Full text data of CCT4
CCT4
(CCTD, SRB)
[Confidence: high (present in two of the MS resources)]
T-complex protein 1 subunit delta; TCP-1-delta (CCT-delta; Stimulator of TAR RNA-binding)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
T-complex protein 1 subunit delta; TCP-1-delta (CCT-delta; Stimulator of TAR RNA-binding)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00302927
IPI00302927 T-complex protein 1, delta subunit T-complex protein 1, delta subunit membrane n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 1 1 n/a n/a n/a n/a n/a n/a n/a n/a cytoskeleton associated n/a found at its expected molecular weight found at molecular weight
IPI00302927 T-complex protein 1, delta subunit T-complex protein 1, delta subunit membrane n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 1 1 n/a n/a n/a n/a n/a n/a n/a n/a cytoskeleton associated n/a found at its expected molecular weight found at molecular weight
UniProt
P50991
ID TCPD_HUMAN Reviewed; 539 AA.
AC P50991; B2R6I3; B7Z8B1; F5H5W3; O14870; Q53QP9; Q96C51;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 4.
DT 22-JAN-2014, entry version 132.
DE RecName: Full=T-complex protein 1 subunit delta;
DE Short=TCP-1-delta;
DE AltName: Full=CCT-delta;
DE AltName: Full=Stimulator of TAR RNA-binding;
GN Name=CCT4; Synonyms=CCTD, SRB;
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] (ISOFORM 1), AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=8626763; DOI=10.1074/jbc.271.8.4201;
RA Wu-Baer F., Lane W.S., Gaynor R.B.;
RT "Identification of a group of cellular cofactors that stimulate the
RT binding of RNA polymerase II and TRP-185 to human immunodeficiency
RT virus 1 TAR RNA.";
RL J. Biol. Chem. 271:4201-4208(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9819444;
RA Won K.-A., Schumacher R.J., Farr G.W., Horwich A.L., Reed S.I.;
RT "Maturation of human cyclin E requires the function of eukaryotic
RT chaperonin CCT.";
RL Mol. Cell. Biol. 18:7584-7589(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Thymus;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 2-8.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [7]
RP PROTEIN SEQUENCE OF 420-435, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V., Barblan J., Quadroni M.;
RL Submitted (MAR-2004) to UniProtKB.
RN [8]
RP INTERACTION WITH PACRG.
RX PubMed=14532270; DOI=10.1074/jbc.M309655200;
RA Imai Y., Soda M., Murakami T., Shoji M., Abe K., Takahashi R.;
RT "A product of the human gene adjacent to parkin is a component of Lewy
RT bodies and suppresses Pael receptor-induced cell death.";
RL J. Biol. Chem. 278:51901-51910(2003).
RN [9]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-288; LYS-302; LYS-319 AND
RP LYS-326, AND 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 [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND IDENTIFICATION IN BBS/CCT COMPLEX.
RX PubMed=20080638; DOI=10.1073/pnas.0910268107;
RA Seo S., Baye L.M., Schulz N.P., Beck J.S., Zhang Q., Slusarski D.C.,
RA Sheffield V.C.;
RT "BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family
RT chaperonins and mediate BBSome assembly.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:1488-1493(2010).
RN [12]
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 [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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).
CC -!- FUNCTION: Molecular chaperone; assists the folding of proteins
CC upon ATP hydrolysis. As part of the BBS/CCT complex may play a
CC role in the assembly of BBSome, a complex involved in ciliogenesis
CC regulating transports vesicles to the cilia. Known to play a role,
CC in vitro, in the folding of actin and tubulin.
CC -!- SUBUNIT: Heterooligomeric complex of about 850 to 900 kDa that
CC forms two stacked rings, 12 to 16 nm in diameter. Interacts with
CC PACRG. Component of the BBS/CCT complex composed at least of MKKS,
CC BBS10, BBS12, TCP1, CCT2, CCT3, CCT4, CCT5 AND CCT8.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Melanosome. Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome.
