Full text data of CC2D1A
CC2D1A
(AKI1)
[Confidence: high (present in two of the MS resources)]
Coiled-coil and C2 domain-containing protein 1A (Akt kinase-interacting protein 1; Five prime repressor element under dual repression-binding protein 1; FRE under dual repression-binding protein 1; Freud-1; Putative NF-kappa-B-activating protein 023N)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Coiled-coil and C2 domain-containing protein 1A (Akt kinase-interacting protein 1; Five prime repressor element under dual repression-binding protein 1; FRE under dual repression-binding protein 1; Freud-1; Putative NF-kappa-B-activating protein 023N)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Comments
Isoform Q6P1N0-2 was detected.
Isoform Q6P1N0-2 was detected.
UniProt
Q6P1N0
ID C2D1A_HUMAN Reviewed; 951 AA.
AC Q6P1N0; Q7Z435; Q86XV0; Q8NF89; Q9H603; Q9NXI1;
DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
read moreDT 05-JUL-2004, sequence version 1.
DT 22-JAN-2014, entry version 92.
DE RecName: Full=Coiled-coil and C2 domain-containing protein 1A;
DE AltName: Full=Akt kinase-interacting protein 1;
DE AltName: Full=Five prime repressor element under dual repression-binding protein 1;
DE Short=FRE under dual repression-binding protein 1;
DE Short=Freud-1;
DE AltName: Full=Putative NF-kappa-B-activating protein 023N;
GN Name=CC2D1A; Synonyms=AKI1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Kidney;
RA Guo J.H., Chen L., Yu L.;
RL Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung fibroblast;
RX PubMed=12761501; DOI=10.1038/sj.onc.1206406;
RA Matsuda A., Suzuki Y., Honda G., Muramatsu S., Matsuzaki O.,
RA Nagano Y., Doi T., Shimotohno K., Harada T., Nishida E., Hayashi H.,
RA Sugano S.;
RT "Large-scale identification and characterization of human genes that
RT activate NF-kappaB and MAPK signaling pathways.";
RL Oncogene 22:3307-3318(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 254-606 AND 622-951 (ISOFORM
RP 1).
RC TISSUE=Ovary;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Ovary;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [6]
RP SUBCELLULAR LOCATION, AND INVOLVEMENT IN MRT3.
RX PubMed=16033914; DOI=10.1136/jmg.2005.035709;
RA Basel-Vanagaite L., Attia R., Yahav M., Ferland R.J., Anteki L.,
RA Walsh C.A., Olender T., Straussberg R., Magal N., Taub E.,
RA Drasinover V., Alkelai A., Bercovich D., Rechavi G., Simon A.J.,
RA Shohat M.;
RT "The CC2D1A, a member of a new gene family with C2 domains, is
RT involved in autosomal recessive non-syndromic mental retardation.";
RL J. Med. Genet. 43:203-210(2006).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-208, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-204; SER-208; SER-253
RP AND SER-455, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP FUNCTION, PHOSPHORYLATION AT SER-208 BY CDK1, AND SUBCELLULAR
RP LOCATION.
RX PubMed=20171170; DOI=10.1016/j.bbrc.2010.02.103;
RA Nakamura A., Naito M., Arai H., Fujita N.;
RT "Mitotic phosphorylation of Aki1 at Ser208 by cyclin B1-Cdk1
RT complex.";
RL Biochem. Biophys. Res. Commun. 393:872-876(2010).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-208 AND SER-455, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-455, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
CC -!- FUNCTION: Transcription factor that binds specifically to the DRE
CC (dual repressor element) and represses HTR1A gene transcription in
CC neuronal cells. The combination of calcium and ATP specifically
CC inactivates the binding with FRE. May play a role in the altered
CC regulation of HTR1A associated with anxiety and major depression.
CC Mediates HDAC-independent repression of HTR1A promoter in neuronal
CC cell. Performs essential function in controlling functional
CC maturation of synapses (By similarity). Plays distinct roles
CC depending on its localization. When cytoplasmic, acts as a
CC scaffold protein in the PI3K/PDK1/AKT pathway. Repressor of HTR1A
CC when nuclear. In the centrosome, regulates spindle pole
CC localization of the cohesin subunit SCC1/RAD21, thereby mediating
CC centriole cohesion during mitosis.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cytoplasm, cytoskeleton,
CC microtubule organizing center, centrosome.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6P1N0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6P1N0-2; Sequence=VSP_019242;
CC Note=No experimental confirmation available;
CC -!- DOMAIN: The C2 domain is required for the repression (By
CC similarity).
CC -!- PTM: Phosphorylation on Ser-208 by CDK1 promotes spindle pole
CC localization and association with SCC1/RAD21.
CC -!- DISEASE: Mental retardation, autosomal recessive 3 (MRT3)
CC [MIM:608443]: A disorder characterized by significantly below
CC average general intellectual functioning associated with
CC impairments in adaptive behavior and manifested during the
CC developmental period. Non-syndromic mental retardation patients do
CC not manifest other clinical signs. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the CC2D1 family.
CC -!- SIMILARITY: Contains 1 C2 domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA91029.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing;
CC Sequence=BAB15464.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
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DR EMBL; AF536205; AAN04488.1; -; mRNA.
