Q5HYA8 (MKS3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Meckelin

Alternative name(s):
Meckel syndrome type 3 protein
Transmembrane protein 67

Gene names

Name:	TMEM67
Synonyms:	MKS3

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	995 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Part of the tectonic-like complex which is required for tissue-specific ciliogenesis and may regulate ciliary membrane composition By similarity. 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. Essential for endoplasmic reticulum-associated degradation (ERAD) of surfactant protein C (SFTPC). Ref.6 Ref.7 Ref.8 Ref.9
Subunit structure	Part of the tectonic-like complex (also named B9 complex) By similarity. Interacts with DNAJB9, DNAJC10 and mutated SFTPC. Interacts with SYNE2 during the early establishment of cell polarity. Interacts (via C-terminus) with FLNA. Ref.6 Ref.8 Ref.9 Ref.10
Subcellular location	Cell membrane; Multi-pass membrane protein. Endoplasmic reticulum membrane; Multi-pass membrane protein. Cytoplasm › cytoskeleton › cilium basal body. Note: Localizes at the transition zone, a region between the basal body and the ciliary axoneme By similarity. Ref.6 Ref.8 Ref.9
Tissue specificity	Widely expressed in adult and fetal tissues. Expressed at higher level in spinal cord. Ref.6 Ref.11
Involvement in disease	Ciliary dysfunction leads to a broad spectrum of disorders, collectively termed ciliopathies. Overlapping clinical features include retinal degeneration, renal cystic disease, skeletal abnormalities, fibrosis of various organ, and a complex range of anatomical and functional defects of the central and peripheral nervous system. The ciliopathy range of diseases includes Meckel-Gruber syndrome, Bardet-Biedl syndrome, Joubert syndrome, and nephronophtisis among others. Single-locus allelism is insufficient to explain the variable penetrance and expressivity of such disorders, leading to the suggestion that variations across multiple sites of the ciliary proteome influence the clinical outcome. Meckel syndrome 3 (MKS3) [MIM:607361]: 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.6 Ref.11 Ref.16 Joubert syndrome 6 (JBTS6) [MIM:610688]: A disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12 Ref.17 Ref.19 Bardet-Biedl syndrome (BBS) [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 gene represented in this entry may act as a disease modifier. TMEM67 variations may influence the expression of Bardet-Biedl syndrome in patients who have causative mutations in other genes. Heterozygosity for a complex mutation in the TMEM67 gene coding for a protein with 2 in cis changes, and homozygosity for a truncating mutation of the CEP290 gene has been found in a patient with Bardet-Biedl syndrome 14. COACH syndrome (COACHS) [MIM:216360]: A disorder characterized by mental retardation, ataxia due to cerebellar hypoplasia, and hepatic fibrosis. Patients present the molar tooth sign, a midbrain-hindbrain malformation pathognomonic for Joubert syndrome and related disorders. Other features, such as coloboma and renal cysts, may be variable. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.15 Ref.18 Nephronophthisis 11 (NPHP11) [MIM:613550]: A disorder characterized by the association of nephronophthisis with hepatic fibrosis. Nephronophthisis is a progressive tubulo-interstitial kidney disorder histologically characterized by modifications of the tubules with thickening of the basement membrane, interstitial fibrosis and, in the advanced stages, medullary cysts. Typical clinical features are chronic renal failure, anemia, polyuria, polydipsia, isosthenuria, and growth retardation. Associations with extrarenal symptoms, especially ocular lesions, are frequent. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.17
Sequence caution	The sequence AAH32835.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BAG52959.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Cilium biogenesis/degradation
Cellular component	Cell membrane Cell projection Cilium Cytoplasm Cytoskeleton Endoplasmic reticulum Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Bardet-Biedl syndrome Ciliopathy Disease mutation Joubert syndrome Meckel syndrome Mental retardation Nephronophthisis Obesity
Domain	Transmembrane Transmembrane helix
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ER-associated protein catabolic process Inferred from mutant phenotype Ref.8. Source: UniProtKB cilium assembly Inferred from mutant phenotype Ref.7. Source: UniProtKB negative regulation of centrosome duplication 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.6. Source: UniProtKB cilium membrane Inferred from direct assay Ref.6. Source: UniProtKB cytoplasmic vesicle membrane Inferred from direct assay Ref.8. Source: UniProtKB endoplasmic reticulum membrane Inferred from direct assay Ref.8. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW microtubule basal body Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q5HYA8-1)

