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CIPC_HUMAN
ID   CIPC_HUMAN              Reviewed;         399 AA.
AC   Q9C0C6; B2RCI1; Q8N389; Q8NDZ1;
DT   31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT   31-OCT-2006, sequence version 2.
DT   03-AUG-2022, entry version 120.
DE   RecName: Full=CLOCK-interacting pacemaker;
DE   AltName: Full=CLOCK-interacting circadian protein;
GN   Name=CIPC; Synonyms=KIAA1737;
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 [LARGE SCALE MRNA].
RC   TISSUE=Brain;
RX   PubMed=11214970; DOI=10.1093/dnares/7.6.347;
RA   Nagase T., Kikuno R., Hattori A., Kondo Y., Okumura K., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. XIX. The
RT   complete sequences of 100 new cDNA clones from brain which code for large
RT   proteins in vitro.";
RL   DNA Res. 7:347-355(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Trachea;
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Melanoma;
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12508121; DOI=10.1038/nature01348;
RA   Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA   Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA   Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA   Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA   Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA   Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA   Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA   Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA   Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA   Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA   Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA   Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA   Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA   Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA   Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA   Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA   Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA   Waterston R., Hood L., Weissenbach J.;
RT   "The DNA sequence and analysis of human chromosome 14.";
RL   Nature 421:601-607(2003).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.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   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PHE-31.
RC   TISSUE=Testis;
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   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-213, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma, and Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [8]
RP   SUBCELLULAR LOCATION, INTERACTION WITH CAD AND HSPA5, AND MUTAGENESIS OF
RP   LYS-186 AND LYS-187.
RX   PubMed=26657846; DOI=10.1016/j.bbrc.2015.11.117;
RA   Matsunaga R., Nishino T., Yokoyama A., Nakashima A., Kikkawa U.,
RA   Konishi H.;
RT   "Versatile function of the circadian protein CIPC as a regulator of Erk
RT   activation.";
RL   Biochem. Biophys. Res. Commun. 469:377-383(2016).
CC   -!- FUNCTION: Transcriptional repressor which may act as a negative-
CC       feedback regulator of CLOCK-ARNTL/BMAL1 transcriptional activity in the
CC       circadian-clock mechanism. May stimulate ARNTL/BMAL1-dependent
CC       phosphorylation of CLOCK. However, the physiogical relevance of these
CC       observations is unsure, since experiments in an animal model showed
CC       that CIPC is not critially required for basic circadian clock.
CC       {ECO:0000250|UniProtKB:Q8R0W1}.
CC   -!- SUBUNIT: Interacts with CLOCK. Forms a ternary complex with the CLOCK-
CC       ARNTL/BMAL1 heterodimer. Interacts with CAD AND HSPA5
CC       (PubMed:26657846). {ECO:0000250|UniProtKB:Q8R0W1,
CC       ECO:0000269|PubMed:26657846}.
CC   -!- INTERACTION:
CC       Q9C0C6; O43639: NCK2; NbExp=3; IntAct=EBI-5654244, EBI-713635;
CC       Q9C0C6; Q9UJ41: RABGEF1; NbExp=3; IntAct=EBI-5654244, EBI-913954;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:26657846}. Cytoplasm,
CC       cytosol {ECO:0000269|PubMed:26657846}. Note=Predominantly localizes to
CC       the nucleus, where it co-localizes with CLOCK. At the G1/S boundary,
CC       partially translocated to the cytosol. {ECO:0000250|UniProtKB:Q8R0W1,
CC       ECO:0000269|PubMed:26657846}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAB21828.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AB051524; BAB21828.1; ALT_INIT; mRNA.
DR   EMBL; AK315124; BAG37578.1; -; mRNA.
DR   EMBL; AL834514; CAD39170.1; -; mRNA.
DR   EMBL; AC007686; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471061; EAW81270.1; -; Genomic_DNA.
DR   EMBL; BC037300; AAH37300.1; -; mRNA.
DR   CCDS; CCDS9855.1; -.
DR   RefSeq; NP_219494.2; NM_033426.2.
DR   AlphaFoldDB; Q9C0C6; -.
DR   SMR; Q9C0C6; -.
DR   BioGRID; 124541; 16.
DR   IntAct; Q9C0C6; 8.
DR   STRING; 9606.ENSP00000355319; -.
DR   iPTMnet; Q9C0C6; -.
DR   PhosphoSitePlus; Q9C0C6; -.
DR   BioMuta; CIPC; -.
DR   DMDM; 117949601; -.
DR   jPOST; Q9C0C6; -.
DR   MassIVE; Q9C0C6; -.
DR   MaxQB; Q9C0C6; -.
DR   PaxDb; Q9C0C6; -.
DR   PeptideAtlas; Q9C0C6; -.
DR   PRIDE; Q9C0C6; -.
DR   ProteomicsDB; 79998; -.
DR   Antibodypedia; 99; 40 antibodies from 9 providers.
DR   DNASU; 85457; -.
