Q9UQN3 (CHM2B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Charged multivesicular body protein 2b

Alternative name(s):
CHMP2.5
Chromatin-modifying protein 2b
Short name=CHMP2b
Vacuolar protein sorting-associated protein 2-2
Short name=Vps2-2
Short name=hVps2-2

Gene names

Name:	CHMP2B
ORF Names:	CGI-84

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	213 AA.
Sequence status	Complete.
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.
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 CHMP2A. Interacts with VPS4A. Interacts with VPS4B; the interaction is direct. Ref.6 Ref.16
Subcellular location	Cytoplasm › cytosol. Late endosome membrane; Peripheral membrane protein Probable Ref.8.
Tissue specificity	Widely expressed. Expressed in brain, heart, skeletal muscle, spleen, kidney, liver, small intestine, pancreas, lung, placenta and leukocytes. In brain, it is expressed in cerebellum, cerebral cortex, medulla, spinal chord, occipital lobe, frontal lobe, temporal lobe and putamen. Ref.8
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 By similarity.
Involvement in disease	Defects in CHMP2B are the cause of frontotemporal dementia, chromosome 3-linked (FTD3) [MIM:600795]. FTD3 is characterized by an onset of dementia in the late 50's initially characterized by behavioral and personality changes including apathy, restlessness, disinhibition and hyperorality, progressing to stereotyped behaviors, non-fluent aphasia, mutism and dystonia, with a marked lack of insight. The brains of individuals with FTD3 have no distinctive neuropathological features. They show global cortical and central atrophy, but no beta-amyloid deposits. Ref.8
Sequence similarities	Belongs to the SNF7 family.

Ontologies

Keywords
Biological process	Protein transport Transport
Cellular component	Cytoplasm Endosome Membrane
Disease	Disease mutation
Domain	Coiled coil
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cellular membrane organization Traceable author statement. Source: Reactome endosome 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 mitochondrion Inferred from direct assay. Source: HPA nucleus Inferred from direct assay. Source: HPA
Molecular function	protein domain specific binding Inferred from physical interaction Ref.16. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 213

213

Charged multivesicular body protein 2b

PRO_0000211469

Regions

Coiled coil

25 – 55

31

Potential

Motif

201 – 211

11

MIT-interacting motif

Amino acid modifications

Modified residue

199

1

Phosphoserine Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14

Natural variations

Natural variant

29

1

I → V. Ref.17

VAR_038373

Natural variant

148

1

D → Y in FTD3. Ref.8

VAR_023383

Natural variant

206

1

Q → H in amyotrophic lateral sclerosis; CHMP2B-related. Ref.17

VAR_038374

Experimental info

Sequence conflict

8

1

K → R Ref.2

Sequence conflict

8

1

K → R Ref.3

Sequence conflict

113

1

N → S in BAD96374. Ref.4

Sequence conflict

201

1

E → V Ref.2

Sequence conflict

201

1

E → V Ref.3

Secondary structure

1

.

.

.

213

Helix Strand Turn

Details...