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: Q5HYA8-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-136: MATRGGAGVA...CHCPIGHILV → MSLSHWPYFR...GMYNIIEEIL

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 995	995	Meckelin		PRO_0000225689
Regions
	Transmembrane	9 – 29	21	Helical; Potential
	Transmembrane	526 – 546	21	Helical; Potential
	Transmembrane	570 – 590	21	Helical; Potential
	Transmembrane	609 – 629	21	Helical; Potential
	Transmembrane	689 – 709	21	Helical; Potential
	Transmembrane	734 – 754	21	Helical; Potential
	Transmembrane	939 – 959	21	Helical; Potential
Amino acid modifications
	Glycosylation	242	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 136	136	MATRG…GHILV → MSLSHWPYFRLVLNFRPQVI CLPQPPKVLGYRLEPPHLTL ACTLEGMYNIIEEIL in isoform 2.		VSP_044475
	Natural variant	54	1	Y → C in MKS3; uncertain pathogenicity. Ref.16		VAR_062310
	Natural variant	82	1	P → R in a patient with Joubert syndrome related disorder without clinically apparent liver disease. Ref.18		VAR_063783
	Natural variant	82	1	P → S in a patient with Joubert syndrome related disorder without clinically apparent liver disease. Ref.18		VAR_063784
	Natural variant	99	1	K → N in COACHS. Ref.18		VAR_063785
	Natural variant	130	1	P → R in COACHS. Ref.15 Ref.18		VAR_063786
	Natural variant	172	1	R → Q in COACHS. Ref.18		VAR_063787
	Natural variant	218	1	G → A. Ref.13		VAR_062311
	Natural variant	242	1	N → T in COACHS. Ref.18		VAR_063788
	Natural variant	245	1	S → F in MKS3; uncertain pathogenicity. Ref.16		VAR_062312
	Natural variant	252	1	M → T in MKS3 and COACHS. Ref.16 Ref.17 Ref.18		VAR_062313
	Natural variant	257	1	M → V in COACHS. Ref.18		VAR_063789
	Natural variant	261	1	D → N. Ref.13		VAR_062314
	Natural variant	290	1	W → L in NPHP11. Ref.17		VAR_064185
	Natural variant	296	1	W → C in MKS3; uncertain pathogenicity. Ref.16		VAR_062315
	Natural variant	320	1	S → C Is a modifier of Bardet-Biedl syndrome; found in a BBS14 patient also carrying a homozygous truncating mutation of the CEP290 gene. Ref.13 Corresponds to variant rs111619594 [ dbSNP | Ensembl ].		VAR_062316
	Natural variant	349	1	L → S in COACHS. Ref.18		VAR_063790
	Natural variant	358	1	P → L in COACHS and JBTS6; found in a patient with Joubert syndrome that also carries mutation 1329-R--S-1332 Del in KIF7. Ref.18 Ref.19		VAR_063791
	Natural variant	372	1	T → K in COACHS. Ref.15 Ref.18		VAR_063792
	Natural variant	376	1	Q → E in COACHS. Ref.18		VAR_063793
	Natural variant	376	1	Q → P in MKS3; leads to endoplasmic reticulum retention and prevents localization at the cell membrane. Ref.6 Ref.11		VAR_025474
	Natural variant	437	1	L → V. Ref.13		VAR_062317
	Natural variant	440	1	R → Q in MKS3 and COACHS. Ref.15 Ref.16		VAR_062318
	Natural variant	441	1	R → C in COACHS. Ref.18		VAR_063794
	Natural variant	485	1	P → S in COACHS. Ref.18		VAR_063795
	Natural variant	513	1	Y → C in JBTS6, MKS3 and COACHS. Ref.12 Ref.16 Ref.18		VAR_031987
