Full text data of CHMP4B
CHMP4B
(C20orf178, SHAX1)
[Confidence: low (only semi-automatic identification from reviews)]
Charged multivesicular body protein 4b (Chromatin-modifying protein 4b; CHMP4b; SNF7 homolog associated with Alix 1; SNF7-2; hSnf7-2; Vacuolar protein sorting-associated protein 32-2; Vps32-2; hVps32-2)
Charged multivesicular body protein 4b (Chromatin-modifying protein 4b; CHMP4b; SNF7 homolog associated with Alix 1; SNF7-2; hSnf7-2; Vacuolar protein sorting-associated protein 32-2; Vps32-2; hVps32-2)
UniProt
Q9H444
ID CHM4B_HUMAN Reviewed; 224 AA.
AC Q9H444; E1P5N4; Q53ZD6;
DT 01-NOV-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAR-2001, sequence version 1.
DT 22-JAN-2014, entry version 107.
DE RecName: Full=Charged multivesicular body protein 4b;
DE AltName: Full=Chromatin-modifying protein 4b;
DE Short=CHMP4b;
DE AltName: Full=SNF7 homolog associated with Alix 1;
DE AltName: Full=SNF7-2;
DE Short=hSnf7-2;
DE AltName: Full=Vacuolar protein sorting-associated protein 32-2;
DE Short=Vps32-2;
DE Short=hVps32-2;
GN Name=CHMP4B; Synonyms=C20orf178, SHAX1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND
RP INTERACTION WITH PDCD6IP.
RX PubMed=12860994; DOI=10.1074/jbc.M301604200;
RA Katoh K., Shibata H., Suzuki H., Narai A., Ishidoh K., Kominami E.,
RA Yoshimori T., Maki M.;
RT "The ALG-2-interacting protein Alix associates with CHMP4b, a human
RT homologue of yeast Snf7 that is involved in multivesicular body
RT sorting.";
RL J. Biol. Chem. 278:39104-39113(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH PDCD6IP.
RX PubMed=14583093; DOI=10.1042/BJ20031347;
RA Peck J.W., Bowden E.T., Burbelo P.D.;
RT "Structure and function of human Vps20 and Snf7 proteins.";
RL Biochem. J. 377:693-700(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M.,
RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J.,
RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M.,
RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R.,
RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M.,
RA Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H.,
RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S.,
RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E.,
RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A.,
RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M.,
RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A.,
RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S.,
RA Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Lung, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 2-28, CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT SER-2, AND MASS SPECTROMETRY.
RC TISSUE=Ovarian carcinoma;
RA Bienvenut W.V., Lempens A., Norman J.C.;
RL Submitted (OCT-2009) to UniProtKB.
RN [7]
RP PROTEIN SEQUENCE OF 18-28 AND 78-107, AND MASS SPECTROMETRY.
RC TISSUE=Fetal brain cortex;
RA Lubec G., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [8]
RP FUNCTION IN HIV-1 BUDDING, AND INTERACTION WITH PDCD6IP.
RX PubMed=14505569; DOI=10.1016/S0092-8674(03)00653-6;
RA Strack B., Calistri A., Craig S., Popova E., Goettlinger H.G.;
RT "AIP1/ALIX is a binding partner for HIV-1 p6 and EIAV p9 functioning
RT in virus budding.";
RL Cell 114:689-699(2003).
RN [9]
RP FUNCTION IN HIV-1 BUDDING, AND INTERACTION WITH CHMP6; CHMP4C;
RP PDCD6IP; VPS4A AND VPS4B.
RX PubMed=14505570; DOI=10.1016/S0092-8674(03)00714-1;
RA von Schwedler U.K., Stuchell M., Mueller B., Ward D.M., Chung H.-Y.,
RA Morita E., Wang H.E., Davis T., He G.P., Cimbora D.M., Scott A.,
RA Kraeusslich H.-G., Kaplan J., Morham S.G., Sundquist W.I.;
RT "The protein network of HIV budding.";
RL Cell 114:701-713(2003).
RN [10]
RP FUNCTION IN HIV-1 BUDDING, SELF-ASSOCIATION, AND INTERACTION WITH
RP CHMP2A; CHMP4A; CHMP4C; CHMP6; PDCD6IP AND VPS4A.
RX PubMed=14519844; DOI=10.1073/pnas.2133846100;
RA Martin-Serrano J., Yarovoy A., Perez-Caballero D., Bieniasz P.D.;
RT "Divergent retroviral late-budding domains recruit vacuolar protein
RT sorting factors by using alternative adaptor proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:12414-12419(2003).
RN [11]
RP ERRATUM.
RA Martin-Serrano J., Yarovoy A., Perez-Caballero D., Bieniasz P.D.;
RL Proc. Natl. Acad. Sci. U.S.A. 100:152845-152845(2003).
RN [12]
RP TISSUE SPECIFICITY, AND INTERACTION WITH PDCD6IP.
RX PubMed=14678797; DOI=10.1016/j.abb.2003.09.038;
RA Katoh K., Shibata H., Hatta K., Maki M.;
RT "CHMP4b is a major binding partner of the ALG-2-interacting protein
RT Alix among the three CHMP4 isoforms.";
RL Arch. Biochem. Biophys. 421:159-165(2004).
RN [13]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH CHMP6.
RX PubMed=15511219; DOI=10.1042/BJ20041227;
RA Yorikawa C., Shibata H., Waguri S., Hatta K., Horii M., Katoh K.,
RA Kobayashi T., Uchiyama Y., Maki M.;
RT "Human CHMP6, a myristoylated ESCRT-III protein, interacts directly
RT with an ESCRT-II component EAP20 and regulates endosomal cargo
RT sorting.";
RL Biochem. J. 387:17-26(2005).
RN [14]
RP INTERACTION WITH MISFOLDED CFTR.
RX PubMed=15007060; DOI=10.1083/jcb.200312018;
RA Sharma M., Pampinella F., Nemes C., Benharouga M., So J., Du K.,
RA Bache K.G., Papsin B., Zerangue N., Stenmark H., Lukacs G.L.;
RT "Misfolding diverts CFTR from recycling to degradation: quality
RT control at early endosomes.";
RL J. Cell Biol. 164:923-933(2004).
RN [15]
RP INTERACTION WITH CHMP7.
RX PubMed=16856878; DOI=10.1042/BJ20060897;
RA Horii M., Shibata H., Kobayashi R., Katoh K., Yorikawa C., Yasuda J.,
RA Maki M.;
RT "CHMP7, a novel ESCRT-III-related protein, associates with CHMP4b and
RT functions in the endosomal sorting pathway.";
RL Biochem. J. 400:23-32(2006).
RN [16]
RP AUTOINHIBITORY MECHANISM, AND INTRAMOLECULAR INTERACTION.
RX PubMed=17146056; DOI=10.1073/pnas.0603788103;
RA Zamborlini A., Usami Y., Radoshitzky S.R., Popova E., Palu G.,
RA Goettlinger H.;
RT "Release of autoinhibition converts ESCRT-III components into potent
RT inhibitors of HIV-1 budding.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:19140-19145(2006).
RN [17]
RP INTERACTION WITH PDCD6IP.
RX PubMed=17428861; DOI=10.1128/JVI.00314-07;
RA Usami Y., Popov S., Goettlinger H.G.;
RT "Potent rescue of human immunodeficiency virus type 1 late domain
RT mutants by ALIX/AIP1 depends on its CHMP4 binding site.";
RL J. Virol. 81:6614-6622(2007).
RN [18]
RP INTERACTION WITH BROX.
RX PubMed=18190528; DOI=10.1111/j.1742-4658.2007.06230.x;
RA Ichioka F., Kobayashi R., Katoh K., Shibata H., Maki M.;
RT "Brox, a novel farnesylated Bro1 domain-containing protein that
RT associates with charged multivesicular body protein 4 (CHMP4).";
RL FEBS J. 275:682-692(2008).
