Q9H444 (CHM4B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Charged multivesicular body protein 4b

Alternative name(s):
Chromatin-modifying protein 4b
Short name=CHMP4b
SNF7 homolog associated with Alix 1
SNF7-2
Short name=hSnf7-2
Vacuolar protein sorting-associated protein 32-2
Short name=Vps32-2
Short name=hVps32-2

Gene names

Name:	CHMP4B
Synonyms:	C20orf178, SHAX1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	224 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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 CHMP4B 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. Ref.1 Ref.8 Ref.9 Ref.10 Ref.19
Subunit structure	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. Interacts with CHMP6 and CHMP4C. Interacts with PDCD6IP; the interaction is direct. Interacts with VPS4A; the interaction is direct. Interacts with VPS4B; the interaction is direct. Interacts with CHMP7. Interacts with CFTR; the interaction requires misfolded CFTR. Ref.1 Ref.2 Ref.8 Ref.9 Ref.10 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18
Subcellular location	Cytoplasm › cytosol. Late endosome membrane; Peripheral membrane protein Probable Ref.1 Ref.13.
Tissue specificity	Widely expressed. Expressed at higher level in heart and skeletal muscle. Also expressed in brain, colon, thymus, spleen, kidney, liver, small intestine, placenta, lung and peripheral blood lymphocytes. Ref.12
Domain	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.
Involvement in disease	Cataract, posterior polar, 3 (CTPP3) [MIM:605387]: A subcapsular opacity, usually disk-shaped, located at the back of the lens. It can have a marked effect on visual acuity. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.25
Miscellaneous	Its overexpression strongly inhibits HIV-1 release.
Sequence similarities	Belongs to the SNF7 family.

Ontologies

Keywords
Biological process	Protein transport Transport
Cellular component	Cytoplasm Endosome Membrane
Disease	Cataract Disease mutation
Domain	Coiled coil
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cellular membrane organization Traceable author statement. Source: Reactome endosomal transport Traceable author statement. Source: Reactome protein transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Traceable author statement. Source: Reactome late endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.6

Chain

2 – 224

223

Charged multivesicular body protein 4b

PRO_0000211489

Regions

Coiled coil

23 – 183

161

Potential

Amino acid modifications

Modified residue

2

1

N-acetylserine Ref.6 Ref.20

Modified residue

6

1

N6-acetyllysine Ref.20

Modified residue

114

1

N6-acetyllysine Ref.20

Modified residue

184

1

Phosphoserine Ref.21

Modified residue

223

1

Phosphoserine Ref.21 Ref.23

Natural variations

Natural variant

129

1

D → V in CTPP3. Ref.25

VAR_037579

Natural variant

161

1

E → K in CTPP3. Ref.25

VAR_037580

Secondary structure

1

.

.

.

.

.

.

.

.

.

224

Helix Strand Turn

Details...

