Q9NXB0 (MKS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Meckel syndrome type 1 protein

Gene names

Name:

MKS1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	559 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. Involved in centrosome migration to the apical cell surface during early ciliogenesis. Required for ciliary structure and function, including a role in regulating length and appropriate number through modulating centrosome duplication. Required for cell branching morphology. Ref.6 Ref.7
Subunit structure	Part of the tectonic-like complex (also named B9 complex) By similarity. Interacts with TCTN3 and AHI1 By similarity. Interacts with FLNA. Ref.6 Ref.9
Subcellular location	Cytoplasm › cytoskeleton › cilium basal body. Cytoplasm › cytoskeleton › centrosome. Note: Localizes at the transition zone, a region between the basal body and the ciliary axoneme By similarity. Ref.6 Ref.8
Involvement in disease	Meckel syndrome 1 (MKS1) [MIM:249000]: A disorder characterized by a combination of renal cysts and variably associated features including developmental anomalies of the central nervous system (typically encephalocele), hepatic ductal dysplasia and cysts, and polydactyly. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.12 Bardet-Biedl syndrome 13 (BBS13) [MIM:209900]: A syndrome characterized by usually severe pigmentary retinopathy, early-onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. Secondary features include diabetes mellitus, hypertension and congenital heart disease. Bardet-Biedl syndrome inheritance is autosomal recessive, but three mutated alleles (two at one locus, and a third at a second locus) may be required for clinical manifestation of some forms of the disease. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10
Sequence similarities	Contains 1 B9 domain.
Sequence caution	The sequence AAH10061.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BAA91105.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Cilium biogenesis/degradation
Cellular component	Cell projection Cilium Cytoplasm Cytoskeleton
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Bardet-Biedl syndrome Ciliopathy Disease mutation Meckel syndrome Mental retardation Obesity
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	branching morphogenesis of an epithelial tube Inferred from electronic annotation. Source: Compara cilium assembly Inferred from mutant phenotype Ref.7. Source: UniProtKB
Cellular_component	TCTN-B9D complex Inferred from sequence or structural similarity. Source: UniProtKB centrosome Inferred from direct assay Ref.8Ref.7. Source: UniProtKB cytoplasm Inferred from direct assay Ref.6. Source: UniProtKB microtubule basal body Inferred from direct assay Ref.8Ref.7. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9NXB0-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9NXB0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     471-559: ERLSRFGLRT...LVSPSGTLVS → LSSSKTKEGR...RLRYELFLSK

Note: No experimental confirmation available.

Isoform 3 (identifier: Q9NXB0-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-26: MAETVWSTDTGEAVYRSRDPVRNLRL → MAVPVSSFAQRTRSRF

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 559	559	Meckel syndrome type 1 protein		PRO_0000225686
Regions
	Domain	311 – 439	129	B9
Natural variations
	Alternative sequence	1 – 26	26	MAETV…RNLRL → MAVPVSSFAQRTRSRF in isoform 3.		VSP_046063
	Alternative sequence	471 – 559	89	ERLSR…GTLVS → LSSSKTKEGRKVDGERVLNP QPVSLSLFPGKPHSTAWGLL RLRYELFLSK in isoform 2.		VSP_017414
	Natural variant	39	1	L → F. Corresponds to variant rs11653070 [ dbSNP | Ensembl ].		VAR_060161
	Natural variant	123	1	R → Q. Ref.10		VAR_062287
	Natural variant	166	1	R → W in MKS1; uncertain pathogenicity. Ref.12		VAR_062288
	Natural variant	286	1	D → G. Ref.10		VAR_062289
	Natural variant	371	1	Missing in BBS13. Ref.10		VAR_062290
	Natural variant	450	1	I → T. Ref.10		VAR_062291
	Natural variant	492	1	C → W in BBS13. Ref.10		VAR_062292

