MKKS_HUMAN
ID MKKS_HUMAN Reviewed; 570 AA.
AC Q9NPJ1; A8K7B0; D3DW18;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Molecular chaperone MKKS {ECO:0000305};
DE AltName: Full=Bardet-Biedl syndrome 6 protein;
DE AltName: Full=McKusick-Kaufman/Bardet-Biedl syndromes putative chaperonin;
GN Name=MKKS {ECO:0000312|HGNC:HGNC:7108};
GN Synonyms=BBS6 {ECO:0000303|PubMed:28753627};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], VARIANTS MKKS CYS-37; TYR-84 AND SER-242, AND
RP VARIANTS VAL-49 AND CYS-517.
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].
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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].
RC TISSUE=Amygdala;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
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., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., 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., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS BBS6 ASP-52; LEU-155;
RP ALA-286; GLU-345 AND SER-499, AND CHARACTERIZATION OF VARIANT PRO-325.
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 INTERACTION WITH CCDC28B.
RX PubMed=16327777; DOI=10.1038/nature04370;
RA Badano J.L., Leitch C.C., Ansley S.J., May-Simera H., Lawson S.,
RA Lewis R.A., Beales P.L., Dietz H.C., Fisher S., Katsanis N.;
RT "Dissection of epistasis in oligogenic Bardet-Biedl syndrome.";
RL Nature 439:326-330(2006).
RN [8]
RP SUBCELLULAR LOCATION, INTERACTION WITH STUB1, AND CHARACTERIZATION OF
RP VARIANTS BBS6 CYS-37; ALA-57; SER-242; GLU-345 AND SER-499.
RX PubMed=18094050; DOI=10.1091/mbc.e07-07-0631;
RA Hirayama S., Yamazaki Y., Kitamura A., Oda Y., Morito D., Okawa K.,
RA Kimura H., Cyr D.M., Kubota H., Nagata K.;
RT "MKKS is a centrosome-shuttling protein degraded by disease-causing
RT mutations via CHIP-mediated ubiquitination.";
RL Mol. Biol. Cell 19:899-911(2008).
RN [9]
RP FUNCTION, IDENTIFICATION IN A MULTIPROTEIN COMPLEX, INTERACTION WITH BBS2,
RP AND CHARACTERIZATION OF VARIANTS BBS6 CYS-37; ASP-52; ALA-57; TYR-84;
RP PRO-236 AND PRO-277.
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 chaperonins and
RT mediate BBSome assembly.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:1488-1493(2010).
RN [10]
RP INTERACTION WITH BBS12, VARIANT BBS6 ARG-395, AND CHARACTERIZATION OF
RP VARIANT BBS6 ARG-395.
RX PubMed=26900326;
RA Hulleman J.D., Nguyen A., Ramprasad V.L., Murugan S., Gupta R.,
RA Mahindrakar A., Angara R., Sankurathri C., Mootha V.V.;
RT "A novel H395R mutation in MKKS/BBS6 causes retinitis pigmentosa and
RT polydactyly without other findings of Bardet-Biedl or McKusick-Kaufman
RT syndrome.";
RL Mol. Vis. 22:73-81(2016).
RN [11]
RP INTERACTION WITH DLEC1.
RX PubMed=33144677; DOI=10.1038/s41598-020-75957-y;
RA Okitsu Y., Nagano M., Yamagata T., Ito C., Toshimori K., Dohra H.,
RA Fujii W., Yogo K.;
RT "Dlec1 is required for spermatogenesis and male fertility in mice.";
RL Sci. Rep. 10:18883-18883(2020).
RN [12]
RP VARIANT BBS6 ASP-52.
RX PubMed=10973238; DOI=10.1038/79116;
RA Slavotinek A.M., Stone E.M., Mykytyn K., Heckenlively J.R., Green J.S.,
RA Heon E., Musarella M.A., Parfrey P.S., Sheffield V.C., Biesecker L.G.;
RT "Mutations in MKKS cause Bardet-Biedl syndrome.";
RL Nat. Genet. 26:15-16(2000).
RN [13]
RP VARIANTS BBS6 CYS-37; ALA-57 AND PRO-277.
RC TISSUE=Peripheral blood lymphocyte;
RX PubMed=10973251; DOI=10.1038/79201;
RA Katsanis N., Beales P.L., Woods M.O., Lewis R.A., Green J.S., Parfrey P.S.,
RA Ansley S.J., Davidson W.S., Lupski J.R.;
RT "Mutations in MKKS cause obesity, retinal dystrophy and renal malformations
RT associated with Bardet-Biedl syndrome.";
RL Nat. Genet. 26:67-70(2000).
