C2D1A_MOUSE
ID C2D1A_MOUSE Reviewed; 943 AA.
AC Q8K1A6; Q2MJB5; Q8R3Z4;
DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2006, sequence version 2.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Coiled-coil and C2 domain-containing protein 1A;
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;
GN Name=Cc2d1a;
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].
RC TISSUE=Eye, and Mammary gland;
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 [MRNA] OF 301-943, AND FUNCTION.
RC STRAIN=Swiss Webster;
RX PubMed=12917378; DOI=10.1523/jneurosci.23-19-07415.2003;
RA Ou X.-M., Lemonde S., Jafar-Nejad H., Bown C.D., Goto A., Rogaeva A.,
RA Albert P.R.;
RT "Freud-1: a neuronal calcium-regulated repressor of the 5-HT1A receptor
RT gene.";
RL J. Neurosci. 23:7415-7425(2003).
RN [3]
RP FUNCTION.
RX PubMed=14756806; DOI=10.1046/j.1471-4159.2003.02223.x;
RA Lemonde S., Rogaeva A., Albert P.R.;
RT "Cell type-dependent recruitment of trichostatin A-sensitive repression of
RT the human 5-HT1A receptor gene.";
RL J. Neurochem. 88:857-868(2004).
RN [4]
RP DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
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., Drasinover V.,
RA Alkelai A., Bercovich D., Rechavi G., Simon A.J., Shohat M.;
RT "The CC2D1A, a member of a new gene family with C2 domains, is involved in
RT autosomal recessive non-syndromic mental retardation.";
RL J. Med. Genet. 43:203-210(2006).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-435, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-435, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Liver, Lung, Pancreas, Spleen, 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 [7]
RP DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND FUNCTION IN SYNAPSE.
RX PubMed=21273312; DOI=10.1152/jn.00950.2010;
RA Zhao M., Raingo J., Chen Z.J., Kavalali E.T.;
RT "Cc2d1a, a C2 domain containing protein linked to nonsyndromic mental
RT retardation, controls functional maturation of central synapses.";
RL J. Neurophysiol. 105:1506-1515(2011).
CC -!- FUNCTION: Transcription factor that binds specifically to the DRE (dual
CC repressor element) and represses HTR1A gene transcription in neuronal
CC cells. The combination of calcium and ATP specifically inactivates the
CC binding with FRE. May play a role in the altered regulation of HTR1A
CC associated with anxiety and major depression. Mediates HDAC-independent
CC repression of HTR1A promoter in neuronal cell. Performs essential
CC function in controlling functional maturation of synapses.
CC {ECO:0000269|PubMed:12917378, ECO:0000269|PubMed:14756806,
CC ECO:0000269|PubMed:21273312}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q6P1N0}. Nucleus
CC {ECO:0000250|UniProtKB:Q66HA5}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000250|UniProtKB:Q6P1N0}.
CC -!- TISSUE SPECIFICITY: Highly expressed in brain, expression is enriched
CC in the gray matter and strongest in the olfactory bulb.
CC {ECO:0000269|PubMed:16033914, ECO:0000269|PubMed:21273312}.
CC -!- DEVELOPMENTAL STAGE: Expressed at 12 dpc throughout the ventricular
CC zone and developing cortical plate and ganglionic eminences. At 16 dpc
CC detected throughout the brain but most strongly in the cortical plate.
CC At postnatal day 3 expressed widely with strong expression in cerebral
CC cortex and hippocampus. {ECO:0000269|PubMed:16033914}.
CC -!- DOMAIN: The C2 domain is required for the repression.
CC -!- DISRUPTION PHENOTYPE: Knockout mice die soon after birth, apparently
CC because of their inability to breathe. {ECO:0000269|PubMed:21273312}.
CC -!- SIMILARITY: Belongs to the CC2D1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH16188.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAH27028.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=ABC56419.1; Type=Frameshift; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BC016188; AAH16188.1; ALT_INIT; mRNA.
DR EMBL; BC027028; AAH27028.1; ALT_INIT; mRNA.
DR EMBL; DQ329239; ABC56419.1; ALT_SEQ; mRNA.
DR CCDS; CCDS40407.1; -.
DR RefSeq; NP_666082.2; NM_145970.1.
DR AlphaFoldDB; Q8K1A6; -.
DR SMR; Q8K1A6; -.
DR BioGRID; 229295; 2.
DR IntAct; Q8K1A6; 1.
DR MINT; Q8K1A6; -.
DR STRING; 10090.ENSMUSP00000046449; -.
DR iPTMnet; Q8K1A6; -.
DR PhosphoSitePlus; Q8K1A6; -.
DR EPD; Q8K1A6; -.
DR jPOST; Q8K1A6; -.
DR MaxQB; Q8K1A6; -.
DR PaxDb; Q8K1A6; -.
DR PeptideAtlas; Q8K1A6; -.
DR PRIDE; Q8K1A6; -.
DR ProteomicsDB; 265468; -.
DR Antibodypedia; 1689; 175 antibodies from 28 providers.