RN [19]
RP FUNCTION, SELF-ASSOCIATION, AND STRUCTURE BY ELECTRON CRYOMICROSCOPY.
RX PubMed=18209100; DOI=10.1083/jcb.200707031;
RA Hanson P.I., Roth R., Lin Y., Heuser J.E.;
RT "Plasma membrane deformation by circular arrays of ESCRT-III protein
RT filaments.";
RL J. Cell Biol. 180:389-402(2008).
RN [20]
RP INTERACTION WITH PTPN23.
RX PubMed=18434552; DOI=10.1073/pnas.0707601105;
RA Doyotte A., Mironov A., McKenzie E., Woodman P.;
RT "The Bro1-related protein HD-PTP/PTPN23 is required for endosomal
RT cargo sorting and multivesicular body morphogenesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:6308-6313(2008).
RN [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2; LYS-6 AND LYS-114, AND
RP MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-184 AND SER-223, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [24]
RP ISGYLATION, AND INTERACTION WITH VPS4A.
RX PubMed=21543490; DOI=10.1128/JVI.02610-10;
RA Kuang Z., Seo E.J., Leis J.;
RT "Mechanism of inhibition of retrovirus release from cells by
RT interferon-induced gene ISG15.";
RL J. Virol. 85:7153-7161(2011).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-223, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [26]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 207-224 IN COMPLEX WITH
RP PDCD6IP.
RX PubMed=18511562; DOI=10.1073/pnas.0801567105;
RA McCullough J., Fisher R.D., Whitby F.G., Sundquist W.I., Hill C.P.;
RT "ALIX-CHMP4 interactions in the human ESCRT pathway.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:7687-7691(2008).
RN [28]
RP VARIANTS CTRCT31 VAL-129 AND LYS-161.
RX PubMed=17701905; DOI=10.1086/519980;
RA Shiels A., Bennett T.M., Knopf H.L.S., Yamada K., Yoshiura K.,
RA Niikawa N., Shim S., Hanson P.I.;
RT "CHMP4B, a novel gene for autosomal dominant cataracts linked to
RT chromosome 20q.";
RL Am. J. Hum. Genet. 81:596-606(2007).
CC -!- FUNCTION: Probable core component of the endosomal sorting
CC required for transport complex III (ESCRT-III) which is involved
CC in multivesicular bodies (MVBs) formation and sorting of endosomal
CC cargo proteins into MVBs. MVBs contain intraluminal vesicles
CC (ILVs) that are generated by invagination and scission from the
CC limiting membrane of the endosome and mostly are delivered to
CC lysosomes enabling degradation of membrane proteins, such as
CC stimulated growth factor receptors, lysosomal enzymes and lipids.
CC The MVB pathway appears to require the sequential function of
CC ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly
CC dissociate from the invaginating membrane before the ILV is
CC released. The ESCRT machinery also functions in topologically
CC equivalent membrane fission events, such as the terminal stages of
CC cytokinesis and the budding of enveloped viruses (HIV-1 and other
CC lentiviruses). ESCRT-III proteins are believed to mediate the
CC necessary vesicle extrusion and/or membrane fission activities,
CC possibly in conjunction with the AAA ATPase VPS4. When
CC overexpressed, membrane-assembled circular arrays of CHMP4B
CC filaments can promote or stabilize negative curvature and outward
CC budding. Via its interaction with PDCD6IP involved in HIV-1 p6-
CC and p9-dependent virus release.
CC -!- SUBUNIT: Probable core component of the endosomal sorting required
CC for transport complex III (ESCRT-III). ESCRT-III components are
CC thought to multimerize to form a flat lattice on the perimeter
CC membrane of the endosome. Several assembly forms of ESCRT-III may
CC exist that interact and act sequentally. Interacts with CHMP6 and
CC CHMP4C. Interacts with PDCD6IP; the interaction is direct.
CC Interacts with VPS4A; the interaction is direct. Interacts with
CC VPS4B; the interaction is direct. Interacts with CHMP7. Interacts
CC with CFTR; the interaction requires misfolded CFTR. Interacts with
CC PTPN23.
CC -!- INTERACTION:
CC Q9H3S7:PTPN23; NbExp=2; IntAct=EBI-749627, EBI-724478;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol. Late endosome membrane;
CC Peripheral membrane protein (Probable).
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed at higher level in
CC heart and skeletal muscle. Also expressed in brain, colon, thymus,
CC spleen, kidney, liver, small intestine, placenta, lung and
CC peripheral blood lymphocytes.
CC -!- DOMAIN: The acidic C-terminus and the basic N-termminus are
CC thought to render the protein in a closed, soluble and inactive
CC conformation through an autoinhibitory intramolecular interaction.
CC The open and active conformation, which enables membrane binding
CC and oligomerization, is achieved by interaction with other
CC cellular binding partners, probably including other ESCRT
CC components.
CC -!- PTM: ISGylated. Isgylation weakens its interaction with VPS4A.
CC -!- DISEASE: Cataract 31, multiple types (CTRCT31) [MIM:605387]: An
CC opacification of the crystalline lens of the eye that frequently
CC results in visual impairment or blindness. Opacities vary in
CC morphology, are often confined to a portion of the lens, and may
CC be static or progressive. In general, the more posteriorly located
CC and dense an opacity, the greater the impact on visual function.
CC CTRCT31 includes posterior polar, progressive posterior
CC subcapsular, nuclear, and anterior subcapsular cataracts. Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- MISCELLANEOUS: Its overexpression strongly inhibits HIV-1 release.
CC -!- SIMILARITY: Belongs to the SNF7 family.
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DR EMBL; AB100261; BAC79375.1; -; mRNA.
DR EMBL; AY329085; AAQ91194.1; -; mRNA.
DR EMBL; AL050349; CAC14088.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76293.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76294.1; -; Genomic_DNA.
DR EMBL; BC033859; AAH33859.1; -; mRNA.
DR RefSeq; NP_789782.1; NM_176812.4.
DR UniGene; Hs.472471; -.
DR PDB; 3C3Q; X-ray; 2.10 A; B=207-224.
DR PDB; 3UM3; X-ray; 3.80 A; B=121-224.
DR PDB; 4ABM; X-ray; 1.80 A; A/B/C/D=23-97.
DR PDBsum; 3C3Q; -.
DR PDBsum; 3UM3; -.
DR PDBsum; 4ABM; -.
DR ProteinModelPortal; Q9H444; -.
DR SMR; Q9H444; 23-97.
DR DIP; DIP-29924N; -.
DR IntAct; Q9H444; 9.
DR MINT; MINT-5000054; -.
DR STRING; 9606.ENSP00000217402; -.
DR PhosphoSite; Q9H444; -.
DR DMDM; 24636296; -.
DR PeptideAtlas; Q9H444; -.
DR PRIDE; Q9H444; -.
DR Ensembl; ENST00000217402; ENSP00000217402; ENSG00000101421.
DR GeneID; 128866; -.
DR KEGG; hsa:128866; -.
DR UCSC; uc002xaa.3; human.
DR CTD; 128866; -.
DR GeneCards; GC20P032399; -.
DR HGNC; HGNC:16171; CHMP4B.
DR HPA; HPA041401; -.
DR MIM; 605387; phenotype.
DR MIM; 610897; gene.
DR neXtProt; NX_Q9H444; -.
DR Orphanet; 98993; Posterior polar cataract.
DR PharmGKB; PA25721; -.
DR HOGENOM; HOG000209960; -.
DR HOVERGEN; HBG050928; -.
DR InParanoid; Q9H444; -.
DR KO; K12194; -.
DR OMA; MKELETW; -.
DR OrthoDB; EOG7PGDSH; -.
DR PhylomeDB; Q9H444; -.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_116125; Disease.
