C2D2A_MOUSE
ID C2D2A_MOUSE Reviewed; 1633 AA.
AC Q8CFW7; Q8BP57;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Coiled-coil and C2 domain-containing protein 2A;
GN Name=Cc2d2a;
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).
RC TISSUE=Eye;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 50-590 (ISOFORM 2).
RC STRAIN=C57BL/6J;
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 [3]
RP INTERACTION WITH MKS1.
RX PubMed=21565611; DOI=10.1016/j.cell.2011.04.019;
RA Sang L., Miller J.J., Corbit K.C., Giles R.H., Brauer M.J., Otto E.A.,
RA Baye L.M., Wen X., Scales S.J., Kwong M., Huntzicker E.G., Sfakianos M.K.,
RA Sandoval W., Bazan J.F., Kulkarni P., Garcia-Gonzalo F.R., Seol A.D.,
RA O'Toole J.F., Held S., Reutter H.M., Lane W.S., Rafiq M.A., Noor A.,
RA Ansar M., Devi A.R., Sheffield V.C., Slusarski D.C., Vincent J.B.,
RA Doherty D.A., Hildebrandt F., Reiter J.F., Jackson P.K.;
RT "Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy disease genes
RT and pathways.";
RL Cell 145:513-528(2011).
RN [4]
RP IDENTIFICATION IN THE TECTONIC-LIKE COMPLEX, AND FUNCTION.
RX PubMed=22179047; DOI=10.1038/ncb2410;
RA Chih B., Liu P., Chinn Y., Chalouni C., Komuves L.G., Hass P.E.,
RA Sandoval W., Peterson A.S.;
RT "A ciliopathy complex at the transition zone protects the cilia as a
RT privileged membrane domain.";
RL Nat. Cell Biol. 14:61-72(2012).
RN [5]
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).
CC -!- FUNCTION: Component of the tectonic-like complex, a complex localized
CC at the transition zone of primary cilia and acting as a barrier that
CC prevents diffusion of transmembrane proteins between the cilia and
CC plasma membranes. Required for ciliogenesis and sonic hedgehog/SHH
CC signaling. {ECO:0000269|PubMed:21725307, ECO:0000269|PubMed:22179047}.
CC -!- SUBUNIT: Part of the tectonic-like complex (also named B9 complex).
CC {ECO:0000269|PubMed:21725307, ECO:0000269|PubMed:22179047}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21725307}.
CC Cytoplasm, cytoskeleton, cilium basal body
CC {ECO:0000269|PubMed:21725307}. Note=Localizes at the transition zone, a
CC region between the basal body and the ciliary axoneme.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8CFW7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8CFW7-2; Sequence=VSP_030925;
CC -!- DISRUPTION PHENOTYPE: Embryos show randomized left-right axes,
CC holoprosencephaly, microphthalmia and a variably expressive curved body
CC axis. Cc2d2a null embryos also have cilia defects, which are
CC exemplified by the absence of Arl13b staining in neural tube and
CC surrounding mesenchyme. {ECO:0000269|PubMed:21725307}.
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DR EMBL; BC032290; AAH32290.1; -; mRNA.
DR EMBL; AK077658; BAC36933.1; -; mRNA.
DR CCDS; CCDS39080.1; -. [Q8CFW7-1]
DR RefSeq; NP_758478.1; NM_172274.2. [Q8CFW7-1]
DR AlphaFoldDB; Q8CFW7; -.
DR SMR; Q8CFW7; -.
DR BioGRID; 231096; 2.
DR CORUM; Q8CFW7; -.
DR IntAct; Q8CFW7; 7.
DR STRING; 10090.ENSMUSP00000048320; -.
DR iPTMnet; Q8CFW7; -.
DR PhosphoSitePlus; Q8CFW7; -.
DR MaxQB; Q8CFW7; -.
DR PaxDb; Q8CFW7; -.
DR PRIDE; Q8CFW7; -.
