C2D2A_HUMAN
ID C2D2A_HUMAN Reviewed; 1620 AA.
AC Q9P2K1; A6ND97; B3FW08; D6RB72; E7EP21; E9PEV5; Q3SYP3; Q9H8A7;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 3.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Coiled-coil and C2 domain-containing protein 2A;
GN Name=CC2D2A; Synonyms=KIAA1345;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND INVOLVEMENT IN MKS6.
RX PubMed=18513680; DOI=10.1016/j.ajhg.2008.05.004;
RA Tallila J., Jakkula E., Peltonen L., Salonen R., Kestilae M.;
RT "Identification of CC2D2A as a Meckel syndrome gene adds an important piece
RT to the ciliopathy puzzle.";
RL Am. J. Hum. Genet. 82:1361-1367(2008).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=10718198; DOI=10.1093/dnares/7.1.65;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVI. The
RT complete sequences of 150 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:65-73(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 1-527 (ISOFORM 2).
RC TISSUE=Uterus;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 283-1620 (ISOFORMS 1/2).
RC TISSUE=Thyroid;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND INVOLVEMENT IN JBTS9.
RX PubMed=18387594; DOI=10.1016/j.ajhg.2008.01.021;
RA Noor A., Windpassinger C., Patel M., Stachowiak B., Mikhailov A., Azam M.,
RA Irfan M., Siddiqui Z.K., Naeem F., Paterson A.D., Lutfullah M.,
RA Vincent J.B., Ayub M.;
RT "CC2D2A, encoding a coiled-coil and C2 domain protein, causes autosomal-
RT recessive mental retardation with retinitis pigmentosa.";
RL Am. J. Hum. Genet. 82:1011-1018(2008).
RN [8]
RP ERRATUM OF PUBMED:18387594.
RX PubMed=19068953; DOI=10.1016/j.ajhg.2008.10.005;
RA Noor A., Windpassinger C., Patel M., Stachowiak B., Mikhailov A., Azam M.,
RA Irfan M., Paterson A.D., Lutufullah M., Doherty D., Vincent J.B., Ayub M.;
RL Am. J. Hum. Genet. 83:656-656(2008).
RN [9]
RP DEVELOPMENTAL STAGE, VARIANTS JBTS9 SER-721; MET-1114 AND VAL-1556, AND
RP VARIANT GLU-800.
RX PubMed=19777577; DOI=10.1002/humu.21116;
RA Mougou-Zerelli S., Thomas S., Szenker E., Audollent S., Elkhartoufi N.,
RA Babarit C., Romano S., Salomon R., Amiel J., Esculpavit C., Gonzales M.,
RA Escudier E., Leheup B., Loget P., Odent S., Roume J., Gerard M.,
RA Delezoide A.-L., Khung S., Patrier S., Cordier M.-P., Bouvier R.,
RA Martinovic J., Gubler M.-C., Boddaert N., Munnich A., Encha-Razavi F.,
RA Valente E.M., Saad A., Saunier S., Vekemans M., Attie-Bitach T.;
RT "CC2D2A mutations in Meckel and Joubert syndromes indicate a genotype-
RT phenotype correlation.";
RL Hum. Mutat. 30:1574-1582(2009).
RN [10]
RP VARIANTS JBTS9 HIS-1096; SER-1122; CYS-1528 AND PRO-1551, TISSUE
RP SPECIFICITY, SUBCELLULAR LOCATION, AND INTERACTION WITH CEP290.
RX PubMed=18950740; DOI=10.1016/j.ajhg.2008.10.002;
RA Gorden N.T., Arts H.H., Parisi M.A., Coene K.L.M., Letteboer S.J.F.,
RA van Beersum S.E.C., Mans D.A., Hikida A., Eckert M., Knutzen D.,
RA Alswaid A.F., Oezyurek H., Dibooglu S., Otto E.A., Liu Y., Davis E.E.,
RA Hutter C.M., Bammler T.K., Farin F.M., Dorschner M., Topcu M., Zackai E.H.,
RA Rosenthal P., Owens K.N., Katsanis N., Vincent J.B., Hildebrandt F.,
RA Rubel E.W., Raible D.W., Knoers N.V.A.M., Chance P.F., Roepman R.,
RA Moens C.B., Glass I.A., Doherty D.;
RT "CC2D2A is mutated in Joubert syndrome and interacts with the ciliopathy-
RT associated basal body protein CEP290.";
RL Am. J. Hum. Genet. 83:559-571(2008).