DR ChiTaRS; CHMP4B; human.
DR EvolutionaryTrace; Q9H444; -.
DR GeneWiki; CHMP4B; -.
DR GenomeRNAi; 128866; -.
DR NextBio; 82502; -.
DR PRO; PR:Q9H444; -.
DR Bgee; Q9H444; -.
DR CleanEx; HS_CHMP4B; -.
DR Genevestigator; Q9H444; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030496; C:midbody; IDA:FlyBase.
DR GO; GO:0016197; P:endosomal transport; TAS:Reactome.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0016032; P:viral process; TAS:Reactome.
DR InterPro; IPR005024; Snf7.
DR Pfam; PF03357; Snf7; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cataract; Coiled coil; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Disease mutation; Endosome;
KW Membrane; Phosphoprotein; Protein transport; Reference proteome;
KW Transport; Ubl conjugation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 224 Charged multivesicular body protein 4b.
FT /FTId=PRO_0000211489.
FT COILED 23 183 Potential.
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 6 6 N6-acetyllysine.
FT MOD_RES 114 114 N6-acetyllysine.
FT MOD_RES 184 184 Phosphoserine.
FT MOD_RES 223 223 Phosphoserine.
FT VARIANT 129 129 D -> V (in CTRCT31).
FT /FTId=VAR_037579.
FT VARIANT 161 161 E -> K (in CTRCT31).
FT /FTId=VAR_037580.
FT HELIX 23 57
FT HELIX 62 96
FT HELIX 209 212
FT HELIX 215 222
SQ SEQUENCE 224 AA; 24950 MW; DB1D79DD3803CB2F CRC64;
MSVFGKLFGA GGGKAGKGGP TPQEAIQRLR DTEEMLSKKQ EFLEKKIEQE LTAAKKHGTK
NKRAALQALK RKKRYEKQLA QIDGTLSTIE FQREALENAN TNTEVLKNMG YAAKAMKAAH
DNMDIDKVDE LMQDIADQQE LAEEISTAIS KPVGFGEEFD EDELMAELEE LEQEELDKNL
LEISGPETVP LPNVPSIALP SKPAKKKEEE DDDMKELENW AGSM
//
ID CHM4B_HUMAN Reviewed; 224 AA.
AC Q9H444; E1P5N4; Q53ZD6;
DT 01-NOV-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAR-2001, sequence version 1.
DT 22-JAN-2014, entry version 107.
DE RecName: Full=Charged multivesicular body protein 4b;
DE AltName: Full=Chromatin-modifying protein 4b;
DE Short=CHMP4b;
DE AltName: Full=SNF7 homolog associated with Alix 1;
DE AltName: Full=SNF7-2;
DE Short=hSnf7-2;
DE AltName: Full=Vacuolar protein sorting-associated protein 32-2;
DE Short=Vps32-2;
DE Short=hVps32-2;
GN Name=CHMP4B; Synonyms=C20orf178, SHAX1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND
RP INTERACTION WITH PDCD6IP.
RX PubMed=12860994; DOI=10.1074/jbc.M301604200;
RA Katoh K., Shibata H., Suzuki H., Narai A., Ishidoh K., Kominami E.,
RA Yoshimori T., Maki M.;
RT "The ALG-2-interacting protein Alix associates with CHMP4b, a human
RT homologue of yeast Snf7 that is involved in multivesicular body
RT sorting.";
RL J. Biol. Chem. 278:39104-39113(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH PDCD6IP.
RX PubMed=14583093; DOI=10.1042/BJ20031347;
RA Peck J.W., Bowden E.T., Burbelo P.D.;
RT "Structure and function of human Vps20 and Snf7 proteins.";
RL Biochem. J. 377:693-700(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M.,
RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J.,
RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M.,
RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R.,
RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M.,
RA Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H.,
RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S.,
RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E.,
RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A.,
RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M.,
RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A.,
RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S.,
RA Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Lung, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 2-28, CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT SER-2, AND MASS SPECTROMETRY.
RC TISSUE=Ovarian carcinoma;
RA Bienvenut W.V., Lempens A., Norman J.C.;
RL Submitted (OCT-2009) to UniProtKB.
RN [7]
RP PROTEIN SEQUENCE OF 18-28 AND 78-107, AND MASS SPECTROMETRY.
RC TISSUE=Fetal brain cortex;
RA Lubec G., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [8]
RP FUNCTION IN HIV-1 BUDDING, AND INTERACTION WITH PDCD6IP.
RX PubMed=14505569; DOI=10.1016/S0092-8674(03)00653-6;
RA Strack B., Calistri A., Craig S., Popova E., Goettlinger H.G.;
RT "AIP1/ALIX is a binding partner for HIV-1 p6 and EIAV p9 functioning
RT in virus budding.";
RL Cell 114:689-699(2003).
RN [9]
RP FUNCTION IN HIV-1 BUDDING, AND INTERACTION WITH CHMP6; CHMP4C;
RP PDCD6IP; VPS4A AND VPS4B.
RX PubMed=14505570; DOI=10.1016/S0092-8674(03)00714-1;
RA von Schwedler U.K., Stuchell M., Mueller B., Ward D.M., Chung H.-Y.,
RA Morita E., Wang H.E., Davis T., He G.P., Cimbora D.M., Scott A.,
RA Kraeusslich H.-G., Kaplan J., Morham S.G., Sundquist W.I.;
RT "The protein network of HIV budding.";
RL Cell 114:701-713(2003).
RN [10]
RP FUNCTION IN HIV-1 BUDDING, SELF-ASSOCIATION, AND INTERACTION WITH
RP CHMP2A; CHMP4A; CHMP4C; CHMP6; PDCD6IP AND VPS4A.
RX PubMed=14519844; DOI=10.1073/pnas.2133846100;
RA Martin-Serrano J., Yarovoy A., Perez-Caballero D., Bieniasz P.D.;
RT "Divergent retroviral late-budding domains recruit vacuolar protein
RT sorting factors by using alternative adaptor proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:12414-12419(2003).
RN [11]
RP ERRATUM.
RA Martin-Serrano J., Yarovoy A., Perez-Caballero D., Bieniasz P.D.;
RL Proc. Natl. Acad. Sci. U.S.A. 100:152845-152845(2003).
RN [12]
RP TISSUE SPECIFICITY, AND INTERACTION WITH PDCD6IP.
RX PubMed=14678797; DOI=10.1016/j.abb.2003.09.038;
RA Katoh K., Shibata H., Hatta K., Maki M.;
RT "CHMP4b is a major binding partner of the ALG-2-interacting protein
RT Alix among the three CHMP4 isoforms.";
RL Arch. Biochem. Biophys. 421:159-165(2004).
RN [13]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH CHMP6.
RX PubMed=15511219; DOI=10.1042/BJ20041227;
RA Yorikawa C., Shibata H., Waguri S., Hatta K., Horii M., Katoh K.,
RA Kobayashi T., Uchiyama Y., Maki M.;
RT "Human CHMP6, a myristoylated ESCRT-III protein, interacts directly
RT with an ESCRT-II component EAP20 and regulates endosomal cargo
RT sorting.";
RL Biochem. J. 387:17-26(2005).
RN [14]
RP INTERACTION WITH MISFOLDED CFTR.
RX PubMed=15007060; DOI=10.1083/jcb.200312018;
RA Sharma M., Pampinella F., Nemes C., Benharouga M., So J., Du K.,
RA Bache K.G., Papsin B., Zerangue N., Stenmark H., Lukacs G.L.;
RT "Misfolding diverts CFTR from recycling to degradation: quality
RT control at early endosomes.";
RL J. Cell Biol. 164:923-933(2004).
RN [15]
RP INTERACTION WITH CHMP7.