	Natural variant	545	1	G → E in JBTS6. Ref.12		VAR_031988
	Natural variant	590	1	F → S in COACHS. Ref.15		VAR_063796
	Natural variant	604	1	I → V. Ref.1 Ref.2 Corresponds to variant rs3134031 [ dbSNP | Ensembl ].		VAR_025475
	Natural variant	615	1	C → R in MKS3, COACHS and NPHP11. Ref.16 Ref.17 Ref.18		VAR_062319
	Natural variant	637	1	F → L in COACHS. Ref.18		VAR_063797
	Natural variant	728	1	S → G in COACHS. Ref.15		VAR_063798
	Natural variant	782	1	H → R in COACHS. Ref.15		VAR_063799
	Natural variant	820	1	R → S in COACHS. Ref.15		VAR_063800
	Natural variant	821	1	G → R in NPHP11. Ref.17		VAR_064186
	Natural variant	821	1	G → S in NPHP11. Ref.17		VAR_064187
	Natural variant	833	1	I → T in COACHS and JBTS6; found in a patient with Joubert syndrome that also carries mutation 1329-R--S-1332 Del in KIF7. Ref.15 Ref.17 Ref.18 Ref.19		VAR_063801
	Natural variant	841	1	Q → P in COACHS. Ref.18		VAR_063802
	Natural variant	942	1	F → C in COACHS. Ref.18		VAR_063803
	Natural variant	966	1	L → P in MKS3. Ref.16		VAR_062320
Experimental info
	Sequence conflict	251	1	N → S in BAG52507. Ref.1
	Sequence conflict	325	1	N → D in BAG52507. Ref.1
Isoform 2:
	Sequence conflict	18	1	Q → R in BAG52507. Ref.1
	Sequence conflict	24	1	Q → R in BAG52507. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 11, 2011. Version 2. Checksum: 48B715BDD610C495	FASTA	995	111,745
	10 20 30 40 50 60 MATRGGAGVA MAVWSLLSAR AVTAFLLLFL PRFLQAQTFS FPFQQPEKCD NNQYFDISAL 70 80 90 100 110 120 SCVPCGANQR QDARGTSCVC LPGFQMISNN GGPAIICKKC PENMKGVTED GWNCISCPSD 130 140 150 160 170 180 LTAEGKCHCP IGHILVERDI NGTLLSQATC ELCDGNENSF MVVNALGDRC VRCEPTFVNT 190 200 210 220 230 240 SRSCACSEPN ILTGGLCFSS TGNFPLRRIS AARYGEVGMS LTSEWFAKYL QSSAAACWVY 250 260 270 280 290 300 ANLTSCQALG NMCVMNMNSY DFATFDACGL FQFIFENTAG LSTVHSISFW RQNLPWLFYG 310 320 330 340 350 360 DQLGLAPQVL SSTSLPTNFS FKGENQNTKL KFVAASYDIR GNFLKWQTLE GGVLQLCPDT 370 380 390 400 410 420 ETRLNAAYSF GTTYQQNCEI PISKILIDFP TPIFYDVYLE YTDENQHQYI LAVPVLNLNL 430 440 450 460 470 480 QHNKIFVNQD SNSGKWLLTR RIFLVDAVSG RENDLGTQPR VIRVATQISL SVHLVPNTIN 490 500 510 520 530 540 GNIYPPLITI AYSDIDIKDA NSQSVKVSFS VTYEMDHGEA HVQTDIALGV LGGLAVLASL 550 560 570 580 590 600 LKTAGWKRRI GSPMIDLQTV VKFLVYYAGD LANVFFIITV GTGLYWLIFF KAQKSVSVLL 610 620 630 640 650 660 PMPIQEERFV TYVGCAFALK ALQFLHKLIS QITIDVFFID WERPKGKVLK AVEGEGGVRS 670 680 690 700 710 720 ATVPVSIWRT YFVANEWNEI QTVRKINSLF QVLTVLFFLE VVGFKNLALM DSSSSLSRNP 730 740 750 760 770 780 PSYIAPYSCI LRYAVSAALW LAIGIIQVVF FAVFYERFIE DKIRQFVDLC SMSNISVFLL 790 800 810 820 830 840 SHKCFGYYIH GRSVHGHADT NMEEMNMNLK REAENLCSQR GLVPNTDGQT FEIAISNQMR 850 860 870 880 890 900 QHYDRIHETL IRKNGPARLL SSSASTFEQS IKAYHMMNKF LGSFIDHVHK EMDYFIKDKL 910 920 930 940 950 960 LLERILGMEF MEPMEKSIFY NDEGYSFSSV LYYGNEATLL IFDLLFFCVV DLACQNFILA 970 980 990 SFLTYLQQEI FRYIRNTVGQ KNLASKTLVD QRFLI
	Isoform 2 [UniParc]. Checksum: B7E458801DEA5E2C	FASTA	914	103,590