RN [11]
RP VARIANT MKS6 MET-1114.
RX PubMed=19466712; DOI=10.1002/humu.21057;
RA Tallila J., Salonen R., Kohlschmidt N., Peltonen L., Kestilae M.;
RT "Mutation spectrum of Meckel syndrome genes: one group of syndromes or
RT several distinct groups?";
RL Hum. Mutat. 30:E813-E830(2009).
RN [12]
RP VARIANTS COACH2 MET-1116 AND CYS-1528.
RX PubMed=19574260; DOI=10.1136/jmg.2009.067249;
RA Doherty D., Parisi M.A., Finn L.S., Gunay-Aygun M., Al-Mateen M., Bates D.,
RA Clericuzio C., Demir H., Dorschner M., van Essen A.J., Gahl W.A.,
RA Gentile M., Gorden N.T., Hikida A., Knutzen D., Ozyurek H., Phelps I.,
RA Rosenthal P., Verloes A., Weigand H., Chance P.F., Dobyns W.B., Glass I.A.;
RT "Mutations in 3 genes (MKS3, CC2D2A and RPGRIP1L) cause COACH syndrome
RT (Joubert syndrome with congenital hepatic fibrosis).";
RL J. Med. Genet. 47:8-21(2010).
RN [13]
RP VARIANTS JBTS9 LYS-1126 AND VAL-1556.
RX PubMed=22425360; DOI=10.1016/j.ajhg.2012.02.011;
RA Srour M., Schwartzentruber J., Hamdan F.F., Ospina L.H., Patry L.,
RA Labuda D., Massicotte C., Dobrzeniecka S., Capo-Chichi J.M.,
RA Papillon-Cavanagh S., Samuels M.E., Boycott K.M., Shevell M.I.,
RA Laframboise R., Desilets V., Maranda B., Rouleau G.A., Majewski J.,
RA Michaud J.L.;
RT "Mutations in C5ORF42 cause Joubert syndrome in the French Canadian
RT population.";
RL Am. J. Hum. Genet. 90:693-700(2012).
RN [14]
RP VARIANTS JBTS9 ARG-117; GLU-507; PRO-559; ALA-1045; HIS-1096; MET-1116;
RP SER-1122; ALA-1151; CYS-1284; HIS-1284; GLN-1330; ALA-1430; CYS-1528 AND
RP VAL-1556, AND VARIANTS ILE-660; ILE-684 AND VAL-701.
RX PubMed=22241855; DOI=10.1136/jmedgenet-2011-100552;
RA Bachmann-Gagescu R., Ishak G.E., Dempsey J.C., Adkins J., O'Day D.,
RA Phelps I.G., Gunay-Aygun M., Kline A.D., Szczaluba K., Martorell L.,
RA Alswaid A., Alrasheed S., Pai S., Izatt L., Ronan A., Parisi M.A.,
RA Mefford H., Glass I., Doherty D.;
RT "Genotype-phenotype correlation in CC2D2A-related Joubert syndrome reveals
RT an association with ventriculomegaly and seizures.";
RL J. Med. Genet. 49:126-137(2012).
RN [15]
RP VARIANTS JBTS9 LYS-1126; SER-1520; VAL-1556 AND HIS-1568.
RX PubMed=23012439; DOI=10.1136/jmedgenet-2012-101132;
RG FORGE Canada Consortium;
RA Srour M., Hamdan F.F., Schwartzentruber J.A., Patry L., Ospina L.H.,
RA Shevell M.I., Desilets V., Dobrzeniecka S., Mathonnet G., Lemyre E.,
RA Massicotte C., Labuda D., Amrom D., Andermann E., Sebire G., Maranda B.,
RA Rouleau G.A., Majewski J., Michaud J.L.;
RT "Mutations in TMEM231 cause Joubert syndrome in French Canadians.";
RL J. Med. Genet. 49:636-641(2012).