DR ProteomicsDB; 265406; -. [Q8CFW7-1]
DR ProteomicsDB; 265407; -. [Q8CFW7-2]
DR Antibodypedia; 50288; 29 antibodies from 15 providers.
DR DNASU; 231214; -.
DR Ensembl; ENSMUST00000048150; ENSMUSP00000048320; ENSMUSG00000039765. [Q8CFW7-1]
DR GeneID; 231214; -.
DR KEGG; mmu:231214; -.
DR UCSC; uc008xhp.2; mouse. [Q8CFW7-1]
DR CTD; 57545; -.
DR MGI; MGI:1924487; Cc2d2a.
DR VEuPathDB; HostDB:ENSMUSG00000039765; -.
DR eggNOG; KOG3639; Eukaryota.
DR GeneTree; ENSGT00940000155482; -.
DR HOGENOM; CLU_001707_0_0_1; -.
DR InParanoid; Q8CFW7; -.
DR OMA; VISVWVF; -.
DR OrthoDB; 246535at2759; -.
DR PhylomeDB; Q8CFW7; -.
DR TreeFam; TF324786; -.
DR Reactome; R-MMU-5620912; Anchoring of the basal body to the plasma membrane.
DR BioGRID-ORCS; 231214; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Cc2d2a; mouse.
DR PRO; PR:Q8CFW7; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q8CFW7; protein.
DR Bgee; ENSMUSG00000039765; Expressed in pigmented layer of retina and 215 other tissues.
DR ExpressionAtlas; Q8CFW7; baseline and differential.
DR Genevisible; Q8CFW7; MM.
DR GO; GO:0035869; C:ciliary transition zone; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-KW.
DR GO; GO:0036038; C:MKS complex; IDA:UniProtKB.
DR GO; GO:0035082; P:axoneme assembly; IMP:MGI.
DR GO; GO:0043010; P:camera-type eye development; IMP:MGI.
DR GO; GO:0060271; P:cilium assembly; IMP:UniProtKB.
DR GO; GO:0007368; P:determination of left/right symmetry; IMP:MGI.
DR GO; GO:1990403; P:embryonic brain development; IMP:MGI.
DR GO; GO:0007507; P:heart development; IMP:MGI.
DR GO; GO:0001822; P:kidney development; IMP:MGI.
DR GO; GO:0044458; P:motile cilium assembly; IMP:MGI.
DR GO; GO:0001843; P:neural tube closure; IMP:MGI.
DR GO; GO:1905515; P:non-motile cilium assembly; IMP:MGI.
DR GO; GO:1904491; P:protein localization to ciliary transition zone; IMP:WormBase.
DR GO; GO:0007224; P:smoothened signaling pathway; IMP:UniProtKB.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR028928; CC2D2AN-C2.
DR InterPro; IPR041510; DUF5523.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF15625; CC2D2AN-C2; 1.
DR Pfam; PF17661; DUF5523; 1.
DR SMART; SM00239; C2; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR PROSITE; PS50004; C2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell projection; Cilium;
KW Cilium biogenesis/degradation; Coiled coil; Cytoplasm; Cytoskeleton;
KW Reference proteome.