	10 20 30 40 50 60 MSLSHWPYFR LVLNFRPQVI CLPQPPKVLG YRLEPPHLTL ACTLEGMYNI IEEILERDIN 70 80 90 100 110 120 GTLLSQATCE LCDGNENSFM VVNALGDRCV RCEPTFVNTS RSCACSEPNI LTGGLCFSST 130 140 150 160 170 180 GNFPLRRISA ARYGEVGMSL TSEWFAKYLQ SSAAACWVYA NLTSCQALGN MCVMNMNSYD 190 200 210 220 230 240 FATFDACGLF QFIFENTAGL STVHSISFWR QNLPWLFYGD QLGLAPQVLS STSLPTNFSF 250 260 270 280 290 300 KGENQNTKLK FVAASYDIRG NFLKWQTLEG GVLQLCPDTE TRLNAAYSFG TTYQQNCEIP 310 320 330 340 350 360 ISKILIDFPT PIFYDVYLEY TDENQHQYIL AVPVLNLNLQ HNKIFVNQDS NSGKWLLTRR 370 380 390 400 410 420 IFLVDAVSGR ENDLGTQPRV IRVATQISLS VHLVPNTING NIYPPLITIA YSDIDIKDAN 430 440 450 460 470 480 SQSVKVSFSV TYEMDHGEAH VQTDIALGVL GGLAVLASLL KTAGWKRRIG SPMIDLQTVV 490 500 510 520 530 540 KFLVYYAGDL ANVFFIITVG TGLYWLIFFK AQKSVSVLLP MPIQEERFVT YVGCAFALKA 550 560 570 580 590 600 LQFLHKLISQ ITIDVFFIDW ERPKGKVLKA VEGEGGVRSA TVPVSIWRTY FVANEWNEIQ 610 620 630 640 650 660 TVRKINSLFQ VLTVLFFLEV VGFKNLALMD SSSSLSRNPP SYIAPYSCIL RYAVSAALWL 670 680 690 700 710 720 AIGIIQVVFF AVFYERFIED KIRQFVDLCS MSNISVFLLS HKCFGYYIHG RSVHGHADTN 730 740 750 760 770 780 MEEMNMNLKR EAENLCSQRG LVPNTDGQTF EIAISNQMRQ HYDRIHETLI RKNGPARLLS 790 800 810 820 830 840 SSASTFEQSI KAYHMMNKFL GSFIDHVHKE MDYFIKDKLL LERILGMEFM EPMEKSIFYN 850 860 870 880 890 900 DEGYSFSSVL YYGNEATLLI FDLLFFCVVD LACQNFILAS FLTYLQQEIF RYIRNTVGQK 910 NLASKTLVDQ RFLI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3-995 (ISOFORM 1), VARIANT VAL-604. Tissue: Corpus callosum.
[2]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT VAL-604. Tissue: Testis.
[3]	"DNA sequence and analysis of human chromosome 8." Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S. Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] OF 5-995 (ISOFORM 1). Tissue: Testis.
[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: TISSUE SPECIFICITY, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT MKS3 PRO-376, FUNCTION, INTERACTION WITH MKS1.
[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]	"Meckel-Gruber syndrome protein MKS3 is required for endoplasmic reticulum-associated degradation of surfactant protein C." Wang M., Bridges J.P., Na C.L., Xu Y., Weaver T.E. J. Biol. Chem. 284:33377-33383(2009) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, TOPOLOGY, FUNCTION, INTERACTION WITH DNAJB9; DNAJC10 AND SFTPC.
[9]	"Nesprin-2 interacts with meckelin and mediates ciliogenesis via remodelling of the actin cytoskeleton." Dawe H.R., Adams M., Wheway G., Szymanska K., Logan C.V., Noegel A.A., Gull K., Johnson C.A. J. Cell Sci. 122:2716-2726(2009) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH SYNE2, FUNCTION.
[10]	"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.
