NPAS4_RAT
ID NPAS4_RAT Reviewed; 802 AA.
AC Q8CJH6;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=Neuronal PAS domain-containing protein 4 {ECO:0000305};
DE Short=Neuronal PAS4 {ECO:0000305};
DE AltName: Full=HLH-PAS transcription factor NXF {ECO:0000303|PubMed:14701734};
GN Name=Npas4 {ECO:0000312|RGD:628866};
GN Synonyms=Nxf {ECO:0000303|PubMed:14701734};
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].
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=14701734; DOI=10.1128/mcb.24.2.608-616.2004;
RA Ooe N., Saito K., Mikami N., Nakatuka I., Kaneko H.;
RT "Identification of a novel basic helix-loop-helix-PAS factor, NXF, reveals
RT a Sim2 competitive, positive regulatory role in dendritic-cytoskeleton
RT modulator drebrin gene expression.";
RL Mol. Cell. Biol. 24:608-616(2004).
RN [2]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=18815592; DOI=10.1038/nature07319;
RA Lin Y., Bloodgood B.L., Hauser J.L., Lapan A.D., Koon A.C., Kim T.K.,
RA Hu L.S., Malik A.N., Greenberg M.E.;
RT "Activity-dependent regulation of inhibitory synapse development by
RT Npas4.";
RL Nature 455:1198-1204(2008).
RN [3]
RP FUNCTION.
RX PubMed=21887312; DOI=10.1371/journal.pone.0023760;
RA Ploski J.E., Monsey M.S., Nguyen T., DiLeone R.J., Schafe G.E.;
RT "The neuronal PAS domain protein 4 (Npas4) is required for new and
RT reactivated fear memories.";
RL PLoS ONE 6:E23760-E23760(2011).
CC -!- FUNCTION: Transcription factor expressed in neurons of the brain that
CC regulates the excitatory-inhibitory balance within neural circuits and
CC is required for contextual memory in the hippocampus (By similarity).
CC Plays a key role in the structural and functional plasticity of neurons
CC (By similarity). Acts as an early-response transcription factor in both
CC excitatory and inhibitory neurons, where it induces distinct but
CC overlapping sets of late-response genes in these two types of neurons,
CC allowing the synapses that form on inhibitory and excitatory neurons to
CC be modified by neuronal activity in a manner specific to their function
CC within a circuit, thereby facilitating appropriate circuit responses to
CC sensory experience (By similarity). In excitatory neurons, activates
CC transcription of BDNF, which in turn controls the number of GABA-
CC releasing synapses that form on excitatory neurons, thereby promoting
CC an increased number of inhibitory synapses on excitatory neurons (By
CC similarity). In inhibitory neurons, regulates a distinct set of target
CC genes that serve to increase excitatory input onto somatostatin
CC neurons, probably resulting in enhanced feedback inhibition within
CC cortical circuits (By similarity). The excitatory and inhibitory
CC balance in neurons affects a number of processes, such as short-term
CC and long-term memory, acquisition of experience, fear memory, response
CC to stress and social behavior (PubMed:21887312). Acts as a regulator of
CC dendritic spine development in olfactory bulb granule cells in a
CC sensory-experience-dependent manner by regulating expression of MDM2
CC (By similarity). Efficient DNA binding requires dimerization with
CC another bHLH protein, such as ARNT, ARNT2 or BMAL1 (By similarity). Can
CC activate the CME (CNS midline enhancer) element (By similarity).
CC {ECO:0000250|UniProtKB:Q8BGD7, ECO:0000269|PubMed:21887312}.
CC -!- SUBUNIT: Efficient DNA binding requires dimerization with another bHLH
CC protein. Heterodimer; forms a heterodimer with ARNT, ARNT2 or BMAL1.
CC {ECO:0000250|UniProtKB:Q8BGD7}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q8BGD7,
CC ECO:0000255|PROSITE-ProRule:PRU00981}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in neurons
CC (PubMed:18815592). Expressed in the lateral nucleus of the amygdala (at
CC protein level) (PubMed:21887312). {ECO:0000269|PubMed:18815592,
CC ECO:0000269|PubMed:21887312}.
CC -!- INDUCTION: Expression is regulated by neuronal activity
CC (PubMed:18815592). Induced in excitatory neurons specifically upon
CC calcium influx (PubMed:18815592). Induced in the lateral nucleus of the
CC amygdala in a learning-dependent manner (at protein level)
CC (PubMed:21887312). {ECO:0000269|PubMed:18815592,
CC ECO:0000269|PubMed:21887312}.
CC -!- PTM: Ubiquitinated, leading to degradation by the proteosome.
CC {ECO:0000250|UniProtKB:Q8BGD7}.
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DR EMBL; AB050103; BAC19832.1; -; mRNA.
DR RefSeq; NP_705890.1; NM_153626.1.
DR RefSeq; XP_017444330.1; XM_017588841.1.
DR AlphaFoldDB; Q8CJH6; -.
DR SMR; Q8CJH6; -.
DR STRING; 10116.ENSRNOP00000027119; -.
DR PaxDb; Q8CJH6; -.
