MKS1_HUMAN
ID MKS1_HUMAN Reviewed; 559 AA.
AC Q9NXB0; B7WNX4; F5H885; Q284T0; Q96G13;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 2.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Tectonic-like complex member MKS1 {ECO:0000305};
DE AltName: Full=Meckel syndrome type 1 protein;
GN Name=MKS1;
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] (ISOFORM 1), AND INVOLVEMENT IN MKS1.
RX PubMed=16415886; DOI=10.1038/ng1714;
RA Kyttaelae M., Tallila J., Salonen R., Kopra O., Kohlschmidt N.,
RA Paavola-Sakki P., Peltonen L., Kestilae M.;
RT "MKS1, encoding a component of the flagellar apparatus basal body proteome,
RT is mutated in Meckel syndrome.";
RL Nat. Genet. 38:155-157(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 86-559 (ISOFORM 1).
RC TISSUE=Hepatoma, and Trachea;
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 GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Ovary;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 144-559 (ISOFORM 1).
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 [6]
RP SUBCELLULAR LOCATION, FUNCTION, AND INTERACTION WITH TMEM67.
RX PubMed=17185389; DOI=10.1093/hmg/ddl459;
RA Dawe H.R., Smith U.M., Cullinane A.R., Gerrelli D., Cox P., Badano J.L.,
RA Blair-Reid S., Sriram N., Katsanis N., Attie-Bitach T., Afford S.C.,
RA Copp A.J., Kelly D.A., Gull K., Johnson C.A.;
RT "The Meckel-Gruber syndrome proteins MKS1 and meckelin interact and are
RT required for primary cilium formation.";
RL Hum. Mol. Genet. 16:173-186(2007).
RN [7]
RP FUNCTION.
RX PubMed=19515853; DOI=10.1093/hmg/ddp272;
RA Tammachote R., Hommerding C.J., Sinders R.M., Miller C.A., Czarnecki P.G.,
RA Leightner A.C., Salisbury J.L., Ward C.J., Torres V.E., Gattone V.H. II,
RA Harris P.C.;
RT "Ciliary and centrosomal defects associated with mutation and depletion of
RT the Meckel syndrome genes MKS1 and MKS3.";
RL Hum. Mol. Genet. 18:3311-3323(2009).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=19208769; DOI=10.1242/jcs.028621;
RA Bialas N.J., Inglis P.N., Li C., Robinson J.F., Parker J.D., Healey M.P.,
RA Davis E.E., Inglis C.D., Toivonen T., Cottell D.C., Blacque O.E.,
RA Quarmby L.M., Katsanis N., Leroux M.R.;
RT "Functional interactions between the ciliopathy-associated Meckel syndrome
RT 1 (MKS1) protein and two novel MKS1-related (MKSR) proteins.";
RL J. Cell Sci. 122:611-624(2009).
RN [9]
RP INTERACTION WITH FLNA.
RX PubMed=22121117; DOI=10.1093/hmg/ddr557;
RA Adams M., Simms R.J., Abdelhamed Z., Dawe H.R., Szymanska K., Logan C.V.,
RA Wheway G., Pitt E., Gull K., Knowles M.A., Blair E., Cross S.H.,
RA Sayer J.A., Johnson C.A.;
RT "A meckelin-filamin A interaction mediates ciliogenesis.";
RL Hum. Mol. Genet. 21:1272-1286(2012).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [11]
RP IDENTIFICATION IN THE TECTONIC-LIKE COMPLEX, AND INTERACTION WITH TMEM107.
RX PubMed=26595381; DOI=10.1038/ncb3273;
RA Lambacher N.J., Bruel A.L., van Dam T.J., Szymanska K., Slaats G.G.,
RA Kuhns S., McManus G.J., Kennedy J.E., Gaff K., Wu K.M., van der Lee R.,
RA Burglen L., Doummar D., Riviere J.B., Faivre L., Attie-Bitach T.,
RA Saunier S., Curd A., Peckham M., Giles R.H., Johnson C.A., Huynen M.A.,
RA Thauvin-Robinet C., Blacque O.E.;
RT "TMEM107 recruits ciliopathy proteins to subdomains of the ciliary
RT transition zone and causes Joubert syndrome.";
RL Nat. Cell Biol. 18:122-131(2016).