RX PubMed=16856878; DOI=10.1042/BJ20060897;
RA Horii M., Shibata H., Kobayashi R., Katoh K., Yorikawa C., Yasuda J.,
RA Maki M.;
RT "CHMP7, a novel ESCRT-III-related protein, associates with CHMP4b and
RT functions in the endosomal sorting pathway.";
RL Biochem. J. 400:23-32(2006).
RN [16]
RP AUTOINHIBITORY MECHANISM, AND INTRAMOLECULAR INTERACTION.
RX PubMed=17146056; DOI=10.1073/pnas.0603788103;
RA Zamborlini A., Usami Y., Radoshitzky S.R., Popova E., Palu G.,
RA Goettlinger H.;
RT "Release of autoinhibition converts ESCRT-III components into potent
RT inhibitors of HIV-1 budding.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:19140-19145(2006).
RN [17]
RP INTERACTION WITH PDCD6IP.
RX PubMed=17428861; DOI=10.1128/JVI.00314-07;
RA Usami Y., Popov S., Goettlinger H.G.;
RT "Potent rescue of human immunodeficiency virus type 1 late domain
RT mutants by ALIX/AIP1 depends on its CHMP4 binding site.";
RL J. Virol. 81:6614-6622(2007).
RN [18]
RP INTERACTION WITH BROX.
RX PubMed=18190528; DOI=10.1111/j.1742-4658.2007.06230.x;
RA Ichioka F., Kobayashi R., Katoh K., Shibata H., Maki M.;
RT "Brox, a novel farnesylated Bro1 domain-containing protein that
RT associates with charged multivesicular body protein 4 (CHMP4).";
RL FEBS J. 275:682-692(2008).
RN [19]
RP FUNCTION, SELF-ASSOCIATION, AND STRUCTURE BY ELECTRON CRYOMICROSCOPY.
RX PubMed=18209100; DOI=10.1083/jcb.200707031;
RA Hanson P.I., Roth R., Lin Y., Heuser J.E.;
RT "Plasma membrane deformation by circular arrays of ESCRT-III protein
RT filaments.";
RL J. Cell Biol. 180:389-402(2008).
RN [20]
RP INTERACTION WITH PTPN23.
RX PubMed=18434552; DOI=10.1073/pnas.0707601105;
RA Doyotte A., Mironov A., McKenzie E., Woodman P.;
RT "The Bro1-related protein HD-PTP/PTPN23 is required for endosomal
RT cargo sorting and multivesicular body morphogenesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:6308-6313(2008).
RN [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2; LYS-6 AND LYS-114, AND
RP MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-184 AND SER-223, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [24]
RP ISGYLATION, AND INTERACTION WITH VPS4A.
RX PubMed=21543490; DOI=10.1128/JVI.02610-10;
RA Kuang Z., Seo E.J., Leis J.;
RT "Mechanism of inhibition of retrovirus release from cells by
RT interferon-induced gene ISG15.";
RL J. Virol. 85:7153-7161(2011).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-223, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [26]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 207-224 IN COMPLEX WITH
RP PDCD6IP.
RX PubMed=18511562; DOI=10.1073/pnas.0801567105;
RA McCullough J., Fisher R.D., Whitby F.G., Sundquist W.I., Hill C.P.;
RT "ALIX-CHMP4 interactions in the human ESCRT pathway.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:7687-7691(2008).
RN [28]
RP VARIANTS CTRCT31 VAL-129 AND LYS-161.
RX PubMed=17701905; DOI=10.1086/519980;
RA Shiels A., Bennett T.M., Knopf H.L.S., Yamada K., Yoshiura K.,
RA Niikawa N., Shim S., Hanson P.I.;
RT "CHMP4B, a novel gene for autosomal dominant cataracts linked to
RT chromosome 20q.";
RL Am. J. Hum. Genet. 81:596-606(2007).
CC -!- FUNCTION: Probable core component of the endosomal sorting
CC required for transport complex III (ESCRT-III) which is involved
CC in multivesicular bodies (MVBs) formation and sorting of endosomal
CC cargo proteins into MVBs. MVBs contain intraluminal vesicles
CC (ILVs) that are generated by invagination and scission from the
CC limiting membrane of the endosome and mostly are delivered to
CC lysosomes enabling degradation of membrane proteins, such as
CC stimulated growth factor receptors, lysosomal enzymes and lipids.
CC The MVB pathway appears to require the sequential function of
CC ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly
CC dissociate from the invaginating membrane before the ILV is
CC released. The ESCRT machinery also functions in topologically
CC equivalent membrane fission events, such as the terminal stages of
CC cytokinesis and the budding of enveloped viruses (HIV-1 and other
CC lentiviruses). ESCRT-III proteins are believed to mediate the
CC necessary vesicle extrusion and/or membrane fission activities,
CC possibly in conjunction with the AAA ATPase VPS4. When
CC overexpressed, membrane-assembled circular arrays of CHMP4B
CC filaments can promote or stabilize negative curvature and outward
CC budding. Via its interaction with PDCD6IP involved in HIV-1 p6-
CC and p9-dependent virus release.
CC -!- SUBUNIT: Probable core component of the endosomal sorting required
CC for transport complex III (ESCRT-III). ESCRT-III components are
CC thought to multimerize to form a flat lattice on the perimeter
CC membrane of the endosome. Several assembly forms of ESCRT-III may
CC exist that interact and act sequentally. Interacts with CHMP6 and
CC CHMP4C. Interacts with PDCD6IP; the interaction is direct.
CC Interacts with VPS4A; the interaction is direct. Interacts with
CC VPS4B; the interaction is direct. Interacts with CHMP7. Interacts
CC with CFTR; the interaction requires misfolded CFTR. Interacts with
CC PTPN23.
CC -!- INTERACTION:
CC Q9H3S7:PTPN23; NbExp=2; IntAct=EBI-749627, EBI-724478;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol. Late endosome membrane;
CC Peripheral membrane protein (Probable).
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed at higher level in
CC heart and skeletal muscle. Also expressed in brain, colon, thymus,
CC spleen, kidney, liver, small intestine, placenta, lung and
CC peripheral blood lymphocytes.
CC -!- DOMAIN: The acidic C-terminus and the basic N-termminus are
CC thought to render the protein in a closed, soluble and inactive
CC conformation through an autoinhibitory intramolecular interaction.
CC The open and active conformation, which enables membrane binding
CC and oligomerization, is achieved by interaction with other
CC cellular binding partners, probably including other ESCRT
CC components.
CC -!- PTM: ISGylated. Isgylation weakens its interaction with VPS4A.
CC -!- DISEASE: Cataract 31, multiple types (CTRCT31) [MIM:605387]: An
CC opacification of the crystalline lens of the eye that frequently
CC results in visual impairment or blindness. Opacities vary in
CC morphology, are often confined to a portion of the lens, and may
CC be static or progressive. In general, the more posteriorly located
CC and dense an opacity, the greater the impact on visual function.
CC CTRCT31 includes posterior polar, progressive posterior
CC subcapsular, nuclear, and anterior subcapsular cataracts. Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- MISCELLANEOUS: Its overexpression strongly inhibits HIV-1 release.
CC -!- SIMILARITY: Belongs to the SNF7 family.
CC -----------------------------------------------------------------------
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DR EMBL; AB100261; BAC79375.1; -; mRNA.
DR EMBL; AY329085; AAQ91194.1; -; mRNA.
DR EMBL; AL050349; CAC14088.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76293.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76294.1; -; Genomic_DNA.
DR EMBL; BC033859; AAH33859.1; -; mRNA.
DR RefSeq; NP_789782.1; NM_176812.4.
DR UniGene; Hs.472471; -.
DR PDB; 3C3Q; X-ray; 2.10 A; B=207-224.
DR PDB; 3UM3; X-ray; 3.80 A; B=121-224.
DR PDB; 4ABM; X-ray; 1.80 A; A/B/C/D=23-97.