DR EMBL; AB097002; BAC77355.1; -; mRNA.
DR EMBL; AK000248; BAA91029.1; ALT_SEQ; mRNA.
DR EMBL; AK026371; BAB15464.1; ALT_INIT; mRNA.
DR EMBL; BC048345; AAH48345.1; -; mRNA.
DR EMBL; BC064981; AAH64981.1; -; mRNA.
DR RefSeq; NP_060191.3; NM_017721.4.
DR RefSeq; XP_005260030.1; XM_005259973.1.
DR UniGene; Hs.269592; -.
DR ProteinModelPortal; Q6P1N0; -.
DR IntAct; Q6P1N0; 3.
DR MINT; MINT-4827481; -.
DR STRING; 9606.ENSP00000313601; -.
DR PhosphoSite; Q6P1N0; -.
DR DMDM; 74737148; -.
DR PaxDb; Q6P1N0; -.
DR PRIDE; Q6P1N0; -.
DR Ensembl; ENST00000318003; ENSP00000313601; ENSG00000132024.
DR Ensembl; ENST00000589606; ENSP00000467526; ENSG00000132024.
DR GeneID; 54862; -.
DR KEGG; hsa:54862; -.
DR UCSC; uc002mxo.2; human.
DR CTD; 54862; -.
DR GeneCards; GC19P014016; -.
DR HGNC; HGNC:30237; CC2D1A.
DR HPA; CAB015220; -.
DR HPA; HPA005436; -.
DR MIM; 608443; phenotype.
DR MIM; 610055; gene.
DR neXtProt; NX_Q6P1N0; -.
DR Orphanet; 88616; Autosomal recessive nonsyndromic intellectual deficit.
DR PharmGKB; PA142672197; -.
DR eggNOG; NOG297234; -.
DR HOGENOM; HOG000285993; -.
DR HOVERGEN; HBG100866; -.
DR InParanoid; Q6P1N0; -.
DR OMA; MERYHVA; -.
DR OrthoDB; EOG71G9TB; -.
DR PhylomeDB; Q6P1N0; -.
DR ChiTaRS; CC2D1A; human.
DR GeneWiki; CC2D1A; -.
DR GenomeRNAi; 54862; -.
DR NextBio; 57750; -.
DR PRO; PR:Q6P1N0; -.
DR Bgee; Q6P1N0; -.
DR CleanEx; HS_CC2D1A; -.
DR Genevestigator; Q6P1N0; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; IEA:Ensembl.
DR GO; GO:0001078; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription; IEA:Ensembl.
DR GO; GO:0004871; F:signal transducer activity; IMP:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IMP:UniProtKB.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR006608; DM14.
DR Pfam; PF00168; C2; 1.
DR SMART; SM00239; C2; 1.
DR SMART; SM00685; DM14; 4.
DR SUPFAM; SSF49562; SSF49562; 1.
DR PROSITE; PS50004; C2; FALSE_NEG.
PE 1: Evidence at protein level;
KW Alternative splicing; Coiled coil; Complete proteome; Cytoplasm;
KW Cytoskeleton; DNA-binding; Mental retardation; Nucleus;
KW Phosphoprotein; Polymorphism; Reference proteome; Repressor;
KW Transcription; Transcription regulation.
FT CHAIN 1 951 Coiled-coil and C2 domain-containing
FT protein 1A.
FT /FTId=PRO_0000239609.
FT DOMAIN 642 755 C2.
FT COILED 346 392 Potential.
FT COILED 484 517 Potential.
FT COMPBIAS 192 345 Pro-rich.
FT MOD_RES 204 204 Phosphothreonine.
FT MOD_RES 208 208 Phosphoserine; by CDK1.
FT MOD_RES 253 253 Phosphoserine.
FT MOD_RES 455 455 Phosphoserine.
FT VAR_SEQ 819 819 Missing (in isoform 2).
FT /FTId=VSP_019242.
FT VARIANT 339 339 T -> P (in dbSNP:rs11883041).
FT /FTId=VAR_026670.
FT VARIANT 635 635 T -> S (in dbSNP:rs2290663).
FT /FTId=VAR_026671.
FT VARIANT 801 801 T -> M (in dbSNP:rs2305777).
FT /FTId=VAR_026672.
FT CONFLICT 646 646 I -> V (in Ref. 1; AAN04488).
FT CONFLICT 824 824 K -> E (in Ref. 2; BAC77355).
FT CONFLICT 837 837 S -> P (in Ref. 2; BAC77355).
FT CONFLICT 906 906 A -> T (in Ref. 2; BAC77355).
FT CONFLICT 943 943 E -> G (in Ref. 2; BAC77355).
