MKS3_MOUSE
ID MKS3_MOUSE Reviewed; 992 AA.
AC Q8BR76; Q78U07;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 2.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Meckelin;
DE AltName: Full=Meckel syndrome type 3 protein homolog;
DE AltName: Full=Transmembrane protein 67;
DE Flags: Precursor;
GN Name=Tmem67; Synonyms=Mks3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 6-995 (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Cerebellum, and Corpora quadrigemina;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP FUNCTION.
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 [3]
RP INVOLVEMENT IN BPCK PHENOTYPE.
RX PubMed=19211713; DOI=10.1681/asn.2008040412;
RA Cook S.A., Collin G.B., Bronson R.T., Naggert J.K., Liu D.P., Akeson E.C.,
RA Davisson M.T.;
RT "A mouse model for Meckel syndrome type 3.";
RL J. Am. Soc. Nephrol. 20:753-764(2009).
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=19815549; DOI=10.1074/jbc.m109.034371;
RA Wang M., Bridges J.P., Na C.L., Xu Y., Weaver T.E.;
RT "Meckel-Gruber syndrome protein MKS3 is required for endoplasmic reticulum-
RT associated degradation of surfactant protein C.";
RL J. Biol. Chem. 284:33377-33383(2009).
RN [5]
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 [6]
RP FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND IDENTIFICATION IN
RP THE TECTONIC-LIKE COMPLEX.
RX PubMed=21725307; DOI=10.1038/ng.891;
RA Garcia-Gonzalo F.R., Corbit K.C., Sirerol-Piquer M.S., Ramaswami G.,
RA Otto E.A., Noriega T.R., Seol A.D., Robinson J.F., Bennett C.L.,
RA Josifova D.J., Garcia-Verdugo J.M., Katsanis N., Hildebrandt F.,
RA Reiter J.F.;
RT "A transition zone complex regulates mammalian ciliogenesis and ciliary
RT membrane composition.";
RL Nat. Genet. 43:776-784(2011).
RN [7]
RP INVOLVEMENT IN BPCK PHENOTYPE.
RX PubMed=23393159; DOI=10.1093/hmg/ddt054;
RA Leightner A.C., Hommerding C.J., Peng Y., Salisbury J.L., Gainullin V.G.,
RA Czarnecki P.G., Sussman C.R., Harris P.C.;
RT "The Meckel syndrome protein meckelin (TMEM67) is a key regulator of cilia
RT function but is not required for tissue planar polarity.";
RL Hum. Mol. Genet. 22:2024-2040(2013).
CC -!- FUNCTION: Part of the tectonic-like complex which is required for
CC tissue-specific ciliogenesis and may regulate ciliary membrane
CC composition. 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. Essential for endoplasmic reticulum-associated degradation
CC (ERAD) of surfactant protein C (sftpc). {ECO:0000269|PubMed:17185389,
CC ECO:0000269|PubMed:19515853, ECO:0000269|PubMed:21725307}.
CC -!- SUBUNIT: Interacts with DNAJB9, DNAJC10 and mutated SFTPC (By
CC similarity). Interacts with SYNE2 during the early establishment of
CC cell polarity (By similarity). Part of the tectonic-like complex (also
CC named B9 complex) (PubMed:21725307). Interacts (via C-terminus) with
CC FLNA (By similarity). Interacts with TMEM218 (By similarity).
CC {ECO:0000250|UniProtKB:Q5HYA8, ECO:0000269|PubMed:21725307}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}. Endoplasmic reticulum membrane; Multi-pass
CC membrane protein. Cytoplasm, cytoskeleton, cilium basal body.
CC Note=Localizes at the transition zone, a region between the basal body
CC and the ciliary axoneme.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8BR76-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BR76-2; Sequence=VSP_017417, VSP_017418;
CC -!- DISEASE: Note=A spontaneous deletion of TMEM67 cause the bilateral
CC polycystic kidneys (bpck) phenotype, a disease mimicking human Meckel-
CC Gruber syndrome 3. Homozygous bpck/bpck mice typically manifest
CC bilateral nephropathy with swollen abdomens resulting from grossly
CC enlarged polycystic kidneys and die by 3 week of age. Some mice also
CC develop hydrocephalus, usually detectable within a few days of birth
CC (PubMed:19211713). Additionally, bpck/bpck mice exhibit retinal
CC degeneration and tissue disorganization in the eye, and cochlear
CC defects (PubMed:23393159). {ECO:0000269|PubMed:19211713,
CC ECO:0000269|PubMed:23393159}.
CC -!- DISRUPTION PHENOTYPE: Mice survive to birth with no overt morphological
CC abnormalities. However, these mice died soon after birth.
CC {ECO:0000269|PubMed:21725307}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC31378.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC32362.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK042835; BAC31378.1; ALT_INIT; mRNA.
DR EMBL; AK045429; BAC32362.1; ALT_INIT; mRNA.
DR CCDS; CCDS17974.1; -. [Q8BR76-1]
DR RefSeq; NP_808529.2; NM_177861.4.
DR AlphaFoldDB; Q8BR76; -.
DR SMR; Q8BR76; -.
DR CORUM; Q8BR76; -.
DR STRING; 10090.ENSMUSP00000103928; -.
DR GlyConnect; 2504; 1 N-Linked glycan (1 site).
DR GlyGen; Q8BR76; 2 sites, 1 N-linked glycan (1 site).
DR iPTMnet; Q8BR76; -.
DR PhosphoSitePlus; Q8BR76; -.
DR MaxQB; Q8BR76; -.
DR PaxDb; Q8BR76; -.
DR PRIDE; Q8BR76; -.
