MKS3_RAT
ID MKS3_RAT Reviewed; 992 AA.
AC P0C152;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 1.
DT 03-AUG-2022, entry version 89.
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, Wpk;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP IDENTIFICATION.
RX PubMed=11095650; DOI=10.1681/asn.v11122272;
RA Nauta J., Goedbloed M.A., Herck H.V., Hesselink D.A., Visser P.,
RA Willemsen R., Van Dokkum R.P.E., Wright C.J., Guay-Woodford L.M.;
RT "New rat model that phenotypically resembles autosomal recessive polycystic
RT kidney disease.";
RL J. Am. Soc. Nephrol. 11:2272-2284(2000).
RN [3]
RP SUBCELLULAR LOCATION, AND FUNCTION.
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 [4]
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 [5]
RP VARIANT WPK LEU-389.
RX PubMed=16415887; DOI=10.1038/ng1713;
RA Smith U.M., Consugar M., Tee L.J., McKee B.M., Maina E.N., Whelan S.,
RA Morgan N.V., Goranson E., Gissen P., Lilliquist S., Aligianis I.A.,
RA Ward C.J., Pasha S., Punyashthiti R., Malik Sharif S., Batman P.A.,
RA Bennett C.P., Woods C.G., McKeown C., Bucourt M., Miller C.A., Cox P.,
RA Algazali L., Trembath R.C., Torres V.E., Attie-Bitach T., Kelly D.A.,
RA Maher E.R., Gattone V.H., Harris P.C., Johnson C.A.;
RT "The transmembrane protein meckelin (MKS3) is mutated in Meckel-Gruber
RT syndrome and the wpk rat.";
RL Nat. Genet. 38:191-196(2006).
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) (By similarity).
CC {ECO:0000250|UniProtKB:Q8BR76, ECO:0000269|PubMed:19515853,
CC ECO:0000269|PubMed:19815549}.
CC -!- SUBUNIT: Part of the tectonic-like complex (also named B9 complex).
CC Interacts with DNAJB9, DNAJC10 and mutated SFTPC. Interacts with SYNE2
CC during the early establishment of cell polarity. Interacts (via C-
CC terminus) with FLNA. Interacts with TMEM218 (By similarity).
CC {ECO:0000250|UniProtKB:Q5HYA8, ECO:0000250|UniProtKB:Q8BR76}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q5HYA8};
CC Multi-pass membrane protein {ECO:0000255}. Endoplasmic reticulum
CC membrane {ECO:0000269|PubMed:19815549}; Multi-pass membrane protein
CC {ECO:0000255}. Cytoplasm, cytoskeleton, cilium basal body
CC {ECO:0000250|UniProtKB:Q5HYA8}. Note=Localizes at the transition zone,
CC a region between the basal body and the ciliary axoneme.
CC {ECO:0000250|UniProtKB:Q5HYA8}.
CC -!- DISEASE: Note=Defects in Tmem67 are the cause of Wistar polycystic
CC kidney (wpk). Homozygous wkp rats develop nephromegaly, hypertension,
CC proteinuria, impaired urine-concentrating capacity, and uremia,
CC resulting in death at 4 week of age. Early cysts are present in the
CC nephrogenic zone at embryonic day 19. {ECO:0000269|PubMed:16415887}.
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DR EMBL; AABR03040910; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03041815; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; P0C152; -.
DR SMR; P0C152; -.
DR STRING; 10116.ENSRNOP00000021839; -.
DR GlyGen; P0C152; 1 site.
DR PaxDb; P0C152; -.
DR UCSC; RGD:1586167; rat.
DR RGD; 1586167; Tmem67.
DR eggNOG; KOG4611; Eukaryota.
DR InParanoid; P0C152; -.
DR PhylomeDB; P0C152; -.
DR Reactome; R-RNO-5620912; Anchoring of the basal body to the plasma membrane.
DR PRO; PR:P0C152; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005813; C:centrosome; ISO:RGD.
DR GO; GO:0060170; C:ciliary membrane; ISO:RGD.
DR GO; GO:0035869; C:ciliary transition zone; ISO:RGD.