RN [14]
RP VARIANTS BBS6 MET-32; ALA-57; PRO-236; ALA-286; SER-499; ALA-511 AND
RP HIS-518, AND VARIANT SER-242.
RX PubMed=11179009; DOI=10.1086/318794;
RA Beales P.L., Katsanis N., Lewis R.A., Ansley S.J., Elcioglu N., Raza J.,
RA Woods M.O., Green J.S., Parfrey P.S., Davidson W.S., Lupski J.R.;
RT "Genetic and mutational analyses of a large multiethnic Bardet-Biedl cohort
RT reveal a minor involvement of BBS6 and delineate the critical intervals of
RT other loci.";
RL Am. J. Hum. Genet. 68:606-616(2001).
RN [15]
RP VARIANTS BBS6 CYS-37; SER-242 AND SER-499.
RX PubMed=11567139; DOI=10.1126/science.1063525;
RA Katsanis N., Ansley S.J., Badano J.L., Eichers E.R., Lewis R.A.,
RA Hoskins B.E., Scambler P.J., Davidson W.S., Beales P.L., Lupski J.R.;
RT "Triallelic inheritance in Bardet-Biedl syndrome, a Mendelian recessive
RT disorder.";
RL Science 293:2256-2259(2001).
RN [16]
RP VARIANTS BBS6 LEU-155; SER-242 AND GLU-345, AND VARIANT VAL-339.
RX PubMed=12107442; DOI=10.1007/s00439-002-0733-3;
RA Slavotinek A.M., Searby C., Al-Gazali L., Hennekam R.C.M.,
RA Schrander-Stumpel C., Orcana-Losa M., Pardo-Reoyo S., Cantani A., Kumar D.,
RA Capellini Q., Neri G., Zackai E., Biesecker L.G.;
RT "Mutation analysis of the MKKS gene in McKusick-Kaufman syndrome and
RT selected Bardet-Biedl syndrome patients.";
RL Hum. Genet. 110:561-567(2002).
RN [17]
RP VARIANT BBS6 PRO-236, AND VARIANT PRO-325.
RX PubMed=12677556; DOI=10.1086/375178;
RA Beales P.L., Badano J.L., Ross A.J., Ansley S.J., Hoskins B.E., Kirsten B.,
RA Mein C.A., Froguel P., Scambler P.J., Lewis R.A., Lupski J.R., Katsanis N.;
RT "Genetic interaction of BBS1 mutations with alleles at other BBS loci can
RT result in non-Mendelian Bardet-Biedl syndrome.";
RL Am. J. Hum. Genet. 72:1187-1199(2003).
RN [18]
RP VARIANT PRO-325, AND CHARACTERIZATION OF VARIANT PRO-325.
RX PubMed=12837689; DOI=10.1093/hmg/ddg188;
RA Badano J.L., Kim J.C., Hoskins B.E., Lewis R.A., Ansley S.J., Cutler D.J.,
RA Castellan C., Beales P.L., Leroux M.R., Katsanis N.;
RT "Heterozygous mutations in BBS1, BBS2 and BBS6 have a potential epistatic
RT effect on Bardet-Biedl patients with two mutations at a second BBS locus.";
RL Hum. Mol. Genet. 12:1651-1659(2003).
RN [19]
RP VARIANTS BBS6 PRO-181 AND ASN-492.
RX PubMed=12920096; DOI=10.1136/jmg.40.8.e104;
RA Fauser S., Munz M., Besch D.;
RT "Further support for digenic inheritance in Bardet-Biedl syndrome.";
RL J. Med. Genet. 40:E104-E104(2003).
RN [20]
RP VARIANTS BBS6 PRO-237 AND PRO-460, AND VARIANTS VAL-339; CYS-517 AND
RP VAL-532.
RX PubMed=15666242; DOI=10.1086/428679;
RA Karmous-Benailly H., Martinovic J., Gubler M.-C., Sirot Y., Clech L.,
RA Ozilou C., Auge J., Brahimi N., Etchevers H., Detrait E., Esculpavit C.,
RA Audollent S., Goudefroye G., Gonzales M., Tantau J., Loget P., Joubert M.,
RA Gaillard D., Jeanne-Pasquier C., Delezoide A.-L., Peter M.-O., Plessis G.,
RA Simon-Bouy B., Dollfus H., Le Merrer M., Munnich A., Encha-Razavi F.,
RA Vekemans M., Attie-Bitach T.;
RT "Antenatal presentation of Bardet-Biedl syndrome may mimic Meckel
RT syndrome.";
RL Am. J. Hum. Genet. 76:493-504(2005).
RN [21]
RP VARIANTS BBS6 ALA-237 AND PRO-237, AND VARIANTS VAL-339; CYS-517 AND
RP VAL-532.