RN [16]
RP VARIANT JBTS9 ALA-1447.
RX PubMed=22246503; DOI=10.1038/ng.1078;
RA Lee J.E., Silhavy J.L., Zaki M.S., Schroth J., Bielas S.L., Marsh S.E.,
RA Olvera J., Brancati F., Iannicelli M., Ikegami K., Schlossman A.M.,
RA Merriman B., Attie-Bitach T., Logan C.V., Glass I.A., Cluckey A.,
RA Louie C.M., Lee J.H., Raynes H.R., Rapin I., Castroviejo I.P., Setou M.,
RA Barbot C., Boltshauser E., Nelson S.F., Hildebrandt F., Johnson C.A.,
RA Doherty D.A., Valente E.M., Gleeson J.G.;
RT "CEP41 is mutated in Joubert syndrome and is required for tubulin
RT glutamylation at the cilium.";
RL Nat. Genet. 44:193-199(2012).
RN [17]
RP VARIANT MKS6 SER-1517.
RX PubMed=24706459; DOI=10.1002/uog.13381;
RA Jones D., Fiozzo F., Waters B., McKnight D., Brown S.;
RT "First-trimester diagnosis of Meckel-Gruber syndrome by fetal ultrasound
RT with molecular identification of CC2D2A mutations by next-generation
RT sequencing.";
RL Ultrasound Obstet. Gynecol. 44:719-721(2014).
RN [18]
RP VARIANTS JBTS9 LYS-1126; SER-1520; VAL-1556 AND HIS-1568.
RX PubMed=26477546; DOI=10.1016/j.ajhg.2015.09.009;
RG Care4Rare Canada Consortium;
RA Srour M., Hamdan F.F., McKnight D., Davis E., Mandel H.,
RA Schwartzentruber J., Martin B., Patry L., Nassif C., Dionne-Laporte A.,
RA Ospina L.H., Lemyre E., Massicotte C., Laframboise R., Maranda B.,
RA Labuda D., Decarie J.C., Rypens F., Goldsher D., Fallet-Bianco C.,
RA Soucy J.F., Laberge A.M., Maftei C., Boycott K., Brais B., Boucher R.M.,
RA Rouleau G.A., Katsanis N., Majewski J., Elpeleg O., Kukolich M.K.,
RA Shalev S., Michaud J.L.;
RT "Joubert Syndrome in French Canadians and Identification of Mutations in
RT CEP104.";
RL Am. J. Hum. Genet. 97:744-753(2015).
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 (By similarity). {ECO:0000250, ECO:0000269|PubMed:18513680}.
CC -!- SUBUNIT: Part of the tectonic-like complex (also named B9 complex).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytoskeleton, cilium basal
CC body. Note=Localizes at the transition zone, a region between the basal
CC body and the ciliary axoneme. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9P2K1-4; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9P2K1-2; Sequence=VSP_030923, VSP_037223;
CC Name=3;
CC IsoId=Q9P2K1-5; Sequence=VSP_045255, VSP_045256;
CC Name=4;
CC IsoId=Q9P2K1-6; Sequence=VSP_045453, VSP_045454;
CC -!- TISSUE SPECIFICITY: Strongly expressed in prostate, pancreas, kidney,
CC lung, liver, retina, kidney, fetal brain and fetal kidney. Lower
CC expression in spleen, small intestine, colon, skeletal muscle, ovary,
CC thymus and heart. {ECO:0000269|PubMed:18387594,
CC ECO:0000269|PubMed:18950740}.
CC -!- DEVELOPMENTAL STAGE: At Carnagie stage 13 (CS13, after 4 weeks of
CC development) and CS14 CC2D2A is ubiquitously expressed, with a distinct
CC signal in the spinal cord and limb buds. At CS17 CC2D2A continue to be
CC widely expressedin particular throughout the central nervous system
CC (CNS), lung, and digestive tract epithelia. At CS22 expression
CC continues to be intense within the CNS, where strong and specific
CC expression is observed in the eye and in external granular layer of
CC cerebellum. CC2D2A expression is also observed in the costal
CC perichondrium. {ECO:0000269|PubMed:19777577}.
