Full text data of CHMP6
CHMP6
(VPS20)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Charged multivesicular body protein 6 (Chromatin-modifying protein 6; Vacuolar protein sorting-associated protein 20; Vps20; hVps20)
Charged multivesicular body protein 6 (Chromatin-modifying protein 6; Vacuolar protein sorting-associated protein 20; Vps20; hVps20)
UniProt
Q96FZ7
ID CHMP6_HUMAN Reviewed; 201 AA.
AC Q96FZ7; A8K7U0; Q53FU4; Q9HAE8;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 104.
DE RecName: Full=Charged multivesicular body protein 6;
DE AltName: Full=Chromatin-modifying protein 6;
DE AltName: Full=Vacuolar protein sorting-associated protein 20;
DE Short=Vps20;
DE Short=hVps20;
GN Name=CHMP6; Synonyms=VPS20;
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], AND SUBCELLULAR LOCATION.
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo, and Synovial cell;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney proximal tubule;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
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 INTERACTION WITH VPS25; CHMP4B; 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 [7]
RP INTERACTION WITH CHMP4A; CHMP4B; CHMP4C; VPS25; SNF8 AND VPS36.
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 [8]
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 [9]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MYRISTOYLATION AT GLY-2,
RP INTERACTION WITH CHMP4B AND VPS25, AND MUTAGENESIS OF GLY-2 AND
RP ARG-49.
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 [10]
RP AUTOINHIBITORY MECHANISM, INTERACTION, AND MUTAGENESIS OF
RP 168-ILE--SER-201.
RX PubMed=17547705; DOI=10.1111/j.1600-0854.2007.00584.x;
RA Shim S., Kimpler L.A., Hanson P.I.;
RT "Structure/function analysis of four core ESCRT-III proteins reveals
RT common regulatory role for extreme C-terminal domain.";
RL Traffic 8:1068-1079(2007).
RN [11]
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 [12]
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 [13]
RP STRUCTURE BY NMR OF 168-179 IN COMPLEX WITH VPS4A, AND MUTAGENESIS OF
RP LEU-170; VAL-173 AND LEU-178.
RX PubMed=18606141; DOI=10.1016/j.devcel.2008.05.014;
RA Kieffer C., Skalicky J.J., Morita E., De Domenico I., Ward D.M.,
RA Kaplan J., Sundquist W.I.;
RT "Two distinct modes of ESCRT-III recognition are required for VPS4
RT functions in lysosomal protein targeting and HIV-1 budding.";
RL Dev. Cell 15:62-73(2008).
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. In the ESCRT-III
CC complex, it probably serves as an acceptor for the ESCRT-II
CC complex on endosomal membranes.
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 VPS4A; the
CC interaction is direct. Interacts with VPS4B; the interaction is
CC direct. Interacts with CHMP4A, CHMP4B and CHMP4C. Interacts with
CC SNF8, VPS25 and VPS36.
CC -!- SUBCELLULAR LOCATION: Endomembrane system. Endosome membrane;
CC Lipid-anchor. Late endosome membrane (Probable). Note=Localizes to
CC endosomal membranes.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
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 in a CHMP5-dependent manner. Isgylation weakens its
CC interaction with VPS4A.
CC -!- SIMILARITY: Belongs to the SNF7 family.
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DR EMBL; AY329087; AAQ91196.1; -; mRNA.
DR EMBL; AK021811; BAB13901.1; -; mRNA.
DR EMBL; CR457284; CAG33565.1; -; mRNA.
DR EMBL; AK223187; BAD96907.1; -; mRNA.
DR EMBL; AK292105; BAF84794.1; -; mRNA.
DR EMBL; BC010108; AAH10108.1; -; mRNA.
DR RefSeq; NP_078867.2; NM_024591.4.
DR UniGene; Hs.514560; -.
DR PDB; 2K3W; NMR; -; B=166-181.
DR PDB; 3HTU; X-ray; 2.00 A; B/D/F/H=11-48.
DR PDBsum; 2K3W; -.
DR PDBsum; 3HTU; -.
DR ProteinModelPortal; Q96FZ7; -.
DR IntAct; Q96FZ7; 3.
DR MINT; MINT-5003442; -.
DR STRING; 9606.ENSP00000317468; -.
DR PhosphoSite; Q96FZ7; -.
DR DMDM; 73917777; -.
DR PaxDb; Q96FZ7; -.
DR PRIDE; Q96FZ7; -.