SQ SEQUENCE 951 AA; 104062 MW; 04D80124FC47729A CRC64;
MHKRKGPPGP PGRGAAAARQ LGLLVDLSPD GLMIPEDGAN DEELEAEFLA LVGGQPPALE
KLKGKGPLPM EAIEKMASLC MRDPDEDEEE GTDEDDLEAD DDLLAELNEV LGEEQKASET
PPPVAQPKPE APHPGLETTL QERLALYQTA IESARQAGDS AKMRRYDRGL KTLENLLASI
RKGNAIDEAD IPPPVAIGKG PASTPTYSPA PTQPAPRIAS APEPRVTLEG PSATAPASSP
GLAKPQMPPG PCSPGPLAQL QSRQRDYKLA ALHAKQQGDT TAAARHFRVA KSFDAVLEAL
SRGEPVDLSC LPPPPDQLPP DPPSPPSQPP TPATAPSTTE VPPPPRTLLE ALEQRMERYQ
VAAAQAKSKG DQRKARMHER IVKQYQDAIR AHKAGRAVDV AELPVPPGFP PIQGLEATKP
TQQSLVGVLE TAMKLANQDE GPEDEEDEVP KKQNSPVAPT AQPKAPPSRT PQSGSAPTAK
APPKATSTRA QQQLAFLEGR KKQLLQAALR AKQKNDVEGA KMHLRQAKGL EPMLEASRNG
LPVDITKVPP APVNKDDFAL VQRPGPGLSQ EAARRYGELT KLIRQQHEMC LNHSNQFTQL
GNITETTKFE KLAEDCKRSM DILKQAFVRG LPTPTARFEQ RTFSVIKIFP DLSSNDMLLF
IVKGINLPTP PGLSPGDLDV FVRFDFPYPN VEEAQKDKTS VIKNTDSPEF KEQFKLCINR
SHRGFRRAIQ TKGIKFEVVH KGGLFKTDRV LGTAQLKLDA LEIACEVREI LEVLDGRRPT
GGRLEVMVRI REPLTAQQLE TTTERWLVID PVPAAVPTQV AGPKGKAPPV PAPARESGNR
SARPLHSLSV LAFDQERLER KILALRQARR PVPPEVAQQY QDIMQRSQWQ RAQLEQGGVG
IRREYAAQLE RQLQFYTEAA RRLGNDGSRD AAKEALYRRN LVESELQRLR R
//
ID C2D1A_HUMAN Reviewed; 951 AA.
AC Q6P1N0; Q7Z435; Q86XV0; Q8NF89; Q9H603; Q9NXI1;
DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
read moreDT 05-JUL-2004, sequence version 1.
DT 22-JAN-2014, entry version 92.
DE RecName: Full=Coiled-coil and C2 domain-containing protein 1A;
DE AltName: Full=Akt kinase-interacting protein 1;
DE AltName: Full=Five prime repressor element under dual repression-binding protein 1;
DE Short=FRE under dual repression-binding protein 1;
DE Short=Freud-1;
DE AltName: Full=Putative NF-kappa-B-activating protein 023N;
GN Name=CC2D1A; Synonyms=AKI1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Kidney;
RA Guo J.H., Chen L., Yu L.;
RL Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung fibroblast;
RX PubMed=12761501; DOI=10.1038/sj.onc.1206406;
RA Matsuda A., Suzuki Y., Honda G., Muramatsu S., Matsuzaki O.,
RA Nagano Y., Doi T., Shimotohno K., Harada T., Nishida E., Hayashi H.,
RA Sugano S.;
RT "Large-scale identification and characterization of human genes that
RT activate NF-kappaB and MAPK signaling pathways.";
RL Oncogene 22:3307-3318(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 254-606 AND 622-951 (ISOFORM
RP 1).
RC TISSUE=Ovary;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Ovary;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [6]
RP SUBCELLULAR LOCATION, AND INVOLVEMENT IN MRT3.
RX PubMed=16033914; DOI=10.1136/jmg.2005.035709;
RA Basel-Vanagaite L., Attia R., Yahav M., Ferland R.J., Anteki L.,
RA Walsh C.A., Olender T., Straussberg R., Magal N., Taub E.,
RA Drasinover V., Alkelai A., Bercovich D., Rechavi G., Simon A.J.,
RA Shohat M.;
RT "The CC2D1A, a member of a new gene family with C2 domains, is
RT involved in autosomal recessive non-syndromic mental retardation.";
RL J. Med. Genet. 43:203-210(2006).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-208, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-204; SER-208; SER-253
RP AND SER-455, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP FUNCTION, PHOSPHORYLATION AT SER-208 BY CDK1, AND SUBCELLULAR
RP LOCATION.
RX PubMed=20171170; DOI=10.1016/j.bbrc.2010.02.103;
RA Nakamura A., Naito M., Arai H., Fujita N.;
RT "Mitotic phosphorylation of Aki1 at Ser208 by cyclin B1-Cdk1
RT complex.";
RL Biochem. Biophys. Res. Commun. 393:872-876(2010).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-208 AND SER-455, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-455, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
CC -!- FUNCTION: Transcription factor that binds specifically to the DRE
CC (dual repressor element) and represses HTR1A gene transcription in
CC neuronal cells. The combination of calcium and ATP specifically
CC inactivates the binding with FRE. May play a role in the altered
CC regulation of HTR1A associated with anxiety and major depression.