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 7, 2006. Version 2. Checksum: 3E4EBFDAFA8FB39D	FASTA	559	64,528
	10 20 30 40 50 60 MAETVWSTDT GEAVYRSRDP VRNLRLRVHL QRITSSNFLH YQPAAELGKD LIDLATFRPQ 70 80 90 100 110 120 PTASGHRPEE DEEEEIVIGW QEKLFSQFEV DLYQNETACQ SPLDYQYRQE ILKLENSGGK 130 140 150 160 170 180 KNRRIFTYTD SDRYTNLEEH CQRMTTAASE VPSFLVERMA NVRRRRQDRR GMEGGILKSR 190 200 210 220 230 240 IVTWEPSEEF VRNNHVINTP LQTMHIMADL GPYKKLGYKK YEHVLCTLKV DSNGVITVKP 250 260 270 280 290 300 DFTGLKGPYR IETEGEKQEL WKYTIDNVSP HAQPEEEERE RRVFKDLYGR HKEYLSSLVG 310 320 330 340 350 360 TDFEMTVPGA LRLFVNGEVV SAQGYEYDNL YVHFFVELPT AHWSSPAFQQ LSGVTQTCTT 370 380 390 400 410 420 KSLAMDKVAH FSYPFTFEAF FLHEDESSDA LPEWPVLYCE VLSLDFWQRY RVEGYGAVVL 430 440 450 460 470 480 PATPGSHTLT VSTWRPVELG TVAELRRFFI GGSLELEDLS YVRIPGSFKG ERLSRFGLRT 490 500 510 520 530 540 ETTGTVTFRL HCLQQSRAFM ESSSLQKRMR SVLDRLEGFS QQSSIHNVLE AFRRARRRMQ 550 EARESLPQDL VSPSGTLVS
	Isoform 2 [UniParc]. Checksum: 505F4279EB7A9E35	FASTA	520	59,869
	10 20 30 40 50 60 MAETVWSTDT GEAVYRSRDP VRNLRLRVHL QRITSSNFLH YQPAAELGKD LIDLATFRPQ 70 80 90 100 110 120 PTASGHRPEE DEEEEIVIGW QEKLFSQFEV DLYQNETACQ SPLDYQYRQE ILKLENSGGK 130 140 150 160 170 180 KNRRIFTYTD SDRYTNLEEH CQRMTTAASE VPSFLVERMA NVRRRRQDRR GMEGGILKSR 190 200 210 220 230 240 IVTWEPSEEF VRNNHVINTP LQTMHIMADL GPYKKLGYKK YEHVLCTLKV DSNGVITVKP 250 260 270 280 290 300 DFTGLKGPYR IETEGEKQEL WKYTIDNVSP HAQPEEEERE RRVFKDLYGR HKEYLSSLVG 310 320 330 340 350 360 TDFEMTVPGA LRLFVNGEVV SAQGYEYDNL YVHFFVELPT AHWSSPAFQQ LSGVTQTCTT 370 380 390 400 410 420 KSLAMDKVAH FSYPFTFEAF FLHEDESSDA LPEWPVLYCE VLSLDFWQRY RVEGYGAVVL 430 440 450 460 470 480 PATPGSHTLT VSTWRPVELG TVAELRRFFI GGSLELEDLS YVRIPGSFKG LSSSKTKEGR 490 500 510 520 KVDGERVLNP QPVSLSLFPG KPHSTAWGLL RLRYELFLSK
	Isoform 3 [UniParc]. Checksum: 6760801F0209F8A5	FASTA	549	63,344
	10 20 30 40 50 60 MAVPVSSFAQ RTRSRFRVHL QRITSSNFLH YQPAAELGKD LIDLATFRPQ PTASGHRPEE 70 80 90 100 110 120 DEEEEIVIGW QEKLFSQFEV DLYQNETACQ SPLDYQYRQE ILKLENSGGK KNRRIFTYTD 130 140 150 160 170 180 SDRYTNLEEH CQRMTTAASE VPSFLVERMA NVRRRRQDRR GMEGGILKSR IVTWEPSEEF 190 200 210 220 230 240 VRNNHVINTP LQTMHIMADL GPYKKLGYKK YEHVLCTLKV DSNGVITVKP DFTGLKGPYR 250 260 270 280 290 300 IETEGEKQEL WKYTIDNVSP HAQPEEEERE RRVFKDLYGR HKEYLSSLVG TDFEMTVPGA 310 320 330 340 350 360 LRLFVNGEVV SAQGYEYDNL YVHFFVELPT AHWSSPAFQQ LSGVTQTCTT KSLAMDKVAH 370 380 390 400 410 420 FSYPFTFEAF FLHEDESSDA LPEWPVLYCE VLSLDFWQRY RVEGYGAVVL PATPGSHTLT 430 440 450 460 470 480 VSTWRPVELG TVAELRRFFI GGSLELEDLS YVRIPGSFKG ERLSRFGLRT ETTGTVTFRL 490 500 510 520 530 540 HCLQQSRAFM ESSSLQKRMR SVLDRLEGFS QQSSIHNVLE AFRRARRRMQ EARESLPQDL VSPSGTLVS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"MKS1, encoding a component of the flagellar apparatus basal body proteome, is mutated in Meckel syndrome." Kyttaelae M., Tallila J., Salonen R., Kopra O., Kohlschmidt N., Paavola-Sakki P., Peltonen L., Kestilae M. Nat. Genet. 38:155-157(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INVOLVEMENT IN MKS1.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 86-559 (ISOFORM 1). Tissue: Hepatoma and Trachea.
[3]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Ovary.
[5]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 144-559 (ISOFORM 1).
[6]	"The Meckel-Gruber syndrome proteins MKS1 and meckelin interact and are required for primary cilium formation." Dawe H.R., Smith U.M., Cullinane A.R., Gerrelli D., Cox P., Badano J.L., Blair-Reid S., Sriram N., Katsanis N., Attie-Bitach T., Afford S.C., Copp A.J., Kelly D.A., Gull K., Johnson C.A. Hum. Mol. Genet. 16:173-186(2007) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, FUNCTION, INTERACTION WITH TMEM67.