RX PubMed=15770229; DOI=10.1038/sj.ejhg.5201372;
RA Hichri H., Stoetzel C., Laurier V., Caron S., Sigaudy S., Sarda P.,
RA Hamel C., Martin-Coignard D., Gilles M., Leheup B., Holder M., Kaplan J.,
RA Bitoun P., Lacombe D., Verloes A., Bonneau D., Perrin-Schmitt F.,
RA Brandt C., Besancon A.-F., Mandel J.-L., Cossee M., Dollfus H.;
RT "Testing for triallelism: analysis of six BBS genes in a Bardet-Biedl
RT syndrome family cohort.";
RL Eur. J. Hum. Genet. 13:607-616(2005).
RN [22]
RP VARIANTS SER-242; CYS-517 AND VAL-532.
RX PubMed=15483080; DOI=10.1210/jc.2004-0465;
RA Andersen K.L., Echwald S.M., Larsen L.H., Hamid Y.H., Glumer C.,
RA Jorgensen T., Borch-Johnsen K., Andersen T., Sorensen T.I., Hansen T.,
RA Pedersen O.;
RT "Variation of the McKusick-Kaufman gene and studies of relationships with
RT common forms of obesity.";
RL J. Clin. Endocrinol. Metab. 90:225-230(2005).
RN [23]
RP VARIANT SER-242, AND DISCUSSION OF THE PATHOLOGICAL ROLE OF VARIANT
RP SER-242.
RX PubMed=20120035; DOI=10.1002/humu.21204;
RA Hjortshoj T.D., Gronskov K., Philp A.R., Nishimura D.Y., Riise R.,
RA Sheffield V.C., Rosenberg T., Brondum-Nielsen K.;
RT "Bardet-Biedl syndrome in Denmark -- report of 13 novel sequence variations
RT in six genes.";
RL Hum. Mutat. 31:429-436(2010).
RN [24]
RP VARIANTS BBS6 ARG-41; ARG-99 AND LEU-299, AND VARIANT THR-488.
RX PubMed=21344540; DOI=10.1002/humu.21480;
RA Deveault C., Billingsley G., Duncan J.L., Bin J., Theal R., Vincent A.,
RA Fieggen K.J., Gerth C., Noordeh N., Traboulsi E.I., Fishman G.A.,
RA Chitayat D., Knueppel T., Millan J.M., Munier F.L., Kennedy D.,
RA Jacobson S.G., Innes A.M., Mitchell G.A., Boycott K., Heon E.;
RT "BBS genotype-phenotype assessment of a multiethnic patient cohort calls
RT for a revision of the disease definition.";
RL Hum. Mutat. 32:610-619(2011).
RN [25]
RP VARIANT BBS6 ALA-57.
RX PubMed=22152675; DOI=10.1016/j.ajhg.2011.11.005;
RA Huang L., Szymanska K., Jensen V.L., Janecke A.R., Innes A.M., Davis E.E.,
RA Frosk P., Li C., Willer J.R., Chodirker B.N., Greenberg C.R., McLeod D.R.,
RA Bernier F.P., Chudley A.E., Muller T., Shboul M., Logan C.V., Loucks C.M.,
RA Beaulieu C.L., Bowie R.V., Bell S.M., Adkins J., Zuniga F.I., Ross K.D.,
RA Wang J., Ban M.R., Becker C., Nurnberg P., Douglas S., Craft C.M.,
RA Akimenko M.A., Hegele R.A., Ober C., Utermann G., Bolz H.J., Bulman D.E.,
RA Katsanis N., Blacque O.E., Doherty D., Parboosingh J.S., Leroux M.R.,
RA Johnson C.A., Boycott K.M.;
RT "TMEM237 is mutated in individuals with a Joubert syndrome related disorder
RT and expands the role of the TMEM family at the ciliary transition zone.";
RL Am. J. Hum. Genet. 89:713-730(2011).
RN [26]
RP VARIANT BBS6 40-SER--ASN-570 DEL.
RX PubMed=28761321;
RA Ullah A., Umair M., Yousaf M., Khan S.A., Nazim-Ud-Din M., Shah K.,
RA Ahmad F., Azeem Z., Ali G., Alhaddad B., Rafique A., Jan A., Haack T.B.,
RA Strom T.M., Meitinger T., Ghous T., Ahmad W.;
RT "Sequence variants in four genes underlying Bardet-Biedl syndrome in
RT consanguineous families.";
RL Mol. Vis. 23:482-494(2017).
RN [27]
RP CHARACTERIZATION OF VARIANTS MKKS CYS-37; TYR-84 AND SER-242, SUBCELLULAR
RP LOCATION, FUNCTION, MUTAGENESIS OF LEU-454, CHARACTERIZATION OF VARIANT
RP BBS6 CYS-37, AND INTERACTION WITH SMARCC1.