CC Mediates HDAC-independent repression of HTR1A promoter in neuronal
CC cell. Performs essential function in controlling functional
CC maturation of synapses (By similarity). Plays distinct roles
CC depending on its localization. When cytoplasmic, acts as a
CC scaffold protein in the PI3K/PDK1/AKT pathway. Repressor of HTR1A
CC when nuclear. In the centrosome, regulates spindle pole
CC localization of the cohesin subunit SCC1/RAD21, thereby mediating
CC centriole cohesion during mitosis.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cytoplasm, cytoskeleton,
CC microtubule organizing center, centrosome.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6P1N0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6P1N0-2; Sequence=VSP_019242;
CC Note=No experimental confirmation available;
CC -!- DOMAIN: The C2 domain is required for the repression (By
CC similarity).
CC -!- PTM: Phosphorylation on Ser-208 by CDK1 promotes spindle pole
CC localization and association with SCC1/RAD21.
CC -!- DISEASE: Mental retardation, autosomal recessive 3 (MRT3)
CC [MIM:608443]: A disorder characterized by significantly below
CC average general intellectual functioning associated with
CC impairments in adaptive behavior and manifested during the
CC developmental period. Non-syndromic mental retardation patients do
CC not manifest other clinical signs. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the CC2D1 family.
CC -!- SIMILARITY: Contains 1 C2 domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA91029.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing;
CC Sequence=BAB15464.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC -----------------------------------------------------------------------
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DR EMBL; AF536205; AAN04488.1; -; mRNA.
DR EMBL; AB097002; BAC77355.1; -; mRNA.
DR EMBL; AK000248; BAA91029.1; ALT_SEQ; mRNA.
DR EMBL; AK026371; BAB15464.1; ALT_INIT; mRNA.
DR EMBL; BC048345; AAH48345.1; -; mRNA.
DR EMBL; BC064981; AAH64981.1; -; mRNA.
DR RefSeq; NP_060191.3; NM_017721.4.
DR RefSeq; XP_005260030.1; XM_005259973.1.
DR UniGene; Hs.269592; -.
DR ProteinModelPortal; Q6P1N0; -.
DR IntAct; Q6P1N0; 3.
DR MINT; MINT-4827481; -.
DR STRING; 9606.ENSP00000313601; -.
DR PhosphoSite; Q6P1N0; -.
DR DMDM; 74737148; -.
DR PaxDb; Q6P1N0; -.
DR PRIDE; Q6P1N0; -.
DR Ensembl; ENST00000318003; ENSP00000313601; ENSG00000132024.
DR Ensembl; ENST00000589606; ENSP00000467526; ENSG00000132024.
DR GeneID; 54862; -.
DR KEGG; hsa:54862; -.
DR UCSC; uc002mxo.2; human.
DR CTD; 54862; -.
DR GeneCards; GC19P014016; -.
DR HGNC; HGNC:30237; CC2D1A.
DR HPA; CAB015220; -.
DR HPA; HPA005436; -.
DR MIM; 608443; phenotype.
DR MIM; 610055; gene.
DR neXtProt; NX_Q6P1N0; -.
DR Orphanet; 88616; Autosomal recessive nonsyndromic intellectual deficit.
DR PharmGKB; PA142672197; -.
DR eggNOG; NOG297234; -.
DR HOGENOM; HOG000285993; -.
DR HOVERGEN; HBG100866; -.
DR InParanoid; Q6P1N0; -.
DR OMA; MERYHVA; -.
DR OrthoDB; EOG71G9TB; -.
DR PhylomeDB; Q6P1N0; -.
DR ChiTaRS; CC2D1A; human.
DR GeneWiki; CC2D1A; -.
DR GenomeRNAi; 54862; -.
DR NextBio; 57750; -.
DR PRO; PR:Q6P1N0; -.
DR Bgee; Q6P1N0; -.
DR CleanEx; HS_CC2D1A; -.
DR Genevestigator; Q6P1N0; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; IEA:Ensembl.
DR GO; GO:0001078; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription; IEA:Ensembl.
DR GO; GO:0004871; F:signal transducer activity; IMP:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IMP:UniProtKB.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR006608; DM14.
DR Pfam; PF00168; C2; 1.
DR SMART; SM00239; C2; 1.
DR SMART; SM00685; DM14; 4.
DR SUPFAM; SSF49562; SSF49562; 1.
DR PROSITE; PS50004; C2; FALSE_NEG.
PE 1: Evidence at protein level;
KW Alternative splicing; Coiled coil; Complete proteome; Cytoplasm;
KW Cytoskeleton; DNA-binding; Mental retardation; Nucleus;
KW Phosphoprotein; Polymorphism; Reference proteome; Repressor;
KW Transcription; Transcription regulation.
FT CHAIN 1 951 Coiled-coil and C2 domain-containing
FT protein 1A.
FT /FTId=PRO_0000239609.
FT DOMAIN 642 755 C2.
FT COILED 346 392 Potential.
FT COILED 484 517 Potential.
FT COMPBIAS 192 345 Pro-rich.
FT MOD_RES 204 204 Phosphothreonine.
FT MOD_RES 208 208 Phosphoserine; by CDK1.
FT MOD_RES 253 253 Phosphoserine.
FT MOD_RES 455 455 Phosphoserine.
FT VAR_SEQ 819 819 Missing (in isoform 2).
FT /FTId=VSP_019242.
FT VARIANT 339 339 T -> P (in dbSNP:rs11883041).
FT /FTId=VAR_026670.