CC -!- DISEASE: Meckel syndrome 6 (MKS6) [MIM:612284]: A disorder
CC characterized by a combination of renal cysts and variably associated
CC features including developmental anomalies of the central nervous
CC system (typically encephalocele), hepatic ductal dysplasia and cysts,
CC and polydactyly. {ECO:0000269|PubMed:18513680,
CC ECO:0000269|PubMed:19466712, ECO:0000269|PubMed:24706459}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Joubert syndrome 9 (JBTS9) [MIM:612285]: A disorder presenting
CC with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal
CC breathing abnormalities and psychomotor delay. Neuroradiologically, it
CC is characterized by cerebellar vermian hypoplasia/aplasia, thickened
CC and reoriented superior cerebellar peduncles, and an abnormally large
CC interpeduncular fossa, giving the appearance of a molar tooth on
CC transaxial slices (molar tooth sign). Additional variable features
CC include retinal dystrophy and renal disease.
CC {ECO:0000269|PubMed:18387594, ECO:0000269|PubMed:18950740,
CC ECO:0000269|PubMed:19777577, ECO:0000269|PubMed:22241855,
CC ECO:0000269|PubMed:22246503, ECO:0000269|PubMed:22425360,
CC ECO:0000269|PubMed:23012439, ECO:0000269|PubMed:26477546}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: COACH syndrome 2 (COACH2) [MIM:619111]: A form of COACH
CC syndrome, a disorder characterized by cerebellar vermis hypoplasia,
CC developmental delay, impaired intellectual development, ataxia, and
CC hepatic fibrosis. Patients present the molar tooth sign, a midbrain-
CC hindbrain malformation pathognomonic for Joubert syndrome and related
CC disorders. Other features, such as coloboma and renal cysts, may be
CC variable. COACH2 inheritance is autosomal recessive.
CC {ECO:0000269|PubMed:19574260}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI03711.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC Sequence=BAA92583.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB14710.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};
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DR EMBL; EU450799; ACC96081.1; -; mRNA.
DR EMBL; AB037766; BAA92583.1; ALT_INIT; mRNA.
DR EMBL; AC007016; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC116651; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471069; EAW92734.1; -; Genomic_DNA.
DR EMBL; BC053865; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC070395; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC103710; AAI03711.1; ALT_SEQ; mRNA.
DR EMBL; AK023876; BAB14710.1; ALT_SEQ; mRNA.
DR CCDS; CCDS47026.1; -. [Q9P2K1-4]
DR CCDS; CCDS47027.2; -. [Q9P2K1-5]
DR CCDS; CCDS54744.1; -. [Q9P2K1-6]
DR RefSeq; NP_001073991.2; NM_001080522.2. [Q9P2K1-4]
DR RefSeq; NP_001158192.1; NM_001164720.1. [Q9P2K1-6]
DR RefSeq; NP_065836.2; NM_020785.2. [Q9P2K1-5]
DR RefSeq; XP_005248234.1; XM_005248177.1.
DR RefSeq; XP_011512176.1; XM_011513874.2. [Q9P2K1-6]
DR AlphaFoldDB; Q9P2K1; -.
DR BioGRID; 121603; 43.
DR CORUM; Q9P2K1; -.
DR IntAct; Q9P2K1; 36.
DR STRING; 9606.ENSP00000403465; -.
DR iPTMnet; Q9P2K1; -.
DR PhosphoSitePlus; Q9P2K1; -.
DR BioMuta; CC2D2A; -.
DR DMDM; 229462975; -.
DR EPD; Q9P2K1; -.
DR jPOST; Q9P2K1; -.
DR MassIVE; Q9P2K1; -.
DR MaxQB; Q9P2K1; -.
DR PaxDb; Q9P2K1; -.
DR PeptideAtlas; Q9P2K1; -.
DR PRIDE; Q9P2K1; -.
DR ProteomicsDB; 13547; -.
DR ProteomicsDB; 17269; -.