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 (PubMed:20080638). Plays a role in the
CC assembly of BBSome, a complex involved in ciliogenesis regulating
CC transports vesicles to the cilia (PubMed:20080638). May play a role in
CC protein processing in limb, cardiac and reproductive system
CC development. May play a role in cytokinesis (PubMed:28753627).
CC {ECO:0000269|PubMed:20080638, 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 (PubMed:20080638).
CC Interacts with STUB1 (PubMed:18094050). Interacts with BBS2 (via coiled
CC coil domain) (PubMed:20080638). Interacts with CCDC28B
CC (PubMed:16327777). Interacts with BBS12 (PubMed:26900326). Interacts
CC with SMARCC1, a component of the SWI/SNF complexes; the interaction
CC takes place predominantly in the cytoplasm and may modulate SMARCC1
CC location (PubMed:28753627). Interacts with DLEC1 (PubMed:33144677).
CC {ECO:0000269|PubMed:16327777, ECO:0000269|PubMed:18094050,
CC ECO:0000269|PubMed:20080638, ECO:0000269|PubMed:26900326,
CC ECO:0000269|PubMed:28753627, ECO:0000269|PubMed:33144677}.
CC -!- INTERACTION:
CC Q9NPJ1; Q6ZW61: BBS12; NbExp=14; IntAct=EBI-721319, EBI-6128352;
CC Q9NPJ1; Q9BXC9: BBS2; NbExp=4; IntAct=EBI-721319, EBI-748297;
CC Q9NPJ1; Q01850: CDR2; NbExp=3; IntAct=EBI-721319, EBI-1181367;
CC Q9NPJ1; O96006: ZBED1; NbExp=3; IntAct=EBI-721319, EBI-740037;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing
CC center, centrosome. Cytoplasm, cytosol {ECO:0000269|PubMed:28753627}.
CC Nucleus {ECO:0000269|PubMed:28753627}. Note=The majority of the protein
CC resides within the pericentriolar material (PCM), a proteinaceous tube
CC surrounding centrioles. During interphase, the protein is confined to
CC the lateral surfaces of the PCM but during mitosis it relocalizes
CC throughout the PCM and is found at the intercellular bridge. The MKSS
CC protein is highly mobile and rapidly shuttles between the cytosol and
CC centrosome.
CC -!- TISSUE SPECIFICITY: Widely expressed in adult and fetal tissues.
CC -!- DOMAIN: The substrate-binding apical domain region is sufficient for
CC centrosomal association.
CC -!- DISEASE: McKusick-Kaufman syndrome (MKKS) [MIM:236700]: Autosomal
CC recessive developmental disorder. It is characterized by
CC hydrometrocolpos, postaxial polydactyly and congenital heart defects.
CC {ECO:0000269|PubMed:10802661, ECO:0000269|PubMed:28753627}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Bardet-Biedl syndrome 6 (BBS6) [MIM:605231]: A syndrome
CC characterized by usually severe pigmentary retinopathy, early-onset
CC obesity, polydactyly, hypogenitalism, renal malformation and
CC intellectual disability. Secondary features include diabetes mellitus,
CC hypertension and congenital heart disease. Bardet-Biedl syndrome
CC inheritance is autosomal recessive, but three mutated alleles (two at
CC one locus, and a third at a second locus) may be required for clinical
CC manifestation of some forms of the disease.
CC {ECO:0000269|PubMed:10973238, ECO:0000269|PubMed:10973251,
CC ECO:0000269|PubMed:11179009, ECO:0000269|PubMed:11567139,
CC ECO:0000269|PubMed:12107442, ECO:0000269|PubMed:12677556,
CC ECO:0000269|PubMed:12920096, ECO:0000269|PubMed:15666242,
CC ECO:0000269|PubMed:15731008, ECO:0000269|PubMed:15770229,
CC ECO:0000269|PubMed:18094050, ECO:0000269|PubMed:20080638,
CC ECO:0000269|PubMed:21344540, ECO:0000269|PubMed:22152675,
CC ECO:0000269|PubMed:26900326, ECO:0000269|PubMed:28753627,
CC ECO:0000269|PubMed:28761321}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the TCP-1 chaperonin family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Mutations of the MKKS gene; Note=Retina
CC International's Scientific Newsletter;
CC URL="https://www.retina-international.org/files/sci-news/mkksmut.htm";
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DR EMBL; AF221992; AAF73872.1; -; mRNA.
DR EMBL; AF221993; AAF73873.1; -; mRNA.
DR EMBL; AK291925; BAF84614.1; -; mRNA.
DR EMBL; AL157427; CAB75652.1; -; mRNA.
