NPAS2_CHICK
ID NPAS2_CHICK Reviewed; 815 AA.
AC Q5ZQU2; Q9DG34;
DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 03-AUG-2022, entry version 106.
DE RecName: Full=Neuronal PAS domain-containing protein 2;
DE Short=Neuronal PAS2;
DE AltName: Full=Member of PAS protein 4;
DE Short=MOP4;
GN Name=NPAS2; Synonyms=MOP4;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Pineal gland;
RA Codd V., Chong N.W.;
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 359-469, TISSUE SPECIFICITY, AND INDUCTION.
RC STRAIN=White leghorn; TISSUE=Pineal gland;
RX PubMed=10931848; DOI=10.1074/jbc.m005671200;
RA Chong N.W., Bernard M., Klein D.C.;
RT "Characterization of the chicken serotonin N-acetyltransferase gene.
RT Activation via clock gene heterodimer/E box interaction.";
RL J. Biol. Chem. 275:32991-32998(2000).
RN [3]
RP FUNCTION, INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=20345751; DOI=10.1111/j.1471-4159.2010.06698.x;
RA Haque R., Ali F.G., Biscoglia R., Abey J., Weller J., Klein D.,
RA Iuvone P.M.;
RT "CLOCK and NPAS2 have overlapping roles in the circadian oscillation of
RT arylalkylamine N-acetyltransferase mRNA in chicken cone photoreceptors.";
RL J. Neurochem. 113:1296-1306(2010).
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, ARNTL/BMAL1, ARNTL2/BMAL2, PER1, PER2, PER3, CRY1 and
CC CRY2) plays a critical role in rhythm generation, whereas delays
CC imposed by post-translational modifications (PTMs) are important for
CC determining the period (tau) of the rhythms (tau refers to the period
CC of a rhythm and is the length, in time, of one complete cycle). A
CC diurnal rhythm is synchronized with the day/night cycle, while the
CC ultradian and infradian rhythms have a period shorter and longer than
CC 24 hours, respectively. Disruptions in the circadian rhythms contribute
CC to the pathology of cardiovascular diseases, cancer, metabolic
CC syndromes and aging. A transcription/translation feedback loop (TTFL)
CC forms the core of the molecular circadian clock mechanism.
CC Transcription factors, CLOCK or NPAS2 and ARNTL/BMAL1 or ARNTL2/BMAL2,
CC form the positive limb of the feedback loop, act in the form of a
CC heterodimer and activate the transcription of core clock genes and
CC clock-controlled genes (involved in key metabolic processes), harboring
CC E-box elements (5'-CACGTG-3') within their promoters. The core clock
CC genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form
CC the negative limb of the feedback loop and interact with the
CC CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/BMAL2 heterodimer inhibiting its
CC activity and thereby negatively regulating their own expression. This
CC heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G,
CC which form a second feedback loop and which activate and repress
CC ARNTL/BMAL1 transcription, respectively. NPAS2 positively regulates the
CC circadian expression of AANAT in the retinal photoreceptor cells.
CC {ECO:0000269|PubMed:20345751}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P97460};
CC -!- ACTIVITY REGULATION: Carbon monoxide (CO) and the redox state of the
CC cell can modulate the transcriptional activity of the NPAS2-ARNTL/BMAL1
CC heterodimer. NADH and NADPH enhance the DNA-binding activity of the
CC heterodimer whereas CO binds the heme group in NPAS2 and inhibits the
CC DNA-binding activity of the heterodimer.
CC {ECO:0000250|UniProtKB:P97460}.
CC -!- SUBUNIT: Component of the circadian clock oscillator which includes the
CC CRY proteins, CLOCK or NPAS2, ARNTL/BMAL1 or ARNTL2/BMAL2, CSNK1D
CC and/or CSNK1E, TIMELESS and the PER proteins. Efficient DNA binding
CC requires dimerization with another bHLH protein. Forms a heterodimer
CC with ARNTL/BMAL1 and this heterodimerization is required for E-box-
CC dependent transactivation. {ECO:0000250|UniProtKB:P97460}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981}.
CC -!- TISSUE SPECIFICITY: Expressed in the retinal photoreceptor cells (at
CC protein level). Expressed in the pineal gland and retina.
CC {ECO:0000269|PubMed:10931848, ECO:0000269|PubMed:20345751}.
CC -!- INDUCTION: Exhibits a circadian rhythm in the retina with peak levels
CC in early subjective night. No circadian rhythm pattern in the pineal
CC gland. {ECO:0000269|PubMed:10931848, ECO:0000269|PubMed:20345751}.
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DR EMBL; AF396828; AAU93340.1; -; mRNA.
DR EMBL; AF193071; AAG24647.1; -; mRNA.
DR RefSeq; NP_001025713.1; NM_001030542.2.