DR DNASU; 79643; -.
DR Ensembl; ENST00000325167; ENSP00000317468; ENSG00000176108.
DR GeneID; 79643; -.
DR KEGG; hsa:79643; -.
DR UCSC; uc002jyw.4; human.
DR CTD; 79643; -.
DR GeneCards; GC17P078965; -.
DR HGNC; HGNC:25675; CHMP6.
DR HPA; HPA023001; -.
DR HPA; HPA024460; -.
DR MIM; 610901; gene.
DR neXtProt; NX_Q96FZ7; -.
DR PharmGKB; PA142672114; -.
DR eggNOG; NOG291677; -.
DR HOGENOM; HOG000208642; -.
DR HOVERGEN; HBG080510; -.
DR InParanoid; Q96FZ7; -.
DR KO; K12195; -.
DR OMA; ECLARDD; -.
DR PhylomeDB; Q96FZ7; -.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_116125; Disease.
DR EvolutionaryTrace; Q96FZ7; -.
DR GeneWiki; CHMP6; -.
DR GenomeRNAi; 79643; -.
DR NextBio; 68773; -.
DR PRO; PR:Q96FZ7; -.
DR ArrayExpress; Q96FZ7; -.
DR Bgee; Q96FZ7; -.
DR CleanEx; HS_CHMP6; -.
DR Genevestigator; Q96FZ7; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0012505; C:endomembrane system; IEA:UniProtKB-SubCell.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
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; Coiled coil; Complete proteome; Endosome; Lipoprotein;
KW Membrane; Myristate; Polymorphism; Protein transport;
KW Reference proteome; Transport; Ubl conjugation.
FT INIT_MET 1 1 Removed (Probable).
FT CHAIN 2 201 Charged multivesicular body protein 6.
FT /FTId=PRO_0000211508.
FT REGION 170 181 Interaction with VPS4A.
FT COILED 10 145 Potential.
FT MOTIF 168 179 Type-2 MIT-interacting motif.
FT LIPID 2 2 N-myristoyl glycine (Probable).
FT VARIANT 55 55 G -> S (in dbSNP:rs61037507).
FT /FTId=VAR_061807.
FT MUTAGEN 2 2 G->A: Abolishes myristoylation.
FT MUTAGEN 49 49 R->E: Does not affect the subcellular
FT location.
FT MUTAGEN 168 201 Missing: Membrane association; releases
FT autoinhibition.
FT MUTAGEN 170 170 L->D: Abolishes interaction with VPS4A.
FT MUTAGEN 173 173 V->D: Abolishes interaction with VPS4A.
FT MUTAGEN 178 178 L->D: Reduces interaction with VPS4A.
FT CONFLICT 17 17 D -> G (in Ref. 4; BAD96907).
FT CONFLICT 106 106 F -> L (in Ref. 2; BAB13901).
FT HELIX 15 43
SQ SEQUENCE 201 AA; 23485 MW; 0D490C4DE047DC02 CRC64;
MGNLFGRKKQ SRVTEQDKAI LQLKQQRDKL RQYQKRIAQQ LERERALARQ LLRDGRKERA
KLLLKKKRYQ EQLLDRTENQ ISSLEAMVQS IEFTQIEMKV MEGLQFGNEC LNKMHQVMSI
EEVERILDET QEAVEYQRQI DELLAGSFTQ EDEDAILEEL SAITQEQIEL PEVPSEPLPE
KIPENVPVKA RPRQAELVAA S
//
ID CHMP6_HUMAN Reviewed; 201 AA.
AC Q96FZ7; A8K7U0; Q53FU4; Q9HAE8;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 104.
DE RecName: Full=Charged multivesicular body protein 6;
DE AltName: Full=Chromatin-modifying protein 6;
DE AltName: Full=Vacuolar protein sorting-associated protein 20;
DE Short=Vps20;
DE Short=hVps20;
GN Name=CHMP6; Synonyms=VPS20;
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], AND SUBCELLULAR LOCATION.
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo, and Synovial cell;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney proximal tubule;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
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 INTERACTION WITH VPS25; CHMP4B; 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 [7]
RP INTERACTION WITH CHMP4A; CHMP4B; CHMP4C; VPS25; SNF8 AND VPS36.
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 [8]
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 [9]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MYRISTOYLATION AT GLY-2,
RP INTERACTION WITH CHMP4B AND VPS25, AND MUTAGENESIS OF GLY-2 AND
RP ARG-49.