DR EMBL; AL034430; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471133; EAX10344.1; -; Genomic_DNA.
DR EMBL; CH471133; EAX10345.1; -; Genomic_DNA.
DR CCDS; CCDS13111.1; -.
DR PIR; T46911; T46911.
DR RefSeq; NP_061336.1; NM_018848.3.
DR RefSeq; NP_740754.1; NM_170784.2.
DR AlphaFoldDB; Q9NPJ1; -.
DR SMR; Q9NPJ1; -.
DR BioGRID; 113837; 14.
DR CORUM; Q9NPJ1; -.
DR DIP; DIP-60349N; -.
DR IntAct; Q9NPJ1; 11.
DR STRING; 9606.ENSP00000246062; -.
DR iPTMnet; Q9NPJ1; -.
DR PhosphoSitePlus; Q9NPJ1; -.
DR BioMuta; MKKS; -.
DR DMDM; 11133565; -.
DR EPD; Q9NPJ1; -.
DR MassIVE; Q9NPJ1; -.
DR PaxDb; Q9NPJ1; -.
DR PeptideAtlas; Q9NPJ1; -.
DR PRIDE; Q9NPJ1; -.
DR ProteomicsDB; 82024; -.
DR Antibodypedia; 24160; 150 antibodies from 24 providers.
DR DNASU; 8195; -.
DR Ensembl; ENST00000347364.7; ENSP00000246062.4; ENSG00000125863.20.
DR Ensembl; ENST00000399054.6; ENSP00000382008.2; ENSG00000125863.20.
DR Ensembl; ENST00000651692.1; ENSP00000498849.1; ENSG00000125863.20.
DR GeneID; 8195; -.
DR KEGG; hsa:8195; -.
DR MANE-Select; ENST00000347364.7; ENSP00000246062.4; NM_170784.3; NP_740754.1.
DR UCSC; uc002wnt.3; human.
DR CTD; 8195; -.
DR DisGeNET; 8195; -.
DR GeneCards; MKKS; -.
DR GeneReviews; MKKS; -.
DR HGNC; HGNC:7108; MKKS.
DR HPA; ENSG00000125863; Low tissue specificity.
DR MalaCards; MKKS; -.
DR MIM; 236700; phenotype.
DR MIM; 604896; gene.
DR MIM; 605231; phenotype.
DR neXtProt; NX_Q9NPJ1; -.
DR OpenTargets; ENSG00000125863; -.
DR Orphanet; 110; Bardet-Biedl syndrome.
DR Orphanet; 2473; McKusick-Kaufman syndrome.
DR PharmGKB; PA30826; -.
DR VEuPathDB; HostDB:ENSG00000125863; -.
DR eggNOG; KOG0360; Eukaryota.
DR GeneTree; ENSGT00390000007214; -.
DR HOGENOM; CLU_478131_0_0_1; -.
DR InParanoid; Q9NPJ1; -.
DR OMA; FVCQKVI; -.
DR OrthoDB; 1539473at2759; -.
DR PhylomeDB; Q9NPJ1; -.
DR TreeFam; TF329106; -.
DR PathwayCommons; Q9NPJ1; -.
DR Reactome; R-HSA-5620922; BBSome-mediated cargo-targeting to cilium.
DR SignaLink; Q9NPJ1; -.
DR BioGRID-ORCS; 8195; 12 hits in 1078 CRISPR screens.
DR ChiTaRS; MKKS; human.
DR GeneWiki; MKKS; -.
DR GenomeRNAi; 8195; -.
DR Pharos; Q9NPJ1; Tbio.
DR PRO; PR:Q9NPJ1; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9NPJ1; protein.
DR Bgee; ENSG00000125863; Expressed in middle temporal gyrus and 188 other tissues.
DR Genevisible; Q9NPJ1; HS.
DR GO; GO:0005813; C:centrosome; IDA:HPA.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:1902636; C:kinociliary basal body; IBA:GO_Central.
DR GO; GO:0031514; C:motile cilium; ISS:BHF-UCL.
DR GO; GO:0005634; C:nucleus; IDA: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; IPI:MGI.
DR GO; GO:0051082; F:unfolded protein binding; TAS:ProtInc.
DR GO; GO:0014824; P:artery smooth muscle contraction; IEA:Ensembl.
DR GO; GO:0048854; P:brain morphogenesis; ISS:BHF-UCL.
DR GO; GO:0051216; P:cartilage development; IEA:Ensembl.
DR GO; GO:0021987; P:cerebral cortex development; ISS:BHF-UCL.
DR GO; GO:0051131; P:chaperone-mediated protein complex assembly; IBA:GO_Central.
DR GO; GO:0060271; P:cilium assembly; IMP:UniProtKB.