DR   Ensembl; ENST00000361786.7; ENSP00000355319.2; ENSG00000198894.8.
DR   GeneID; 85457; -.
DR   KEGG; hsa:85457; -.
DR   MANE-Select; ENST00000361786.7; ENSP00000355319.2; NM_033426.3; NP_219494.2.
DR   UCSC; uc001xtd.4; human.
DR   CTD; 85457; -.
DR   GeneCards; CIPC; -.
DR   HGNC; HGNC:20365; CIPC.
DR   HPA; ENSG00000198894; Tissue enhanced (skeletal).
DR   MIM; 616995; gene.
DR   neXtProt; NX_Q9C0C6; -.
DR   OpenTargets; ENSG00000198894; -.
DR   PharmGKB; PA134877961; -.
DR   VEuPathDB; HostDB:ENSG00000198894; -.
DR   eggNOG; ENOG502RJ2N; Eukaryota.
DR   GeneTree; ENSGT00510000048522; -.
DR   HOGENOM; CLU_056483_0_0_1; -.
DR   InParanoid; Q9C0C6; -.
DR   OMA; PHPVGKK; -.
DR   OrthoDB; 1183035at2759; -.
DR   PhylomeDB; Q9C0C6; -.
DR   TreeFam; TF332579; -.
DR   PathwayCommons; Q9C0C6; -.
DR   SignaLink; Q9C0C6; -.
DR   BioGRID-ORCS; 85457; 12 hits in 1081 CRISPR screens.
DR   ChiTaRS; CIPC; human.
DR   GenomeRNAi; 85457; -.
DR   Pharos; Q9C0C6; Tdark.
DR   PRO; PR:Q9C0C6; -.
DR   Proteomes; UP000005640; Chromosome 14.
DR   RNAct; Q9C0C6; protein.
DR   Bgee; ENSG00000198894; Expressed in skeletal muscle tissue of rectus abdominis and 190 other tissues.
DR   ExpressionAtlas; Q9C0C6; baseline and differential.
DR   Genevisible; Q9C0C6; HS.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0005730; C:nucleolus; IDA:HPA.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0042754; P:negative regulation of circadian rhythm; ISS:UniProtKB.
DR   GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR   GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR   InterPro; IPR031602; CIPC.
DR   PANTHER; PTHR34648; PTHR34648; 1.
DR   Pfam; PF15800; CiPC; 1.
PE   1: Evidence at protein level;
KW   Biological rhythms; Coiled coil; Cytoplasm; Nucleus; Phosphoprotein;
KW   Reference proteome; Repressor; Transcription; Transcription regulation.
FT   CHAIN           1..399
FT                   /note="CLOCK-interacting pacemaker"
FT                   /id="PRO_0000256133"
FT   REGION          1..85
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          162..224
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          378..399
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          333..359
FT                   /evidence="ECO:0000255"
FT   MOTIF           186..187
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000305|PubMed:26657846"
FT   COMPBIAS        1..24
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        45..60
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        192..210
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         213
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   VARIANT         31
FT                   /note="L -> F (in dbSNP:rs11552006)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_028881"
FT   VARIANT         203
FT                   /note="T -> A (in dbSNP:rs759593)"
FT                   /id="VAR_049526"
FT   MUTAGEN         186
FT                   /note="K->A: Loss of predominant localization in the
FT                   nucleus; when associated with A-187. No effect on CAD- AND
FT                   HSPA5-binding; when associated with A-187."
FT                   /evidence="ECO:0000269|PubMed:26657846"
FT   MUTAGEN         187
FT                   /note="K->A: Loss of predominant localization in the
FT                   nucleus; when associated with A-186. No effect on CAD- AND
FT                   HSPA5-binding; when associated with A-186."
FT                   /evidence="ECO:0000269|PubMed:26657846"
SQ   SEQUENCE   399 AA;  42692 MW;  A02AE8F6543781D9 CRC64;
     MERKNPSRES PRRLSAKVGK GTEMKKVARQ LGMAAAESDK DSGFSDGSSE CLSSAEQMES
     EDMLSALGWS REDRPRQNSK TAKNAFPTLS PMVVMKNVLV KQGSSSSQLQ SWTVQPSFEV
     ISAQPQLLFL HPPVPSPVSP CHTGEKKSDS RNYLPILNSY TKIAPHPGKR GLSLGPEEKG
     TSGVQKKICT ERLGPSLSSS EPTKAGAVPS SPSTPAPPSA KLAEDSALQG VPSLVAGGSP
     QTLQPVSSSH VAKAPSLTFA SPASPVCASD STLHGLESNS PLSPLSANYS SPLWAAEHLC
     RSPDIFSEQR QSKHRRFQNT LVVLHKSGLL EITLKTKELI RQNQATQVEL DQLKEQTQLF
     IEATKSRAPQ AWAKLQASLT PGSSNTGSDL EAFSDHPAI
 
 
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