FT CHAIN 1..1633
FT /note="Coiled-coil and C2 domain-containing protein 2A"
FT /id="PRO_0000317251"
FT DOMAIN 1031..1209
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 1..188
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 200..245
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 590..673
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1068..1094
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 440..501
FT /evidence="ECO:0000255"
FT COILED 554..611
FT /evidence="ECO:0000255"
FT COMPBIAS 1..28
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 98..112
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 123..145
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 152..177
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 203..245
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 634..648
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..49
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_030925"
FT CONFLICT 345
FT /note="G -> E (in Ref. 2; BAC36933)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1633 AA; 187530 MW; 33C9B365385B7BFB CRC64;
MNTNDEKMKI ISEDFTGDGV DTEAGRRKKN SKVRRQQRKK KPPASPPEEM VSDKFQDGGQ
QEVVEEEPET NLLSLTARRG PRSLPPIPSA SRTGFAEFSM RERMREKLQA ARSKAESALL
RDVPTPRPRR LRSPSREKET ETEFGTEPST EVQDTQKEDD TKSYSRIKFR DSVRKIKSKP
QLPPGFPSAE EAYNFFTFNF DPEPEESEEK SPVKGGERAH HEDQEGEEGT QAQERAKKTE
EEELLNGKDA EDFLLGLDPT AHDFVAVRAA EYKSARIQLQ KEKEILFTPS RLTVPTYKKL
PENIQPRFLE DEGLYIGARP EVARTNENIM ENRLLIQEPG SKWFGDDGRI LALPSPIKPF
PSRPSLTTRE QSPKAGLETL YKKAEKYVHS RQHMIGSGDP PGNFQLDIDI SGLIFTHHPC
FSREHVLASK LAQLYDQYLA RQQRNKTKFL TDKLQALRKA VQTSLNPEKP HQSLDTTQKT
INEYKSEIRQ TRKLRDAEQE KDRTLLKTII KVWKEMKSLR EFQRFTNTPL KLVLRKEKVD
PKLDEDAYEA EIQAEIHELL EEHMEEYATK MEEYRTSHQQ WKAWRKAQRA KKKKKKQTTE
EHLEEEEAEE SFPEEEVTKP IPPEPTDPAV IEQQVRERAA HSRRRPGEPT LIPELSLAGN
VTPNDQCPRV EVSRREDVRR RSVYLKVVFN SKEVSRTVSR PLGADFRVHF GQIFNLQIFN
WPESLMLQVY ETIGHSGTTL LAEVFLPIPE TTLVTGRAPI EEVEFSSNQH VTLDHEGVGS
GVPFSFEADG SNQLTLMTSG KVSHSVAWAV GENGIPLIPP LSQQNIGFRS ALRRADAISS
IGTSGLTDMK KLAKWAAESK LDPNDPNHAP LMQLISVATS GESYVPDFFR LEQLQQEFNF
VSEEELNRSK RFRLLHLRSQ EVPEFRNYKQ IPAYDREIME KVFQDYEKRL RDRNVIETKD
HLDMHRATVA KYLQQVREAV VNRFLTAKHH FLLTDLVVEE EVPNISSEGS GILGLSLFKL
AEQKRPLRPR RKGRKKVTAQ NLSDGDIKLL VNIIRAYDIP VRKPVVSKFQ QPSRSSRTFS
EKQTASPSTH SPLHNADYPL GQVLVRPFVE VSFQRTICHT TTAEGPNPSW NEELELPFRA
PNGDYSTASL QSVKDDVYIN IFDEVLYDIL EDDRERGSGI HTRIERHWLG CVKIPFSTIY
FQARIDGTFK IDIPPVLLGY SKERNIIMER AFDSARSLSE GSYITLFITI EPQLVPGEPM
REKMSDMLKK FDTQEDEKLL QATEKFQAEC ALKFPQRQCL TTVTDMTGKT VFITRYLKPL
NPPQELLHVY PNNPQATAEL VARYVSLIPF LPDSVSFAGV CDLWSTSDQF LDLLAGDEEE
HAVLLCNYFL FLGKKAWLVM GSAIPEGPTA YVLTWEKNYY LIWNPCSGHC YGQFDAFCPL
KSVGCLIGPD NIWFNIQHHD SPLRINFDVT KPKLWKSFFS RSLPYPGLSS VQPEELIYQH
TDKAVAAELQ DRIEKILKEK IMDWRPRHLT RWNRYCTSTL RHFLPLLERS QGEDIEDDHR
AELLKQLGDY RFSGFPLHMP YSEVKPLVEA VYSTGVHNID LPNVEFALAV YIHPYPKNVL
SVWIYVASLV RNR