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 [10]
RP AUTOINHIBITORY MECHANISM, INTERACTION, AND MUTAGENESIS OF
RP 168-ILE--SER-201.
RX PubMed=17547705; DOI=10.1111/j.1600-0854.2007.00584.x;
RA Shim S., Kimpler L.A., Hanson P.I.;
RT "Structure/function analysis of four core ESCRT-III proteins reveals
RT common regulatory role for extreme C-terminal domain.";
RL Traffic 8:1068-1079(2007).
RN [11]
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 [12]
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 [13]
RP STRUCTURE BY NMR OF 168-179 IN COMPLEX WITH VPS4A, AND MUTAGENESIS OF
RP LEU-170; VAL-173 AND LEU-178.
RX PubMed=18606141; DOI=10.1016/j.devcel.2008.05.014;
RA Kieffer C., Skalicky J.J., Morita E., De Domenico I., Ward D.M.,
RA Kaplan J., Sundquist W.I.;
RT "Two distinct modes of ESCRT-III recognition are required for VPS4
RT functions in lysosomal protein targeting and HIV-1 budding.";
RL Dev. Cell 15:62-73(2008).
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. In the ESCRT-III
CC complex, it probably serves as an acceptor for the ESCRT-II
CC complex on endosomal membranes.
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 VPS4A; the
CC interaction is direct. Interacts with VPS4B; the interaction is
CC direct. Interacts with CHMP4A, CHMP4B and CHMP4C. Interacts with
CC SNF8, VPS25 and VPS36.
CC -!- SUBCELLULAR LOCATION: Endomembrane system. Endosome membrane;
CC Lipid-anchor. Late endosome membrane (Probable). Note=Localizes to
CC endosomal membranes.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
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 in a CHMP5-dependent manner. Isgylation weakens its
CC interaction with VPS4A.
CC -!- SIMILARITY: Belongs to the SNF7 family.
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DR EMBL; AY329087; AAQ91196.1; -; mRNA.
DR EMBL; AK021811; BAB13901.1; -; mRNA.
DR EMBL; CR457284; CAG33565.1; -; mRNA.
DR EMBL; AK223187; BAD96907.1; -; mRNA.
DR EMBL; AK292105; BAF84794.1; -; mRNA.
DR EMBL; BC010108; AAH10108.1; -; mRNA.
DR RefSeq; NP_078867.2; NM_024591.4.
DR UniGene; Hs.514560; -.
DR PDB; 2K3W; NMR; -; B=166-181.
DR PDB; 3HTU; X-ray; 2.00 A; B/D/F/H=11-48.
DR PDBsum; 2K3W; -.
DR PDBsum; 3HTU; -.
DR ProteinModelPortal; Q96FZ7; -.
DR IntAct; Q96FZ7; 3.
DR MINT; MINT-5003442; -.
DR STRING; 9606.ENSP00000317468; -.
DR PhosphoSite; Q96FZ7; -.
DR DMDM; 73917777; -.
DR PaxDb; Q96FZ7; -.
DR PRIDE; Q96FZ7; -.
DR DNASU; 79643; -.
DR Ensembl; ENST00000325167; ENSP00000317468; ENSG00000176108.
DR GeneID; 79643; -.
DR KEGG; hsa:79643; -.
DR UCSC; uc002jyw.4; human.
DR CTD; 79643; -.
DR GeneCards; GC17P078965; -.
DR HGNC; HGNC:25675; CHMP6.
DR HPA; HPA023001; -.
DR HPA; HPA024460; -.
DR MIM; 610901; gene.
DR neXtProt; NX_Q96FZ7; -.
DR PharmGKB; PA142672114; -.
DR eggNOG; NOG291677; -.
DR HOGENOM; HOG000208642; -.
DR HOVERGEN; HBG080510; -.
DR InParanoid; Q96FZ7; -.
DR KO; K12195; -.
DR OMA; ECLARDD; -.
DR PhylomeDB; Q96FZ7; -.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_116125; Disease.
DR EvolutionaryTrace; Q96FZ7; -.
DR GeneWiki; CHMP6; -.
DR GenomeRNAi; 79643; -.
DR NextBio; 68773; -.
DR PRO; PR:Q96FZ7; -.
DR ArrayExpress; Q96FZ7; -.
DR Bgee; Q96FZ7; -.
DR CleanEx; HS_CHMP6; -.