RN [12]
RP VARIANTS BBS13 PHE-371 DEL AND TRP-492, AND VARIANTS GLN-123; GLY-286 AND
RP THR-450.
RX PubMed=18327255; DOI=10.1038/ng.97;
RA Leitch C.C., Zaghloul N.A., Davis E.E., Stoetzel C., Diaz-Font A., Rix S.,
RA Alfadhel M., Lewis R.A., Eyaid W., Banin E., Dollfus H., Beales P.L.,
RA Badano J.L., Katsanis N.;
RT "Hypomorphic mutations in syndromic encephalocele genes are associated with
RT Bardet-Biedl syndrome.";
RL Nat. Genet. 40:443-448(2008).
RN [13]
RP ERRATUM OF PUBMED:18327255.
RA Leitch C.C., Zaghloul N.A., Davis E.E., Stoetzel C., Diaz-Font A., Rix S.,
RA Alfadhel M., Lewis R.A., Eyaid W., Banin E., Dollfus H., Beales P.L.,
RA Badano J.L., Katsanis N.;
RL Nat. Genet. 40:927-927(2008).
RN [14]
RP VARIANT MKS1 TRP-166.
RX PubMed=19466712; DOI=10.1002/humu.21057;
RA Tallila J., Salonen R., Kohlschmidt N., Peltonen L., Kestilae M.;
RT "Mutation spectrum of Meckel syndrome genes: one group of syndromes or
RT several distinct groups?";
RL Hum. Mutat. 30:E813-E830(2009).
RN [15]
RP VARIANT JBTS28 SER-362 DEL, AND INVOLVEMENT IN JBTS28.
RX PubMed=24886560; DOI=10.1186/1750-1172-9-72;
RA Romani M., Micalizzi A., Kraoua I., Dotti M.T., Cavallin M., Sztriha L.,
RA Ruta R., Mancini F., Mazza T., Castellana S., Hanene B., Carluccio M.A.,
RA Darra F., Mate A., Zimmermann A., Gouider-Khouja N., Valente E.M.;
RT "Mutations in B9D1 and MKS1 cause mild Joubert syndrome: expanding the
RT genetic overlap with the lethal ciliopathy Meckel syndrome.";
RL Orphanet J. Rare Dis. 9:72-72(2014).
RN [16]
RP VARIANT CYS-80.
RX PubMed=27377014; DOI=10.1016/j.ejmg.2016.06.007;
RA Bader I., Decker E., Mayr J.A., Lunzer V., Koch J., Boltshauser E.,
RA Sperl W., Pietsch P., Ertl-Wagner B., Bolz H., Bergmann C., Rittinger O.;
RT "MKS1 mutations cause Joubert syndrome with agenesis of the corpus
RT callosum.";
RL Eur. J. Med. Genet. 59:386-391(2016).
RN [17]
RP VARIANTS MKS1 TYR-19; GLU-317; SER-372 DEL; LEU-403 AND SER-421,
RP CHARACTERIZATION OF VARIANTS MKS1 TYR-19; GLU-317; SER-372 DEL; LEU-403 AND
RP SER-421, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=26490104; DOI=10.1136/jmedgenet-2015-103250;
RA Slaats G.G., Isabella C.R., Kroes H.Y., Dempsey J.C., Gremmels H.,
RA Monroe G.R., Phelps I.G., Duran K.J., Adkins J., Kumar S.A., Knutzen D.M.,
RA Knoers N.V., Mendelsohn N.J., Neubauer D., Mastroyianni S.D., Vogt J.,
RA Worgan L., Karp N., Bowdin S., Glass I.A., Parisi M.A., Otto E.A.,
RA Johnson C.A., Hildebrandt F., van Haaften G., Giles R.H., Doherty D.;
RT "MKS1 regulates ciliary INPP5E levels in Joubert syndrome.";
RL J. Med. Genet. 53:62-72(2016).