[11]	"The transmembrane protein meckelin (MKS3) is mutated in Meckel-Gruber syndrome and the wpk rat." Smith U.M., Consugar M., Tee L.J., McKee B.M., Maina E.N., Whelan S., Morgan N.V., Goranson E., Gissen P., Lilliquist S., Aligianis I.A., Ward C.J., Pasha S., Punyashthiti R., Malik Sharif S., Batman P.A., Bennett C.P., Woods C.G. , McKeown C., Bucourt M., Miller C.A., Cox P., Algazali L., Trembath R.C., Torres V.E., Attie-Bitach T., Kelly D.A., Maher E.R., Gattone V.H., Harris P.C., Johnson C.A. Nat. Genet. 38:191-196(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MKS3 PRO-376, TISSUE SPECIFICITY.
[12]	"The Meckel-Gruber syndrome gene, MKS3, is mutated in Joubert syndrome." Baala L., Romano S., Khaddour R., Saunier S., Smith U.M., Audollent S., Ozilou C., Faivre L., Laurent N., Foliguet B., Munnich A., Lyonnet S., Salomon R., Encha-Razavi F., Gubler M.-C., Boddaert N., de Lonlay P., Johnson C.A. , Vekemans M., Antignac C., Attie-Bitach T. Am. J. Hum. Genet. 80:186-194(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS JBTS6 CYS-513 AND GLU-545.
[13]	"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 ALA-218; ASN-261; CYS-320 AND VAL-437, INVOLVEMENT IN BARDET-BIEDL SYNDROME.
[14]	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)
[15]	"MKS3/TMEM67 mutations are a major cause of COACH Syndrome, a Joubert Syndrome related disorder with liver involvement." Brancati F., Iannicelli M., Travaglini L., Mazzotta A., Bertini E., Boltshauser E., D'Arrigo S., Emma F., Fazzi E., Gallizzi R., Gentile M., Loncarevic D., Mejaski-Bosnjak V., Pantaleoni C., Rigoli L., Salpietro C.D., Signorini S., Stringini G.R. , Verloes A., Zabloka D., Dallapiccola B., Gleeson J.G., Valente E.M. Hum. Mutat. 30:E432-E442(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS COACHS ARG-130; LYS-372; GLN-440; SER-590; GLY-728; ARG-782; SER-820 AND THR-833.
[16]	"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: VARIANTS MKS3 CYS-54; PHE-245; THR-252; CYS-296 GLN-440; CYS-513; ARG-615 AND PRO-966.
[17]	"Hypomorphic mutations in meckelin (MKS3/TMEM67) cause nephronophthisis with liver fibrosis (NPHP11)." Otto E.A., Tory K., Attanasio M., Zhou W., Chaki M., Paruchuri Y., Wise E.L., Wolf M.T.F., Utsch B., Becker C., Nuernberg G., Nuernberg P., Nayir A., Saunier S., Antignac C., Hildebrandt F. J. Med. Genet. 46:663-670(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS NPHP11 LEU-290; ARG-615; SER-821 AND ARG-821, VARIANTS JBTS6 THR-252; ARG-615; ARG-821 AND THR-833.
[18]	"Mutations in 3 genes (MKS3, CC2D2A and RPGRIP1L) cause COACH syndrome (Joubert syndrome with congenital hepatic fibrosis)." Doherty D., Parisi M.A., Finn L.S., Gunay-Aygun M., Al-Mateen M., Bates D., Clericuzio C., Demir H., Dorschner M., van Essen A.J., Gahl W.A., Gentile M., Gorden N.T., Hikida A., Knutzen D., Ozyurek H., Phelps I., Rosenthal P. , Verloes A., Weigand H., Chance P.F., Dobyns W.B., Glass I.A. J. Med. Genet. 47:8-21(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS COACHS ASN-99; ARG-130; GLN-172; THR-242; THR-252; VAL-257; SER-349; LEU-358; LYS-372; GLU-376; CYS-441; SER-485; CYS-513; ARG-615; LEU-637; THR-833; PRO-841 AND CYS-942, VARIANTS ARG-82 AND SER-82.