Helix

23 – 57

35

Helix

62 – 96

35

Helix

209 – 212

4

Helix

215 – 222

8

Sequences

	Sequence		Length	Mass (Da)
	Q9H444 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: DB1D79DD3803CB2F	FASTA	224	24,950
	10 20 30 40 50 60 MSVFGKLFGA GGGKAGKGGP TPQEAIQRLR DTEEMLSKKQ EFLEKKIEQE LTAAKKHGTK 70 80 90 100 110 120 NKRAALQALK RKKRYEKQLA QIDGTLSTIE FQREALENAN TNTEVLKNMG YAAKAMKAAH 130 140 150 160 170 180 DNMDIDKVDE LMQDIADQQE LAEEISTAIS KPVGFGEEFD EDELMAELEE LEQEELDKNL 190 200 210 220 LEISGPETVP LPNVPSIALP SKPAKKKEEE DDDMKELENW AGSM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The ALG-2-interacting protein Alix associates with CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting." Katoh K., Shibata H., Suzuki H., Narai A., Ishidoh K., Kominami E., Yoshimori T., Maki M. J. Biol. Chem. 278:39104-39113(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PDCD6IP.
[2]	"Structure and function of human Vps20 and Snf7 proteins." Peck J.W., Bowden E.T., Burbelo P.D. Biochem. J. 377:693-700(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH PDCD6IP.
[3]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain, Lung and Testis.
[6]	Bienvenut W.V., Lempens A., Norman J.C. Submitted (OCT-2009) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-28, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, MASS SPECTROMETRY. Tissue: Ovarian carcinoma.
[7]	Lubec G., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 18-28 AND 78-107, MASS SPECTROMETRY. Tissue: Fetal brain cortex.
[8]	"AIP1/ALIX is a binding partner for HIV-1 p6 and EIAV p9 functioning in virus budding." Strack B., Calistri A., Craig S., Popova E., Goettlinger H.G. Cell 114:689-699(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN HIV-1 BUDDING, INTERACTION WITH PDCD6IP.
[9]	"The protein network of HIV budding." von Schwedler U.K., Stuchell M., Mueller B., Ward D.M., Chung H.-Y., Morita E., Wang H.E., Davis T., He G.P., Cimbora D.M., Scott A., Kraeusslich H.-G., Kaplan J., Morham S.G., Sundquist W.I. Cell 114:701-713(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN HIV-1 BUDDING, INTERACTION WITH CHMP6; CHMP4C; PDCD6IP; VPS4A AND VPS4B.
[10]	"Divergent retroviral late-budding domains recruit vacuolar protein sorting factors by using alternative adaptor proteins." Martin-Serrano J., Yarovoy A., Perez-Caballero D., Bieniasz P.D. Proc. Natl. Acad. Sci. U.S.A. 100:12414-12419(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN HIV-1 BUDDING, SELF-ASSOCIATION, INTERACTION WITH CHMP2A; CHMP4A; CHMP4C; CHMP6; PDCD6IP AND VPS4A.
[11]	Erratum Martin-Serrano J., Yarovoy A., Perez-Caballero D., Bieniasz P.D. Proc. Natl. Acad. Sci. U.S.A. 100:152845-152845(2003)
[12]	"CHMP4b is a major binding partner of the ALG-2-interacting protein Alix among the three CHMP4 isoforms." Katoh K., Shibata H., Hatta K., Maki M. Arch. Biochem. Biophys. 421:159-165(2004) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, INTERACTION WITH PDCD6IP.
[13]	"Human CHMP6, a myristoylated ESCRT-III protein, interacts directly with an ESCRT-II component EAP20 and regulates endosomal cargo sorting." Yorikawa C., Shibata H., Waguri S., Hatta K., Horii M., Katoh K., Kobayashi T., Uchiyama Y., Maki M. Biochem. J. 387:17-26(2005) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH CHMP6.
[14]	"Misfolding diverts CFTR from recycling to degradation: quality control at early endosomes." Sharma M., Pampinella F., Nemes C., Benharouga M., So J., Du K., Bache K.G., Papsin B., Zerangue N., Stenmark H., Lukacs G.L. J. Cell Biol. 164:923-933(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MISFOLDED CFTR.
[15]	"CHMP7, a novel ESCRT-III-related protein, associates with CHMP4b and functions in the endosomal sorting pathway." Horii M., Shibata H., Kobayashi R., Katoh K., Yorikawa C., Yasuda J., Maki M. Biochem. J. 400:23-32(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CHMP7.
[16]	"Release of autoinhibition converts ESCRT-III components into potent inhibitors of HIV-1 budding." Zamborlini A., Usami Y., Radoshitzky S.R., Popova E., Palu G., Goettlinger H. Proc. Natl. Acad. Sci. U.S.A. 103:19140-19145(2006) [PubMed] [Europe PMC] [Abstract] Cited for: AUTOINHIBITORY MECHANISM, INTRAMOLECULAR INTERACTION.
[17]	"Potent rescue of human immunodeficiency virus type 1 late domain mutants by ALIX/AIP1 depends on its CHMP4 binding site." Usami Y., Popov S., Goettlinger H.G. J. Virol. 81:6614-6622(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PDCD6IP.
[18]	"Brox, a novel farnesylated Bro1 domain-containing protein that associates with charged multivesicular body protein 4 (CHMP4)." Ichioka F., Kobayashi R., Katoh K., Shibata H., Maki M. FEBS J. 275:682-692(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BROX.
[19]	"Plasma membrane deformation by circular arrays of ESCRT-III protein filaments." Hanson P.I., Roth R., Lin Y., Heuser J.E. J. Cell Biol. 180:389-402(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SELF-ASSOCIATION, STRUCTURE BY ELECTRON CRYOMICROSCOPY.
[20]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2; LYS-6 AND LYS-114, MASS SPECTROMETRY.
[21]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-184 AND SER-223, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[22]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[23]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-223, MASS SPECTROMETRY.
[24]	"ALIX-CHMP4 interactions in the human ESCRT pathway." McCullough J., Fisher R.D., Whitby F.G., Sundquist W.I., Hill C.P. Proc. Natl. Acad. Sci. U.S.A. 105:7687-7691(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 207-224 IN COMPLEX WITH PDCD6IP.
[25]	"CHMP4B, a novel gene for autosomal dominant cataracts linked to chromosome 20q." Shiels A., Bennett T.M., Knopf H.L.S., Yamada K., Yoshiura K., Niikawa N., Shim S., Hanson P.I. Am. J. Hum. Genet. 81:596-606(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CTPP3 VAL-129 AND LYS-161.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB100261 mRNA. Translation: BAC79375.1.
AY329085 mRNA. Translation: AAQ91194.1.
AL050349 Genomic DNA. Translation: CAC14088.1.
CH471077 Genomic DNA. Translation: EAW76293.1.
CH471077 Genomic DNA. Translation: EAW76294.1.
BC033859 mRNA. Translation: AAH33859.1.

