ID CLOCK_RAT Reviewed; 862 AA.
AC Q9WVS9; Q920Y1;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 08-NOV-2023, entry version 159.
DE RecName: Full=Circadian locomoter output cycles protein kaput;
DE Short=rCLOCK;
DE EC=2.3.1.48;
GN Name=Clock;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, AND
RP INDUCTION.
RC TISSUE=Brain;
RX PubMed=10095082; DOI=10.1016/s0169-328x(99)00031-5;
RA Abe H., Honma S., Namihira M., Tanahashi Y., Ikeda M., Yu W., Honma K.;
RT "Phase-dependent induction by light of rat Clock gene expression in the
RT suprachiasmatic nucleus.";
RL Brain Res. Mol. Brain Res. 66:104-110(1999).
CC -!- FUNCTION: Transcriptional activator which forms a core component of the
CC circadian clock. The circadian clock, an internal time-keeping system,
CC regulates various physiological processes through the generation of
CC approximately 24 hour circadian rhythms in gene expression, which are
CC translated into rhythms in metabolism and behavior. It is derived from
CC the Latin roots 'circa' (about) and 'diem' (day) and acts as an
CC important regulator of a wide array of physiological functions
CC including metabolism, sleep, body temperature, blood pressure,
CC endocrine, immune, cardiovascular, and renal function. Consists of two
CC major components: the central clock, residing in the suprachiasmatic
CC nucleus (SCN) of the brain, and the peripheral clocks that are present
CC in nearly every tissue and organ system. Both the central and
CC peripheral clocks can be reset by environmental cues, also known as
CC Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the
CC central clock is light, which is sensed by retina and signals directly
CC to the SCN. The central clock entrains the peripheral clocks through
CC neuronal and hormonal signals, body temperature and feeding-related
CC cues, aligning all clocks with the external light/dark cycle. Circadian
CC rhythms allow an organism to achieve temporal homeostasis with its
CC environment at the molecular level by regulating gene expression to
CC create a peak of protein expression once every 24 hours to control when
CC a particular physiological process is most active with respect to the
CC solar day. Transcription and translation of core clock components
CC (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a
CC critical role in rhythm generation, whereas delays imposed by post-
CC translational modifications (PTMs) are important for determining the
CC period (tau) of the rhythms (tau refers to the period of a rhythm and
CC is the length, in time, of one complete cycle). A diurnal rhythm is
CC synchronized with the day/night cycle, while the ultradian and
CC infradian rhythms have a period shorter and longer than 24 hours,
CC respectively. Disruptions in the circadian rhythms contribute to the
CC pathology of cardiovascular diseases, cancer, metabolic syndromes and
CC aging. A transcription/translation feedback loop (TTFL) forms the core
CC of the molecular circadian clock mechanism. Transcription factors,
CC CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the
CC feedback loop, act in the form of a heterodimer and activate the
CC transcription of core clock genes and clock-controlled genes (involved
CC in key metabolic processes), harboring E-box elements (5'-CACGTG-3')
CC within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which
CC are transcriptional repressors form the negative limb of the feedback
CC loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer
CC inhibiting its activity and thereby negatively regulating their own
CC expression. This heterodimer also activates nuclear receptors NR1D1/2
CC and RORA/B/G, which form a second feedback loop and which activate and
CC repress BMAL1 transcription, respectively. Regulates the circadian
CC expression of ICAM1, VCAM1, CCL2, THPO and MPL and also acts as an
CC enhancer of the transactivation potential of NF-kappaB. Plays an
CC important role in the homeostatic regulation of sleep. The CLOCK-BMAL1
CC heterodimer regulates the circadian expression of SERPINE1/PAI1, VWF,
CC B3, CCRN4L/NOC, NAMPT, DBP, MYOD1, PPARGC1A, PPARGC1B, SIRT1, GYS2, F7,
CC NGFR, GNRHR, BHLHE40/DEC1, ATF4, MTA1, KLF10 and also genes implicated
CC in glucose and lipid metabolism. Promotes rhythmic chromatin opening,
CC regulating the DNA accessibility of other transcription factors. The
CC CLOCK-BMAL2 heterodimer activates the transcription of SERPINE1/PAI1
CC and BHLHE40/DEC1. The preferred binding motif for the CLOCK-BMAL1
CC heterodimer is 5'-CACGTGA-3', which contains a flanking adenine
CC nucleotide at the 3-prime end of the canonical 6-nucleotide E-box
CC sequence. CLOCK specifically binds to the half-site 5'-CAC-3', while
CC BMAL1 binds to the half-site 5'-GTGA-3'. The CLOCK-BMAL1 heterodimer
CC also recognizes the non-canonical E-box motifs 5'-AACGTGA-3' and 5'-
CC CATGTGA-3'. CLOCK has an intrinsic acetyltransferase activity, which
CC enables circadian chromatin remodeling by acetylating histones and
CC nonhistone proteins, including its own partner BMAL1. Represses
CC glucocorticoid receptor NR3C1/GR-induced transcriptional activity by
CC reducing the association of NR3C1/GR to glucocorticoid response
CC elements (GREs) via the acetylation of multiple lysine residues located
CC in its hinge region. The acetyltransferase activity of CLOCK is as
CC important as its transcription activity in circadian control.