DR ProteomicsDB; 83826; -. [Q9P2K1-4]
DR ProteomicsDB; 83827; -. [Q9P2K1-2]
DR Antibodypedia; 50288; 29 antibodies from 15 providers.
DR DNASU; 57545; -.
DR Ensembl; ENST00000424120.6; ENSP00000403465.1; ENSG00000048342.18. [Q9P2K1-4]
DR Ensembl; ENST00000503292.6; ENSP00000421809.1; ENSG00000048342.18. [Q9P2K1-4]
DR Ensembl; ENST00000503658.2; ENSP00000426846.1; ENSG00000048342.18. [Q9P2K1-5]
DR Ensembl; ENST00000507954.5; ENSP00000427221.1; ENSG00000048342.18. [Q9P2K1-6]
DR Ensembl; ENST00000515124.6; ENSP00000424368.1; ENSG00000048342.18. [Q9P2K1-6]
DR Ensembl; ENST00000674945.1; ENSP00000502333.1; ENSG00000048342.18. [Q9P2K1-2]
DR GeneID; 57545; -.
DR KEGG; hsa:57545; -.
DR MANE-Select; ENST00000424120.6; ENSP00000403465.1; NM_001378615.1; NP_001365544.1.
DR UCSC; uc003gnq.5; human. [Q9P2K1-4]
DR CTD; 57545; -.
DR DisGeNET; 57545; -.
DR GeneCards; CC2D2A; -.
DR GeneReviews; CC2D2A; -.
DR HGNC; HGNC:29253; CC2D2A.
DR HPA; ENSG00000048342; Tissue enhanced (retina).
DR MalaCards; CC2D2A; -.
DR MIM; 612013; gene.
DR MIM; 612284; phenotype.
DR MIM; 612285; phenotype.
DR MIM; 619111; phenotype.
DR neXtProt; NX_Q9P2K1; -.
DR OpenTargets; ENSG00000048342; -.
DR Orphanet; 1454; Joubert syndrome with hepatic defect.
DR Orphanet; 2318; Joubert syndrome with oculorenal defect.
DR Orphanet; 564; Meckel syndrome.
DR PharmGKB; PA162381194; -.
DR VEuPathDB; HostDB:ENSG00000048342; -.
DR eggNOG; KOG3639; Eukaryota.
DR GeneTree; ENSGT00940000155482; -.
DR HOGENOM; CLU_164860_0_0_1; -.
DR InParanoid; Q9P2K1; -.
DR OMA; VISVWVF; -.
DR OrthoDB; 246535at2759; -.
DR PhylomeDB; Q9P2K1; -.
DR TreeFam; TF324786; -.
DR PathwayCommons; Q9P2K1; -.
DR Reactome; R-HSA-5620912; Anchoring of the basal body to the plasma membrane.
DR SignaLink; Q9P2K1; -.
DR BioGRID-ORCS; 57545; 9 hits in 1070 CRISPR screens.
DR ChiTaRS; CC2D2A; human.
DR GeneWiki; CC2D2A; -.
DR GenomeRNAi; 57545; -.
DR Pharos; Q9P2K1; Tbio.
DR PRO; PR:Q9P2K1; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q9P2K1; protein.
DR Bgee; ENSG00000048342; Expressed in right uterine tube and 171 other tissues.
DR ExpressionAtlas; Q9P2K1; baseline and differential.
DR Genevisible; Q9P2K1; HS.
DR GO; GO:0035869; C:ciliary transition zone; ISS:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0036038; C:MKS complex; ISS:UniProtKB.
DR GO; GO:0035082; P:axoneme assembly; IEA:Ensembl.
DR GO; GO:0043010; P:camera-type eye development; IEA:Ensembl.
DR GO; GO:0060271; P:cilium assembly; ISS:UniProtKB.
DR GO; GO:0007368; P:determination of left/right symmetry; IEA:Ensembl.
DR GO; GO:1990403; P:embryonic brain development; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0001822; P:kidney development; IEA:Ensembl.
DR GO; GO:0044458; P:motile cilium assembly; IEA:Ensembl.
DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl.
DR GO; GO:1905515; P:non-motile cilium assembly; IBA:GO_Central.