DR ProteomicsDB; 295636; -. [Q8BR76-1]
DR ProteomicsDB; 295637; -. [Q8BR76-2]
DR DNASU; 329795; -.
DR GeneID; 329795; -.
DR KEGG; mmu:329795; -.
DR UCSC; uc008saj.1; mouse. [Q8BR76-2]
DR CTD; 91147; -.
DR MGI; MGI:1923928; Tmem67.
DR eggNOG; KOG4611; Eukaryota.
DR InParanoid; Q8BR76; -.
DR Reactome; R-MMU-5620912; Anchoring of the basal body to the plasma membrane.
DR BioGRID-ORCS; 329795; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Tmem67; mouse.
DR PRO; PR:Q8BR76; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q8BR76; protein.
DR GO; GO:0005930; C:axoneme; ISO:MGI.
DR GO; GO:0005813; C:centrosome; ISO:MGI.
DR GO; GO:0060170; C:ciliary membrane; ISO:MGI.
DR GO; GO:0035869; C:ciliary transition zone; ISO:MGI.
DR GO; GO:0005929; C:cilium; ISO:MGI.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0036038; C:MKS complex; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0031005; F:filamin binding; ISO:MGI.
DR GO; GO:0051787; F:misfolded protein binding; ISO:MGI.
DR GO; GO:0051082; F:unfolded protein binding; ISO:MGI.
DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; IMP:UniProtKB.
DR GO; GO:0060271; P:cilium assembly; IMP:UniProtKB.
DR GO; GO:0007368; P:determination of left/right symmetry; IMP:MGI.
DR GO; GO:0060322; P:head development; ISO:MGI.
DR GO; GO:0007507; P:heart development; IMP:MGI.
DR GO; GO:0001822; P:kidney development; IMP:MGI.
DR GO; GO:0010826; P:negative regulation of centrosome duplication; IMP:UniProtKB.
DR GO; GO:0035845; P:photoreceptor cell outer segment organization; ISO:MGI.
DR GO; GO:1904294; P:positive regulation of ERAD pathway; ISO:MGI.
DR GO; GO:1902857; P:positive regulation of non-motile cilium assembly; ISO:MGI.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; ISO:MGI.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR019170; Meckelin.
DR PANTHER; PTHR21274; PTHR21274; 1.
DR Pfam; PF09773; Meckelin; 1.
DR SUPFAM; SSF57184; SSF57184; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cell projection; Cilium;
KW Cilium biogenesis/degradation; Cytoplasm; Cytoskeleton;
KW Endoplasmic reticulum; Glycoprotein; Membrane; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..35
FT /evidence="ECO:0000255"
FT CHAIN 36..992
FT /note="Meckelin"
FT /evidence="ECO:0000255"
FT /id="PRO_0000225690"
FT TRANSMEM 523..543
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 567..587
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 606..626
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 686..706
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 731..751
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 936..956
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CARBOHYD 242
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 136..164
FT /note="VERNVSGSLLAQATCELCDESENSFTKAN -> GKNNIYKIMVMNFCVYFIK
FT DINLNGFVVV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_017417"
FT VAR_SEQ 165..992
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_017418"
SQ SEQUENCE 992 AA; 111810 MW; 9D97AFEB54B1786F CRC64;
MVTRTRPVAA MAVRSRSSSR TGTAYLLLVL CEVSWAQIFS FPFRRPETCD FNQYFDISAL
SCAPCGANQR RDALGTSCVC LPGYHMISNN GGPSIICKKC PENMKGVTKD GWDCISCPSG
LTAEGKCHCP TGHILVERNV SGSLLAQATC ELCDESENSF TKANALGTRC VRCEPTFVNT
SRSCSCSEPH TLTGGLCFSN TGNFHQRVIS TARYGELGMS LNSEWFAKYL QATAAACWTH
ANLTSCQALG NMCVMNMNSY DSTTLDACRL FHYIFESTAG LISVHSVPFW RQNLPWLFYG
DQPGLAPQVL STTPLPTNFS FKGQNQLKFV AASYDIRGNF IKWQPLEGGV LQLCPDTERR
LDAAYAFGTT YQQNCEISLS KLLVDFSSPV FYDVYLEYTD EEQHRYLWPI PVLNLNLQHN
KLFVNQDSSS SKWLLTRRIF LVDAVSGREN DLGNQPRVIR VATQISLSIR LVPNTKNGNI
YTPLLTIAYS DIDIKNAHSQ SAKISFSVKY EMNQGDASVH TDIALGVLGG LAVLSSLLKT
AGWKRRVGSP MIDLQTVMKF LLYYAGDLAN VFFIITVGTG LYWLIFFKAQ KSVSVLLPMP
VQEERFVTYV GCAFAMKALQ FLHKFISQIS IDIFFIDWER PKGKVLKAVE GEGGVRSATV
PVSIWRTYFV ANEWNEIQTV RKINPLFQVL TTLFFLEVVG FKNLALMDSS SSLSRNPSDY
TAPYSRILRY AVATAIWLVI GIIQVVFFAA FYERFIEDKI RQFVDLCSMS NVSVFLLSHR
CFGYYIHGRS VHGHADTNME EMNMNLKREA ENLCSQRGLV PNTDGQTFQI AVSSQMRQHY
DRIHETLTRR NGPARLLSSS GSTFEQSIKA YHAMNKFLGS FIDHVHKEMD YFIKDKLLLE
RILGMEFMEP MEKSIFYNDE GHSFSSVLYY GNEATLLIFD LLFFCVVDLA CQDFVLASFL
TYLQQEIFRF IRNTVGQKNL ATKTLVDERF LI