CC Note=Identified by mass spectrometry in melanosome fractions from
CC stage I to stage IV.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P50991-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P50991-2; Sequence=VSP_045537;
CC Note=No experimental confirmation available;
CC -!- SIMILARITY: Belongs to the TCP-1 chaperonin family.
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DR EMBL; U38846; AAC50384.1; -; mRNA.
DR EMBL; AF026291; AAC96010.1; -; mRNA.
DR EMBL; AK303082; BAH13897.1; -; mRNA.
DR EMBL; AK312586; BAG35480.1; -; mRNA.
DR EMBL; AC107081; AAY24140.1; -; Genomic_DNA.
DR EMBL; BC014676; AAH14676.1; -; mRNA.
DR EMBL; BC106934; AAI06935.1; -; mRNA.
DR EMBL; BC106933; AAI06934.1; -; mRNA.
DR RefSeq; NP_001243650.1; NM_001256721.1.
DR RefSeq; NP_006421.2; NM_006430.3.
DR UniGene; Hs.421509; -.
DR ProteinModelPortal; P50991; -.
DR SMR; P50991; 18-539.
DR DIP; DIP-32971N; -.
DR IntAct; P50991; 44.
DR MINT; MINT-1157924; -.
DR STRING; 9606.ENSP00000377958; -.
DR PhosphoSite; P50991; -.
DR DMDM; 52001478; -.
DR REPRODUCTION-2DPAGE; IPI00302927; -.
DR UCD-2DPAGE; P50991; -.
DR PaxDb; P50991; -.
DR PeptideAtlas; P50991; -.
DR PRIDE; P50991; -.
DR DNASU; 10575; -.
DR Ensembl; ENST00000394440; ENSP00000377958; ENSG00000115484.
DR Ensembl; ENST00000544079; ENSP00000443061; ENSG00000115484.
DR GeneID; 10575; -.
DR KEGG; hsa:10575; -.
DR UCSC; uc010yps.3; human.
DR CTD; 10575; -.
DR GeneCards; GC02M062095; -.
DR HGNC; HGNC:1617; CCT4.
DR HPA; HPA029349; -.
DR MIM; 605142; gene.
DR neXtProt; NX_P50991; -.
DR PharmGKB; PA26181; -.
DR eggNOG; COG0459; -.
DR HOGENOM; HOG000226735; -.
DR HOVERGEN; HBG106507; -.
DR InParanoid; P50991; -.
DR KO; K09496; -.
DR OMA; MNVIHPA; -.
DR OrthoDB; EOG722J8B; -.
DR PhylomeDB; P50991; -.
DR Reactome; REACT_17015; Metabolism of proteins.
DR ChiTaRS; CCT4; human.
DR GeneWiki; CCT4; -.
DR GenomeRNAi; 10575; -.
DR NextBio; 40137; -.
DR PMAP-CutDB; P50991; -.
DR PRO; PR:P50991; -.
DR ArrayExpress; P50991; -.
DR Bgee; P50991; -.
DR CleanEx; HS_CCT4; -.
DR Genevestigator; P50991; -.
DR GO; GO:0005813; C:centrosome; IDA:MGI.
DR GO; GO:0005832; C:chaperonin-containing T-complex; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005874; C:microtubule; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0002199; C:zona pellucida receptor complex; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0051082; F:unfolded protein binding; TAS:ProtInc.
DR GO; GO:0051084; P:'de novo' posttranslational protein folding; TAS:Reactome.
DR GO; GO:0007339; P:binding of sperm to zona pellucida; IEA:Ensembl.
DR Gene3D; 1.10.560.10; -; 2.
DR Gene3D; 3.30.260.10; -; 2.
DR Gene3D; 3.50.7.10; -; 1.
DR InterPro; IPR012717; Chap_CCT_delta.
DR InterPro; IPR017998; Chaperone_TCP-1.
DR InterPro; IPR002194; Chaperonin_TCP-1_CS.
DR InterPro; IPR002423; Cpn60/TCP-1.
DR InterPro; IPR027409; GroEL-like_apical_dom.
