CCD66_MOUSE
ID CCD66_MOUSE Reviewed; 935 AA.
AC Q6NS45; Q3ULU6; Q8C304; Q8C6T6;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 3.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=Coiled-coil domain-containing protein 66 {ECO:0000305};
GN Name=Ccdc66 {ECO:0000312|MGI:MGI:2443639};
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 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 34-481 (ISOFORM 3).
RC STRAIN=C57BL/6J; TISSUE=Lung, Mammary gland, Oviduct, and Visual cortex;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-366 AND SER-595, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, Kidney, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP SUBUNIT, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=19777273; DOI=10.1007/s10048-009-0223-z;
RA Dekomien G., Vollrath C., Petrasch-Parwez E., Boeve M.H., Akkad D.A.,
RA Gerding W.M., Epplen J.T.;
RT "Progressive retinal atrophy in Schapendoes dogs: mutation of the newly
RT identified CCDC66 gene.";
RL Neurogenetics 11:163-174(2010).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=21680557; DOI=10.1093/hmg/ddr282;
RA Gerding W.M., Schreiber S., Schulte-Middelmann T., de Castro Marques A.,
RA Atorf J., Akkad D.A., Dekomien G., Kremers J., Dermietzel R., Gal A.,
RA Ruelicke T., Ibrahim S., Epplen J.T., Petrasch-Parwez E.;
RT "Ccdc66 null mutation causes retinal degeneration and dysfunction.";
RL Hum. Mol. Genet. 20:3620-3631(2011).
CC -!- FUNCTION: Microtubule-binding protein required for ciliogenesis. May
CC function in ciliogenesis by mediating the transport of proteins like
CC BBS4 to the cilium, but also through the organization of the centriolar
CC satellites (By similarity). Plays a role in retina morphogenesis and/or
CC homeostasis (PubMed:21680557). {ECO:0000250|UniProtKB:A2RUB6,
CC ECO:0000269|PubMed:21680557}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (Probable). Interacts with CEP290.
CC Interacts with PCM1 (By similarity). Interacts with ARMC9, TOGARAM1,
CC CSPP1 and CEP104 (By similarity). {ECO:0000250|UniProtKB:A2RUB6,
CC ECO:0000305|PubMed:19777273}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing
CC center, centrosome {ECO:0000250|UniProtKB:A2RUB6}. Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome, centriolar
CC satellite {ECO:0000250|UniProtKB:A2RUB6}. Cell projection, cilium
CC {ECO:0000250|UniProtKB:A2RUB6}. Cytoplasm, cytoskeleton, cilium basal
CC body {ECO:0000250|UniProtKB:A2RUB6}. Photoreceptor inner segment
CC {ECO:0000269|PubMed:19777273}. Cell projection, cilium, photoreceptor
CC outer segment {ECO:0000269|PubMed:19777273}. Note=Restricted to the
CC centrosomes and the spindle microtubules during mitosis (By
CC similarity). Enriched in the inner segment of the photoreceptor
CC (PubMed:19777273). {ECO:0000250|UniProtKB:A2RUB6,
CC ECO:0000269|PubMed:19777273}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q6NS45-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6NS45-2; Sequence=VSP_031589, VSP_031590;
CC Name=3;
CC IsoId=Q6NS45-3; Sequence=VSP_031588;
CC -!- TISSUE SPECIFICITY: Widely expressed (PubMed:19777273). Expressed in
CC retina by rod photoreceptors but also detected in outer plexiform and
CC ganglion cell layers (at protein level) (PubMed:21680557,
CC PubMed:19777273). {ECO:0000269|PubMed:19777273,
CC ECO:0000269|PubMed:21680557}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the retina from postnatal stages to
CC adulthood. Highest levels are observed at postnatal stage P1 and P4 and
CC expression decreases afterward. Steady levels are observed from P12 to
CC adulthood. Expression increases in the outer segments from P12 to P19
CC paralleling the differentiation of outer segments.
CC {ECO:0000269|PubMed:21680557}.