DR PDBsum; 3C3Q; -.
DR PDBsum; 3UM3; -.
DR PDBsum; 4ABM; -.
DR ProteinModelPortal; Q9H444; -.
DR SMR; Q9H444; 23-97.
DR DIP; DIP-29924N; -.
DR IntAct; Q9H444; 9.
DR MINT; MINT-5000054; -.
DR STRING; 9606.ENSP00000217402; -.
DR PhosphoSite; Q9H444; -.
DR DMDM; 24636296; -.
DR PeptideAtlas; Q9H444; -.
DR PRIDE; Q9H444; -.
DR Ensembl; ENST00000217402; ENSP00000217402; ENSG00000101421.
DR GeneID; 128866; -.
DR KEGG; hsa:128866; -.
DR UCSC; uc002xaa.3; human.
DR CTD; 128866; -.
DR GeneCards; GC20P032399; -.
DR HGNC; HGNC:16171; CHMP4B.
DR HPA; HPA041401; -.
DR MIM; 605387; phenotype.
DR MIM; 610897; gene.
DR neXtProt; NX_Q9H444; -.
DR Orphanet; 98993; Posterior polar cataract.
DR PharmGKB; PA25721; -.
DR HOGENOM; HOG000209960; -.
DR HOVERGEN; HBG050928; -.
DR InParanoid; Q9H444; -.
DR KO; K12194; -.
DR OMA; MKELETW; -.
DR OrthoDB; EOG7PGDSH; -.
DR PhylomeDB; Q9H444; -.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_116125; Disease.
DR ChiTaRS; CHMP4B; human.
DR EvolutionaryTrace; Q9H444; -.
DR GeneWiki; CHMP4B; -.
DR GenomeRNAi; 128866; -.
DR NextBio; 82502; -.
DR PRO; PR:Q9H444; -.
DR Bgee; Q9H444; -.
DR CleanEx; HS_CHMP4B; -.
DR Genevestigator; Q9H444; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030496; C:midbody; IDA:FlyBase.
DR GO; GO:0016197; P:endosomal transport; TAS:Reactome.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0016032; P:viral process; TAS:Reactome.
DR InterPro; IPR005024; Snf7.
DR Pfam; PF03357; Snf7; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cataract; Coiled coil; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Disease mutation; Endosome;
KW Membrane; Phosphoprotein; Protein transport; Reference proteome;
KW Transport; Ubl conjugation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 224 Charged multivesicular body protein 4b.
FT /FTId=PRO_0000211489.
FT COILED 23 183 Potential.
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 6 6 N6-acetyllysine.
FT MOD_RES 114 114 N6-acetyllysine.
FT MOD_RES 184 184 Phosphoserine.
FT MOD_RES 223 223 Phosphoserine.
FT VARIANT 129 129 D -> V (in CTRCT31).
FT /FTId=VAR_037579.
FT VARIANT 161 161 E -> K (in CTRCT31).
FT /FTId=VAR_037580.
FT HELIX 23 57
FT HELIX 62 96
FT HELIX 209 212
FT HELIX 215 222
SQ SEQUENCE 224 AA; 24950 MW; DB1D79DD3803CB2F CRC64;
MSVFGKLFGA GGGKAGKGGP TPQEAIQRLR DTEEMLSKKQ EFLEKKIEQE LTAAKKHGTK
NKRAALQALK RKKRYEKQLA QIDGTLSTIE FQREALENAN TNTEVLKNMG YAAKAMKAAH
DNMDIDKVDE LMQDIADQQE LAEEISTAIS KPVGFGEEFD EDELMAELEE LEQEELDKNL
LEISGPETVP LPNVPSIALP SKPAKKKEEE DDDMKELENW AGSM
//
MIM
605387
*RECORD*
*FIELD* NO
605387
*FIELD* TI
#605387 CATARACT 31, MULTIPLE TYPES; CTRCT31
;;CATARACT, POSTERIOR POLAR, 3; CTPP3; CPP3
read more*FIELD* TX
A number sign (#) is used with this entry because of evidence that
multiple types of cataract are caused by heterozygous mutation in the
CHMP4B gene (610897) on chromosome 20q11.
DESCRIPTION
Mutations in the CHMP4B gene have been found to cause multiple types of
cataract, which have been described as posterior polar, progressive
posterior subcapsular, nuclear, and anterior subcapsular.
The preferred title/symbol of this entry was formerly 'Cataract,
Posterior Polar, 3; CTPP3.'
CLINICAL FEATURES
Yamada et al. (2000) described a Japanese family in which 10 members in
4 generations were affected with autosomal dominant posterior polar
cataract. The cataract was characterized by progressive, disc-shaped,
posterior subcapsular opacity.
Shiels et al. (2007) reported 15 affected individuals in a large
6-generation Caucasian family with progressive childhood posterior
subcapsular cataracts. Cataracts progressed with age to affect the
nucleus and anterior subcapsular regions of the lens. Age at diagnosis
varied from 4 to 20 years.
MAPPING
By linkage analysis of the Japanese family with cataract described by
Yamada et al. (2000), Yamada et al. (2000) assigned the locus, which
they designated CPP3, to chromosome 20p12-q12.
MOLECULAR GENETICS
Since the BFSP1 gene (603307), which encodes the lens-specific beaded
filament structural protein-1, maps to the same region, Yamada et al.
(2000) performed sequence analysis on its entire coding region, but
found no base substitutions or deletions in the CPP3 patients.
Shiels et al. (2007) performed linkage analysis in a large 6-generation
Caucasian family with autosomal dominant progressive childhood posterior
subcapsular cataract and, after excluding known autosomal dominant
cataract loci, found significant linkage on chromosome 20q with a
maximum 2-point lod score of 5.50 at D20S847. Analysis of recombinant
events in affected individuals followed by genotyping with biallelic SNP
markers narrowed the region of interest to a 0.9-Mb interval containing
approximately 80 genes, none of which were obvious functional candidates
for cataracts. Sequence analysis of positional candidate genes revealed
a heterozygous mutation (D129V; 610897.0001) in the CHMP4B gene that
cosegregated with disease and was not found in 384 control chromosomes.
The mutation was not found in unaffected family members except for a
17-year-old male who was believed to be either nonpenetrant or
presymptomatic. Shiels et al. (2007) also identified a heterozygous
mutation (E161K; 610897.0002) in the CHMP4B gene in affected individuals
of the Japanese family previously reported by Yamada et al. (2000) and
Yamada et al. (2000).
*FIELD* RF
1. Shiels, A.; Bennett, T. M.; Knopf, H. L. S.; Yamada, K.; Yoshiura,
K.; Niikawa, N.; Shim, S.; Hanson, P. I.: CHMP4B, a novel gene for
autosomal dominant cataracts linked to chromosome 20q. Am. J. Hum.
Genet. 81: 596-606, 2007.
2. Yamada, K.; Tomita, H.; Kanazawa, S.; Mera, A.; Amemiya, T.; Niikawa,
N.: Genetically distinct autosomal dominant posterior polar cataract
in a four-generation Japanese family. Am. J. Ophthal. 129: 159-165,
2000.
3. Yamada, K.; Tomita, H.; Yoshiura, K.; Kondo, S.; Wakui, K.; Fukushima,
Y.; Ikegawa, S.; Nakamura, Y.; Amemiya, T.; Niikawa, N.: An autosomal
dominant posterior polar cataract locus maps to human chromosome 20p12-q12. Europ.