DR InterPro; IPR027413; GROEL-like_equatorial.
DR InterPro; IPR027410; TCP-1-like_intermed.
DR PANTHER; PTHR11353; PTHR11353; 1.
DR Pfam; PF00118; Cpn60_TCP1; 1.
DR PRINTS; PR00304; TCOMPLEXTCP1.
DR SUPFAM; SSF48592; SSF48592; 2.
DR SUPFAM; SSF52029; SSF52029; 1.
DR TIGRFAMs; TIGR02342; chap_CCT_delta; 1.
DR PROSITE; PS00750; TCP1_1; 1.
DR PROSITE; PS00751; TCP1_2; 1.
DR PROSITE; PS00995; TCP1_3; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; ATP-binding; Chaperone;
KW Complete proteome; Cytoplasm; Cytoskeleton; Direct protein sequencing;
KW Nucleotide-binding; Polymorphism; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 539 T-complex protein 1 subunit delta.
FT /FTId=PRO_0000128332.
FT MOD_RES 288 288 N6-acetyllysine.
FT MOD_RES 302 302 N6-acetyllysine.
FT MOD_RES 319 319 N6-acetyllysine.
FT MOD_RES 326 326 N6-acetyllysine.
FT VAR_SEQ 60 89 Missing (in isoform 2).
FT /FTId=VSP_045537.
FT VARIANT 112 112 I -> V (in dbSNP:rs2272428).
FT /FTId=VAR_052266.
FT CONFLICT 435 435 R -> A (in Ref. 1; AAC50384).
FT CONFLICT 531 531 K -> R (in Ref. 3; BAH13897).
SQ SEQUENCE 539 AA; 57924 MW; 39913C0D0735180D CRC64;
MPENVAPRSG ATAGAAGGRG KGAYQDRDKP AQIRFSNISA AKAVADAIRT SLGPKGMDKM
IQDGKGDVTI TNDGATILKQ MQVLHPAARM LVELSKAQDI EAGDGTTSVV IIAGSLLDSC
TKLLQKGIHP TIISESFQKA LEKGIEILTD MSRPVELSDR ETLLNSATTS LNSKVVSQYS
SLLSPMSVNA VMKVIDPATA TSVDLRDIKI VKKLGGTIDD CELVEGLVLT QKVSNSGITR
VEKAKIGLIQ FCLSAPKTDM DNQIVVSDYA QMDRVLREER AYILNLVKQI KKTGCNVLLI
QKSILRDALS DLALHFLNKM KIMVIKDIER EDIEFICKTI GTKPVAHIDQ FTADMLGSAE
LAEEVNLNGS GKLLKITGCA SPGKTVTIVV RGSNKLVIEE AERSIHDALC VIRCLVKKRA
LIAGGGAPEI ELALRLTEYS RTLSGMESYC VRAFADAMEV IPSTLAENAG LNPISTVTEL
RNRHAQGEKT AGINVRKGGI SNILEELVVQ PLLVSVSALT LATETVRSIL KIDDVVNTR
//
ID TCPD_HUMAN Reviewed; 539 AA.
AC P50991; B2R6I3; B7Z8B1; F5H5W3; O14870; Q53QP9; Q96C51;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 4.
DT 22-JAN-2014, entry version 132.
DE RecName: Full=T-complex protein 1 subunit delta;
DE Short=TCP-1-delta;
DE AltName: Full=CCT-delta;
DE AltName: Full=Stimulator of TAR RNA-binding;
GN Name=CCT4; Synonyms=CCTD, SRB;
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] (ISOFORM 1), AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=8626763; DOI=10.1074/jbc.271.8.4201;
RA Wu-Baer F., Lane W.S., Gaynor R.B.;
RT "Identification of a group of cellular cofactors that stimulate the
RT binding of RNA polymerase II and TRP-185 to human immunodeficiency
RT virus 1 TAR RNA.";
RL J. Biol. Chem. 271:4201-4208(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9819444;
RA Won K.-A., Schumacher R.J., Farr G.W., Horwich A.L., Reed S.I.;
RT "Maturation of human cyclin E requires the function of eukaryotic
RT chaperonin CCT.";
RL Mol. Cell. Biol. 18:7584-7589(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Thymus;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 2-8.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [7]
RP PROTEIN SEQUENCE OF 420-435, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V., Barblan J., Quadroni M.;
RL Submitted (MAR-2004) to UniProtKB.