CC -!- DISRUPTION PHENOTYPE: Mice lacking Ccdc66 are viable but display
CC degeneration of the retina. Initial formation of the retina is normal
CC up to postnatal stage P10. Malformation of photoreceptors develops
CC around P13. The degeneration progresses slowly until 3 months after
CC birth, when the outer nuclear layer is reduced to 5-6 rows. From 5 to 7
CC months, only a thin outer nuclear and photoreceptor layer with severely
CC shrunken outer and inner segments is preserved. It is associated with
CC impaired photoreceptor function with early visual impairment detectable
CC 1 month after birth and progressing slightly until 7 months.
CC {ECO:0000269|PubMed:21680557}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH70471.2; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAH72583.1; Type=Miscellaneous discrepancy; Note=Partial nucleotide duplication in position 392 that disrupts the frame.; Evidence={ECO:0000305};
CC Sequence=BAC35302.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAC39936.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAE34603.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK053185; BAC35302.1; ALT_INIT; mRNA.
DR EMBL; AK087583; BAC39936.1; ALT_INIT; mRNA.
DR EMBL; AK145297; BAE26352.1; -; mRNA.
DR EMBL; AK158666; BAE34603.1; ALT_INIT; mRNA.
DR EMBL; BC070471; AAH70471.2; ALT_FRAME; mRNA.
DR EMBL; BC072583; AAH72583.1; ALT_SEQ; mRNA.
DR CCDS; CCDS36843.1; -. [Q6NS45-1]
DR RefSeq; NP_796085.3; NM_177111.3. [Q6NS45-1]
DR RefSeq; XP_006519190.1; XM_006519127.3. [Q6NS45-3]
DR RefSeq; XP_006519194.1; XM_006519131.3. [Q6NS45-2]
DR AlphaFoldDB; Q6NS45; -.
DR SMR; Q6NS45; -.
DR STRING; 10090.ENSMUSP00000052546; -.
DR iPTMnet; Q6NS45; -.
DR PhosphoSitePlus; Q6NS45; -.
DR EPD; Q6NS45; -.
DR MaxQB; Q6NS45; -.
DR PaxDb; Q6NS45; -.
DR PRIDE; Q6NS45; -.
DR ProteomicsDB; 265715; -. [Q6NS45-1]
DR ProteomicsDB; 265716; -. [Q6NS45-2]
DR ProteomicsDB; 265717; -. [Q6NS45-3]
DR Antibodypedia; 31476; 108 antibodies from 17 providers.
DR DNASU; 320234; -.
DR Ensembl; ENSMUST00000050480; ENSMUSP00000052546; ENSMUSG00000046753. [Q6NS45-2]
DR Ensembl; ENSMUST00000223689; ENSMUSP00000153023; ENSMUSG00000046753. [Q6NS45-1]
DR GeneID; 320234; -.
DR KEGG; mmu:320234; -.
DR UCSC; uc007stw.2; mouse. [Q6NS45-1]
DR UCSC; uc011zhw.2; mouse. [Q6NS45-2]
DR CTD; 285331; -.
DR MGI; MGI:2443639; Ccdc66.
DR VEuPathDB; HostDB:ENSMUSG00000046753; -.
DR eggNOG; ENOG502R1PQ; Eukaryota.
DR GeneTree; ENSGT00390000012411; -.
DR HOGENOM; CLU_016964_0_0_1; -.
DR InParanoid; Q6NS45; -.
DR OMA; QVEYNAS; -.
DR OrthoDB; 1468611at2759; -.
DR PhylomeDB; Q6NS45; -.
DR TreeFam; TF350489; -.
DR BioGRID-ORCS; 320234; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Ccdc66; mouse.
DR PRO; PR:Q6NS45; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q6NS45; protein.
DR Bgee; ENSMUSG00000046753; Expressed in otolith organ and 223 other tissues.
DR Genevisible; Q6NS45; MM.
DR GO; GO:0030054; C:cell junction; ISO:MGI.
DR GO; GO:0034451; C:centriolar satellite; ISS:UniProtKB.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0036064; C:ciliary basal body; ISS:UniProtKB.
DR GO; GO:0005929; C:cilium; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0090543; C:Flemming body; ISO:MGI.
DR GO; GO:0005874; C:microtubule; ISS:UniProtKB.
DR GO; GO:0001917; C:photoreceptor inner segment; IDA:UniProtKB.
DR GO; GO:0001750; C:photoreceptor outer segment; IEA:UniProtKB-SubCell.