J. Hum. Genet. 8: 535-539, 2000.
*FIELD* CN
Marla J. F. O'Neill - updated: 10/23/2007
*FIELD* CD
Victor A. McKusick: 11/2/2000
*FIELD* ED
carol: 07/22/2013
carol: 5/7/2013
wwang: 10/24/2007
terry: 10/23/2007
wwang: 7/30/2007
carol: 12/15/2006
wwang: 12/8/2006
carol: 11/30/2006
mgross: 3/19/2004
carol: 11/2/2000
*RECORD*
*FIELD* NO
605387
*FIELD* TI
#605387 CATARACT 31, MULTIPLE TYPES; CTRCT31
;;CATARACT, POSTERIOR POLAR, 3; CTPP3; CPP3
read more*FIELD* TX
A number sign (#) is used with this entry because of evidence that
multiple types of cataract are caused by heterozygous mutation in the
CHMP4B gene (610897) on chromosome 20q11.
DESCRIPTION
Mutations in the CHMP4B gene have been found to cause multiple types of
cataract, which have been described as posterior polar, progressive
posterior subcapsular, nuclear, and anterior subcapsular.
The preferred title/symbol of this entry was formerly 'Cataract,
Posterior Polar, 3; CTPP3.'
CLINICAL FEATURES
Yamada et al. (2000) described a Japanese family in which 10 members in
4 generations were affected with autosomal dominant posterior polar
cataract. The cataract was characterized by progressive, disc-shaped,
posterior subcapsular opacity.
Shiels et al. (2007) reported 15 affected individuals in a large
6-generation Caucasian family with progressive childhood posterior
subcapsular cataracts. Cataracts progressed with age to affect the
nucleus and anterior subcapsular regions of the lens. Age at diagnosis
varied from 4 to 20 years.
MAPPING
By linkage analysis of the Japanese family with cataract described by
Yamada et al. (2000), Yamada et al. (2000) assigned the locus, which
they designated CPP3, to chromosome 20p12-q12.
MOLECULAR GENETICS
Since the BFSP1 gene (603307), which encodes the lens-specific beaded
filament structural protein-1, maps to the same region, Yamada et al.
(2000) performed sequence analysis on its entire coding region, but
found no base substitutions or deletions in the CPP3 patients.
Shiels et al. (2007) performed linkage analysis in a large 6-generation
Caucasian family with autosomal dominant progressive childhood posterior
subcapsular cataract and, after excluding known autosomal dominant
cataract loci, found significant linkage on chromosome 20q with a
maximum 2-point lod score of 5.50 at D20S847. Analysis of recombinant
events in affected individuals followed by genotyping with biallelic SNP
markers narrowed the region of interest to a 0.9-Mb interval containing
approximately 80 genes, none of which were obvious functional candidates
for cataracts. Sequence analysis of positional candidate genes revealed
a heterozygous mutation (D129V; 610897.0001) in the CHMP4B gene that
cosegregated with disease and was not found in 384 control chromosomes.
The mutation was not found in unaffected family members except for a
17-year-old male who was believed to be either nonpenetrant or
presymptomatic. Shiels et al. (2007) also identified a heterozygous
mutation (E161K; 610897.0002) in the CHMP4B gene in affected individuals
of the Japanese family previously reported by Yamada et al. (2000) and
Yamada et al. (2000).
*FIELD* RF
1. Shiels, A.; Bennett, T. M.; Knopf, H. L. S.; Yamada, K.; Yoshiura,
K.; Niikawa, N.; Shim, S.; Hanson, P. I.: CHMP4B, a novel gene for
autosomal dominant cataracts linked to chromosome 20q. Am. J. Hum.
Genet. 81: 596-606, 2007.
2. Yamada, K.; Tomita, H.; Kanazawa, S.; Mera, A.; Amemiya, T.; Niikawa,
N.: Genetically distinct autosomal dominant posterior polar cataract
in a four-generation Japanese family. Am. J. Ophthal. 129: 159-165,
2000.
3. Yamada, K.; Tomita, H.; Yoshiura, K.; Kondo, S.; Wakui, K.; Fukushima,
Y.; Ikegawa, S.; Nakamura, Y.; Amemiya, T.; Niikawa, N.: An autosomal
dominant posterior polar cataract locus maps to human chromosome 20p12-q12. Europ.
J. Hum. Genet. 8: 535-539, 2000.
*FIELD* CN
Marla J. F. O'Neill - updated: 10/23/2007
*FIELD* CD
Victor A. McKusick: 11/2/2000
*FIELD* ED
carol: 07/22/2013
carol: 5/7/2013
wwang: 10/24/2007
terry: 10/23/2007
wwang: 7/30/2007
carol: 12/15/2006
wwang: 12/8/2006
carol: 11/30/2006
mgross: 3/19/2004
carol: 11/2/2000
MIM
610897
*RECORD*
*FIELD* NO
610897
*FIELD* TI
*610897 CHMP FAMILY, MEMBER 4B; CHMP4B
;;CHROMATIN-MODIFYING PROTEIN 4B;;
CHARGED MULTIVESICULAR BODY PROTEIN 4B;;
read moreSNF7, YEAST, HOMOLOG OF, 2;;
SNF7-2
*FIELD* TX
DESCRIPTION
CHMP4B belongs to the chromatin-modifying protein/charged multivesicular
body protein (CHMP) family. These proteins are components of ESCRT-III
(endosomal sorting complex required for transport III), a complex
involved in degradation of surface receptor proteins and formation of
endocytic multivesicular bodies (MVBs). Some CHMPs have both nuclear and
cytoplasmic/vesicular distributions, and one such CHMP, CHMP1A (164010),
is required for both MVB formation and regulation of cell cycle
progression (Tsang et al., 2006).
CLONING
Using the N-terminal region of ALIX (PDCD6IP; 608074) as bait in a yeast
2-hybrid screen of a HeLa cell cDNA library, Katoh et al. (2003) cloned
CHMP4B. The deduced 224-amino acid protein has 3 coiled-coil regions, a
basic N-terminal half, and an acidic C-terminal half. Fluorescence
microscopy revealed a diffuse cytoplasmic distribution of CHMP4B
following stable expression in HEK293 cells. CHMP4B transiently
overexpressed in HeLa cells exhibited a punctate distribution in the
perinuclear area that partly overlapped the distributions of early and
late endosomal markers.
Using Northern blot analysis, Katoh et al. (2004) detected expression of
1.2- and 1.8-kb CHMP4B transcripts in all tissues examined, with highest
expression in heart and skeletal muscle, and moderate expression in
brain, spleen, kidney, placenta, and peripheral blood leukocytes.
GENE STRUCTURE
Shiels et al. (2007) noted that the CHMP4B gene contains 5 exons.
MAPPING
By genomic sequence analysis, Katoh et al. (2003) mapped the CHMP4B gene
to chromosome 20q11.21.
GENE FUNCTION
By yeast 2-hybrid analysis, coimmunoprecipitation analysis, and in vitro
protein pull-down assays, Katoh et al. (2003) showed that CHMP4B
interacted with ALIX. Overexpression of CHMP4B in HeLa cells caused
redistribution of ALIX from the cytoplasm to the perinuclear area, where
the 2 proteins colocalized. Transient overexpression of the ALIX
N-terminal region in HEK293 cells stably expressing CHMP4B induced
formation of vesicle-like structures in which CHMP4B and truncated ALIX
colocalized. Overexpression of CHMP4B in HeLa cells induced accumulation
of ubiquitinated proteins and inhibited degradation of endocytosed EGF
(131530). A dominant-negative form of the AAA-type ATPase SKD1 (VPS4B;
609983), which plays critical roles in the endocytic pathway,
coimmunoprecipitated with CHMP4B. Furthermore, both CHMP4B and ALIX
colocalized with dominant-negative SKD1 in perinuclear dot-like
distributions in transfected HeLa cells, suggesting that the 3 proteins
are involved in formation of multivesicular bodies.
Using in vitro pull-down assays, Katoh et al. (2004) showed that ALIX
interacted more strongly with CHMP4B than with CHMP4A (610051) or CHMP4C
(610899).