CC Acetylates metabolic enzymes IMPDH2 and NDUFA9 in a circadian manner.
CC Facilitated by BMAL1, rhythmically interacts and acetylates
CC argininosuccinate synthase 1 (ASS1) leading to enzymatic inhibition of
CC ASS1 as well as the circadian oscillation of arginine biosynthesis and
CC subsequent ureagenesis (By similarity). Drives the circadian rhythm of
CC blood pressure through transcriptional activation of ATP1B1 (By
CC similarity). {ECO:0000250|UniProtKB:O08785,
CC ECO:0000250|UniProtKB:O15516}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + L-lysyl-[protein] = CoA + H(+) + N(6)-acetyl-L-
CC lysyl-[protein]; Xref=Rhea:RHEA:45948, Rhea:RHEA-COMP:9752,
CC Rhea:RHEA-COMP:10731, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:61930; EC=2.3.1.48;
CC -!- SUBUNIT: Component of the circadian clock oscillator which includes the
CC CRY proteins, CLOCK or NPAS2, BMAL1 or BMAL2, CSNK1D and/or CSNK1E,
CC TIMELESS and the PER proteins (By similarity). Forms a heterodimer with
CC BMAL1 (By similarity). The CLOCK-BMAL1 heterodimer is required for E-
CC box-dependent transactivation, for CLOCK nuclear translocation and
CC degradation, and for phosphorylation of both CLOCK and BMAL1 (By
CC similarity). Interacts with NR3C1 in a ligand-dependent fashion (By
CC similarity). Interacts with ESR1 and estrogen stimulates this
CC interaction (By similarity). Interacts with the complex p35/CDK5 (By
CC similarity). Interacts with RELA/p65 (By similarity). Interacts with
CC KAT2B, CREBBP and EP300 (By similarity). Interacts with ID1 and ID3 (By
CC similarity). Interacts with ID2 (By similarity). Interacts with MTA1
CC (By similarity). Interacts with OGA (By similarity). Interacts with
CC SIRT1 (By similarity). Interacts with CIPC (By similarity). Interacts
CC with EZH2 (By similarity). Interacts with EIF4E, PIWIL1 and DDX4 (By
CC similarity). Interacts with PER1, PER2, CRY1 and CRY2 and this
CC interaction requires a translocation to the nucleus (By similarity).
CC Interaction of the CLOCK-BMAL1 heterodimer with PER or CRY inhibits
CC transcription activation (By similarity). Interaction of the CLOCK-
CC BMAL1 with CRY1 is independent of DNA but with PER2 is off DNA (By
CC similarity). The CLOCK-BMAL1 heterodimer interacts with GSK3B (By
CC similarity). Interacts with KDM5A (By similarity). Interacts with
CC KMT2A; in a circadian manner (By similarity). Interacts with MYBBP1A
CC (By similarity). Interacts with THRAP3 (By similarity). Interacts with
CC MED1; this interaction requires the presence of THRAP3 (By similarity).