FT VARIANT 635 635 T -> S (in dbSNP:rs2290663).
FT /FTId=VAR_026671.
FT VARIANT 801 801 T -> M (in dbSNP:rs2305777).
FT /FTId=VAR_026672.
FT CONFLICT 646 646 I -> V (in Ref. 1; AAN04488).
FT CONFLICT 824 824 K -> E (in Ref. 2; BAC77355).
FT CONFLICT 837 837 S -> P (in Ref. 2; BAC77355).
FT CONFLICT 906 906 A -> T (in Ref. 2; BAC77355).
FT CONFLICT 943 943 E -> G (in Ref. 2; BAC77355).
SQ SEQUENCE 951 AA; 104062 MW; 04D80124FC47729A CRC64;
MHKRKGPPGP PGRGAAAARQ LGLLVDLSPD GLMIPEDGAN DEELEAEFLA LVGGQPPALE
KLKGKGPLPM EAIEKMASLC MRDPDEDEEE GTDEDDLEAD DDLLAELNEV LGEEQKASET
PPPVAQPKPE APHPGLETTL QERLALYQTA IESARQAGDS AKMRRYDRGL KTLENLLASI
RKGNAIDEAD IPPPVAIGKG PASTPTYSPA PTQPAPRIAS APEPRVTLEG PSATAPASSP
GLAKPQMPPG PCSPGPLAQL QSRQRDYKLA ALHAKQQGDT TAAARHFRVA KSFDAVLEAL
SRGEPVDLSC LPPPPDQLPP DPPSPPSQPP TPATAPSTTE VPPPPRTLLE ALEQRMERYQ
VAAAQAKSKG DQRKARMHER IVKQYQDAIR AHKAGRAVDV AELPVPPGFP PIQGLEATKP
TQQSLVGVLE TAMKLANQDE GPEDEEDEVP KKQNSPVAPT AQPKAPPSRT PQSGSAPTAK
APPKATSTRA QQQLAFLEGR KKQLLQAALR AKQKNDVEGA KMHLRQAKGL EPMLEASRNG
LPVDITKVPP APVNKDDFAL VQRPGPGLSQ EAARRYGELT KLIRQQHEMC LNHSNQFTQL
GNITETTKFE KLAEDCKRSM DILKQAFVRG LPTPTARFEQ RTFSVIKIFP DLSSNDMLLF
IVKGINLPTP PGLSPGDLDV FVRFDFPYPN VEEAQKDKTS VIKNTDSPEF KEQFKLCINR
SHRGFRRAIQ TKGIKFEVVH KGGLFKTDRV LGTAQLKLDA LEIACEVREI LEVLDGRRPT
GGRLEVMVRI REPLTAQQLE TTTERWLVID PVPAAVPTQV AGPKGKAPPV PAPARESGNR
SARPLHSLSV LAFDQERLER KILALRQARR PVPPEVAQQY QDIMQRSQWQ RAQLEQGGVG
IRREYAAQLE RQLQFYTEAA RRLGNDGSRD AAKEALYRRN LVESELQRLR R
//
MIM
608443
*RECORD*
*FIELD* NO
608443
*FIELD* TI
#608443 MENTAL RETARDATION, AUTOSOMAL RECESSIVE 3; MRT3
*FIELD* TX
A number sign (#) is used with this entry because autosomal recessive
read morenonsyndromic mental retardation-3 can be caused by homozygous mutation
in the CC2D1A gene (610055).
CLINICAL FEATURES
Basel-Vanagaite et al. (2003) studied nonsyndromic mental retardation in
4 consanguineous families of Israeli-Arab origin with 10 affected and 24
unaffected members. All families originated from the same small village
and had the same family name. Basel-Vanagaite et al. (2006) reported 5
additional families with nonsyndromic mental retardation from the same
village with the same family name, for a total of 16 affected
individuals. The initial clinical presentation in all affected family
members was psychomotor developmental delay in early childhood. All had
no or only single words and were severely mentally retarded; none had
autistic features or seizures, and there were no dysmorphic features.
MAPPING
In 4 consanguineous, interrelated Israeli-Arab families with
nonsyndromic mental retardation from the same village, Basel-Vanagaite
et al. (2003) established linkage with marker D19S840 at 19p13.2-p13.12
(maximum lod = 7.06 at theta = 0.00). All affected individuals were
found to be homozygous for a common haplotype within a 2.4-Mb critical
region between the markers D19S547 proximally and D19S1165 distally.
In 4 consanguineous Israeli-Arab families originally reported by
Basel-Vanagaite et al. (2003) and 5 additional families with
nonsyndromic mental retardation from the same village and with the same
family name, Basel-Vanagaite et al. (2006) identified a common
homozygous disease-bearing haplotype for the polymorphic markers RFX1
and D19S840 that defined a critical 0.9-Mb region between D19S564 and
D19S547 on chromosome 19p13.12. Basel-Vanagaite et al. (2006) suggested
that the disease was caused by a single mutation derived from a single
ancestral founder in all the families.