DR GO; GO:0060027; P:convergent extension involved in gastrulation; ISS:BHF-UCL.
DR GO; GO:0050910; P:detection of mechanical stimulus involved in sensory perception of sound; ISS:BHF-UCL.
DR GO; GO:0007368; P:determination of left/right symmetry; ISS:BHF-UCL.
DR GO; GO:0032502; P:developmental process; IBA:GO_Central.
DR GO; GO:0060324; P:face development; IEA:Ensembl.
DR GO; GO:0045444; P:fat cell differentiation; ISS:BHF-UCL.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0008406; P:gonad development; TAS:ProtInc.
DR GO; GO:0007507; P:heart development; TAS:ProtInc.
DR GO; GO:0001947; P:heart looping; ISS:BHF-UCL.
DR GO; GO:0021766; P:hippocampus development; ISS:BHF-UCL.
DR GO; GO:0046907; P:intracellular transport; ISS:BHF-UCL.
DR GO; GO:0032402; P:melanosome transport; ISS:BHF-UCL.
DR GO; GO:0030837; P:negative regulation of actin filament polymerization; IEA:Ensembl.
DR GO; GO:0038108; P:negative regulation of appetite by leptin-mediated signaling pathway; ISS:BHF-UCL.
DR GO; GO:0045776; P:negative regulation of blood pressure; IEA:Ensembl.
DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
DR GO; GO:0034260; P:negative regulation of GTPase activity; IEA:Ensembl.
DR GO; GO:1905515; P:non-motile cilium assembly; IEA:Ensembl.
DR GO; GO:0045494; P:photoreceptor cell maintenance; ISS:BHF-UCL.
DR GO; GO:0051877; P:pigment granule aggregation in cell center; ISS:BHF-UCL.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IEA:Ensembl.
DR GO; GO:0006457; P:protein folding; TAS:ProtInc.
DR GO; GO:0060296; P:regulation of cilium beat frequency involved in ciliary motility; ISS:BHF-UCL.
DR GO; GO:0051492; P:regulation of stress fiber assembly; IEA:Ensembl.
DR GO; GO:0007608; P:sensory perception of smell; ISS:BHF-UCL.
DR GO; GO:0035176; P:social behavior; ISS:BHF-UCL.
DR GO; GO:0007286; P:spermatid development; ISS:BHF-UCL.
DR GO; GO:0021756; P:striatum development; ISS:BHF-UCL.
DR GO; GO:0042311; P:vasodilation; IEA:Ensembl.
DR GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
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 1: Evidence at protein level;
KW ATP-binding; Bardet-Biedl syndrome; Chaperone; Ciliopathy; Cytoplasm;
KW Cytoskeleton; Disease variant; Intellectual disability; Nucleotide-binding;
KW Nucleus; Obesity; Reference proteome; Sensory transduction; Vision.
FT CHAIN 1..570
FT /note="Molecular chaperone MKKS"
FT /id="PRO_0000128415"
FT REGION 198..370
FT /note="Substrate-binding apical domain"
FT BINDING 192..199
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT VARIANT 32
FT /note="I -> M (in BBS6)"
FT /evidence="ECO:0000269|PubMed:11179009"
FT /id="VAR_017035"
FT VARIANT 37
FT /note="Y -> C (in MKKS and BBS6; causes both increased MKKS
FT protein degradation and reduced solubility relative to
FT wild-type and Tyr-84 mutant; the mutant is immobilized at
FT the centrosome even in the absence of proteasome
FT inhibition; the mutant is also highly polyubiquitinated; no
FT effect on import to the nucleus; dbSNP:rs74315396)"
FT /evidence="ECO:0000269|PubMed:10802661,
FT ECO:0000269|PubMed:10973251, ECO:0000269|PubMed:11567139,
FT ECO:0000269|PubMed:18094050, ECO:0000269|PubMed:20080638,
FT ECO:0000269|PubMed:28753627"
FT /id="VAR_009864"
FT VARIANT 40..570
FT /note="Missing (in BBS6)"
FT /evidence="ECO:0000269|PubMed:28761321"
FT /id="VAR_080223"
FT VARIANT 41
FT /note="G -> R (in BBS6; dbSNP:rs766132697)"