CC -!- FUNCTION: Component of the tectonic-like complex, a complex localized
CC at the transition zone of primary cilia and acting as a barrier that
CC prevents diffusion of transmembrane proteins between the cilia and
CC plasma membranes. Involved in centrosome migration to the apical cell
CC surface during early ciliogenesis. Required for ciliary structure and
CC function, including a role in regulating length and appropriate number
CC through modulating centrosome duplication. Required for cell branching
CC morphology. {ECO:0000269|PubMed:17185389, ECO:0000269|PubMed:19515853,
CC ECO:0000269|PubMed:26490104}.
CC -!- SUBUNIT: Part of the tectonic-like complex (also named B9 complex)
CC (PubMed:26595381). Interacts with TMEM107 (PubMed:26595381). Interacts
CC with TCTN3, AHI1, TCTN1, TCTN2, CC2D2A (By similarity). Interacts with
CC FLNA (PubMed:22121117). Interacts with TMEM67 (PubMed:17185389).
CC Interacts with B9D1 and B9D2 (By similarity).
CC {ECO:0000250|UniProtKB:Q5SW45, ECO:0000269|PubMed:17185389,
CC ECO:0000269|PubMed:22121117, ECO:0000269|PubMed:26595381}.
CC -!- INTERACTION:
CC Q9NXB0; Q9BPU9: B9D2; NbExp=8; IntAct=EBI-719269, EBI-6958971;
CC Q9NXB0; Q6UX40: TMEM107; NbExp=2; IntAct=EBI-719269, EBI-12845616;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body.
CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome.
CC Note=Localizes at the transition zone, a region between the basal body
CC and the ciliary axoneme. {ECO:0000269|PubMed:26490104}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9NXB0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NXB0-2; Sequence=VSP_017414;
CC Name=3;
CC IsoId=Q9NXB0-3; Sequence=VSP_046063;
CC -!- DISEASE: Meckel syndrome 1 (MKS1) [MIM:249000]: A disorder
CC characterized by a combination of renal cysts and variably associated
CC features including developmental anomalies of the central nervous
CC system (typically encephalocele), hepatic ductal dysplasia and cysts,
CC and polydactyly. {ECO:0000269|PubMed:16415886,
CC ECO:0000269|PubMed:19466712, ECO:0000269|PubMed:26490104}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Bardet-Biedl syndrome 13 (BBS13) [MIM:615990]: 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:18327255}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Joubert syndrome 28 (JBTS28) [MIM:617121]: A form of Joubert
CC syndrome, a disorder presenting with cerebellar ataxia, oculomotor
CC apraxia, hypotonia, neonatal breathing abnormalities and psychomotor
CC delay. Neuroradiologically, it is characterized by cerebellar vermian
CC hypoplasia/aplasia, thickened and reoriented superior cerebellar
CC peduncles, and an abnormally large interpeduncular fossa, giving the
CC appearance of a molar tooth on transaxial slices (molar tooth sign).
CC Additional variable features include retinal dystrophy, renal disease,
CC liver fibrosis, and polydactyly. JBTS28 inheritance is autosomal
CC recessive. {ECO:0000269|PubMed:24886560}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH10061.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA91105.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; DQ185029; AAZ94714.1; -; mRNA.
DR EMBL; AK000352; BAA91105.1; ALT_INIT; mRNA.
DR EMBL; AK310815; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC005962; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC010061; AAH10061.1; ALT_INIT; mRNA.
DR EMBL; CR457229; CAG33510.1; -; mRNA.
DR CCDS; CCDS11603.2; -. [Q9NXB0-1]
DR RefSeq; NP_001159399.1; NM_001165927.1. [Q9NXB0-3]
DR RefSeq; NP_001308197.1; NM_001321268.1.
DR RefSeq; NP_001308198.1; NM_001321269.1.
DR RefSeq; NP_060247.2; NM_017777.3. [Q9NXB0-1]
DR RefSeq; XP_016880294.1; XM_017024805.1.