DR GO; GO:1904491; P:protein localization to ciliary transition zone; IBA:GO_Central.
DR GO; GO:0007224; P:smoothened signaling pathway; ISS: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 PROSITE; PS50004; C2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell projection; Ciliopathy; Cilium;
KW Cilium biogenesis/degradation; Coiled coil; Cytoplasm; Cytoskeleton;
KW Disease variant; Joubert syndrome; Meckel syndrome; Reference proteome.
FT CHAIN 1..1620
FT /note="Coiled-coil and C2 domain-containing protein 2A"
FT /id="PRO_0000317250"
FT DOMAIN 1025..1203
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 1..241
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 592..628
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1062..1087
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 439..493
FT /evidence="ECO:0000255"
FT COILED 532..582
FT /evidence="ECO:0000255"
FT COMPBIAS 1..30
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 129..156
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 202..221
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 597..613
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:10718198,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_030923"
FT VAR_SEQ 42..122
FT /note="PPTAVPKEMVSEKSHLGNPQEPVQEEPKTRLLSMTVRRGPRSLPPIPSTSRT
FT GFAEFSMRGRMREKLQAARSKAESALLQE -> KPTPFSRACWQILPHLSAGVPLLGWE
FT HPVQGKSFQATNCCPQGNGVRKIPPWQPPGACAGGAQDPPPEYDSPERPTERAGC (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_045255"
FT VAR_SEQ 83..111
FT /note="SLPPIPSTSRTGFAEFSMRGRMREKLQAA -> RELVVKKSLGRPGTVTHVC
FT NPSTLEGRGG (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_045453"
FT VAR_SEQ 112..1620
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_045454"
FT VAR_SEQ 123..1620
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_045256"
FT VAR_SEQ 1199..1257
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10718198,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_037223"
FT VARIANT 117
FT /note="S -> R (in JBTS9; unknown pathological significance;
FT dbSNP:rs186264635)"
FT /evidence="ECO:0000269|PubMed:22241855"
FT /id="VAR_076881"
FT VARIANT 376
FT /note="E -> A (in dbSNP:rs16892095)"
FT /id="VAR_038489"
FT VARIANT 507
FT /note="K -> E (in JBTS9; benign variant;
FT dbSNP:rs144439937)"
FT /evidence="ECO:0000269|PubMed:22241855"
FT /id="VAR_076882"
FT VARIANT 559
FT /note="L -> P (in JBTS9; dbSNP:rs754221308)"
FT /evidence="ECO:0000269|PubMed:22241855"
FT /id="VAR_076883"
FT VARIANT 660
FT /note="V -> I (in dbSNP:rs16892134)"
FT /evidence="ECO:0000269|PubMed:22241855"
FT /id="VAR_038490"
FT VARIANT 684
FT /note="L -> I (in dbSNP:rs190698163)"
FT /evidence="ECO:0000269|PubMed:22241855"