[7]	"Ciliary and centrosomal defects associated with mutation and depletion of the Meckel syndrome genes MKS1 and MKS3." Tammachote R., Hommerding C.J., Sinders R.M., Miller C.A., Czarnecki P.G., Leightner A.C., Salisbury J.L., Ward C.J., Torres V.E., Gattone V.H. II, Harris P.C. Hum. Mol. Genet. 18:3311-3323(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"Functional interactions between the ciliopathy-associated Meckel syndrome 1 (MKS1) protein and two novel MKS1-related (MKSR) proteins." Bialas N.J., Inglis P.N., Li C., Robinson J.F., Parker J.D., Healey M.P., Davis E.E., Inglis C.D., Toivonen T., Cottell D.C., Blacque O.E., Quarmby L.M., Katsanis N., Leroux M.R. J. Cell Sci. 122:611-624(2009) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[9]	"A meckelin-filamin A interaction mediates ciliogenesis." Adams M., Simms R.J., Abdelhamed Z., Dawe H.R., Szymanska K., Logan C.V., Wheway G., Pitt E., Gull K., Knowles M.A., Blair E., Cross S.H., Sayer J.A., Johnson C.A. Hum. Mol. Genet. 21:1272-1286(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FLNA.
[10]	"Hypomorphic mutations in syndromic encephalocele genes are associated with Bardet-Biedl syndrome." Leitch C.C., Zaghloul N.A., Davis E.E., Stoetzel C., Diaz-Font A., Rix S., Alfadhel M., Lewis R.A., Eyaid W., Banin E., Dollfus H., Beales P.L., Badano J.L., Katsanis N. Nat. Genet. 40:443-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS BBS13 PHE-371 DEL AND TRP-492, VARIANTS GLN-123; GLY-286 AND THR-450.
[11]	Erratum Leitch C.C., Zaghloul N.A., Davis E.E., Stoetzel C., Diaz-Font A., Rix S., Alfadhel M., Lewis R.A., Eyaid W., Banin E., Dollfus H., Beales P.L., Badano J.L., Katsanis N. Nat. Genet. 40:927-927(2008)
[12]	"Mutation spectrum of Meckel syndrome genes: one group of syndromes or several distinct groups?" Tallila J., Salonen R., Kohlschmidt N., Peltonen L., Kestilae M. Hum. Mutat. 30:E813-E830(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MKS1 TRP-166.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	DQ185029 mRNA. Translation: AAZ94714.1. AK000352 mRNA. Translation: BAA91105.1. Different initiation. AK310815 mRNA. No translation available. AC005962 Genomic DNA. No translation available. BC010061 mRNA. Translation: AAH10061.1. Different initiation. CR457229 mRNA. Translation: CAG33510.1.
IPI	IPI00015720. IPI00186410. IPI00794034.
RefSeq	NP_001159399.1. NM_001165927.1. NP_060247.2. NM_017777.3.
UniGene	Hs.408843.
3D structure databases
ProteinModelPortal	Q9NXB0.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NXB0. 2 interactions.
MINT	MINT-1415211.
STRING	9606.ENSP00000376827.
PTM databases
PhosphoSite	Q9NXB0.
Polymorphism databases
DMDM	92087008.
Proteomic databases
PaxDb	Q9NXB0.
PRIDE	Q9NXB0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000393119; ENSP00000376827; ENSG00000011143. ENST00000537529; ENSP00000442096; ENSG00000011143.
GeneID	54903.
KEGG	hsa:54903.
UCSC	uc002ivr.2. human. uc021uam.1. human.
Organism-specific databases
CTD	54903.
GeneCards	GC17M056282.
HGNC	HGNC:7121. MKS1.
HPA	HPA021372. HPA021812.
MIM	209900. phenotype. 249000. phenotype. 609883. gene.
neXtProt	NX_Q9NXB0.
Orphanet	110. Bardet-Biedl syndrome. 564. Meckel syndrome.
PharmGKB	PA30840.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG306467.
HOGENOM	HOG000251592.
HOVERGEN	HBG079759.
InParanoid	Q9NXB0.
OMA	TFKGERL.
OrthoDB	EOG4ZGPC3.
Gene expression databases
ArrayExpress	Q9NXB0.
Bgee	Q9NXB0.
CleanEx	HS_MKS1.
Genevestigator	Q9NXB0.
GermOnline	ENSG00000011143. Homo sapiens.
Family and domain databases
InterPro	IPR010796. B9_dom. [Graphical view]
Pfam	PF07162. B9-C2. 1 hit. [Graphical view]
PROSITE	PS51381. B9. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	54903.
NextBio	57936.
SOURCE	Search...

Entry information

Entry name

MKS1_HUMAN

Accession

Primary (citable) accession number: Q9NXB0
Secondary accession number(s): B7WNX4 , F5H885, Q284T0, Q96G13

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 7, 2006
Last sequence update:	March 7, 2006
Last modified:	May 29, 2013
This is version 79 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.