RN [8]
RP INTERACTION WITH PACRG.
RX PubMed=14532270; DOI=10.1074/jbc.M309655200;
RA Imai Y., Soda M., Murakami T., Shoji M., Abe K., Takahashi R.;
RT "A product of the human gene adjacent to parkin is a component of Lewy
RT bodies and suppresses Pael receptor-induced cell death.";
RL J. Biol. Chem. 278:51901-51910(2003).
RN [9]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-288; LYS-302; LYS-319 AND
RP LYS-326, AND 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 [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND IDENTIFICATION IN BBS/CCT COMPLEX.
RX PubMed=20080638; DOI=10.1073/pnas.0910268107;
RA Seo S., Baye L.M., Schulz N.P., Beck J.S., Zhang Q., Slusarski D.C.,
RA Sheffield V.C.;
RT "BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family
RT chaperonins and mediate BBSome assembly.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:1488-1493(2010).
RN [12]
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 [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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).
CC -!- FUNCTION: Molecular chaperone; assists the folding of proteins
CC upon ATP hydrolysis. As part of the BBS/CCT complex may play a
CC role in the assembly of BBSome, a complex involved in ciliogenesis
CC regulating transports vesicles to the cilia. Known to play a role,
CC in vitro, in the folding of actin and tubulin.
CC -!- SUBUNIT: Heterooligomeric complex of about 850 to 900 kDa that
CC forms two stacked rings, 12 to 16 nm in diameter. Interacts with
CC PACRG. Component of the BBS/CCT complex composed at least of MKKS,
CC BBS10, BBS12, TCP1, CCT2, CCT3, CCT4, CCT5 AND CCT8.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Melanosome. Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome.
CC Note=Identified by mass spectrometry in melanosome fractions from
CC stage I to stage IV.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P50991-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P50991-2; Sequence=VSP_045537;
CC Note=No experimental confirmation available;
CC -!- SIMILARITY: Belongs to the TCP-1 chaperonin family.
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DR EMBL; U38846; AAC50384.1; -; mRNA.
DR EMBL; AF026291; AAC96010.1; -; mRNA.
DR EMBL; AK303082; BAH13897.1; -; mRNA.
DR EMBL; AK312586; BAG35480.1; -; mRNA.
DR EMBL; AC107081; AAY24140.1; -; Genomic_DNA.
DR EMBL; BC014676; AAH14676.1; -; mRNA.
DR EMBL; BC106934; AAI06935.1; -; mRNA.
DR EMBL; BC106933; AAI06934.1; -; mRNA.
DR RefSeq; NP_001243650.1; NM_001256721.1.
DR RefSeq; NP_006421.2; NM_006430.3.
DR UniGene; Hs.421509; -.
DR ProteinModelPortal; P50991; -.
DR SMR; P50991; 18-539.
DR DIP; DIP-32971N; -.
DR IntAct; P50991; 44.
DR MINT; MINT-1157924; -.
DR STRING; 9606.ENSP00000377958; -.
DR PhosphoSite; P50991; -.
DR DMDM; 52001478; -.
DR REPRODUCTION-2DPAGE; IPI00302927; -.
DR UCD-2DPAGE; P50991; -.
DR PaxDb; P50991; -.
DR PeptideAtlas; P50991; -.
DR PRIDE; P50991; -.
DR DNASU; 10575; -.
DR Ensembl; ENST00000394440; ENSP00000377958; ENSG00000115484.
DR Ensembl; ENST00000544079; ENSP00000443061; ENSG00000115484.
DR GeneID; 10575; -.
DR KEGG; hsa:10575; -.
DR UCSC; uc010yps.3; human.
DR CTD; 10575; -.