DR PRIDE; Q8CJH6; -.
DR ABCD; Q8CJH6; 3 sequenced antibodies.
DR Ensembl; ENSRNOT00000027119; ENSRNOP00000027119; ENSRNOG00000020009.
DR GeneID; 266734; -.
DR KEGG; rno:266734; -.
DR UCSC; RGD:628866; rat.
DR CTD; 266743; -.
DR RGD; 628866; Npas4.
DR eggNOG; ENOG502QRXX; Eukaryota.
DR GeneTree; ENSGT00530000064165; -.
DR HOGENOM; CLU_013890_0_0_1; -.
DR InParanoid; Q8CJH6; -.
DR OMA; KTYFTQE; -.
DR OrthoDB; 219290at2759; -.
DR PhylomeDB; Q8CJH6; -.
DR TreeFam; TF319684; -.
DR PRO; PR:Q8CJH6; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000020009; Expressed in frontal cortex and 6 other tissues.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0098794; C:postsynapse; IEA:GOC.
DR GO; GO:0005667; C:transcription regulator complex; ISO:RGD.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0071386; P:cellular response to corticosterone stimulus; ISO:RGD.
DR GO; GO:0060079; P:excitatory postsynaptic potential; ISS:UniProtKB.
DR GO; GO:0060080; P:inhibitory postsynaptic potential; ISS:UniProtKB.
DR GO; GO:1904862; P:inhibitory synapse assembly; ISS:UniProtKB.
DR GO; GO:0007612; P:learning; ISS:UniProtKB.
DR GO; GO:0007616; P:long-term memory; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0048167; P:regulation of synaptic plasticity; ISS:UniProtKB.
DR GO; GO:0032228; P:regulation of synaptic transmission, GABAergic; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0007614; P:short-term memory; ISS:UniProtKB.
DR GO; GO:0035176; P:social behavior; ISS:UniProtKB.
DR CDD; cd00130; PAS; 2.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR000014; PAS.
DR InterPro; IPR035965; PAS-like_dom_sf.
DR InterPro; IPR013655; PAS_fold_3.
DR Pfam; PF08447; PAS_3; 1.
DR SMART; SM00091; PAS; 2.
DR SUPFAM; SSF55785; SSF55785; 2.
DR PROSITE; PS50888; BHLH; 1.
DR PROSITE; PS50112; PAS; 2.
PE 1: Evidence at protein level;
KW Activator; Coiled coil; Differentiation; DNA-binding; Neurogenesis;
KW Nucleus; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..802
FT /note="Neuronal PAS domain-containing protein 4"
FT /id="PRO_0000248224"
FT DOMAIN 1..53
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 70..144
FT /note="PAS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 203..275
FT /note="PAS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 280..319
FT /note="PAC"
FT REGION 1..13
FT /note="Basic motif; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 14..53
FT /note="Helix-loop-helix motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 472..555
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 5..38
FT /evidence="ECO:0000255"
FT COILED 624..648
FT /evidence="ECO:0000255"
SQ SEQUENCE 802 AA; 87318 MW; 600AA9FBB6D11E25 CRC64;
MYRSTKGASK ARRDQINAEI RNLKELLPLA EADKVRLSYL HIMSLACIYT RKGVFFAGGT
PLAGPTGLLS AQELEDIVAA LPGFLLVFTA EGKLLYLSES VSEHLGHSMV DLVAQGDSIY
DIIDPADHLT VRQQLTMPSA LDADRLFRCR FNTSKSLRRQ SAGNKLVLIR GRFHAHPPGA
YWAGNPVFTA FCAPLEPRPR PGPGPGPGPG PASLFLAMFQ SRHAKDLALL DISESVLIYL
GFERSELLCK SWYGLLHPED LAHASSQHYR LLAENGDIQA EMVVRLQAKH GGWTWIYCML
YSDGPEGPIT ANNYPISDTE AWSLRQQLNS ENTQAAYVLG TPAVLPSFSE NVFSQEHCSN
PLFTPALGTP RSASFPRAPE LGVISTSEEL AQPSKELDFS YLPFPARPEP SLQADLSKDL
VCTPPYTPHQ PGGCAFLFSL HEPFQTHLPP PSSSLQEQLT PSTVTFSEQL TPSSATFPDP
LTSSLQGQLT ESSARSFEEQ LTPCTSTFPD QLLPSTATFP EPLGSPTHEQ LTPPSTAFQA
HLNSPSQTFP EQLSPNPTKT YFAQEGCSFL YEKLPPSPSS PGNGDCTLLA LAQLRGPLSV
DVPLVPEGLL TPEASPVKQS FFHYTEKEQN EIDRLIQQIS QLAQGMDRPF SAEAGTGGLE
PLGGLEPLNP NLSLSGAGPP VLSLDLKPWK CQELDFLVDP DNLFLEETPV EDIFMDLSTP
DPNGEWGSGD PEAEVPGGTL SPCNNLSPED HSFLEDLATY ETAFETGVST FPYEGFADEL
HQLQSQVQDS FHEDGSGGEP TF
