MKKS_MOUSE
ID MKKS_MOUSE Reviewed; 570 AA.
AC Q9JI70; Q8BGQ3;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Molecular chaperone MKKS {ECO:0000305};
DE AltName: Full=McKusick-Kaufman/Bardet-Biedl syndromes putative chaperonin;
DE AltName: Full=Protein Bbs6 homolog;
GN Name=Mkks; Synonyms=Bbs6;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10802661; DOI=10.1038/75637;
RA Stone D.L., Slavotinek A.M., Bouffard G.G., Banerjee-Basu S.,
RA Baxevanis A.D., Barr M., Biesecker L.G.;
RT "Mutation of a gene encoding a putative chaperonin causes McKusick-Kaufman
RT syndrome.";
RL Nat. Genet. 25:79-82(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Olfactory bulb;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=15772095; DOI=10.1093/hmg/ddi123;
RA Fath M.A., Mullins R.F., Searby C., Nishimura D.Y., Wei J., Rahmouni K.,
RA Davis R.E., Tayeh M.K., Andrews M., Yang B., Sigmund C.D., Stone E.M.,
RA Sheffield V.C.;
RT "Mkks-null mice have a phenotype resembling Bardet-Biedl syndrome.";
RL Hum. Mol. Genet. 14:1109-1118(2005).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=15731008; DOI=10.1242/jcs.01676;
RA Kim J.C., Ou Y.Y., Badano J.L., Esmail M.A., Leitch C.C., Fiedrich E.,
RA Beales P.L., Archibald J.M., Katsanis N., Rattner J.B., Leroux M.R.;
RT "MKKS/BBS6, a divergent chaperonin-like protein linked to the obesity
RT disorder Bardet-Biedl syndrome, is a novel centrosomal component required
RT for cytokinesis.";
RL J. Cell Sci. 118:1007-1020(2005).
RN [7]
RP DISRUPTION PHENOTYPE.
RX PubMed=18317593; DOI=10.1172/jci32357;
RA Rahmouni K., Fath M.A., Seo S., Thedens D.R., Berry C.J., Weiss R.,
RA Nishimura D.Y., Sheffield V.C.;
RT "Leptin resistance contributes to obesity and hypertension in mouse models
RT of Bardet-Biedl syndrome.";
RL J. Clin. Invest. 118:1458-1467(2008).
RN [8]
RP FUNCTION.
RX PubMed=28753627; DOI=10.1371/journal.pgen.1006936;
RA Scott C.A., Marsden A.N., Rebagliati M.R., Zhang Q., Chamling X.,
RA Searby C.C., Baye L.M., Sheffield V.C., Slusarski D.C.;
RT "Nuclear/cytoplasmic transport defects in BBS6 underlie congenital heart
RT disease through perturbation of a chromatin remodeling protein.";
RL PLoS Genet. 13:E1006936-E1006936(2017).
CC -!- FUNCTION: Probable molecular chaperone that assists the folding of
CC proteins upon ATP hydrolysis (By similarity). Plays a role in the
CC assembly of BBSome, a complex involved in ciliogenesis regulating
CC transports vesicles to the cilia (PubMed:28753627). May play a role in
CC protein processing in limb, cardiac and reproductive system
CC development. May play a role in cytokinesis (By similarity).
CC {ECO:0000250|UniProtKB:Q9NPJ1, ECO:0000269|PubMed:28753627}.
CC -!- SUBUNIT: Component of a complex composed at least of MKKS, BBS10,
CC BBS12, TCP1, CCT2, CCT3, CCT4, CCT5 AND CCT8. Interacts with STUB1.
CC Interacts with BBS2 (via coiled coil domain). Interacts with CCDC28B.
CC Interacts with BBS12. Interacts with SMARCC1, a component of the
CC SWI/SNF complexes; the interaction takes place predominantly in the
CC cytoplasm and may modulate SMARCC1 location (By similarity). Interacts
CC with DLEC1 (By similarity). {ECO:0000250|UniProtKB:Q9NPJ1}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing
CC center, centrosome {ECO:0000250|UniProtKB:Q9NPJ1}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q9NPJ1}. Nucleus {ECO:0000250|UniProtKB:Q9NPJ1}.
CC Note=The majority of the protein resides within the pericentriolar
CC material (PCM), a proteinaceous tube surrounding centrioles. During
CC interphase, the protein is confined to the lateral surfaces of the PCM
CC but during mitosis it relocalizes throughout the PCM and is found at
CC the intercellular bridge. The MKSS protein is highly mobile and rapidly
CC shuttles between the cytosol and centrosome.
CC {ECO:0000250|UniProtKB:Q9NPJ1}.
CC -!- TISSUE SPECIFICITY: Widely expressed in adult and fetal tissues.