FT /evidence="ECO:0000269|PubMed:21344540"
FT /id="VAR_066262"
FT VARIANT 49
FT /note="G -> V (in dbSNP:rs528833454)"
FT /evidence="ECO:0000269|PubMed:10802661"
FT /id="VAR_009865"
FT VARIANT 52
FT /note="G -> D (in BBS6; fails to associate with centrosome;
FT dbSNP:rs28937875)"
FT /evidence="ECO:0000269|PubMed:10973238,
FT ECO:0000269|PubMed:15731008, ECO:0000269|PubMed:20080638"
FT /id="VAR_009882"
FT VARIANT 57
FT /note="T -> A (in BBS6; found in a patient also carrying A-
FT 155 in TMEM237; causes both increased MKKS protein
FT degradation and reduced solubility relative to wild-type
FT and Y-84 mutant; greatly reduces the ability to interact
FT with BBS12; dbSNP:rs74315399)"
FT /evidence="ECO:0000269|PubMed:10973251,
FT ECO:0000269|PubMed:11179009, ECO:0000269|PubMed:18094050,
FT ECO:0000269|PubMed:20080638, ECO:0000269|PubMed:22152675"
FT /id="VAR_009883"
FT VARIANT 84
FT /note="H -> Y (in MKKS; associated with S-242; decreased
FT interaction with BBS12; no effect on ciliogenesis; disrupts
FT import to the nucleus; no effect on interaction with
FT SMARCC1; may affect modulation of SMARCC1 subcellular
FT location; dbSNP:rs281797258)"
FT /evidence="ECO:0000269|PubMed:10802661,
FT ECO:0000269|PubMed:20080638, ECO:0000269|PubMed:28753627"
FT /id="VAR_009866"
FT VARIANT 99
FT /note="C -> R (in BBS6; dbSNP:rs1297985227)"
FT /evidence="ECO:0000269|PubMed:21344540"
FT /id="VAR_066263"
FT VARIANT 155
FT /note="R -> L (in BBS6; increases MKKS protein degradation;
FT localizes properly to the centrosome; dbSNP:rs138111422)"
FT /evidence="ECO:0000269|PubMed:12107442,
FT ECO:0000269|PubMed:15731008"
FT /id="VAR_017040"
FT VARIANT 181
FT /note="A -> P (in BBS6)"
FT /evidence="ECO:0000269|PubMed:12920096"
FT /id="VAR_038898"
FT VARIANT 236
FT /note="S -> P (in BBS6)"
FT /evidence="ECO:0000269|PubMed:11179009,
FT ECO:0000269|PubMed:12677556, ECO:0000269|PubMed:20080638"
FT /id="VAR_017036"
FT VARIANT 237
FT /note="T -> A (in BBS6; dbSNP:rs760185677)"
FT /evidence="ECO:0000269|PubMed:15770229"
FT /id="VAR_038899"
FT VARIANT 237
FT /note="T -> P (in BBS6)"
FT /evidence="ECO:0000269|PubMed:15666242,
FT ECO:0000269|PubMed:15770229"
FT /id="VAR_038900"
FT VARIANT 242
FT /note="A -> S (in MKKS and BBS6; associated with Y-84 in
FT MKKS; unknown pathological significance; increases MKKS
FT protein degradation; no effect on ciliogenesis; disrupts
FT import to the nucleus; no effect on interaction with
FT SMARCC1; may affect modulation of SMARCC1 subcellular
FT location; dbSNP:rs74315394)"
FT /evidence="ECO:0000269|PubMed:10802661,
FT ECO:0000269|PubMed:11179009, ECO:0000269|PubMed:11567139,
FT ECO:0000269|PubMed:12107442, ECO:0000269|PubMed:15483080,
FT ECO:0000269|PubMed:18094050, ECO:0000269|PubMed:20120035,
FT ECO:0000269|PubMed:28753627"
FT /id="VAR_009867"
FT VARIANT 277
FT /note="L -> P (in BBS6; moderately affects interaction with
FT BBS2; greatly reduces the ability to interact with BBS12;
FT dbSNP:rs74315398)"
FT /evidence="ECO:0000269|PubMed:10973251,
FT ECO:0000269|PubMed:20080638"
FT /id="VAR_009884"
FT VARIANT 286
FT /note="D -> A (in BBS6; fails to associate with
FT centrosome)"
FT /evidence="ECO:0000269|PubMed:11179009,
FT ECO:0000269|PubMed:15731008"
FT /id="VAR_017037"
FT VARIANT 299
FT /note="P -> L (in BBS6; dbSNP:rs756083063)"
FT /evidence="ECO:0000269|PubMed:21344540"
FT /id="VAR_066264"
FT VARIANT 325
FT /note="T -> P (has a modifier effect on BBS; causes a