MOLECULAR GENETICS
In 9 consanguineous Israeli-Arab families with nonsyndromic mental
retardation from the same village and with the same family name,
Basel-Vanagaite et al. (2006) analyzed 14 candidate genes located in a
haplotype-defined critical region on chromosome 19p13.12. Homozygosity
for a protein-truncating mutation in the CC2D1A gene (610055.0001) was
identified in all affected family members; parents were heterozygous for
the mutation.
*FIELD* RF
1. Basel-Vanagaite, L.; Alkelai, A.; Straussberg, R.; Magal, N.; Inbar,
D.; Mahajna, M.; Shohat, M.: Mapping of a new locus for autosomal
recessive non-syndromic mental retardation in the chromosomal region
19p13.12-p13.2: further genetic heterogeneity. J. Med. Genet. 40:
729-732, 2003.
2. Basel-Vanagaite, L.; Attia, R.; Yahav, M.; Ferland, R. J.; Anteki,
L.; Walsh, C. A.; Olender, T.; Straussberg, R.; Magal, N.; Taub, E.;
Drasinover, V.; Alkelai, A.; Bercovich, D.; Rechavi, G.; Simon, A.
J.; Shohat, M.: The CC2D1A, a member of a new gene family with C2
domains, is involved in autosomal recessive non-syndromic mental retardation. J.
Med. Genet. 43: 203-210, 2006.
*FIELD* CS
INHERITANCE:
Autosomal recessive
HEAD AND NECK:
[Face];
Dull facial expression
NEUROLOGIC:
[Central nervous system];
Delayed psychomotor development;
Mental retardation, severe;
Limited verbal comprehension;
Speech limited to single word or no words;
Incomprehensible speech;
[Behavioral/psychiatric manifestations];
Dull facial expression;
Hyperactivity;
Easily frustrated;
Short attention span
MISCELLANEOUS:
Onset in early childhood
MOLECULAR BASIS:
Caused by mutation in the coiled-coil and C2 domain-containing 1A
gene (CC2D1A, 610055.0001)
*FIELD* CN
Cassandra L. Kniffin - updated: 7/18/2006
*FIELD* CD
Cassandra L. Kniffin: 3/30/2004
*FIELD* ED
joanna: 02/07/2011
joanna: 12/9/2008
ckniffin: 7/18/2006
ckniffin: 3/30/2004
*FIELD* CN
Marla J. F. O'Neill - updated: 4/17/2006
*FIELD* CD
Victor A. McKusick: 2/4/2004
*FIELD* ED
carol: 06/08/2011
alopez: 10/10/2007
carol: 4/17/2006
carol: 2/20/2006
carol: 3/18/2004
carol: 2/6/2004
tkritzer: 2/4/2004
*RECORD*
*FIELD* NO
608443
*FIELD* TI
#608443 MENTAL RETARDATION, AUTOSOMAL RECESSIVE 3; MRT3
*FIELD* TX
A number sign (#) is used with this entry because autosomal recessive
read morenonsyndromic mental retardation-3 can be caused by homozygous mutation
in the CC2D1A gene (610055).
CLINICAL FEATURES
Basel-Vanagaite et al. (2003) studied nonsyndromic mental retardation in
4 consanguineous families of Israeli-Arab origin with 10 affected and 24
unaffected members. All families originated from the same small village
and had the same family name. Basel-Vanagaite et al. (2006) reported 5
additional families with nonsyndromic mental retardation from the same
village with the same family name, for a total of 16 affected
individuals. The initial clinical presentation in all affected family
members was psychomotor developmental delay in early childhood. All had
no or only single words and were severely mentally retarded; none had
autistic features or seizures, and there were no dysmorphic features.
MAPPING
In 4 consanguineous, interrelated Israeli-Arab families with
nonsyndromic mental retardation from the same village, Basel-Vanagaite
et al. (2003) established linkage with marker D19S840 at 19p13.2-p13.12
(maximum lod = 7.06 at theta = 0.00). All affected individuals were
found to be homozygous for a common haplotype within a 2.4-Mb critical
region between the markers D19S547 proximally and D19S1165 distally.
In 4 consanguineous Israeli-Arab families originally reported by
Basel-Vanagaite et al. (2003) and 5 additional families with
nonsyndromic mental retardation from the same village and with the same
family name, Basel-Vanagaite et al. (2006) identified a common
homozygous disease-bearing haplotype for the polymorphic markers RFX1
and D19S840 that defined a critical 0.9-Mb region between D19S564 and
D19S547 on chromosome 19p13.12. Basel-Vanagaite et al. (2006) suggested
that the disease was caused by a single mutation derived from a single
ancestral founder in all the families.
MOLECULAR GENETICS
In 9 consanguineous Israeli-Arab families with nonsyndromic mental
retardation from the same village and with the same family name,
Basel-Vanagaite et al. (2006) analyzed 14 candidate genes located in a
haplotype-defined critical region on chromosome 19p13.12. Homozygosity
for a protein-truncating mutation in the CC2D1A gene (610055.0001) was
identified in all affected family members; parents were heterozygous for
the mutation.
*FIELD* RF
1. Basel-Vanagaite, L.; Alkelai, A.; Straussberg, R.; Magal, N.; Inbar,
D.; Mahajna, M.; Shohat, M.: Mapping of a new locus for autosomal
recessive non-syndromic mental retardation in the chromosomal region
19p13.12-p13.2: further genetic heterogeneity. J. Med. Genet. 40:
729-732, 2003.