CC Expressed in the developing heart, brain retina, limb buds, as well as
CC in the developing neural tube. Expressed in the embryo in the first and
CC second branchial arches. Expressed in parafin embedded tissue sections
CC of brain, kidney, retina, olfactory epithelium and the ependymal layer
CC of ventricles. Detected only in restricted regions of these tissue
CC sections, including the ciliated border of renal tubules, the
CC connecting cilium and the inner and outer nuclear layers of retina, and
CC the ciliated layer of olfactory epithelia.
CC {ECO:0000269|PubMed:15731008}.
CC -!- DISRUPTION PHENOTYPE: Mice demonstrate retinal degeneration, failure of
CC spermatozoa flagella formation, elevated blood pressure, olfactory
CC deficits, and social dominance, but no polydactyly nor vaginal
CC abnormalities. The phenotype closely resembles the phenotype of other
CC mouse models of Bardet-Biedl syndrome (Bbs2 deficient and Bbs4
CC deficient). Obesity is associated with hyperleptinemia and resistance
CC to the anorectic and weight-reducing effects of leptin. Although mice
CC are resistant to the metabolic actions of leptin, mice remain
CC responsive to the effects of leptin on renal sympathetic nerve activity
CC and arterial pressure and develop hypertension. BBS mice have decreased
CC hypothalamic expression of proopiomelanocortin (POMC). BBS genes play
CC an important role in maintaining leptin sensitivity in POMC neurons.
CC {ECO:0000269|PubMed:15772095, ECO:0000269|PubMed:18317593}.
CC -!- SIMILARITY: Belongs to the TCP-1 chaperonin family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF254074; AAF73965.1; -; mRNA.
DR EMBL; AK032528; BAC27912.1; -; mRNA.
DR EMBL; AK032554; BAC27921.1; -; mRNA.
DR EMBL; AL731706; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC117836; AAI17837.1; -; mRNA.
DR CCDS; CCDS16794.1; -.
DR RefSeq; NP_001135418.1; NM_001141946.1.
DR RefSeq; NP_067502.2; NM_021527.2.
DR RefSeq; XP_006500033.1; XM_006499970.1.
DR RefSeq; XP_011238023.1; XM_011239721.1.
DR AlphaFoldDB; Q9JI70; -.
DR SMR; Q9JI70; -.
DR DIP; DIP-60355N; -.
DR IntAct; Q9JI70; 5.
DR STRING; 10090.ENSMUSP00000105716; -.
DR iPTMnet; Q9JI70; -.
DR PhosphoSitePlus; Q9JI70; -.
DR PaxDb; Q9JI70; -.
DR PRIDE; Q9JI70; -.
DR ProteomicsDB; 295951; -.
DR Antibodypedia; 24160; 150 antibodies from 24 providers.
DR DNASU; 59030; -.
DR Ensembl; ENSMUST00000028730; ENSMUSP00000028730; ENSMUSG00000027274.
DR Ensembl; ENSMUST00000110089; ENSMUSP00000105716; ENSMUSG00000027274.
DR GeneID; 59030; -.
DR KEGG; mmu:59030; -.
DR UCSC; uc008moq.2; mouse.
DR CTD; 8195; -.
DR MGI; MGI:1891836; Mkks.
DR VEuPathDB; HostDB:ENSMUSG00000027274; -.
DR eggNOG; KOG0360; Eukaryota.
DR GeneTree; ENSGT00390000007214; -.
DR HOGENOM; CLU_478131_0_0_1; -.
DR InParanoid; Q9JI70; -.
DR OMA; FVCQKVI; -.
DR OrthoDB; 1539473at2759; -.
DR PhylomeDB; Q9JI70; -.
DR TreeFam; TF329106; -.
DR Reactome; R-MMU-5620922; BBSome-mediated cargo-targeting to cilium.
DR BioGRID-ORCS; 59030; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Mkks; mouse.
DR PRO; PR:Q9JI70; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q9JI70; protein.
DR Bgee; ENSMUSG00000027274; Expressed in dentate gyrus of hippocampal formation granule cell and 204 other tissues.
DR Genevisible; Q9JI70; MM.
DR GO; GO:0005813; C:centrosome; ISO:MGI.
DR GO; GO:0036064; C:ciliary basal body; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:1902636; C:kinociliary basal body; IDA:MGI.
DR GO; GO:0031514; C:motile cilium; IMP:BHF-UCL.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:MGI.
DR GO; GO:0051082; F:unfolded protein binding; IEA:InterPro.
DR GO; GO:0014824; P:artery smooth muscle contraction; IMP:MGI.
DR GO; GO:0048854; P:brain morphogenesis; IMP:MGI.
DR GO; GO:0051216; P:cartilage development; IMP:MGI.
DR GO; GO:0021987; P:cerebral cortex development; IMP:MGI.
DR GO; GO:0051131; P:chaperone-mediated protein complex assembly; IMP:MGI.