Helix

201 – 210

10

Sequences

	Sequence		Length	Mass (Da)
	Q9UQN3 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: BA192A0EAC45C19B	FASTA	213	23,907
	10 20 30 40 50 60 MASLFKKKTV DDVIKEQNRE LRGTQRAIIR DRAALEKQEK QLELEIKKMA KIGNKEACKV 70 80 90 100 110 120 LAKQLVHLRK QKTRTFAVSS KVTSMSTQTK VMNSQMKMAG AMSTTAKTMQ AVNKKMDPQK 130 140 150 160 170 180 TLQTMQNFQK ENMKMEMTEE MINDTLDDIF DGSDDEEESQ DIVNQVLDEI GIEISGKMAK 190 200 210 APSAARSLPS ASTSKATISD EEIERQLKAL GVD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics." Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C. Genome Res. 10:703-713(2000) [PubMed: 10810093] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[2]	"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs." Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A. Genome Res. 11:422-435(2001) [PubMed: 11230166] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[3]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Cerebellum.
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Cervix.
[6]	"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: 14519844] [Abstract] Cited for: INTERACTION WITH CHMP2A.
[7]	Erratum Martin-Serrano J., Yarovoy A., Perez-Caballero D., Bieniasz P.D. Proc. Natl. Acad. Sci. U.S.A. 100:152845-152845(2003)
[8]	"Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia." Skibinski G., Parkinson N.J., Brown J.M., Chakrabarti L., Lloyd S.L., Hummerich H., Nielsen J.E., Hodges J.R., Spillantini M.G., Thusgaard T., Brandner S., Brun A., Rossor M.N., Gade A., Johannsen P., Soerensen S.A., Gydesen S., Fisher E.M.C., Collinge J. Nat. Genet. 37:806-808(2005) [PubMed: 16041373] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANT FTD3 TYR-148.
[9]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-199, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"Phosphoproteome analysis of the human mitotic spindle." Nousiainen M., Sillje H.H.W., Sauer G., Nigg E.A., Koerner R. Proc. Natl. Acad. Sci. U.S.A. 103:5391-5396(2006) [PubMed: 16565220] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-199, MASS SPECTROMETRY. Tissue: Cervix adenocarcinoma.
[11]	"Evaluation of the low-specificity protease elastase for large-scale phosphoproteome analysis." Wang B., Malik R., Nigg E.A., Korner R. Anal. Chem. 80:9526-9533(2008) [PubMed: 19007248] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-199, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-199, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-199, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[14]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-199, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[15]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]	"ESCRT-III recognition by VPS4 ATPases." Stuchell-Brereton M.D., Skalicky J.J., Kieffer C., Karren M.A., Ghaffarian S., Sundquist W.I. Nature 449:740-744(2007) [PubMed: 17928862] [Abstract] Cited for: STRUCTURE BY NMR OF 195-213 IN COMPLEX WITH VPS4B, INTERACTION WITH VPS4A.
[17]	"ALS phenotypes with mutations in CHMP2B (charged multivesicular body protein 2B)." Parkinson N., Ince P.G., Smith M.O., Highley R., Skibinski G., Andersen P.M., Morrison K.E., Pall H.S., Hardiman O., Collinge J., Shaw P.J., Fisher E.M. Neurology 67:1074-1077(2006) [PubMed: 16807408] [Abstract] Cited for: VARIANT AMYOTROPHIC LATERAL SCLEROSIS HIS-206, VARIANT VAL-29.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF151842 mRNA. Translation: AAD34079.1.
AL080122 mRNA. Translation: CAB45721.1.
CR533456 mRNA. Translation: CAG38487.1.
AK222654 mRNA. Translation: BAD96374.1.
BC001553 mRNA. Translation: AAH01553.1.

IPI

IPI00550181.

PIR

T12468.

RefSeq

NP_054762.2. NM_014043.3.

UniGene

Hs.476930.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2JQK	NMR	-	B	195-213	[»]

ProteinModelPortal

Q9UQN3.

SMR

Q9UQN3. Positions 4-182.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9UQN3. 4 interactions.

MINT

MINT-1430090.

STRING

Q9UQN3.

PTM databases

PhosphoSite

Q9UQN3.

Polymorphism databases

DMDM

73917746.

Proteomic databases

PRIDE

Q9UQN3.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000263780; ENSP00000263780; ENSG00000083937.

GeneID

25978.

KEGG

hsa:25978.

UCSC

uc003dqp.2. human.

Organism-specific databases

CTD

25978.

GeneCards

GC03P087360.

H-InvDB

HIX0003479.

HGNC

HGNC:24537. CHMP2B.

HPA

HPA035069.

MIM

600795. phenotype.
609512. gene.

neXtProt

NX_Q9UQN3.

Orphanet

282. Frontotemporal dementia.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG16139.

GeneTree

ENSGT00550000074737.

HOGENOM

HBG464741.

HOVERGEN

HBG102628.

InParanoid

Q9UQN3.

OMA

GNKEACK.

PhylomeDB

Q9UQN3.

Enzyme and pathway databases

Reactome

REACT_11123. Membrane Trafficking.

Gene expression databases

ArrayExpress

Q9UQN3.

Bgee

Q9UQN3.

CleanEx

HS_CHMP2B.

Genevestigator

Q9UQN3.

GermOnline

ENSG00000083937. Homo sapiens.

Family and domain databases

InterPro

IPR005024. Snf7.
[Graphical view]

KO

K12192.

Pfam

PF03357. Snf7. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

47630.

SOURCE

Search...

Entry information

Entry name

CHM2B_HUMAN

Accession

Primary (citable) accession number: Q9UQN3
Secondary accession number(s): Q53HC7, Q9Y4U6

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 30, 2005
Last sequence update:	May 1, 2000
Last modified:	December 14, 2011
This is version 92 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.