2. Basel-Vanagaite, L.; Attia, R.; Yahav, M.; Ferland, R. J.; Anteki,
L.; Walsh, C. A.; Olender, T.; Straussberg, R.; Magal, N.; Taub, E.;
Drasinover, V.; Alkelai, A.; Bercovich, D.; Rechavi, G.; Simon, A.
J.; Shohat, M.: The CC2D1A, a member of a new gene family with C2
domains, is involved in autosomal recessive non-syndromic mental retardation. J.
Med. Genet. 43: 203-210, 2006.
*FIELD* CS
INHERITANCE:
Autosomal recessive
HEAD AND NECK:
[Face];
Dull facial expression
NEUROLOGIC:
[Central nervous system];
Delayed psychomotor development;
Mental retardation, severe;
Limited verbal comprehension;
Speech limited to single word or no words;
Incomprehensible speech;
[Behavioral/psychiatric manifestations];
Dull facial expression;
Hyperactivity;
Easily frustrated;
Short attention span
MISCELLANEOUS:
Onset in early childhood
MOLECULAR BASIS:
Caused by mutation in the coiled-coil and C2 domain-containing 1A
gene (CC2D1A, 610055.0001)
*FIELD* CN
Cassandra L. Kniffin - updated: 7/18/2006
*FIELD* CD
Cassandra L. Kniffin: 3/30/2004
*FIELD* ED
joanna: 02/07/2011
joanna: 12/9/2008
ckniffin: 7/18/2006
ckniffin: 3/30/2004
*FIELD* CN
Marla J. F. O'Neill - updated: 4/17/2006
*FIELD* CD
Victor A. McKusick: 2/4/2004
*FIELD* ED
carol: 06/08/2011
alopez: 10/10/2007
carol: 4/17/2006
carol: 2/20/2006
carol: 3/18/2004
carol: 2/6/2004
tkritzer: 2/4/2004
MIM
610055
*RECORD*
*FIELD* NO
610055
*FIELD* TI
*610055 COILED-COIL AND C2 DOMAINS-CONTAINING PROTEIN 1A; CC2D1A
*FIELD* TX
CLONING
read more
By searching for genes along a region of chromosome 19 associated with
autosomal recessive nonsyndromic mental retardation, Basel-Vanagaite et
al. (2006) identified CC2D1A. The deduced 950-amino acid protein
contains a C2 domain and a DM14 motif. A deduced 338-amino acid isoform
does not contain the DM motif. In situ hybridization of day 12 mouse
embryos detected Cc2d1a throughout the ventricular zone and developing
cortical plate and ganglionic eminences. By embryonic day 16, expression
was strongest in the cortical plate; from postnatal day 3 into
adulthood, expression was strongest in the cerebral cortex and
hippocampus, particularly in hippocampal region CA3. Western blot
analysis of normal human lymphoblastoid cells detected CC2D1A at an
apparent molecular mass of 104 kD. Immunohistochemical analysis detected
CC2D1a in the cytoplasm of human osteosarcoma cells.
GENE FUNCTION
Gallagher and Knoblich (2006) and Jaekel and Klein (2006) found that
Drosophila Lgd, an ortholog of CC2D1A and CC2D1B, regulated endocytosis
and was required for endosomal trafficking of Notch (190198). Jaekel and
Klein (2006) showed that, in the absence of Lgd, Notch was activated in
a ligand-independent manner. They also found that murine Cc2d1a and
Cc2d1b could substitute for loss of Lgd function in flies.
GENE STRUCTURE
Basel-Vanagaite et al. (2006) determined that the CC2D1A gene contains
31 exons and spans 37 kb.
MAPPING
By genomic sequence analysis, Basel-Vanagaite et al. (2006) mapped the
CC2D1A gene to chromosome 19p13.12.
MOLECULAR GENETICS
In affected members of 9 consanguineous Israeli-Arab families with
nonsyndromic mental retardation-3 (MRT3; 608443) from the same village
and with the same family name, Basel-Vanagaite et al. (2006) identified
homozygosity for a protein-truncating mutation in the CC2D1A gene
(610055.0001). The parents were heterozygous for the mutation, which was
not found in 300 control chromosomes.
*FIELD* AV
.0001
MENTAL RETARDATION, AUTOSOMAL RECESSIVE 3
CC2D1A, IVS13-16DEL
In affected members of 9 consanguineous Israeli-Arab families with
nonsyndromic mental retardation-3 (608443) from the same village and
with the same family name, Basel-Vanagaite et al. (2006) identified
homozygosity for a deletion of 3,589 nucleotides beginning in intron 13
and ending in intron 16 of the CC2D1A gene. The deletion introduces a
frameshift, creating a 30-amino acid nonsense peptide and a stop codon
at position 438 of the mutant protein. The parents were heterozygous for
the mutation, which was not found in 300 control chromosomes.
*FIELD* RF
1. Basel-Vanagaite, L.; Attia, R.; Yahav, M.; Ferland, R. J.; Anteki,
L.; Walsh, C. A.; Olender, T.; Straussberg, R.; Magal, N.; Taub, E.;
Drasinover, V.; Alkelai, A.; Bercovich, D.; Rechavi, G.; Simon, A.