By coimmunoprecipitation of epitope-tagged proteins expressed in HEK293
cells, Yorikawa et al. (2005) showed that CHMP6 (610901) interacted with
CHMP4B and EAP20 (VPS25; 610907). In vitro pull-down assays using
recombinant proteins demonstrated direct physical interaction that was
mediated by the N-terminal basic half of CHMP6.
Tsang et al. (2006) performed a systematic yeast 2-hybrid analysis of
human ESCRT-III components, including CHMP4B. CHMP4B interacted with the
ESCRT-III protein VPS4A (609982) and with the signal transduction
molecule CC2D1A (610055). In addition, CHMP4B interacted with the SUMO
(see SUMO1; 601912)-conjugating enzyme UBE2I (601661) and appeared to be
part of a network connecting CHMP1A, CHMP4B, and CHMP5 (610900) with
UBE2I, SUMO1, PIAS2 (603567), and HIPK2 (606868), all of which are
involved in nuclear sumoylation processes.
MOLECULAR GENETICS
Shiels et al. (2007) performed linkage analysis in a large 6-generation
Caucasian family with autosomal dominant progressive childhood posterior
subcapsular cataract (CTPP3; 605387) and found significant linkage on
chromosome 20q with a maximum 2-point lod score of 5.50 at D20S847.
Analysis of recombinant events in affected individuals followed by
genotyping with biallelic SNP markers narrowed the region of interest to
a 0.9-Mb interval containing approximately 80 genes, none of which were
obvious functional candidates for cataracts. Sequence analysis of
positional candidate genes revealed a heterozygous mutation (D129V;
610897.0001) in the CHMP4B gene that cosegregated with disease and was
not found in 384 control chromosomes. Shiels et al. (2007) also
identified a heterozygous mutation (E161K; 610897.0002) in the CHMP4B
gene in affected individuals of a Japanese family with a similar
juvenile progressive cataract phenotype, previously reported by Yamada
et al. (2000) and Yamada et al. (2000).
*FIELD* AV
.0001
CATARACT 31, MULTIPLE TYPES
CHMP4B, ASP129VAL
In affected members of a 6-generation Caucasian family segregating
autosomal dominant childhood posterior subcapsular cataract, progressing
to affect the nucleus and anterior subcapsular regions (CTRCT31;
605387), Shiels et al. (2007) identified heterozygosity for a 386A-T
transversion in exon 3 of the CHMP4B gene, resulting in an asp129-to-val
(D129V) substitution. The mutation was not found in unaffected family
members except for a 17-year-old male who was believed to be either
nonpenetrant or presymptomatic, and was not found in 384 control
chromosomes. Transfection studies of cultured cells revealed that a
truncated form of recombinant D129V-CHMP4B had a different subcellular
distribution than wildtype and an increased capacity to inhibit release
of virus-like particles from the cell surface, consistent with
deleterious gain-of-function effects. Shiels et al. (2007) concluded
that CHMP4B plays a vital role in the maintenance of lens transparency.
.0002
CATARACT 31, POSTERIOR POLAR
CHMP4B, GLU161LYS
In affected members of a Japanese family with a juvenile progressive
subcapsular form of autosomal dominant posterior polar cataract
(CTRCT31; 605387), previously described by Yamada et al. (2000), Shiels
et al. (2007) identified heterozygosity for a 481G-A transition in exon
3 of the CHMP4B gene, resulting in a glu161-to-lys (E161K) substitution.
The mutation was not found in unaffected members of the family or in 384
control chromosomes.
*FIELD* RF
1. Katoh, K.; Shibata, H.; Hatta, K.; Maki, M.: CHMP4b is a major
binding partner of the ALG-2-interacting protein Alix among the three
CHMP4 isoforms. Arch. Biochem. Biophys. 421: 159-165, 2004.
2. Katoh, K.; Shibata, H.; Suzuki, H.; Nara, A.; Ishidoh, K.; Kominami,
E.; Yoshimori, T.; Maki, M.: The ALG-2-interacting protein Alix associates
with CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular
body sorting. J. Biol. Chem. 278: 39104-39113, 2003.
3. Shiels, A.; Bennett, T. M.; Knopf, H. L. S.; Yamada, K.; Yoshiura,
K.; Niikawa, N.; Shim, S.; Hanson, P. I.: CHMP4B, a novel gene for
autosomal dominant cataracts linked to chromosome 20q. Am. J. Hum.
Genet. 81: 596-606, 2007.
4. Tsang, H. T. H.; Connell, J. W.; Brown, S. E.; Thompson, A.; Reid,
E.; Sanderson, C. M.: A systematic analysis of human CHMP protein
interactions: additional MIT domain-containing proteins bind to multiple
components of the human ESCRT III complex. Genomics 88: 333-346,
2006.
5. Yamada, K.; Tomita, H.; Kanazawa, S.; Mera, A.; Amemiya, T.; Niikawa,
N.: Genetically distinct autosomal dominant posterior polar cataract
in a four-generation Japanese family. Am. J. Ophthal. 129: 159-165,
2000.
6. Yamada, K.; Tomita, H.; Yoshiura, K.; Kondo, S.; Wakui, K.; Fukushima,
Y.; Ikegawa, S.; Nakamura, Y.; Amemiya, T.; Niikawa, N.: An autosomal
dominant posterior polar cataract locus maps to human chromosome 20p12-q12. Europ.
J. Hum. Genet. 8: 535-539, 2000.
7. Yorikawa, C.; Shibata, H.; Waguri, S.; Hatta, K.; Horii, M.; Katoh,
K.; Kobayashi, T.; Uchiyama, Y.; Maki, M.: Human CHMP6, a myristoylated
ESCRT-III protein, interacts directly with an ESCRT-II component EAP20
and regulates endosomal cargo sorting. Biochem. J. 387: 17-26, 2005.
*FIELD* CN
Marla J. F. O'Neill - updated: 10/23/2007
*FIELD* CD
Patricia A. Hartz: 3/28/2007
*FIELD* ED
carol: 07/22/2013
mgross: 6/13/2008
terry: 5/30/2008
wwang: 10/24/2007
terry: 10/23/2007
mgross: 4/2/2007
mgross: 3/29/2007
mgross: 3/28/2007
*RECORD*
*FIELD* NO
610897
*FIELD* TI
*610897 CHMP FAMILY, MEMBER 4B; CHMP4B
;;CHROMATIN-MODIFYING PROTEIN 4B;;
CHARGED MULTIVESICULAR BODY PROTEIN 4B;;
read moreSNF7, YEAST, HOMOLOG OF, 2;;
SNF7-2
*FIELD* TX
DESCRIPTION
CHMP4B belongs to the chromatin-modifying protein/charged multivesicular
body protein (CHMP) family. These proteins are components of ESCRT-III
(endosomal sorting complex required for transport III), a complex
involved in degradation of surface receptor proteins and formation of
endocytic multivesicular bodies (MVBs). Some CHMPs have both nuclear and
cytoplasmic/vesicular distributions, and one such CHMP, CHMP1A (164010),
is required for both MVB formation and regulation of cell cycle
progression (Tsang et al., 2006).
CLONING
Using the N-terminal region of ALIX (PDCD6IP; 608074) as bait in a yeast
2-hybrid screen of a HeLa cell cDNA library, Katoh et al. (2003) cloned
CHMP4B. The deduced 224-amino acid protein has 3 coiled-coil regions, a
basic N-terminal half, and an acidic C-terminal half. Fluorescence
microscopy revealed a diffuse cytoplasmic distribution of CHMP4B
following stable expression in HEK293 cells. CHMP4B transiently
overexpressed in HeLa cells exhibited a punctate distribution in the
perinuclear area that partly overlapped the distributions of early and
late endosomal markers.
Using Northern blot analysis, Katoh et al. (2004) detected expression of
1.2- and 1.8-kb CHMP4B transcripts in all tissues examined, with highest
expression in heart and skeletal muscle, and moderate expression in
brain, spleen, kidney, placenta, and peripheral blood leukocytes.