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; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0031005; F:filamin binding; ISO:RGD.
DR GO; GO:0051787; F:misfolded protein binding; IDA:RGD.
DR GO; GO:0051082; F:unfolded protein binding; ISO:RGD.
DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; ISO:RGD.
DR GO; GO:0060271; P:cilium assembly; IMP:UniProtKB.
DR GO; GO:0007368; P:determination of left/right symmetry; ISO:RGD.
DR GO; GO:0060322; P:head development; IMP:RGD.
DR GO; GO:0007507; P:heart development; ISO:RGD.
DR GO; GO:0001822; P:kidney development; ISO:RGD.
DR GO; GO:0010826; P:negative regulation of centrosome duplication; IMP:RGD.
DR GO; GO:0035845; P:photoreceptor cell outer segment organization; IMP:RGD.
DR GO; GO:1904294; P:positive regulation of ERAD pathway; IMP:RGD.
DR GO; GO:1902857; P:positive regulation of non-motile cilium assembly; IMP:RGD.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; ISO:RGD.
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 Cell membrane; Cell projection; Cilium; Cilium biogenesis/degradation;
KW Cytoplasm; Cytoskeleton; Disease variant; Endoplasmic reticulum;
KW Glycoprotein; Membrane; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..35
FT /evidence="ECO:0000255"
FT CHAIN 36..992
FT /note="Meckelin"
FT /evidence="ECO:0000255"
FT /id="PRO_0000225691"
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 VARIANT 389
FT /note="P -> L (in Wpk)"
FT /evidence="ECO:0000269|PubMed:16415887"
SQ SEQUENCE 992 AA; 111740 MW; 042CCE7E736BD6BF CRC64;
MVMRTRPLAA MAVRSCFSAL TGTVYLLLVL CEVSWAQIFS FPFQRPETCD LNQYFDISAL
SCAPCGANQR RDALGTSCIC LPGYHMISNN GGPSIICKKC PENMKGVTKD GWDCISCPNG
LTAEGKCHCP SGHILVERNV SGSLLSQATC ELCDGNENSF TKPNALGTRC VRCEPTFVNT
SRSCSCSEPH ISTGGLCFSN TGNFPQRLIS TERYGELGMS SNSEWFTKYL QATAAACWTH
SNLTSCQALG NMCVMNMNSY DSTTFDACRL FHYVFEGAAG LTGVHSVPFW RQNLPWLFYG
DQPGLASQVL STTPLPTNFS FKGQNQLKFV AASYDIRGNF IRWQTVKGGV LQLCPDTERR
LDAAYSFGTT YQQNCEISLS KLLADFPSPV FYDIYLEYTD EVQHHYLWAI PVLNLNLQHN
KLFVNQDSSS SKWLLTRRIF LVDAVSGREN DLGNQPRVIR VATQISLSIR LVPNTKNGNI
YTPLLTIAYS DIDIKNAYSQ SVKISFSVKY EMNQGDAFVQ TDIALGVLGG LAVLSSLLKT
AGWKRRIGSP MIDLQTVMKF LLYYAGDLAN VFFIITVGTG LYWLIFFKAQ KSVSVLLPMP
VQEERFVTYV GCAFAMKALQ FLHKLISQIT IDIFFIDWER PKGKVLKAVE GEGGVRSATV
PVSIWRTYFV ANEWNEIQTV RKINPLFQVL TTLFFLEVVG FKNLALMDPS SSLSRSLSDY
AAPYSRILRY AVATTIWLVI GIVQVVFFAA FYERFIEDKI RQFVDLCSMS NVSVFLLSHR
CFGYYIHGRS VHGHADTNME DMNMNLRREA ENLCSQRGLV PNTDGQTFQI AVSSQMRQHY
DRIHETLTRR NGPARLLSSS GSTLEQSIKA YHAMNKFLGS FIDHVHKEMD YFIKDKLLLE
KILGMEFMEP LEKSIFYNDE SHSFSSVLYY GNEATLLIFD LLFFCVVDLA CQNFVLASFL
TYLQQEIFRF IRNTVGQKNL ATKTLVDERF LI