CC Interacts with NCOA2 (By similarity). The CLOCK-BMAL1 heterodimer
CC interacts with PASD1. Interacts with ASS1 and IMPDH2; in a circadian
CC manner. Interacts with NDUFA9 (By similarity). Interacts with PIWIL2
CC (via PIWI domain) (By similarity). Interacts with HNF4A (By
CC similarity). {ECO:0000250|UniProtKB:O08785,
CC ECO:0000250|UniProtKB:O15516}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O08785}. Nucleus
CC {ECO:0000255|PROSITE-ProRule:PRU00981}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:O15516}. Note=Localizes to sites of DNA damage
CC in a H2AX-independent manner. Shuttling between the cytoplasm and the
CC nucleus is under circadian regulation and is BMAL1-dependent.
CC Phosphorylated form located in the nucleus while the nonphosphorylated
CC form found only in the cytoplasm. Sequestered to the cytoplasm in the
CC presence of ID2. {ECO:0000250|UniProtKB:O08785,
CC ECO:0000250|UniProtKB:O15516}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Long, Clock-L;
CC IsoId=Q9WVS9-1; Sequence=Displayed;
CC Name=2; Synonyms=Short, Clock-S;
CC IsoId=Q9WVS9-2; Sequence=VSP_021795;
CC -!- TISSUE SPECIFICITY: Expressed in the suprachiasmatic nucleus (SCN), and
CC in the piriform cortex (PC). {ECO:0000269|PubMed:10095082}.
CC -!- INDUCTION: Without light exposure, high levels at ZT6 and low levels at
CC ZT18 and ZT22. Light exposure increases levels in the SCN in phase
CC dependent manner. Levels increased significantly during the subjective
CC night (ZT10-20). In the piriform cortex, levels increased by light at
CC ZT14. {ECO:0000269|PubMed:10095082}.
CC -!- PTM: Ubiquitinated, leading to its proteasomal degradation.
CC {ECO:0000250|UniProtKB:O08785}.
CC -!- PTM: O-glycosylated; contains O-GlcNAc. O-glycosylation by OGT prevents
CC protein degradation by inhibiting ubiquitination. It also stabilizes
CC the CLOCK-BMAL1 heterodimer thereby increasing CLOCK-BMAL1-mediated
CC transcriptional activation of PER1/2/3 and CRY1/2.
CC {ECO:0000250|UniProtKB:O08785}.
CC -!- PTM: Phosphorylation is dependent on the CLOCK-BMAL1 heterodimer
CC formation. Phosphorylation enhances the transcriptional activity,
CC alters the subcellular localization and decreases the stability of the
CC heterodimer by promoting its degradation. Phosphorylation shows
CC circadian variations in the liver. May be phosphorylated by CSNK1D and
CC CKSN1E. {ECO:0000250|UniProtKB:O08785}.
CC -!- PTM: Sumoylation enhances its transcriptional activity and interaction
CC with ESR1, resulting in up-regulation of ESR1 activity. Estrogen
CC stimulates sumoylation. Desumoylation by SENP1 negatively regulates its
CC transcriptional activity. {ECO:0000250|UniProtKB:O08785}.
CC -!- PTM: Undergoes lysosome-mediated degradation in a time-dependent manner
CC in the liver. {ECO:0000250|UniProtKB:O08785}.
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DR EMBL; AB019258; BAA81819.1; -; mRNA.
DR EMBL; AB019259; BAB68768.1; -; mRNA.
DR RefSeq; NP_001276761.1; NM_001289832.1.
DR RefSeq; NP_068628.1; NM_021856.2.
DR AlphaFoldDB; Q9WVS9; -.
DR SMR; Q9WVS9; -.
DR STRING; 10116.ENSRNOP00000002976; -.
DR iPTMnet; Q9WVS9; -.
DR PhosphoSitePlus; Q9WVS9; -.
DR PaxDb; 10116-ENSRNOP00000002976; -.
DR PeptideAtlas; Q9WVS9; -.
DR GeneID; 60447; -.
DR KEGG; rno:60447; -.
DR UCSC; RGD:620271; rat. [Q9WVS9-1]
DR AGR; RGD:620271; -.
DR CTD; 9575; -.