DR GeneCards; GC02M062095; -.
DR HGNC; HGNC:1617; CCT4.
DR HPA; HPA029349; -.
DR MIM; 605142; gene.
DR neXtProt; NX_P50991; -.
DR PharmGKB; PA26181; -.
DR eggNOG; COG0459; -.
DR HOGENOM; HOG000226735; -.
DR HOVERGEN; HBG106507; -.
DR InParanoid; P50991; -.
DR KO; K09496; -.
DR OMA; MNVIHPA; -.
DR OrthoDB; EOG722J8B; -.
DR PhylomeDB; P50991; -.
DR Reactome; REACT_17015; Metabolism of proteins.
DR ChiTaRS; CCT4; human.
DR GeneWiki; CCT4; -.
DR GenomeRNAi; 10575; -.
DR NextBio; 40137; -.
DR PMAP-CutDB; P50991; -.
DR PRO; PR:P50991; -.
DR ArrayExpress; P50991; -.
DR Bgee; P50991; -.
DR CleanEx; HS_CCT4; -.
DR Genevestigator; P50991; -.
DR GO; GO:0005813; C:centrosome; IDA:MGI.
DR GO; GO:0005832; C:chaperonin-containing T-complex; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005874; C:microtubule; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0002199; C:zona pellucida receptor complex; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0051082; F:unfolded protein binding; TAS:ProtInc.
DR GO; GO:0051084; P:'de novo' posttranslational protein folding; TAS:Reactome.
DR GO; GO:0007339; P:binding of sperm to zona pellucida; IEA:Ensembl.
DR Gene3D; 1.10.560.10; -; 2.
DR Gene3D; 3.30.260.10; -; 2.
DR Gene3D; 3.50.7.10; -; 1.
DR InterPro; IPR012717; Chap_CCT_delta.
DR InterPro; IPR017998; Chaperone_TCP-1.
DR InterPro; IPR002194; Chaperonin_TCP-1_CS.
DR InterPro; IPR002423; Cpn60/TCP-1.
DR InterPro; IPR027409; GroEL-like_apical_dom.
DR InterPro; IPR027413; GROEL-like_equatorial.
DR InterPro; IPR027410; TCP-1-like_intermed.
DR PANTHER; PTHR11353; PTHR11353; 1.
DR Pfam; PF00118; Cpn60_TCP1; 1.
DR PRINTS; PR00304; TCOMPLEXTCP1.
DR SUPFAM; SSF48592; SSF48592; 2.
DR SUPFAM; SSF52029; SSF52029; 1.
DR TIGRFAMs; TIGR02342; chap_CCT_delta; 1.
DR PROSITE; PS00750; TCP1_1; 1.
DR PROSITE; PS00751; TCP1_2; 1.
DR PROSITE; PS00995; TCP1_3; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; ATP-binding; Chaperone;
KW Complete proteome; Cytoplasm; Cytoskeleton; Direct protein sequencing;
KW Nucleotide-binding; Polymorphism; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 539 T-complex protein 1 subunit delta.
FT /FTId=PRO_0000128332.
FT MOD_RES 288 288 N6-acetyllysine.
FT MOD_RES 302 302 N6-acetyllysine.
FT MOD_RES 319 319 N6-acetyllysine.
FT MOD_RES 326 326 N6-acetyllysine.
FT VAR_SEQ 60 89 Missing (in isoform 2).
FT /FTId=VSP_045537.
FT VARIANT 112 112 I -> V (in dbSNP:rs2272428).
FT /FTId=VAR_052266.
FT CONFLICT 435 435 R -> A (in Ref. 1; AAC50384).
FT CONFLICT 531 531 K -> R (in Ref. 3; BAH13897).