J.; Shohat, M.: The CC2D1A, a member of a new gene family with C2
domains, is involved in autosomal recessive non-syndromic mental retardation. J.
Med. Genet. 43: 203-210, 2006.
2. Gallagher, C. M.; Knoblich, J. A.: The conserved C2 domain protein
lethal (2) giant discs regulates protein trafficking in Drosophila. Dev.
Cell 11: 641-653, 2006.
3. Jaekel, R.; Klein, T.: The Drosophila Notch inhibitor and tumor
suppressor gene lethal (2) giant discs encodes a conserved regulator
of endosomal trafficking. Dev. Cell 11: 655-669, 2006.
*FIELD* CN
Patricia A. Hartz - updated: 1/3/2007
*FIELD* CD
Patricia A. Hartz: 4/17/2006
*FIELD* ED
mgross: 04/25/2008
mgross: 1/3/2007
carol: 4/17/2006
*RECORD*
*FIELD* NO
610055
*FIELD* TI
*610055 COILED-COIL AND C2 DOMAINS-CONTAINING PROTEIN 1A; CC2D1A
*FIELD* TX
CLONING
read more
By searching for genes along a region of chromosome 19 associated with
autosomal recessive nonsyndromic mental retardation, Basel-Vanagaite et
al. (2006) identified CC2D1A. The deduced 950-amino acid protein
contains a C2 domain and a DM14 motif. A deduced 338-amino acid isoform
does not contain the DM motif. In situ hybridization of day 12 mouse
embryos detected Cc2d1a throughout the ventricular zone and developing
cortical plate and ganglionic eminences. By embryonic day 16, expression
was strongest in the cortical plate; from postnatal day 3 into
adulthood, expression was strongest in the cerebral cortex and
hippocampus, particularly in hippocampal region CA3. Western blot
analysis of normal human lymphoblastoid cells detected CC2D1A at an
apparent molecular mass of 104 kD. Immunohistochemical analysis detected
CC2D1a in the cytoplasm of human osteosarcoma cells.
GENE FUNCTION
Gallagher and Knoblich (2006) and Jaekel and Klein (2006) found that
Drosophila Lgd, an ortholog of CC2D1A and CC2D1B, regulated endocytosis
and was required for endosomal trafficking of Notch (190198). Jaekel and
Klein (2006) showed that, in the absence of Lgd, Notch was activated in
a ligand-independent manner. They also found that murine Cc2d1a and
Cc2d1b could substitute for loss of Lgd function in flies.
GENE STRUCTURE
Basel-Vanagaite et al. (2006) determined that the CC2D1A gene contains
31 exons and spans 37 kb.
MAPPING
By genomic sequence analysis, Basel-Vanagaite et al. (2006) mapped the
CC2D1A gene to chromosome 19p13.12.
MOLECULAR GENETICS
In affected members of 9 consanguineous Israeli-Arab families with
nonsyndromic mental retardation-3 (MRT3; 608443) from the same village
and with the same family name, Basel-Vanagaite et al. (2006) identified
homozygosity for a protein-truncating mutation in the CC2D1A gene
(610055.0001). The parents were heterozygous for the mutation, which was
not found in 300 control chromosomes.
*FIELD* AV
.0001
MENTAL RETARDATION, AUTOSOMAL RECESSIVE 3
CC2D1A, IVS13-16DEL
In affected members of 9 consanguineous Israeli-Arab families with
nonsyndromic mental retardation-3 (608443) from the same village and
with the same family name, Basel-Vanagaite et al. (2006) identified
homozygosity for a deletion of 3,589 nucleotides beginning in intron 13
and ending in intron 16 of the CC2D1A gene. The deletion introduces a
frameshift, creating a 30-amino acid nonsense peptide and a stop codon
at position 438 of the mutant protein. The parents were heterozygous for
the mutation, which was not found in 300 control chromosomes.
*FIELD* RF
1. Basel-Vanagaite, L.; Attia, R.; Yahav, M.; Ferland, R. J.; Anteki,
L.; Walsh, C. A.; Olender, T.; Straussberg, R.; Magal, N.; Taub, E.;
Drasinover, V.; Alkelai, A.; Bercovich, D.; Rechavi, G.; Simon, A.
J.; Shohat, M.: The CC2D1A, a member of a new gene family with C2
domains, is involved in autosomal recessive non-syndromic mental retardation. J.
Med. Genet. 43: 203-210, 2006.
2. Gallagher, C. M.; Knoblich, J. A.: The conserved C2 domain protein
lethal (2) giant discs regulates protein trafficking in Drosophila. Dev.
Cell 11: 641-653, 2006.
3. Jaekel, R.; Klein, T.: The Drosophila Notch inhibitor and tumor
suppressor gene lethal (2) giant discs encodes a conserved regulator
of endosomal trafficking. Dev. Cell 11: 655-669, 2006.
*FIELD* CN
Patricia A. Hartz - updated: 1/3/2007
*FIELD* CD
Patricia A. Hartz: 4/17/2006
*FIELD* ED
mgross: 04/25/2008
mgross: 1/3/2007
carol: 4/17/2006