DR AlphaFoldDB; Q9NXB0; -.
DR BioGRID; 120249; 121.
DR CORUM; Q9NXB0; -.
DR DIP; DIP-56251N; -.
DR IntAct; Q9NXB0; 80.
DR STRING; 9606.ENSP00000376827; -.
DR TCDB; 8.A.170.1.1; the b9-domain protein complex diffusion barrier for ciliary membrane proteins (cb9db) family.
DR iPTMnet; Q9NXB0; -.
DR PhosphoSitePlus; Q9NXB0; -.
DR BioMuta; MKS1; -.
DR DMDM; 92087008; -.
DR EPD; Q9NXB0; -.
DR MassIVE; Q9NXB0; -.
DR MaxQB; Q9NXB0; -.
DR PaxDb; Q9NXB0; -.
DR PeptideAtlas; Q9NXB0; -.
DR PRIDE; Q9NXB0; -.
DR ProteomicsDB; 27713; -.
DR ProteomicsDB; 83068; -. [Q9NXB0-1]
DR ProteomicsDB; 83069; -. [Q9NXB0-2]
DR Antibodypedia; 18351; 109 antibodies from 20 providers.
DR DNASU; 54903; -.
DR Ensembl; ENST00000393119.7; ENSP00000376827.2; ENSG00000011143.19. [Q9NXB0-1]
DR GeneID; 54903; -.
DR KEGG; hsa:54903; -.
DR MANE-Select; ENST00000393119.7; ENSP00000376827.2; NM_017777.4; NP_060247.2.
DR UCSC; uc002ivr.3; human. [Q9NXB0-1]
DR CTD; 54903; -.
DR DisGeNET; 54903; -.
DR GeneCards; MKS1; -.
DR GeneReviews; MKS1; -.
DR HGNC; HGNC:7121; MKS1.
DR HPA; ENSG00000011143; Low tissue specificity.
DR MalaCards; MKS1; -.
DR MIM; 249000; phenotype.
DR MIM; 609883; gene.
DR MIM; 615990; phenotype.
DR MIM; 617121; phenotype.
DR neXtProt; NX_Q9NXB0; -.
DR OpenTargets; ENSG00000011143; -.
DR Orphanet; 110; Bardet-Biedl syndrome.
DR Orphanet; 475; Joubert syndrome.
DR Orphanet; 220493; Joubert syndrome with ocular defect.
DR Orphanet; 564; Meckel syndrome.
DR PharmGKB; PA30840; -.
DR VEuPathDB; HostDB:ENSG00000011143; -.
DR eggNOG; KOG4446; Eukaryota.
DR GeneTree; ENSGT00510000047471; -.
DR HOGENOM; CLU_026711_0_1_1; -.
DR InParanoid; Q9NXB0; -.
DR OMA; YEHVLCI; -.
DR OrthoDB; 1091079at2759; -.
DR PhylomeDB; Q9NXB0; -.
DR TreeFam; TF323812; -.
DR PathwayCommons; Q9NXB0; -.
DR Reactome; R-HSA-5610787; Hedgehog 'off' state.
DR Reactome; R-HSA-5620912; Anchoring of the basal body to the plasma membrane.
DR SignaLink; Q9NXB0; -.
DR BioGRID-ORCS; 54903; 15 hits in 1072 CRISPR screens.
DR ChiTaRS; MKS1; human.
DR GeneWiki; MKS1; -.
DR GenomeRNAi; 54903; -.
DR Pharos; Q9NXB0; Tbio.
DR PRO; PR:Q9NXB0; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9NXB0; protein.
DR Bgee; ENSG00000011143; Expressed in right uterine tube and 108 other tissues.
DR ExpressionAtlas; Q9NXB0; baseline and differential.
DR Genevisible; Q9NXB0; HS.
DR GO; GO:0005814; C:centriole; IEA:Ensembl.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0036064; C:ciliary basal body; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016020; C:membrane; IEA:Ensembl.
DR GO; GO:0036038; C:MKS complex; ISS:UniProtKB.
DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; IEA:Ensembl.
DR GO; GO:0060411; P:cardiac septum morphogenesis; IEA:Ensembl.
DR GO; GO:0060271; P:cilium assembly; IMP:UniProtKB.
DR GO; GO:0061009; P:common bile duct development; IEA:Ensembl.
DR GO; GO:0007368; P:determination of left/right symmetry; IEA:Ensembl.
DR GO; GO:1990403; P:embryonic brain development; IEA:Ensembl.
DR GO; GO:0042733; P:embryonic digit morphogenesis; IEA:Ensembl.
DR GO; GO:0048706; P:embryonic skeletal system development; IEA:Ensembl.
DR GO; GO:0010669; P:epithelial structure maintenance; IEA:Ensembl.
DR GO; GO:0060322; P:head development; IEA:Ensembl.
DR GO; GO:0060122; P:inner ear receptor cell stereocilium organization; IEA:Ensembl.
DR GO; GO:0044458; P:motile cilium assembly; IEA:Ensembl.
DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl.
DR GO; GO:1905515; P:non-motile cilium assembly; IEA:Ensembl.
DR GO; GO:0060828; P:regulation of canonical Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:1901620; P:regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning; IEA:Ensembl.
DR GO; GO:2000095; P:regulation of Wnt signaling pathway, planar cell polarity pathway; IEA:Ensembl.
DR GO; GO:0003271; P:smoothened signaling pathway involved in regulation of secondary heart field cardioblast proliferation; IEA:Ensembl.
DR InterPro; IPR010796; C2_B9-type_dom.
DR PANTHER; PTHR12968; PTHR12968; 1.
DR Pfam; PF07162; B9-C2; 1.
DR PROSITE; PS51381; C2_B9; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Bardet-Biedl syndrome; Cell projection; Ciliopathy;
KW Cilium; Cilium biogenesis/degradation; Cytoplasm; Cytoskeleton;
KW Disease variant; Intellectual disability; Joubert syndrome;
KW Meckel syndrome; Obesity; Reference proteome.
FT CHAIN 1..559
FT /note="Tectonic-like complex member MKS1"
FT /id="PRO_0000225686"
FT DOMAIN 311..439
FT /note="C2 B9-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00713"
FT VAR_SEQ 1..26
FT /note="MAETVWSTDTGEAVYRSRDPVRNLRL -> MAVPVSSFAQRTRSRF (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046063"
FT VAR_SEQ 471..559
FT /note="ERLSRFGLRTETTGTVTFRLHCLQQSRAFMESSSLQKRMRSVLDRLEGFSQQ
FT SSIHNVLEAFRRARRRMQEARESLPQDLVSPSGTLVS -> LSSSKTKEGRKVDGERVL
FT NPQPVSLSLFPGKPHSTAWGLLRLRYELFLSK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_017414"
FT VARIANT 19
FT /note="D -> Y (in MKS1; no rescue of ciliation defects in
FT an MKS1-knockdown cell line; dbSNP:rs863225205)"
FT /evidence="ECO:0000269|PubMed:26490104"
FT /id="VAR_077515"
FT VARIANT 39
FT /note="L -> F (in dbSNP:rs11653070)"
FT /id="VAR_060161"
FT VARIANT 80
FT /note="W -> C (found in a patient with Joubert syndrome
FT also carrying a deletion in MKS1 intron 15 and a missense
FT mutation in TCTN3 gene 'P-95'; unknown pathological
FT significance; dbSNP:rs1114167302)"
FT /evidence="ECO:0000269|PubMed:27377014"
FT /id="VAR_077516"
FT VARIANT 123
FT /note="R -> Q (in dbSNP:rs202112856)"
FT /evidence="ECO:0000269|PubMed:18327255"