SQ SEQUENCE 539 AA; 57924 MW; 39913C0D0735180D CRC64;
MPENVAPRSG ATAGAAGGRG KGAYQDRDKP AQIRFSNISA AKAVADAIRT SLGPKGMDKM
IQDGKGDVTI TNDGATILKQ MQVLHPAARM LVELSKAQDI EAGDGTTSVV IIAGSLLDSC
TKLLQKGIHP TIISESFQKA LEKGIEILTD MSRPVELSDR ETLLNSATTS LNSKVVSQYS
SLLSPMSVNA VMKVIDPATA TSVDLRDIKI VKKLGGTIDD CELVEGLVLT QKVSNSGITR
VEKAKIGLIQ FCLSAPKTDM DNQIVVSDYA QMDRVLREER AYILNLVKQI KKTGCNVLLI
QKSILRDALS DLALHFLNKM KIMVIKDIER EDIEFICKTI GTKPVAHIDQ FTADMLGSAE
LAEEVNLNGS GKLLKITGCA SPGKTVTIVV RGSNKLVIEE AERSIHDALC VIRCLVKKRA
LIAGGGAPEI ELALRLTEYS RTLSGMESYC VRAFADAMEV IPSTLAENAG LNPISTVTEL
RNRHAQGEKT AGINVRKGGI SNILEELVVQ PLLVSVSALT LATETVRSIL KIDDVVNTR
//
MIM
605142
*RECORD*
*FIELD* NO
605142
*FIELD* TI
*605142 CHAPERONIN CONTAINING T-COMPLEX POLYPEPTIDE 1, SUBUNIT 4; CCT4
;;CHAPERONIN CONTAINING TCP1, SUBUNIT 4;;
read moreCCT-DELTA; CCTD;;
STIMULATOR OF TAR RNA-BINDING PROTEINS; SRB
*FIELD* TX
DESCRIPTION
The chaperonin containing TCP1 (186980) complex (CCT), also called the
TCP1 ring complex, consists of 2 back-to-back rings, each containing 8
unique but homologous subunits, such as CCT4. CCT assists the folding of
newly translated polypeptide substrates through multiple rounds of
ATP-driven release and rebinding of partially folded intermediate forms.
Substrates of CCT include the cytoskeletal proteins actin (see 102560)
and tubulin (see 191130), as well as alpha-transducin (139330) (Won et
al., 1998).
CLONING
Human immunodeficiency virus-1 (HIV-1) expression is dependent on a
number of regulatory elements in the long terminal repeat. The binding
of both RNA polymerase II and TAR-binding protein-1 (TARBP1; 605052) to
the TAR regulatory element is enhanced by the presence of cofactors that
are unable to bind TAR independently. By purifying cofactor proteins
capable of enhancing the binding of TARBP1 to TAR, microsequence
analysis, and PCR using degenerate primers on HeLa cell cDNA, Wu-Baer et
al. (1996) isolated a cDNA encoding CCT4, which they called SRB
(stimulator of TAR RNA-binding proteins). The deduced 539-amino acid
CCT4 protein shares homology with a number of chaperonin family
proteins. Northern blot analysis detected a 2.0-kb CCT4 transcript in
all tissues tested. Western blot analysis showed that CCT4 is expressed
as a 62-kD protein.
Cyclin E (CCNE1; 123837), a partner of the cyclin-dependent kinase CDK2
(116953), is implicated in the positive control of the G1/S phase
transition. CCNE1 degradation is regulated by ubiquitination and
proteasomal action, which occur upon autophosphorylation and activation
of the CCNE1-CDK2 complex. Using a yeast-based screen to identify
proteins that interact with CCNE1, Won et al. (1998) obtained a cDNA
encoding CCT4, which they called CCT-delta.
GENE FUNCTION
Binding analysis by Wu-Baer et al. (1996) confirmed that CCT4 enhances
the binding of TARBP1 and RNA polymerase II to TAR. The binding was
further enhanced by the presence of other recombinant cofactors, such as
EEF1A1 (130590) and PTB (600693).
By mutational analysis Won et al. (1998) found that CCT is essential for
CCNE1 maturation and accumulation.
ANIMAL MODEL
Jacobs et al. (1981) described an autosomal recessive early-onset
sensory neuropathy in a Sprague-Dawley rat strain, which they named
'mutilated foot' (mf). The main clinical features included ataxia,
insensitivity to pain, and foot ulceration. The pathologic features
included a severe reduction in the number of sensory ganglia and fibers.
