ID CLOCK_SPAJD Reviewed; 865 AA. AC Q91YA8; DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2001, sequence version 1. DT 16-JUN-2009, entry version 47. DE RecName: Full=Circadian locomoter output cycles protein kaput; DE EC=2.3.1.48; GN Name=Clock; OS Spalax judaei (Blind subterranean mole rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Spalacidae; Spalacinae; Spalax. OX NCBI_TaxID=134510; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Brain; RX PubMed=11707566; DOI=10.1073/pnas.181484498; RA Avivi A., Albrecht U., Oster H., Joel A., Beiles A., Nevo E.; RT "Biological clock in total darkness: the Clock/MOP3 circadian system RT of the blind subterranean mole rat."; RL Proc. Natl. Acad. Sci. U.S.A. 98:13751-13756(2001). CC -!- FUNCTION: ARNTL/2-CLOCK heterodimers activate E-box element (3'- CC CACGTG-5') transcription of a number of proteins of the circadian CC clock. Activates transcription of PER1 and PER2. This CC transcription is inhibited in a feedback loop by PER and CRY CC proteins. Has intrinsic histone acetyltransferase activity and CC this enzymatic function contributes to chromatin-remodeling events CC implicated in circadian control of gene expression. Acetylates CC primarily histones H3 and H4. Acetylates also a non-histone CC substrate: ARNTL (By similarity). CC -!- CATALYTIC ACTIVITY: Acetyl-CoA + histone = CoA + acetylhistone. CC -!- SUBUNIT: Component of the circadian clock oscillator which CC includes the CRY proteins, CLOCK or NPAS2, ARNTL or ARNTL2, CSNK1D CC and/or CSNK1E, TIMELESS and the PER proteins. Efficient DNA CC binding requires dimerization with another bHLH protein. CC Heterodimerization with ARNTL is required for E-box-dependent CC transactivation, for CLOCK nuclear translocation and degradation, CC and, for phosphorylation of both CLOCK and ARNTL. Interaction with CC PER and CRY proteins requires translocation to the nucleus. CC Interaction of the CLOCK-ARNTL heterodimer with PER or CRY CC inhibits transcription activation. Binds weakly ARNTL and ARNTL2 CC to form heterodimers which bind poorly to the E-box motif (By CC similarity). CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By CC similarity). Note=Shuffling between the cytoplasm and the nucleus CC is under circadian regulation and is ARNTL-dependent (By CC similarity). CC -!- PTM: Phosphorylation is dependent on CLOCK-ARNTL heterodimer CC formation (By similarity). CC -!- SIMILARITY: Contains 1 basic helix-loop-helix (bHLH) domain. CC -!- SIMILARITY: Contains 1 PAC (PAS-associated C-terminal) domain. CC -!- SIMILARITY: Contains 2 PAS (PER-ARNT-SIM) domains. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AJ318059; CAC85405.1; -; mRNA. DR HSSP; Q99814; 1P97. DR HOVERGEN; Q91YA8; -. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0004402; F:histone acetyltransferase activity; IEA:EC. DR GO; GO:0004871; F:signal transducer activity; IEA:InterPro. DR GO; GO:0003700; F:transcription factor activity; IEA:InterPro. DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW. DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW. DR GO; GO:0007165; P:signal transduction; IEA:InterPro. DR GO; GO:0006350; P:transcription; IEA:UniProtKB-KW. DR InterPro; IPR001092; HLH_basic. DR InterPro; IPR011598; HLH_DNA_bd. DR InterPro; IPR001067; Nuc_translocat. DR InterPro; IPR001610; PAC. DR InterPro; IPR000014; PAS. DR InterPro; IPR013767; PAS_fold. DR InterPro; IPR013655; PAS_fold_3. DR Gene3D; G3DSA:4.10.280.10; HLH_DNA_bd; 1. DR Pfam; PF00010; HLH; 1. DR Pfam; PF00989; PAS; 1. DR Pfam; PF08447; PAS_3; 1. DR PRINTS; PR00785; NCTRNSLOCATR. DR SMART; SM00353; HLH; 1. DR SMART; SM00086; PAC; 1. DR SMART; SM00091; PAS; 2. DR PROSITE; PS50888; HLH; 1. DR PROSITE; PS50113; PAC; FALSE_NEG. DR PROSITE; PS50112; PAS; 2. PE 2: Evidence at transcript level; KW Activator; Biological rhythms; Cytoplasm; DNA-binding; Nucleus; KW Phosphoprotein; Repeat; Transcription; Transcription regulation; KW Transferase. FT CHAIN 1 865 Circadian locomoter output cycles protein FT kaput. FT /FTId=PRO_0000262641. FT DOMAIN 48 85 Helix-loop-helix motif. FT DOMAIN 107 177 PAS 1. FT DOMAIN 262 332 PAS 2. FT DOMAIN 336 379 PAC. FT DNA_BIND 35 47 Basic motif. FT REGION 514 564 Implicated in the circadian rhythmicity FT (By similarity). FT COMPBIAS 483 847 Gln-rich. FT MOD_RES 408 408 Phosphoserine (By similarity). SQ SEQUENCE 865 AA; 97421 MW; B85AB1B359A5750B CRC64; MLFTVSCSKM SSIVDRDDSS IFDGLVEEDD KNKAKRVSRN KSEKKRRDQF NVLIKELGSM LPGNAREMDK STVLQKSIDF LRKHKEITAQ SDASEIRQDW KPTFLSNEEF TQLMLEALDG FFLAIMTDGS IIYVSESVTS LLEHLPSDLV DQSVFNFIPE GEHSEVYKIL STHLLESDSL TPEYLKSKNQ LEFCCHMLRG TIDPKEPSTY EYMRFIGNFK SLNSVPTSAH NGFEGTIQRT HRLSYEDRVC SVATVRLATP QFIKEMCTVE EPNEEFTSRH SLEWKFLFLD HRAPPIIGYL PFEVLGTSGY DYYHVDDLEN LAKCHEHLMQ YGKGKSCYYR FLTKGQQWIW LQTHYYITYH QWNSRPEFIV CTHTVVSYAE VRAERRRELG IEESLPDATA DKGQDSGSDN RINTVSLKEA LERFDHSPTP SASSRSSRKS SHTAVSDPSS TPTKIPTDTS TPPRQHLPAH EKMAQRRSSF SSQSMNSQSV GPSLTQPVIS QAANLPVPQG MSQFQFSAQL GAMQHLKDQL EQRTRMIEAN IHRQQEELRK IQEQLQMVHG QGLQMFLQQS NPGLNFGSVQ LSSGNSSNIQ QLTPINMQGQ VVPTNQIQSG MNAGHIGTSQ HLIQQQSLQS TSTQQSQQSV MSGHSQQTSL ASQTQSTLTA PLYNTMVISQ PAPGSMVQIP SSMPQNSTQS ATVTTFTQDR QIRFSQGQQL VTKLVTAPVA CGAVMVPSTM LMGQVVTAYP TFATQQQQAQ TLSVTQQQPQ QQQPQQQQPQ QQQPQQQQQS SQEQQLPSVP QPSQAQLTQS PQQFLQTSRL LHGNPSTQLI LSAAFPLQQS TFPPSHHQQH QSQQQQQLSR HRTDSLTDPS KVQPQ //