DR GO; GO:0008017; F:microtubule binding; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0060271; P:cilium assembly; ISS:UniProtKB.
DR GO; GO:0050908; P:detection of light stimulus involved in visual perception; IMP:CACAO.
DR GO; GO:0001578; P:microtubule bundle formation; ISS:UniProtKB.
DR GO; GO:1903564; P:regulation of protein localization to cilium; ISS:UniProtKB.
DR GO; GO:0001895; P:retina homeostasis; ISS:UniProtKB.
DR InterPro; IPR039183; CCD66.
DR InterPro; IPR040467; CCDC66_dom.
DR PANTHER; PTHR22736; PTHR22736; 1.
DR Pfam; PF15236; CCDC66; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell projection; Cilium;
KW Cilium biogenesis/degradation; Coiled coil; Cytoplasm; Cytoskeleton;
KW Disulfide bond; Phosphoprotein; Reference proteome.
FT CHAIN 1..935
FT /note="Coiled-coil domain-containing protein 66"
FT /id="PRO_0000320038"
FT REGION 76..103
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 470..491
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 577..602
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 738..794
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 462..555
FT /evidence="ECO:0000255"
FT COMPBIAS 76..97
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 738..753
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 754..776
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 777..794
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 114
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:A2RUB6"
FT MOD_RES 366
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 595
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1..34
FT /note="MNLGDGLKLETELLDGKTKLILSPYEHKSKVSVK -> M (in isoform
FT 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_031588"
FT VAR_SEQ 26
FT /note="E -> G (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_031589"
FT VAR_SEQ 27..182
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_031590"
FT CONFLICT 137
FT /note="K -> T (in Ref. 1; BAE26352)"
FT /evidence="ECO:0000305"
FT CONFLICT 405
FT /note="F -> Y (in Ref. 1; BAE26352)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 935 AA; 107372 MW; E6535220E4B5BE78 CRC64;
MNLGDGLKLE TELLDGKTKL ILSPYEHKSK VSVKMGNKFK IAKCPLRTKQ TGHTLKSTQN
TYIGNENLSQ KKISTLDTSQ AKPENSRLTF SPSTDKQYSE KDSVRVQKEI SPTTSNIRKI
INTTGTCPVA KQKPCKKNPT AETMNSGLVC LTQDQLRQIL MLSVNQGNGS VCLTETGEEE
ASQDSLHLIN IPSQPKDVND TGFLQNTEAA SPVTSEHEHV HRRAQEAFQQ CEQKAATENE
WKPADIFSTL GERERDKSLL EARRAQWKKE LDEQVALKKK EKEASQKWHN PWKPSDIECE
KSQVHDQSKE ARLLESPCSA IKQEQQRKWI EELNKQVEDD QQRKAEERMI YSKGEEHDRW
AVHFDSLKSH PGSQSRLSSQ LTHQHLESLC VSPDTQELAD VNGVFTPPPG VQAEPSEKEQ
RARPVLEMAV SHGPKTNFLR SMTALLDPAQ IEERERRRQK QLEHQKAIMA QVEENRRKKR
LEEEQRKKEE QELELRLARE REEMQRQYEE DILKQRQREE IMTLKTNELF HTMQRAQELA
QRLKQEQRIR ELAQKGHDTS RLIQNLGAQV DYKAFTTISS SHSDPEETAD TSTASPKKDT
GVQTDDVNLG IFNDALPPCG SVTEKGIRNI SSPEISAEFS GQTDIRKENQ ELSMNKGTNL
DKENSWHNGQ CNQYRRTEKQ TKLMKKCPKK PAWNINKPLK KYVPASAKYP AHLQKEKEEK
KVQRQMELLH LVERNNPENL SQNRGISPLA TSHRETESES RLHLIKKVEE PLKTPSVSKE
RFQTSPAVKN RTQQTQSNVL HLPLKNNDYE KETLTLGDGH TKLSDEMSEP SHFIPYVRTN
EIYYLDPDAP LSRPSTQDNQ YQKSHDCARE QELFDSDHIR DPLLNPKLVK NRDRQQAILK
GLSELRQGLL QKQKELETNL IPLTANQEDN FSSSF