Lee et al. (2003) mapped the mf locus to the distal end of rat
chromosome 14, a region syntenic to mouse proximal 11 and human 2p15.
Sequence analysis of 4 candidate genes revealed a 1349G-A transition in
CCT4, resulting in a cys450-to-tyr (C450Y) substitution at a highly
conserved residue, segregating with the mf phenotype. No mutations were
identified in the human CCT4 gene within a cohort of 39 patients with
hereditary sensory neuropathy or axonal Charcot-Marie-Tooth disease type
2 (see 118210). As CCT4 is involved in folding tubulin (191130), actin
(102560), and other cytosolic proteins, Lee et al. (2003) suggested that
misfolding of proteins may be a cause of this group of neuropathies.
*FIELD* RF
1. Jacobs, J. M.; Scaravilli, F.; Duchen, L. W.; Mertin, J.: A new
neurological rat mutant 'mutilated foot.' J. Anat. 132: 525-543,
1981.
2. Lee, M.-J.; Stephenson, D. A.; Groves, M. J.; Sweeney, M. G.; Davis,
M. B.; An, S.-F.; Houlden, H.; Salih, M. A. M.; Timmerman, V.; de
Jonghe, P.; Auer-Grumbach, M.; Di Maria, E.; Scaravilli, F.; Wood,
N. W.; Reilly, M. M.: Hereditary sensory neuropathy is caused by
a mutation in the delta subunit of the cytosolic chaperonin-containing
t-complex peptide-1 (Cct4) gene. Hum. Molec. Genet. 12: 1917-1925,
2003.
3. Won, K.-A.; Schumacher, R. J.; Farr, G. W.; Horwich, A. L.; Reed,
S. I.: Maturation of human cyclin E requires the function of eukaryotic
chaperonin CCT. Molec. Cell. Biol. 18: 7584-7589, 1998.
4. Wu-Baer, F.; Lane, W. S.; Gaynor, R. B.: Identification of a group
of cellular cofactors that stimulate the binding of RNA polymerase
II and TRP-185 to human immunodeficiency virus 1 TAR RNA. J. Biol.
Chem. 271: 4201-4208, 1996.
*FIELD* CN
George E. Tiller - updated: 5/6/2005
*FIELD* CD
Paul J. Converse: 7/13/2000
*FIELD* ED
carol: 10/31/2007
mgross: 11/20/2006
tkritzer: 5/6/2005
mgross: 7/13/2000
*RECORD*
*FIELD* NO
605142
*FIELD* TI
*605142 CHAPERONIN CONTAINING T-COMPLEX POLYPEPTIDE 1, SUBUNIT 4; CCT4
;;CHAPERONIN CONTAINING TCP1, SUBUNIT 4;;
read moreCCT-DELTA; CCTD;;
STIMULATOR OF TAR RNA-BINDING PROTEINS; SRB
*FIELD* TX
DESCRIPTION
The chaperonin containing TCP1 (186980) complex (CCT), also called the
TCP1 ring complex, consists of 2 back-to-back rings, each containing 8
unique but homologous subunits, such as CCT4. CCT assists the folding of
newly translated polypeptide substrates through multiple rounds of
ATP-driven release and rebinding of partially folded intermediate forms.
Substrates of CCT include the cytoskeletal proteins actin (see 102560)
and tubulin (see 191130), as well as alpha-transducin (139330) (Won et
al., 1998).
CLONING
Human immunodeficiency virus-1 (HIV-1) expression is dependent on a
number of regulatory elements in the long terminal repeat. The binding
of both RNA polymerase II and TAR-binding protein-1 (TARBP1; 605052) to
the TAR regulatory element is enhanced by the presence of cofactors that
are unable to bind TAR independently. By purifying cofactor proteins
capable of enhancing the binding of TARBP1 to TAR, microsequence
analysis, and PCR using degenerate primers on HeLa cell cDNA, Wu-Baer et
al. (1996) isolated a cDNA encoding CCT4, which they called SRB
(stimulator of TAR RNA-binding proteins). The deduced 539-amino acid
CCT4 protein shares homology with a number of chaperonin family
proteins. Northern blot analysis detected a 2.0-kb CCT4 transcript in
all tissues tested. Western blot analysis showed that CCT4 is expressed
as a 62-kD protein.