FT /id="VAR_076884"
FT VARIANT 701
FT /note="L -> V (in dbSNP:rs537906621)"
FT /evidence="ECO:0000269|PubMed:22241855"
FT /id="VAR_076885"
FT VARIANT 721
FT /note="P -> S (in JBTS9; dbSNP:rs199768782)"
FT /evidence="ECO:0000269|PubMed:19777577"
FT /id="VAR_062804"
FT VARIANT 800
FT /note="K -> E (in dbSNP:rs751256652)"
FT /evidence="ECO:0000269|PubMed:19777577"
FT /id="VAR_062805"
FT VARIANT 1045
FT /note="V -> A (in JBTS9; dbSNP:rs863225173)"
FT /evidence="ECO:0000269|PubMed:22241855"
FT /id="VAR_076886"
FT VARIANT 1096
FT /note="Q -> H (in JBTS9; dbSNP:rs863225169)"
FT /evidence="ECO:0000269|PubMed:18950740,
FT ECO:0000269|PubMed:22241855"
FT /id="VAR_055321"
FT VARIANT 1114
FT /note="T -> M (in MKS6 and JBTS9; dbSNP:rs386833752)"
FT /evidence="ECO:0000269|PubMed:19466712,
FT ECO:0000269|PubMed:19777577"
FT /id="VAR_062293"
FT VARIANT 1116
FT /note="T -> M (in COACH2 and JBTS9; dbSNP:rs267606709)"
FT /evidence="ECO:0000269|PubMed:19574260,
FT ECO:0000269|PubMed:22241855"
FT /id="VAR_063804"
FT VARIANT 1122
FT /note="P -> S (in JBTS9; dbSNP:rs118204051)"
FT /evidence="ECO:0000269|PubMed:18950740,
FT ECO:0000269|PubMed:22241855"
FT /id="VAR_055322"
FT VARIANT 1126
FT /note="E -> K (in JBTS9; dbSNP:rs1473532901)"
FT /evidence="ECO:0000269|PubMed:22425360,
FT ECO:0000269|PubMed:23012439, ECO:0000269|PubMed:26477546"
FT /id="VAR_068169"
FT VARIANT 1151
FT /note="V -> A (in JBTS9; dbSNP:rs863225170)"
FT /evidence="ECO:0000269|PubMed:22241855"
FT /id="VAR_076887"
FT VARIANT 1182
FT /note="W -> R (in JBTS9; dbSNP:rs386833755)"
FT /evidence="ECO:0000269|PubMed:26477546"
FT /id="VAR_075698"
FT VARIANT 1284
FT /note="R -> C (in JBTS9; dbSNP:rs779823379)"
FT /evidence="ECO:0000269|PubMed:22241855"
FT /id="VAR_076888"
FT VARIANT 1284
FT /note="R -> H (in JBTS9; dbSNP:rs754586025)"
FT /evidence="ECO:0000269|PubMed:22241855"
FT /id="VAR_076889"
FT VARIANT 1330
FT /note="R -> Q (in JBTS9; unknown pathological significance;
FT dbSNP:rs763486732)"
FT /evidence="ECO:0000269|PubMed:22241855"
FT /id="VAR_076890"
FT VARIANT 1430
FT /note="V -> A (in JBTS9; dbSNP:rs863225168)"
FT /evidence="ECO:0000269|PubMed:22241855"
FT /id="VAR_076891"
FT VARIANT 1447
FT /note="E -> A (in JBTS9; digenic inheritance; the patient
FT also carries mutation C-360 in CEP41; dbSNP:rs387907058)"
FT /evidence="ECO:0000269|PubMed:22246503"
FT /id="VAR_067535"
FT VARIANT 1517
FT /note="T -> S (in MKS6; unknown pathological significance;
FT dbSNP:rs780673487)"
FT /evidence="ECO:0000269|PubMed:24706459"
FT /id="VAR_077560"
FT VARIANT 1520
FT /note="N -> S (in JBTS9; dbSNP:rs1478902342)"
FT /evidence="ECO:0000269|PubMed:23012439,
FT ECO:0000269|PubMed:26477546"