DR Ensembl; ENSMUST00000040383; ENSMUSP00000046449; ENSMUSG00000036686.
DR GeneID; 212139; -.
DR KEGG; mmu:212139; -.
DR UCSC; uc009mma.1; mouse.
DR CTD; 54862; -.
DR MGI; MGI:2384831; Cc2d1a.
DR VEuPathDB; HostDB:ENSMUSG00000036686; -.
DR eggNOG; KOG3837; Eukaryota.
DR GeneTree; ENSGT00390000009595; -.
DR InParanoid; Q8K1A6; -.
DR OMA; LHRIKIM; -.
DR OrthoDB; 959801at2759; -.
DR PhylomeDB; Q8K1A6; -.
DR TreeFam; TF314229; -.
DR BioGRID-ORCS; 212139; 2 hits in 72 CRISPR screens.
DR PRO; PR:Q8K1A6; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q8K1A6; protein.
DR Bgee; ENSMUSG00000036686; Expressed in embryonic brain and 233 other tissues.
DR ExpressionAtlas; Q8K1A6; baseline and differential.
DR Genevisible; Q8K1A6; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0001650; C:fibrillar center; ISO:MGI.
DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:MGI.
DR GO; GO:1905381; P:negative regulation of snRNA transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR CDD; cd08690; C2_Freud-1; 1.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR037772; C2_Freud.
DR InterPro; IPR039725; CC2D1A/B.
DR InterPro; IPR006608; DM14.
DR PANTHER; PTHR13076; PTHR13076; 1.
DR Pfam; PF00168; C2; 1.
DR SMART; SM00239; C2; 1.
DR SMART; SM00685; DM14; 4.
DR SUPFAM; SSF49562; SSF49562; 1.
DR PROSITE; PS50004; C2; 1.
PE 1: Evidence at protein level;
KW Coiled coil; Cytoplasm; Cytoskeleton; DNA-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repressor; Transcription; Transcription regulation.
FT CHAIN 1..943
FT /note="Coiled-coil and C2 domain-containing protein 1A"
FT /id="PRO_0000239610"
FT DOMAIN 630..764
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 186..250
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 300..337
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 430..483
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 339..385
FT /evidence="ECO:0000255"
FT COILED 477..510
FT /evidence="ECO:0000255"
FT COMPBIAS 203..236
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 306..320
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 430..445
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 446..462
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 91
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q66HA5"
FT MOD_RES 248
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6P1N0"
FT MOD_RES 435
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT CONFLICT 446
FT /note="Q -> H (in Ref. 2; ABC56419)"
FT /evidence="ECO:0000305"
FT CONFLICT 863
FT /note="P -> S (in Ref. 2; ABC56419)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 943 AA; 103698 MW; A730FF6E950DFA81 CRC64;
MHKRNGPQAP PGRGAVTARQ LGLLVDFSPD GLMIPEDGIN EEELEAEFLA LVGGQPQALE
KLKGQGPLPM EAIEKMARLC MRDLDEDEEG TDEDDVEADE DLLAELNEVL GEEQKAVEPL
MPVAQPKPSG PNPGVEATLQ ERLTLYQSAL ESARQAGDSA KMRRYDRGLK TLENLLVSAK
KGNIINEADI PPPVASGKGA AAGHSHTQAT SQLASVSPPA PESSGTLEAP STTTPTSAKP
QLPPDPCSPL ARLQSLQHEY KLAALRAKHQ DDTATATRHL RIAKSFDPVL EALSRGELVD
LSRLPPPPDQ LSPEPPLPAA QPLTSASTLT RPEVPQPPRN LLEALEQRME RYHVAAAQAK
AKGDQRKARM HERIVKQYQD AIRAHKAGRA VDVAELPVPP GFPPMQGLES AEPSQQSLVG
VLETAMRLAN HDEGSDDEEE ETPKKQNTPA ASTTQLKSSP SKAPPSGPAP AGKAAPKGTS
NRAQQQLAFL EGRKKQLLQA ALRAKQKNDV EGAKMHLRQA KGLEPMLEAS RNGLPVDIAK
VPPAPVNKDD FVLVQRPGPG LSQEAVRRYG ELTKLLRQQH EMCLNHSTQF THLGNIAETI
KFEKLAEDCK RSMDTLKQAF ARSLPTPAAR FEQRTFSVIK VFPDLSNSDM LLFIVKGINL
PTPTGLSPSD LDAFVRFDFP YPNVEEAQKD KTSVIKNTDS PEFKEQFKLC INRGHRGFRR
AIQTKGIKFE VVHKGGLFKT DRVLGTAQLK LGTLETACEV HEILEVLDGR RPTGGRLEVM
VRIREPLTAQ QLETTTERWL VIDHIPAAMP TVTGPKAKAP LIPASSREAG NRSARPLHSL
SVLAFDQERL ERKILALRQA RRPVPPEVAQ QYQDVVQRSQ WQRAQLEQGG AALRREYASH
LERQLHFYTE AARRLGYDGS REAAKEALYR RNLVESELQR LRR
