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Protein

Charged multivesicular body protein 4a

Gene

CHMP4A

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). 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

  • cell separation after cytokinesis Source: UniProtKB
  • endosomal transport Source: Reactome
  • macroautophagy Source: ParkinsonsUK-UCL
  • membrane invagination 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
  • plasma membrane tubulation Source: UniProtKB
  • posttranslational protein targeting to endoplasmic reticulum membrane Source: UniProtKB
  • protein homooligomerization Source: UniProtKB
  • protein polymerization Source: UniProtKB
  • vacuolar transport Source: InterPro
  • vesicle budding from membrane Source: UniProtKB
  • viral budding via host ESCRT complex Source: UniProtKB
  • viral life cycle Source: Reactome

Keywordsi

Biological processProtein transport, Transport
LigandLipid-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

EuPathDBiHostDB:ENSG00000254505.9
HGNCiHGNC:20274 CHMP4A
MIMi610051 gene
neXtProtiNX_Q9BY43

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

Cytoplasmic vesicle, Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi182 – 222Missing : Membrane association; releases autoinhibition. 1 PublicationAdd BLAST41
Mutagenesisi209E → A: Reduces interaction with PDCD6IP. 1 Publication1
Mutagenesisi214L → A: Abolishes interaction with PDCD6IP. 1 Publication1
Mutagenesisi217L → A: Abolishes interaction with PDCD6IP. 1 Publication1
Mutagenesisi220W → A: Abolishes interaction with PDCD6IP. 1 Publication1

Organism-specific databases

DisGeNETi29082
OpenTargetsiENSG00000254505
PharmGKBiPA134888743

Polymorphism and mutation databases

BioMutaiCHMP4A
DMDMi90152096

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002114881 – 222Charged multivesicular body protein 4aAdd BLAST222

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei196PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9BY43
MaxQBiQ9BY43
PaxDbiQ9BY43
PeptideAtlasiQ9BY43
PRIDEiQ9BY43
ProteomicsDBi79580

PTM databases

iPTMnetiQ9BY43
PhosphoSitePlusiQ9BY43

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

HPAiHPA068473

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; 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

Show more details

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi118852, 51 interactors
ComplexPortaliCPX-329 ESCRT-III complex
CORUMiQ9BY43
DIPiDIP-39082N
IntActiQ9BY43, 20 interactors
MINTiQ9BY43
STRINGi9606.ENSP00000324205

Structurei

Secondary structure

1222
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi212 – 218Combined sources7

3D structure databases

ProteinModelPortaliQ9BY43
SMRiQ9BY43
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9BY43

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 150Intramolecular interaction with C-terminusBy similarityAdd BLAST150
Regioni1 – 116Interaction with phosphoinosidesAdd BLAST116
Regioni151 – 222Intramolecular interaction with N-terminusBy similarityAdd BLAST72

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili20 – 105Sequence analysisAdd BLAST86
Coiled coili155 – 180Sequence analysisAdd BLAST26

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

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

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)DescriptionActionsGraphical viewLength
Sequence conflicti16G → R in AAF29098 (PubMed:11042152).Curated1
Sequence conflicti66L → S in AAF29098 (PubMed:11042152).Curated1
Sequence conflicti152 – 153FG → LLE in AAF29098 (PubMed:11042152).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_023384153G → R2 PublicationsCorresponds to variant dbSNP:rs2295322Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0562641M → MSRRRPEDGLGKAGPCVMRH HPPRSKAEVWRTLRGGGGRG ELAM in isoform 2. 1 Publication1

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]
ENST00000645179; ENSP00000495781; ENSG00000285302 [Q9BY43-1]
ENST00000645308; ENSP00000495982; ENSG00000285302 [Q9BY43-2]
GeneIDi29082
KEGGihsa:29082
UCSCiuc001wni.4 human [Q9BY43-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCHM4A_HUMAN
AccessioniPrimary (citable) accession number: Q9BY43
Secondary accession number(s): Q14D22
, Q32Q79, Q86SZ8, Q96QJ9, Q9P026
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 2002
Last sequence update: February 7, 2006
Last modified: June 20, 2018
This is version 155 of the entry and version 3 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. 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

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