GENE STRUCTURE
Shiels et al. (2007) noted that the CHMP4B gene contains 5 exons.
MAPPING
By genomic sequence analysis, Katoh et al. (2003) mapped the CHMP4B gene
to chromosome 20q11.21.
GENE FUNCTION
By yeast 2-hybrid analysis, coimmunoprecipitation analysis, and in vitro
protein pull-down assays, Katoh et al. (2003) showed that CHMP4B
interacted with ALIX. Overexpression of CHMP4B in HeLa cells caused
redistribution of ALIX from the cytoplasm to the perinuclear area, where
the 2 proteins colocalized. Transient overexpression of the ALIX
N-terminal region in HEK293 cells stably expressing CHMP4B induced
formation of vesicle-like structures in which CHMP4B and truncated ALIX
colocalized. Overexpression of CHMP4B in HeLa cells induced accumulation
of ubiquitinated proteins and inhibited degradation of endocytosed EGF
(131530). A dominant-negative form of the AAA-type ATPase SKD1 (VPS4B;
609983), which plays critical roles in the endocytic pathway,
coimmunoprecipitated with CHMP4B. Furthermore, both CHMP4B and ALIX
colocalized with dominant-negative SKD1 in perinuclear dot-like
distributions in transfected HeLa cells, suggesting that the 3 proteins
are involved in formation of multivesicular bodies.
Using in vitro pull-down assays, Katoh et al. (2004) showed that ALIX
interacted more strongly with CHMP4B than with CHMP4A (610051) or CHMP4C
(610899).
By coimmunoprecipitation of epitope-tagged proteins expressed in HEK293
cells, Yorikawa et al. (2005) showed that CHMP6 (610901) interacted with
CHMP4B and EAP20 (VPS25; 610907). In vitro pull-down assays using
recombinant proteins demonstrated direct physical interaction that was
mediated by the N-terminal basic half of CHMP6.
Tsang et al. (2006) performed a systematic yeast 2-hybrid analysis of
human ESCRT-III components, including CHMP4B. CHMP4B interacted with the
ESCRT-III protein VPS4A (609982) and with the signal transduction
molecule CC2D1A (610055). In addition, CHMP4B interacted with the SUMO
(see SUMO1; 601912)-conjugating enzyme UBE2I (601661) and appeared to be
part of a network connecting CHMP1A, CHMP4B, and CHMP5 (610900) with
UBE2I, SUMO1, PIAS2 (603567), and HIPK2 (606868), all of which are
involved in nuclear sumoylation processes.
MOLECULAR GENETICS
Shiels et al. (2007) performed linkage analysis in a large 6-generation
Caucasian family with autosomal dominant progressive childhood posterior
subcapsular cataract (CTPP3; 605387) and found significant linkage on
chromosome 20q with a maximum 2-point lod score of 5.50 at D20S847.
Analysis of recombinant events in affected individuals followed by
genotyping with biallelic SNP markers narrowed the region of interest to
a 0.9-Mb interval containing approximately 80 genes, none of which were
obvious functional candidates for cataracts. Sequence analysis of
positional candidate genes revealed a heterozygous mutation (D129V;
610897.0001) in the CHMP4B gene that cosegregated with disease and was
not found in 384 control chromosomes. Shiels et al. (2007) also
identified a heterozygous mutation (E161K; 610897.0002) in the CHMP4B
gene in affected individuals of a Japanese family with a similar
juvenile progressive cataract phenotype, previously reported by Yamada
et al. (2000) and Yamada et al. (2000).
*FIELD* AV
.0001
CATARACT 31, MULTIPLE TYPES
CHMP4B, ASP129VAL
In affected members of a 6-generation Caucasian family segregating
autosomal dominant childhood posterior subcapsular cataract, progressing
to affect the nucleus and anterior subcapsular regions (CTRCT31;
605387), Shiels et al. (2007) identified heterozygosity for a 386A-T
transversion in exon 3 of the CHMP4B gene, resulting in an asp129-to-val
(D129V) substitution. The mutation was not found in unaffected family
members except for a 17-year-old male who was believed to be either
nonpenetrant or presymptomatic, and was not found in 384 control
chromosomes. Transfection studies of cultured cells revealed that a
truncated form of recombinant D129V-CHMP4B had a different subcellular
distribution than wildtype and an increased capacity to inhibit release
of virus-like particles from the cell surface, consistent with
deleterious gain-of-function effects. Shiels et al. (2007) concluded
that CHMP4B plays a vital role in the maintenance of lens transparency.
.0002
CATARACT 31, POSTERIOR POLAR
CHMP4B, GLU161LYS
In affected members of a Japanese family with a juvenile progressive
subcapsular form of autosomal dominant posterior polar cataract
(CTRCT31; 605387), previously described by Yamada et al. (2000), Shiels
et al. (2007) identified heterozygosity for a 481G-A transition in exon
3 of the CHMP4B gene, resulting in a glu161-to-lys (E161K) substitution.
The mutation was not found in unaffected members of the family or in 384
control chromosomes.
*FIELD* RF
1. Katoh, K.; Shibata, H.; Hatta, K.; Maki, M.: CHMP4b is a major
binding partner of the ALG-2-interacting protein Alix among the three
CHMP4 isoforms. Arch. Biochem. Biophys. 421: 159-165, 2004.
2. Katoh, K.; Shibata, H.; Suzuki, H.; Nara, A.; Ishidoh, K.; Kominami,
E.; Yoshimori, T.; Maki, M.: The ALG-2-interacting protein Alix associates
with CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular
body sorting. J. Biol. Chem. 278: 39104-39113, 2003.
3. Shiels, A.; Bennett, T. M.; Knopf, H. L. S.; Yamada, K.; Yoshiura,
K.; Niikawa, N.; Shim, S.; Hanson, P. I.: CHMP4B, a novel gene for
autosomal dominant cataracts linked to chromosome 20q. Am. J. Hum.
Genet. 81: 596-606, 2007.
4. Tsang, H. T. H.; Connell, J. W.; Brown, S. E.; Thompson, A.; Reid,
E.; Sanderson, C. M.: A systematic analysis of human CHMP protein
interactions: additional MIT domain-containing proteins bind to multiple
components of the human ESCRT III complex. Genomics 88: 333-346,
2006.
5. Yamada, K.; Tomita, H.; Kanazawa, S.; Mera, A.; Amemiya, T.; Niikawa,
N.: Genetically distinct autosomal dominant posterior polar cataract
in a four-generation Japanese family. Am. J. Ophthal. 129: 159-165,
2000.
6. Yamada, K.; Tomita, H.; Yoshiura, K.; Kondo, S.; Wakui, K.; Fukushima,
Y.; Ikegawa, S.; Nakamura, Y.; Amemiya, T.; Niikawa, N.: An autosomal
dominant posterior polar cataract locus maps to human chromosome 20p12-q12. Europ.
J. Hum. Genet. 8: 535-539, 2000.
7. Yorikawa, C.; Shibata, H.; Waguri, S.; Hatta, K.; Horii, M.; Katoh,
K.; Kobayashi, T.; Uchiyama, Y.; Maki, M.: Human CHMP6, a myristoylated
ESCRT-III protein, interacts directly with an ESCRT-II component EAP20
and regulates endosomal cargo sorting. Biochem. J. 387: 17-26, 2005.
*FIELD* CN
Marla J. F. O'Neill - updated: 10/23/2007
*FIELD* CD
Patricia A. Hartz: 3/28/2007
*FIELD* ED
carol: 07/22/2013
mgross: 6/13/2008
terry: 5/30/2008
wwang: 10/24/2007
terry: 10/23/2007
mgross: 4/2/2007
mgross: 3/29/2007
mgross: 3/28/2007