
ENST00000609024; ENSP00000476412; ENSG00000254505. [Q9BY43-1]
GeneIDi29082.
KEGGihsa:29082.
UCSCiuc001wni.4. human. [Q9BY43-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB100262 mRNA. Translation: BAC79376.2.
AY329084 mRNA. Translation: AAQ91193.1.
AF212243 mRNA. Translation: AAK14928.1.
AF161483 mRNA. Translation: AAF29098.1.
BX161512 mRNA. Translation: CAD61949.1. Different initiation.
AL096870 Genomic DNA. No translation available.
AL136295 Genomic DNA. No translation available.
BC010893 mRNA. Translation: AAH10893.2. Different initiation.
BC107699 mRNA. Translation: AAI07700.1. Different initiation.
BC113533 mRNA. Translation: AAI13534.1.
BC113535 mRNA. Translation: AAI13536.1.
CCDSiCCDS9619.1. [Q9BY43-2]
RefSeqiNP_054888.2. NM_014169.3. [Q9BY43-2]
UniGeneiHs.279761.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3C3OX-ray2.15B210-222[»]
ProteinModelPortaliQ9BY43.
SMRiQ9BY43. Positions 20-94.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118852. 38 interactions.
DIPiDIP-39082N.
IntActiQ9BY43. 17 interactions.
MINTiMINT-3063754.
STRINGi9606.ENSP00000324205.

PTM databases

iPTMnetiQ9BY43.
PhosphoSiteiQ9BY43.

Polymorphism and mutation databases

BioMutaiCHMP4A.
DMDMi90152096.

Proteomic databases

EPDiQ9BY43.
MaxQBiQ9BY43.
PaxDbiQ9BY43.
PeptideAtlasiQ9BY43.
PRIDEiQ9BY43.

Protocols and materials databases

DNASUi29082.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000347519; ENSP00000324205; ENSG00000254505. [Q9BY43-2]
ENST00000609024; ENSP00000476412; ENSG00000254505. [Q9BY43-1]
GeneIDi29082.
KEGGihsa:29082.
UCSCiuc001wni.4. human. [Q9BY43-1]

Organism-specific databases

CTDi29082.
GeneCardsiCHMP4A.
HGNCiHGNC:20274. CHMP4A.
HPAiHPA046909.
HPA066797.
HPA068473.
MIMi610051. gene.
neXtProtiNX_Q9BY43.
PharmGKBiPA134888743.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1277. Eukaryota.
ENOG410XSVB. LUCA.
GeneTreeiENSGT00390000005006.
HOGENOMiHOG000209959.
HOVERGENiHBG050928.
InParanoidiQ9BY43.
KOiK12194.
OMAiAGPCVMR.
OrthoDBiEOG091G0V7X.
PhylomeDBiQ9BY43.

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).
SignaLinkiQ9BY43.

Miscellaneous databases

ChiTaRSiCHMP4A. human.
EvolutionaryTraceiQ9BY43.
GeneWikiiCHMP4A.
GenomeRNAii29082.
PROiQ9BY43.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000254505.
CleanExiHS_CHMP4A.
ExpressionAtlasiQ9BY43. baseline and differential.
GenevisibleiQ9BY43. HS.

Family and domain databases

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

Entry informationi

Entry nameiCHM4A_HUMAN
AccessioniPrimary (citable) accession number: Q9BY43
Secondary accession number(s): Q14D22
, Q32Q79, Q86SZ8, Q96QJ9, Q9P026
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 2002
Last sequence update: February 7, 2006
Last modified: September 7, 2016
This is version 142 of the entry and version 3 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: 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.