Cyclin E (CCNE1; 123837), a partner of the cyclin-dependent kinase CDK2
(116953), is implicated in the positive control of the G1/S phase
transition. CCNE1 degradation is regulated by ubiquitination and
proteasomal action, which occur upon autophosphorylation and activation
of the CCNE1-CDK2 complex. Using a yeast-based screen to identify
proteins that interact with CCNE1, Won et al. (1998) obtained a cDNA
encoding CCT4, which they called CCT-delta.
GENE FUNCTION
Binding analysis by Wu-Baer et al. (1996) confirmed that CCT4 enhances
the binding of TARBP1 and RNA polymerase II to TAR. The binding was
further enhanced by the presence of other recombinant cofactors, such as
EEF1A1 (130590) and PTB (600693).
By mutational analysis Won et al. (1998) found that CCT is essential for
CCNE1 maturation and accumulation.
ANIMAL MODEL
Jacobs et al. (1981) described an autosomal recessive early-onset
sensory neuropathy in a Sprague-Dawley rat strain, which they named
'mutilated foot' (mf). The main clinical features included ataxia,
insensitivity to pain, and foot ulceration. The pathologic features
included a severe reduction in the number of sensory ganglia and fibers.
Lee et al. (2003) mapped the mf locus to the distal end of rat
chromosome 14, a region syntenic to mouse proximal 11 and human 2p15.
Sequence analysis of 4 candidate genes revealed a 1349G-A transition in
CCT4, resulting in a cys450-to-tyr (C450Y) substitution at a highly
conserved residue, segregating with the mf phenotype. No mutations were
identified in the human CCT4 gene within a cohort of 39 patients with
hereditary sensory neuropathy or axonal Charcot-Marie-Tooth disease type
2 (see 118210). As CCT4 is involved in folding tubulin (191130), actin
(102560), and other cytosolic proteins, Lee et al. (2003) suggested that
misfolding of proteins may be a cause of this group of neuropathies.
*FIELD* RF
1. Jacobs, J. M.; Scaravilli, F.; Duchen, L. W.; Mertin, J.: A new
neurological rat mutant 'mutilated foot.' J. Anat. 132: 525-543,
1981.
2. Lee, M.-J.; Stephenson, D. A.; Groves, M. J.; Sweeney, M. G.; Davis,
M. B.; An, S.-F.; Houlden, H.; Salih, M. A. M.; Timmerman, V.; de
Jonghe, P.; Auer-Grumbach, M.; Di Maria, E.; Scaravilli, F.; Wood,
N. W.; Reilly, M. M.: Hereditary sensory neuropathy is caused by
a mutation in the delta subunit of the cytosolic chaperonin-containing
t-complex peptide-1 (Cct4) gene. Hum. Molec. Genet. 12: 1917-1925,
2003.
3. Won, K.-A.; Schumacher, R. J.; Farr, G. W.; Horwich, A. L.; Reed,
S. I.: Maturation of human cyclin E requires the function of eukaryotic
chaperonin CCT. Molec. Cell. Biol. 18: 7584-7589, 1998.
4. Wu-Baer, F.; Lane, W. S.; Gaynor, R. B.: Identification of a group
of cellular cofactors that stimulate the binding of RNA polymerase
II and TRP-185 to human immunodeficiency virus 1 TAR RNA. J. Biol.
Chem. 271: 4201-4208, 1996.
*FIELD* CN
George E. Tiller - updated: 5/6/2005
*FIELD* CD
Paul J. Converse: 7/13/2000
*FIELD* ED
carol: 10/31/2007
mgross: 11/20/2006
tkritzer: 5/6/2005
mgross: 7/13/2000