IPI

IPI00025974.

RefSeq

NP_789782.1. NM_176812.4.

UniGene

Hs.472471.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3C3Q	X-ray	2.10	B	207-224	[»]
3UM3	X-ray	3.80	B	121-224	[»]
4ABM	X-ray	1.80	A/B/C/D	23-97	[»]

ProteinModelPortal

Q9H444.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29924N.

IntAct

Q9H444. 6 interactions.

MINT

MINT-5000054.

STRING

9606.ENSP00000217402.

PTM databases

PhosphoSite

Q9H444.

Polymorphism databases

DMDM

24636296.

Proteomic databases

PeptideAtlas

Q9H444.

PRIDE

Q9H444.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000217402; ENSP00000217402; ENSG00000101421.

GeneID

128866.

KEGG

hsa:128866.

UCSC

uc002xaa.3. human.

Organism-specific databases

CTD

128866.

GeneCards

GC20P032399.

HGNC

HGNC:16171. CHMP4B.

HPA

HPA041401.

MIM

605387. phenotype.
610897. gene.

neXtProt

NX_Q9H444.

Orphanet

98993. Posterior polar cataract.

PharmGKB

PA25721.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HOG000209960.

HOVERGEN

HBG050928.

InParanoid

Q9H444.

KO

K12194.

OMA

MKELEAW.

OrthoDB

EOG49GKHS.

PhylomeDB

Q9H444.

Enzyme and pathway databases

Reactome

REACT_11123. Membrane Trafficking.

Gene expression databases

Bgee

Q9H444.

CleanEx

HS_CHMP4B.

Genevestigator

Q9H444.

GermOnline

ENSG00000101421. Homo sapiens.

Family and domain databases

InterPro

IPR005024. Snf7.
[Graphical view]

Pfam

PF03357. Snf7. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

CHMP4B. human.

EvolutionaryTrace

Q9H444.

GenomeRNAi

128866.

NextBio

82502.

SOURCE

Search...

Entry information

Entry name

CHM4B_HUMAN

Accession

Primary (citable) accession number: Q9H444
Secondary accession number(s): E1P5N4, Q53ZD6

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 2002
Last sequence update:	March 1, 2001
Last modified:	May 1, 2013
This is version 100 of the entry and version 1 of the sequence. [Complete history]

Entry status

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.