FT /id="VAR_069045"
FT VARIANT 1528
FT /note="R -> C (in JBTS9 and COACH2; dbSNP:rs118204052)"
FT /evidence="ECO:0000269|PubMed:18950740,
FT ECO:0000269|PubMed:19574260, ECO:0000269|PubMed:22241855"
FT /id="VAR_055323"
FT VARIANT 1551
FT /note="L -> P (in JBTS9; dbSNP:rs763425007)"
FT /evidence="ECO:0000269|PubMed:18950740"
FT /id="VAR_055324"
FT VARIANT 1556
FT /note="D -> V (in JBTS9; dbSNP:rs201502401)"
FT /evidence="ECO:0000269|PubMed:19777577,
FT ECO:0000269|PubMed:22241855, ECO:0000269|PubMed:22425360,
FT ECO:0000269|PubMed:23012439, ECO:0000269|PubMed:26477546"
FT /id="VAR_062806"
FT VARIANT 1568
FT /note="Y -> H (in JBTS9)"
FT /evidence="ECO:0000269|PubMed:23012439,
FT ECO:0000269|PubMed:26477546"
FT /id="VAR_069046"
FT CONFLICT 524
FT /note="R -> S (in Ref. 5; AAI03711)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1620 AA; 186185 MW; 1AF2635A40B3EF4A CRC64;
MNPREEKVKI ITEEFIENDE DADMGRQNKN SKVRRQPRKK QPPTAVPKEM VSEKSHLGNP
QEPVQEEPKT RLLSMTVRRG PRSLPPIPST SRTGFAEFSM RGRMREKLQA ARSKAESALL
QEIPTPRPRR LRSPSKKELE TEFGTEPGKE VERTQQEVDS QSYSRVKFHD SARKIKPKPQ
VPPGFPSAEE AYNFFTFNFD PEPEGSEEKP KARHRAGTNQ EEEEGEEEEP PAQGGGKEMD
EEELLNGDDA EDFLLGLDHV ADDFVAVRPA DYESIHDRLQ MEREMLFIPS RQTVPTYKKL
PENVQPRFLE DEGLYTGVRP EVARTNQNIM ENRLLMQDPE RRWFGDDGRI LALPNPIKPF
PSRPPVLTQE QSIKAELETL YKKAVKYVHS SQHVIRSGDP PGNFQLDIDI SGLIFTHHPC
FSREHVLAAK LAQLYDQYLA RHQRNKAKFL TDKLQALRNA VQTGLDPEKP HQSLDTIQKT
INEYKSEIRQ TRKFRDAEQE KDRTLLKTII KVWKEMKSLR EFQRFTNTPL KLVLRKEKAD
QKADEEAYEA EIQAEISELL EEHTEEYAQK MEEYRTSLQQ WKAWRKVQRA KKKKRKQAAE
EHPGDEIAEP YPEEDLVKPS PPEPTDRAVI EQEVRERAAQ SRRRPWEPTL VPELSLAGSV
TPNDQCPRAE VSRREDVKKR SVYLKVLFNN KEVSRTVSRP LGADFRVHFG QIFNLQIVNW
PESLTLQVYE TVGHSSPTLL AEVFLPIPET TVVTGRAPTE EVEFSSNQHV TLDHEGVGSG
VPFSFEADGS NQLTLMTSGK VSHSVAWAIG ENGIPLIPPL SQQNIGFRSA LKKADAISSI
GTSGLTDMKK LAKWAAESKL DPNDPNNAPL MQLISVATSG ESYVPDFFRL EQLQQEFNFV
SDQELNRSKR FRLLHLRSQE VPEFRNYKQV PVYDREIMEK VFQDYEKRLR DRNVIETKEH
IDTHRAIVAK YLQQVRESVI NRFLIAKQYF LLADMIVEEE VPNISILGLS LFKLAEQKRP
LRPRRKGRKK VTAQNLSDGD IKLLVNIVRA YDIPVRKPAV SKFQQPSRSS RMFSEKHAAS
PSTYSPTHNA DYPLGQVLVR PFVEVSFQRT VCHTTTAEGP NPSWNEELEL PFRAPNGDYS
TASLQSVKDV VFINIFDEVL HDVLEDDRER GSGIHTRIER HWLGCVKMPF STIYFQARID
GTFKIDIPPV LLGYSKERNM ILERGFDSVR SLSEGSYITL FITIEPQLVP GESIREKFES
QEDEKLLQAT EKFQAECALK FPNRQCLTTV IDISGKTVFI TRYLKPLNPP QELLNVYPNN
LQATAELVAR YVSLIPFLPD TVSFGGICDL WSTSDQFLDL LAGDEEEHAV LLCNYFLSLG
KKAWLLMGNA IPEGPTAYVL TWEQGRYLIW NPCSGHFYGQ FDTFCPLKNV GCLIGPDNIW
FNIQRYESPL RINFDVTRPK LWKSFFSRSL PYPGLSSVQP EELIYQRSDK AAAAELQDRI
EKILKEKIMD WRPRHLTRWN RYCTSTLRHF LPLLEKSQGE DVEDDHRAEL LKQLGDYRFS
GFPLHMPYSE VKPLIDAVYS TGVHNIDVPN VEFALAVYIH PYPKNVLSVW IYVASLIRNR