DR RGD; 620271; Clock.
DR eggNOG; KOG3561; Eukaryota.
DR InParanoid; Q9WVS9; -.
DR OrthoDB; 2899615at2759; -.
DR PhylomeDB; Q9WVS9; -.
DR PRO; PR:Q9WVS9; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0033391; C:chromatoid body; ISS:UniProtKB.
DR GO; GO:0005694; C:chromosome; ISO:RGD.
DR GO; GO:1990513; C:CLOCK-BMAL transcription complex; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005726; C:perichromatin fibrils; IDA:RGD.
DR GO; GO:0005667; C:transcription regulator complex; ISS:UniProtKB.
DR GO; GO:0031490; F:chromatin DNA binding; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0070888; F:E-box binding; ISS:UniProtKB.
DR GO; GO:0004402; F:histone acetyltransferase activity; ISS:UniProtKB.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:RGD.
DR GO; GO:0071479; P:cellular response to ionizing radiation; ISO:RGD.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; IEP:RGD.
DR GO; GO:0000077; P:DNA damage checkpoint signaling; ISO:RGD.
DR GO; GO:0009649; P:entrainment of circadian clock; IEP:RGD.
DR GO; GO:0007565; P:female pregnancy; IEP:RGD.
DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISS:UniProtKB.
DR GO; GO:2000323; P:negative regulation of glucocorticoid receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0042753; P:positive regulation of circadian rhythm; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISO:RGD.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0006473; P:protein acetylation; ISS:UniProtKB.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of DNA-templated transcription; ISS:UniProtKB.
DR GO; GO:0042634; P:regulation of hair cycle; ISS:UniProtKB.
DR GO; GO:0050796; P:regulation of insulin secretion; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:2000074; P:regulation of type B pancreatic cell development; ISS:UniProtKB.
DR GO; GO:0009416; P:response to light stimulus; IEP:RGD.
DR GO; GO:0051775; P:response to redox state; ISS:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
DR CDD; cd19734; bHLH-PAS_CLOCK; 1.
DR CDD; cd00130; PAS; 2.
DR Gene3D; 4.10.280.10; Helix-loop-helix DNA-binding domain; 1.
DR Gene3D; 3.30.450.20; PAS domain; 2.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR047230; CLOCK-like.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR001067; Nuc_translocat.
DR InterPro; IPR001610; PAC.
DR InterPro; IPR000014; PAS.
DR InterPro; IPR035965; PAS-like_dom_sf.
DR InterPro; IPR013767; PAS_fold.
DR PANTHER; PTHR46055; CIRCADIAN LOCOMOTER OUTPUT CYCLES PROTEIN KAPUT; 1.
DR PANTHER; PTHR46055:SF2; CIRCADIAN LOCOMOTER OUTPUT CYCLES PROTEIN KAPUT; 1.
DR Pfam; PF00010; HLH; 1.
DR Pfam; PF00989; PAS; 1.
DR Pfam; PF14598; PAS_11; 1.
DR PRINTS; PR00785; NCTRNSLOCATR.
DR SMART; SM00353; HLH; 1.
DR SMART; SM00086; PAC; 1.
DR SMART; SM00091; PAS; 2.
DR SUPFAM; SSF47459; HLH, helix-loop-helix DNA-binding domain; 1.
DR SUPFAM; SSF55785; PYP-like sensor domain (PAS domain); 2.
DR PROSITE; PS50888; BHLH; 1.
DR PROSITE; PS50112; PAS; 2.
PE 2: Evidence at transcript level;
KW Activator; Alternative splicing; Biological rhythms; Cytoplasm; DNA damage;
KW DNA-binding; Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; Transcription; Transcription regulation; Transferase;
KW Ubl conjugation.