DR Genevestigator; Q96FZ7; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0012505; C:endomembrane system; IEA:UniProtKB-SubCell.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
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; Coiled coil; Complete proteome; Endosome; Lipoprotein;
KW Membrane; Myristate; Polymorphism; Protein transport;
KW Reference proteome; Transport; Ubl conjugation.
FT INIT_MET 1 1 Removed (Probable).
FT CHAIN 2 201 Charged multivesicular body protein 6.
FT /FTId=PRO_0000211508.
FT REGION 170 181 Interaction with VPS4A.
FT COILED 10 145 Potential.
FT MOTIF 168 179 Type-2 MIT-interacting motif.
FT LIPID 2 2 N-myristoyl glycine (Probable).
FT VARIANT 55 55 G -> S (in dbSNP:rs61037507).
FT /FTId=VAR_061807.
FT MUTAGEN 2 2 G->A: Abolishes myristoylation.
FT MUTAGEN 49 49 R->E: Does not affect the subcellular
FT location.
FT MUTAGEN 168 201 Missing: Membrane association; releases
FT autoinhibition.
FT MUTAGEN 170 170 L->D: Abolishes interaction with VPS4A.
FT MUTAGEN 173 173 V->D: Abolishes interaction with VPS4A.
FT MUTAGEN 178 178 L->D: Reduces interaction with VPS4A.
FT CONFLICT 17 17 D -> G (in Ref. 4; BAD96907).
FT CONFLICT 106 106 F -> L (in Ref. 2; BAB13901).
FT HELIX 15 43
SQ SEQUENCE 201 AA; 23485 MW; 0D490C4DE047DC02 CRC64;
MGNLFGRKKQ SRVTEQDKAI LQLKQQRDKL RQYQKRIAQQ LERERALARQ LLRDGRKERA
KLLLKKKRYQ EQLLDRTENQ ISSLEAMVQS IEFTQIEMKV MEGLQFGNEC LNKMHQVMSI
EEVERILDET QEAVEYQRQI DELLAGSFTQ EDEDAILEEL SAITQEQIEL PEVPSEPLPE
KIPENVPVKA RPRQAELVAA S
//
MIM
610901
*RECORD*
*FIELD* NO
610901
*FIELD* TI
*610901 CHMP FAMILY, MEMBER 6; CHMP6
;;CHROMATIN-MODIFYING PROTEIN 6;;
CHARGED MULTIVESICULAR BODY PROTEIN 6;;
read moreVPS20, YEAST, HOMOLOG OF; VPS20
*FIELD* TX
DESCRIPTION
CHMP6 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 PCR, Yorikawa et al. (2005) cloned CHMP6 from a human fetus cDNA
library. The deduced 201-amino acid protein contains 2 coiled-coil
domains, an N-myristoylation site, and clusters of basic and acidic
residues in its N- and C-terminal regions, respectively. Metabolic
labeling confirmed that CHMP6 is myristoylated. Fluorescence-tagged
CHMP6 localized in a punctate distribution in HeLa cells, mostly in the
perinuclear area. It colocalized with an early endosomal marker and
partially colocalized with a marker of both late endosomes and
lysosomes.
GENE FUNCTION
By coimmunoprecipitation of epitope-tagged proteins expressed in HEK293
cells, Yorikawa et al. (2005) showed that CHMP6 interacted with CHMP4B
(610897) 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. In transfected HeLa
cells, CHMP6 colocalized with lysobisphosphatidic acid, a major
phospholipid of internal vesicles of the MVB. Immunoelectron microscopy
showed that CHMP6 localized in internal membranes of MVB-like
structures, as well as on limiting membranes. Overexpression of CHMP6
interfered with transferrin receptor (TFRC; 190010) recycling from the
plasma membrane and caused it to accumulate in the cytoplasm.
Ubiquitinated proteins and endocytosed EGF (131530) also accumulated in
CHMP6-expressing cells. Yorikawa et al. (2005) concluded that CHMP6 acts
as an acceptor for ESCRT-II on endosomal membranes and regulates cargo
sorting.
In S. cerevisiae, ESCRT-III consists of Vps20, Snf7 (610051), Vps24
(610052), and Vps2 (610893), which assemble in that order and require
the ATPase Vps4 (see 609982) for their disassembly. Wollert et al.