DR AlphaFoldDB; Q5ZQU2; -.
DR SMR; Q5ZQU2; -.
DR STRING; 9031.ENSGALP00000035797; -.
DR PaxDb; Q5ZQU2; -.
DR GeneID; 395433; -.
DR KEGG; gga:395433; -.
DR CTD; 4862; -.
DR VEuPathDB; HostDB:geneid_395433; -.
DR eggNOG; KOG3561; Eukaryota.
DR InParanoid; Q5ZQU2; -.
DR OrthoDB; 205871at2759; -.
DR PhylomeDB; Q5ZQU2; -.
DR PRO; PR:Q5ZQU2; -.
DR Proteomes; UP000000539; Unplaced.
DR GO; GO:1990513; C:CLOCK-BMAL transcription complex; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IEA:InterPro.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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; IDA:UniProtKB.
DR GO; GO:0032922; P:circadian regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0060548; P:negative regulation of cell death; ISS:UniProtKB.
DR GO; GO:0045739; P:positive regulation of DNA repair; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:2001020; P:regulation of response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0051775; P:response to redox state; ISS:UniProtKB.
DR CDD; cd00130; PAS; 2.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
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 Pfam; PF00010; HLH; 1.
DR Pfam; PF00989; PAS; 1.
DR PRINTS; PR00785; NCTRNSLOCATR.
DR SMART; SM00353; HLH; 1.
DR SMART; SM00086; PAC; 1.
DR SMART; SM00091; PAS; 2.
DR SUPFAM; SSF47459; SSF47459; 1.
DR SUPFAM; SSF55785; SSF55785; 2.
DR PROSITE; PS50888; BHLH; 1.
DR PROSITE; PS50112; PAS; 2.
PE 1: Evidence at protein level;
KW Activator; Biological rhythms; DNA-binding; Heme; Iron; Metal-binding;
KW Nucleus; Reference proteome; Repeat; Transcription;
KW Transcription regulation.
FT CHAIN 1..815
FT /note="Neuronal PAS domain-containing protein 2"
FT /id="PRO_0000273634"
FT DOMAIN 9..59
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 82..152
FT /note="PAS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 237..307
FT /note="PAS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 311..354
FT /note="PAC"
FT REGION 1..61
FT /note="Sufficient for heterodimer formation with
FT ARNTL/BMAL1, E-box binding and for the effect of NADPH"
FT /evidence="ECO:0000250|UniProtKB:P97460"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 405..467
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 584..656
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 728..815
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 584..643
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 119
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P97460"
FT BINDING 171
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P97460"
FT CONFLICT 359..369
FT /note="ERRQEMGLEEV -> GEETGDGLGRM (in Ref. 2; AAG24647)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 815 AA; 91178 MW; 40E3D4A518BFF90E CRC64;
MDEDEKDRAK RASRNKSEKK RRDQFNVLIK ELSSMLPGNT RKMDKTTVLE KVIGFLQKHN
EVSAQTEISE IQQDWKPSFL SNEEFTQLML EALDGFIIAV TTGGSIIYVS DSITPLLGHL
PCDVLDQNLL NFLPEQEHSE IYKMLSSCML MTDSASSDCL KTDNELEFYC HLLRGSLNPK
EFPTYEYIKF VGNFRSYSNV PNSTCNGFDE AVPRAYRASP GKQICFVATV RLATPQFLKE
MCIVEEPLEE FTSRHSLEWK FLFLDHRAPP IIGYLPFEVL GTSGYDYYHI DDLELLARCH
EHLMQFGKGK SCCYRFLTKG QQWIWLQTHY YITYHQWNSK PEFIVCTHMV VSYADVRVER
RQEMGLEEVS SEVVSSALKD SGSSLDPEQH FNALDIGASI LSASRTPSVS SRSSPKSSHT
PKSDPASTPT KLTAEASTPL QRTSSTQQDL SAHRLSQPTA LQASLPSQPS CELLPQQLLP
QATLQSQPAP LAQFSAQFSM FQTIKDQLEQ RTRILQANIR WQQEELQKIQ EQLCLVQDSS
VQMFLQQPAV SLSFSNIQQP EPQPLQQRPG VISQQQLVLS PQLPGQIASP QTPSQQVLRE
ASVISSQGPK AERSTELTTG SSRPTRSTAT LFGPSTSLSR RGPGPSSGPG ASAAGCSHDQ
QLRLLLSQPI QPMMPTSCNA RHPSDLSMAG SQAKYSQNQQ MFQSLEVQTS SSGSPIVLMG
QAVLNQGFAT TPPSQSSSLP PMQLQHQQHQ QQRYLQVQTP SSLHNEQTDS LLLSSYSPQQ
GNMGYHQTQQ QQQQQQLPRR SNSLSESSNL PQPLR