FT /id="VAR_062287"
FT VARIANT 166
FT /note="R -> W (in MKS1; unknown pathological significance;
FT dbSNP:rs201845154)"
FT /evidence="ECO:0000269|PubMed:19466712"
FT /id="VAR_062288"
FT VARIANT 286
FT /note="D -> G (in dbSNP:rs151023718)"
FT /evidence="ECO:0000269|PubMed:18327255"
FT /id="VAR_062289"
FT VARIANT 317
FT /note="G -> E (in MKS1; unknown pathological significance;
FT no defect of primary cilia formation in starved fibroblasts
FT from a patient also carrying a deletion of S-372; no effect
FT on the localization to the transition zone;
FT dbSNP:rs863225208)"
FT /evidence="ECO:0000269|PubMed:26490104"
FT /id="VAR_077517"
FT VARIANT 362
FT /note="Missing (in JBTS28)"
FT /evidence="ECO:0000269|PubMed:24886560"
FT /id="VAR_076978"
FT VARIANT 371
FT /note="Missing (in BBS13)"
FT /evidence="ECO:0000269|PubMed:18327255"
FT /id="VAR_062290"
FT VARIANT 372
FT /note="Missing (in MKS1; unknown pathological significance;
FT no defect of primary cilia formation in starved fibroblasts
FT from a patient also carrying E-317; no effect on the
FT localization to the transition zone)"
FT /evidence="ECO:0000269|PubMed:26490104"
FT /id="VAR_077518"
FT VARIANT 403
FT /note="S -> L (in MKS1; unknown pathological significance;
FT decreased primary cilia formation in starved fibroblasts
FT from a patient also carrying a mutation potentially
FT affecting splicing; complete rescue of ciliation defects in
FT an MKS1-knockdown cell line; no effect on the localization
FT to the transition zone; dbSNP:rs773684291)"
FT /evidence="ECO:0000269|PubMed:26490104"
FT /id="VAR_077519"
FT VARIANT 421
FT /note="P -> S (in MKS1; unknown pathological significance;
FT no effect on primary cilia formation in starved fibroblasts
FT from a patient also carrying a mutation creating a
FT frameshift and a premature stop codon; partial rescue of
FT ciliation defects in an MKS1-knockdown cell line; no effect
FT on the localization to the transition zone;
FT dbSNP:rs863225210)"
FT /evidence="ECO:0000269|PubMed:26490104"
FT /id="VAR_077520"
FT VARIANT 450
FT /note="I -> T (in dbSNP:rs200865108)"
FT /evidence="ECO:0000269|PubMed:18327255"
FT /id="VAR_062291"
FT VARIANT 492
FT /note="C -> W (in BBS13; dbSNP:rs137853105)"
FT /evidence="ECO:0000269|PubMed:18327255"
FT /id="VAR_062292"
SQ SEQUENCE 559 AA; 64528 MW; 3E4EBFDAFA8FB39D CRC64;
MAETVWSTDT GEAVYRSRDP VRNLRLRVHL QRITSSNFLH YQPAAELGKD LIDLATFRPQ
PTASGHRPEE DEEEEIVIGW QEKLFSQFEV DLYQNETACQ SPLDYQYRQE ILKLENSGGK
KNRRIFTYTD SDRYTNLEEH CQRMTTAASE VPSFLVERMA NVRRRRQDRR GMEGGILKSR
IVTWEPSEEF VRNNHVINTP LQTMHIMADL GPYKKLGYKK YEHVLCTLKV DSNGVITVKP
DFTGLKGPYR IETEGEKQEL WKYTIDNVSP HAQPEEEERE RRVFKDLYGR HKEYLSSLVG
TDFEMTVPGA LRLFVNGEVV SAQGYEYDNL YVHFFVELPT AHWSSPAFQQ LSGVTQTCTT
KSLAMDKVAH FSYPFTFEAF FLHEDESSDA LPEWPVLYCE VLSLDFWQRY RVEGYGAVVL
PATPGSHTLT VSTWRPVELG TVAELRRFFI GGSLELEDLS YVRIPGSFKG ERLSRFGLRT
ETTGTVTFRL HCLQQSRAFM ESSSLQKRMR SVLDRLEGFS QQSSIHNVLE AFRRARRRMQ
EARESLPQDL VSPSGTLVS