(2009) reconstituted and visualized by fluorescence microscopy the
ESCRT-III-dependent budding and scission of intralumenal vesicles into
giant unilamellar vesicles. Wollert et al. (2009) showed that 3 subunits
of ESCRT-III, Vps20, Snf7, and Vps24, are sufficient to detach
intralumenal vesicles. Vps2, the ESCRT-III subunit responsible for
recruiting Vps4, and the ATPase activity of Vps4 were required for
ESCRT-III recycling and supported additional rounds of budding. The
minimum set of ESCRT-III and Vps4 proteins capable of multiple cycles of
vesicle detachment corresponds to the ancient set of ESCRT proteins
conserved from archaea to animals.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the CHMP6
gene to chromosome 17 (TMAP RH102270).
*FIELD* RF
1. 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.
2. Wollert, T.; Wunder, C.; Lippincott-Schwartz, J.; Hurley, J. H.
: Membrane scission by the ESCRT-III complex. Nature 458: 172-177,
2009.
3. 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
Ada Hamosh - updated: 5/12/2009
*FIELD* CD
Patricia A. Hartz: 3/29/2007
*FIELD* ED
alopez: 05/15/2009
terry: 5/12/2009
mgross: 4/2/2007
mgross: 3/29/2007
*RECORD*
*FIELD* NO
610901
*FIELD* TI
*610901 CHMP FAMILY, MEMBER 6; CHMP6
;;CHROMATIN-MODIFYING PROTEIN 6;;
CHARGED MULTIVESICULAR BODY PROTEIN 6;;
read moreVPS20, YEAST, HOMOLOG OF; VPS20
*FIELD* TX
DESCRIPTION
CHMP6 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 PCR, Yorikawa et al. (2005) cloned CHMP6 from a human fetus cDNA
library. The deduced 201-amino acid protein contains 2 coiled-coil
domains, an N-myristoylation site, and clusters of basic and acidic
residues in its N- and C-terminal regions, respectively. Metabolic
labeling confirmed that CHMP6 is myristoylated. Fluorescence-tagged
CHMP6 localized in a punctate distribution in HeLa cells, mostly in the
perinuclear area. It colocalized with an early endosomal marker and
partially colocalized with a marker of both late endosomes and
lysosomes.
GENE FUNCTION
By coimmunoprecipitation of epitope-tagged proteins expressed in HEK293
cells, Yorikawa et al. (2005) showed that CHMP6 interacted with CHMP4B
(610897) 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. In transfected HeLa
cells, CHMP6 colocalized with lysobisphosphatidic acid, a major
phospholipid of internal vesicles of the MVB. Immunoelectron microscopy
showed that CHMP6 localized in internal membranes of MVB-like
structures, as well as on limiting membranes. Overexpression of CHMP6
interfered with transferrin receptor (TFRC; 190010) recycling from the
plasma membrane and caused it to accumulate in the cytoplasm.
Ubiquitinated proteins and endocytosed EGF (131530) also accumulated in
CHMP6-expressing cells. Yorikawa et al. (2005) concluded that CHMP6 acts
as an acceptor for ESCRT-II on endosomal membranes and regulates cargo
sorting.
In S. cerevisiae, ESCRT-III consists of Vps20, Snf7 (610051), Vps24
(610052), and Vps2 (610893), which assemble in that order and require
the ATPase Vps4 (see 609982) for their disassembly. Wollert et al.
(2009) reconstituted and visualized by fluorescence microscopy the
ESCRT-III-dependent budding and scission of intralumenal vesicles into
giant unilamellar vesicles. Wollert et al. (2009) showed that 3 subunits
of ESCRT-III, Vps20, Snf7, and Vps24, are sufficient to detach
intralumenal vesicles. Vps2, the ESCRT-III subunit responsible for
recruiting Vps4, and the ATPase activity of Vps4 were required for
ESCRT-III recycling and supported additional rounds of budding. The
minimum set of ESCRT-III and Vps4 proteins capable of multiple cycles of
vesicle detachment corresponds to the ancient set of ESCRT proteins
conserved from archaea to animals.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the CHMP6
gene to chromosome 17 (TMAP RH102270).
*FIELD* RF
1. 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.
2. Wollert, T.; Wunder, C.; Lippincott-Schwartz, J.; Hurley, J. H.
: Membrane scission by the ESCRT-III complex. Nature 458: 172-177,
2009.
3. 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
Ada Hamosh - updated: 5/12/2009
*FIELD* CD
Patricia A. Hartz: 3/29/2007
*FIELD* ED
alopez: 05/15/2009
terry: 5/12/2009
mgross: 4/2/2007
mgross: 3/29/2007