FT mislocalization of the protein; fails to associate with
FT centrosome; dbSNP:rs137853156)"
FT /evidence="ECO:0000269|PubMed:12677556,
FT ECO:0000269|PubMed:12837689, ECO:0000269|PubMed:15731008"
FT /id="VAR_038901"
FT VARIANT 339
FT /note="I -> V (in dbSNP:rs137853909)"
FT /evidence="ECO:0000269|PubMed:12107442,
FT ECO:0000269|PubMed:15666242, ECO:0000269|PubMed:15770229"
FT /id="VAR_017041"
FT VARIANT 345
FT /note="G -> E (in BBS6; increases MKKS protein degradation;
FT fails to associate with centrosome; the mutant is highly
FT polyubiquitinated and rapidly degraded by the ubiquitin-
FT proteasome protein degradation pathway; dbSNP:rs779116830)"
FT /evidence="ECO:0000269|PubMed:12107442,
FT ECO:0000269|PubMed:15731008, ECO:0000269|PubMed:18094050"
FT /id="VAR_017042"
FT VARIANT 395
FT /note="H -> R (in BBS6; atypical mild phenotype consisting
FT of retinitis pigmentosa and polydactyly without other signs
FT of Bardet-Biedl syndrome; results in decreased interaction
FT with BBS12; dbSNP:rs912923677)"
FT /evidence="ECO:0000269|PubMed:26900326"
FT /id="VAR_077208"
FT VARIANT 460
FT /note="S -> P (in BBS6)"
FT /evidence="ECO:0000269|PubMed:15666242"
FT /id="VAR_038902"
FT VARIANT 488
FT /note="A -> T (in a patient with Bardet-Biedl syndrome
FT compound heterozygote for mutations in BBS12; uncertain
FT pathological role; dbSNP:rs61734546)"
FT /evidence="ECO:0000269|PubMed:21344540"
FT /id="VAR_066265"
FT VARIANT 492
FT /note="D -> N (in BBS6; unknown pathological significance;
FT dbSNP:rs142327258)"
FT /evidence="ECO:0000269|PubMed:12920096"
FT /id="VAR_038903"
FT VARIANT 499
FT /note="C -> S (in BBS6; causes both increased MKKS protein
FT degradation and reduced solubility relative to wild-type
FT and Tyr-84 mutant; localizes properly to the centrosome;
FT dbSNP:rs281797259 and dbSNP:rs137853155)"
FT /evidence="ECO:0000269|PubMed:11179009,
FT ECO:0000269|PubMed:11567139, ECO:0000269|PubMed:15731008,
FT ECO:0000269|PubMed:18094050"
FT /id="VAR_013161"
FT VARIANT 511
FT /note="S -> A (in BBS6)"
FT /evidence="ECO:0000269|PubMed:11179009"
FT /id="VAR_017038"
FT VARIANT 517
FT /note="R -> C (in dbSNP:rs1547)"
FT /evidence="ECO:0000269|PubMed:10802661,
FT ECO:0000269|PubMed:15483080, ECO:0000269|PubMed:15666242,
FT ECO:0000269|PubMed:15770229"
FT /id="VAR_009868"
FT VARIANT 518
FT /note="R -> H (in BBS6; dbSNP:rs149051148)"
FT /evidence="ECO:0000269|PubMed:11179009"
FT /id="VAR_017039"
FT VARIANT 532
FT /note="G -> V (in dbSNP:rs1545)"
FT /evidence="ECO:0000269|PubMed:15483080,
FT ECO:0000269|PubMed:15666242, ECO:0000269|PubMed:15770229"
FT /id="VAR_009869"
FT MUTAGEN 454
FT /note="L->P: No effect on import to the nucleus."
FT /evidence="ECO:0000269|PubMed:28753627"
SQ SEQUENCE 570 AA; 62342 MW; 14BA57FF8AEA0AF7 CRC64;
MSRLEAKKPS LCKSEPLTTE RVRTTLSVLK RIVTSCYGPS GRLKQLHNGF GGYVCTTSQS
SALLSHLLVT HPILKILTAS IQNHVSSFSD CGLFTAILCC NLIENVQRLG LTPTTVIRLN
KHLLSLCISY LKSETCGCRI PVDFSSTQIL LCLVRSILTS KPACMLTRKE TEHVSALILR
AFLLTIPENA EGHIILGKSL IVPLKGQRVI DSTVLPGILI EMSEVQLMRL LPIKKSTALK
VALFCTTLSG DTSDTGEGTV VVSYGVSLEN AVLDQLLNLG RQLISDHVDL VLCQKVIHPS
LKQFLNMHRI IAIDRIGVTL MEPLTKMTGT QPIGSLGSIC PNSYGSVKDV CTAKFGSKHF
FHLIPNEATI CSLLLCNRND TAWDELKLTC QTALHVLQLT LKEPWALLGG GCTETHLAAY
IRHKTHNDPE SILKDDECTQ TELQLIAEAF CSALESVVGS LEHDGGEILT DMKYGHLWSV
QADSPCVANW PDLLSQCGCG LYNSQEELNW SFLRSTRRPF VPQSCLPHEA VGSASNLTLD
CLTAKLSGLQ VAVETANLIL DLSYVIEDKN