FT CHAIN 1..862
FT /note="Circadian locomoter output cycles protein kaput"
FT /id="PRO_0000262638"
FT DOMAIN 34..84
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 107..177
FT /note="PAS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 262..332
FT /note="PAS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 336..379
FT /note="PAC"
FT REGION 371..861
FT /note="Interaction with NR3C1"
FT /evidence="ECO:0000250|UniProtKB:O08785"
FT REGION 388..497
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 450..570
FT /note="Interaction with SIRT1"
FT /evidence="ECO:0000250|UniProtKB:O08785"
FT REGION 514..564
FT /note="Implicated in the circadian rhythmicity"
FT /evidence="ECO:0000250"
FT REGION 623..652
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 768..802
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 822..862
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 32..47
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:O08785"
FT COMPBIAS 400..415
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 427..457
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 474..497
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 822..840
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 39
FT /note="Interaction with E-box DNA"
FT /evidence="ECO:0000250|UniProtKB:O15516"
FT SITE 43
FT /note="Interaction with E-box DNA"
FT /evidence="ECO:0000250|UniProtKB:O15516"
FT SITE 47
FT /note="Interaction with E-box DNA"
FT /evidence="ECO:0000250|UniProtKB:O15516"
FT SITE 84
FT /note="Important for interaction with BMAL1"
FT /evidence="ECO:0000250|UniProtKB:O15516"
FT MOD_RES 38
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O08785"
FT MOD_RES 42
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O08785"
FT MOD_RES 408
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O08785"
FT MOD_RES 427
FT /note="Phosphoserine; by GSK3-beta"
FT /evidence="ECO:0000250|UniProtKB:O08785"
FT MOD_RES 431
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O08785"
FT MOD_RES 451
FT /note="Phosphothreonine; by CDK5"
FT /evidence="ECO:0000250|UniProtKB:O15516"
FT MOD_RES 461
FT /note="Phosphothreonine; by CDK5"
FT /evidence="ECO:0000250|UniProtKB:O15516"
FT CROSSLNK 67
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1)"
FT /evidence="ECO:0000250|UniProtKB:O08785"
FT CROSSLNK 858
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1)"
FT /evidence="ECO:0000250|UniProtKB:O08785"
FT VAR_SEQ 484..513
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10095082"
FT /id="VSP_021795"
SQ SEQUENCE 862 AA; 97004 MW; D031E4A3758907EC CRC64;
MLFTVSCSKM SSIVDRDDSS IFDGLVEEDD KDKAKRVSRN KSEKKRRDQF NVLIKELGSM
LPGNARKMDK STVLQKSIDF LRKHKEITAQ SDASEIRQDW KPTFLSNEEF TQLMLEALDG
FFLAIMTDGS IIYVSETVTS LLEHLPSDLV DQSIFNFIPE GEHSEVYKIL STHLLESDSL
TPEDLKSKNQ LEFCCHMLRG TIDPKEPSTY EYVRFIGNFK SLNSVSTSTH NGFEGTIQRT
HRPSYEDRVC FVATVRLATP QFIKEMCTVE EPNEEFTSRH SLEWKFLFLD HRAPPIIGYL
PFEVLGTSGY DYYHVDDLES LAKCHEHLMQ YGKGKSCYYR FLTKGQQWIW LQTHYYITYH
QWNSRPEFIV CTHTVVSYAE VRAERRRELG VEESLPETAA DKSQDSGSDN RINTVSLKEA
LERFDHSPTP SASSRSSRKS SHTAVSDPSS TPTKIPTDTS TPPRPHLPAH EKMTQRRSSF
SSQSINSQSV GSSLTQPAMS QAANLPIPQG MSQFQLSAQL GAMQHLKDQL EQRTRMIEAN
IHRQQEELRK IQEQLQMVHG QGLQMFLQQS NPGLNLGSVQ LSSGNSNIQQ LTPINMQGQV
VPVNQIQSGV NAGHVSTGQH MIQQQTLQST STQSQQSVMS GHSQPTSLPN QTPSTLTAPL
YNTMVISQPA AGSMVPIPSS MPQNSTQSAT VTTFTQDRQI RFSQGQQLVT KLVTAPVACG
AVMVPSTMLM GQVVTAYPTF ATQQQQAQAL SVTQQQQQQQ QQQQQQQQQQ PQQAQQPQSQ
QSSQDQPHPS VQQPAQLTQP PQQFLQTSRL LHGNPSTQLI LSAAFPLQQS TFPPSHHQQH
QQQQLHRHRT DSLTDPSKVQ PQ
//