DR GO; GO:0060271; P:cilium assembly; IMP:BHF-UCL.
DR GO; GO:0050910; P:detection of mechanical stimulus involved in sensory perception of sound; IMP:MGI.
DR GO; GO:0032502; P:developmental process; IBA:GO_Central.
DR GO; GO:0060324; P:face development; IMP:MGI.
DR GO; GO:0045444; P:fat cell differentiation; IEP:BHF-UCL.
DR GO; GO:0010467; P:gene expression; IMP:MGI.
DR GO; GO:0021766; P:hippocampus development; IMP:MGI.
DR GO; GO:0046907; P:intracellular transport; IBA:GO_Central.
DR GO; GO:0033210; P:leptin-mediated signaling pathway; IMP:MGI.
DR GO; GO:0030837; P:negative regulation of actin filament polymerization; IMP:MGI.
DR GO; GO:0038108; P:negative regulation of appetite by leptin-mediated signaling pathway; IMP:BHF-UCL.
DR GO; GO:0045776; P:negative regulation of blood pressure; IMP:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:MGI.
DR GO; GO:0034260; P:negative regulation of GTPase activity; IMP:MGI.
DR GO; GO:1905515; P:non-motile cilium assembly; IMP:MGI.
DR GO; GO:0045494; P:photoreceptor cell maintenance; IMP:MGI.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IMP:MGI.
DR GO; GO:0006457; P:protein folding; IEA:InterPro.
DR GO; GO:0060296; P:regulation of cilium beat frequency involved in ciliary motility; IMP:BHF-UCL.
DR GO; GO:0051492; P:regulation of stress fiber assembly; IMP:MGI.
DR GO; GO:0044321; P:response to leptin; IMP:MGI.
DR GO; GO:0007608; P:sensory perception of smell; IMP:MGI.
DR GO; GO:0035176; P:social behavior; IMP:MGI.
DR GO; GO:0007286; P:spermatid development; IMP:MGI.
DR GO; GO:0021756; P:striatum development; IMP:MGI.
DR GO; GO:0042311; P:vasodilation; IMP:MGI.
DR Gene3D; 1.10.560.10; -; 1.
DR Gene3D; 3.30.260.10; -; 1.
DR Gene3D; 3.50.7.10; -; 1.
DR InterPro; IPR002423; Cpn60/GroEL/TCP-1.
DR InterPro; IPR027409; GroEL-like_apical_dom_sf.
DR InterPro; IPR027413; GROEL-like_equatorial_sf.
DR InterPro; IPR028790; MKKS.
DR InterPro; IPR027410; TCP-1-like_intermed_sf.
DR PANTHER; PTHR46787; PTHR46787; 1.
DR Pfam; PF00118; Cpn60_TCP1; 1.
DR SUPFAM; SSF48592; SSF48592; 1.
DR SUPFAM; SSF52029; SSF52029; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Chaperone; Cytoplasm; Cytoskeleton; Nucleotide-binding;
KW Nucleus; Reference proteome.
FT CHAIN 1..570
FT /note="Molecular chaperone MKKS"
FT /id="PRO_0000128416"
FT REGION 198..370
FT /note="Substrate-binding apical domain"
FT /evidence="ECO:0000250|UniProtKB:Q9NPJ1"
FT BINDING 192..199
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT CONFLICT 302
FT /note="K -> R (in Ref. 1; AAF73965)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 570 AA; 61924 MW; 7E2AA28D43028800 CRC64;
MSRLEAKKPS LCKTEPLTSE KVRSTLSVLK GVIASCYGPS GRLKQLHNGL GGCVYTTSQS
SALLRNLSVT HPVLKILTSS VQNHVSCFSD CGLFTAILCC NLIENIQRLD LTPATAIKLN
KYLLSLCTSY LKSEACSCRI PVDFRSTHTF LSLVHSILTS KPACMLTRKE TDHIGALILK
AFLLTIPEST EERMVLGKSI IVPLKGQRVT DSTVLPGLLI EASEVQLRRL LPTQKASGLR
VALFCTSLSG DFSNAGEGVV VAHYQVSLEN AVLEQLLNLG RRLVTDHVDL VLCQKVIHPS
LKQFFSERHV MAIDRVGVTL MESLSKVTGA TPIGSLNPIV STTYGSVKDV CSARFGSKHF
FHLLPNEATV CTLLLCSRND TAWEELKLTC QTAMHVLQLT IKEPWVLLGG GCTETHLAAY
VRHKVHHEAE AIVRDDGCTQ AKLHVAAEAF CSALESVAGS LEHDGGEILI DTKYGHLWSC
QADSASVGNW SDTLSRCGCG LYNSQEELSW SVLRSTYHPF APQTCLPQAA LGSASNLTVD
CFTAKLSGLQ VAVETANLIL DLSYVIEDKN