[19]	"Mutations in KIF7 link Joubert syndrome with Sonic Hedgehog signaling and microtubule dynamics." Dafinger C., Liebau M.C., Elsayed S.M., Hellenbroich Y., Boltshauser E., Korenke G.C., Fabretti F., Janecke A.R., Ebermann I., Nurnberg G., Nurnberg P., Zentgraf H., Koerber F., Addicks K., Elsobky E., Benzing T., Schermer B., Bolz H.J. J. Clin. Invest. 121:2662-2667(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS JBTS6 LEU-358 AND THR-833.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK092244 mRNA. Translation: BAG52507.1. AK094935 mRNA. Translation: BAG52959.1. Different initiation. BX648768 mRNA. Translation: CAI45999.1. AC010834 Genomic DNA. No translation available. CH471060 Genomic DNA. Translation: EAW91703.1. BC032835 mRNA. Translation: AAH32835.1. Different initiation.
IPI	IPI00217830. IPI00746257.
RefSeq	NP_001135773.1. NM_001142301.1. NP_714915.3. NM_153704.5.
UniGene	Hs.116240.
3D structure databases
ProteinModelPortal	Q5HYA8.
SMR	Q5HYA8. Positions 73-118.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000389998.
Protein family/group databases
TCDB	9.B.77.1.1. meckel syndrome protein (Meckelin) family.
PTM databases
PhosphoSite	Q5HYA8.
Polymorphism databases
DMDM	74707893.
Proteomic databases
PaxDb	Q5HYA8.
PRIDE	Q5HYA8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000323130; ENSP00000314488; ENSG00000164953. ENST00000409623; ENSP00000386966; ENSG00000164953. ENST00000453321; ENSP00000389998; ENSG00000164953.
GeneID	91147.
KEGG	hsa:91147.
UCSC	uc003yga.4. human.
Organism-specific databases
CTD	91147.
GeneCards	GC08P094837.
H-InvDB	HIX0007648.
HGNC	HGNC:28396. TMEM67.
HPA	HPA039940.
MIM	209900. phenotype. 216360. phenotype. 607361. phenotype. 609884. gene. 610688. phenotype. 613550. phenotype.
neXtProt	NX_Q5HYA8.
Orphanet	475. Joubert syndrome. 1454. Joubert syndrome with hepatic defect. 564. Meckel syndrome. 84081. Senior-Boichis syndrome.
PharmGKB	PA142670780.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG277231.
HOGENOM	HOG000231576.
HOVERGEN	HBG080334.
InParanoid	Q5HYA8.
OMA	TTYQQNC.
Gene expression databases
ArrayExpress	Q5HYA8.
Bgee	Q5HYA8.
CleanEx	HS_TMEM67.
Genevestigator	Q5HYA8.
GermOnline	ENSG00000164953. Homo sapiens.
Family and domain databases
InterPro	IPR009030. Growth_fac_rcpt. IPR019170. Meckelin. [Graphical view]
Pfam	PF09773. Meckelin. 1 hit. [Graphical view]
SUPFAM	SSF57184. Grow_fac_recept. 1 hit.
ProtoNet	Search...
Other
GenomeRNAi	91147.
NextBio	77120.
SOURCE	Search...

Entry information

Entry name

MKS3_HUMAN

Accession

Primary (citable) accession number: Q5HYA8
Secondary accession number(s): B3KRU5 , B3KT47, G5E9H2, Q3ZCX3, Q7Z5T8, Q8IZ06

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 7, 2006
Last sequence update:	January 11, 2011
Last modified:	May 1, 2013
This is version 86 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.