NPAS1_MOUSE
ID NPAS1_MOUSE Reviewed; 594 AA.
AC P97459;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Neuronal PAS domain-containing protein 1;
DE Short=Neuronal PAS1;
GN Name=Npas1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=9012850; DOI=10.1073/pnas.94.2.713;
RA Zhou Y.-D., Barnard M., Tian H., Li X., Ring H.Z., Francke U., Shelton J.,
RA Richardson J., Russell D.W., McKnight S.L.;
RT "Molecular characterization of two mammalian bHLH-PAS domain proteins
RT selectively expressed in the central nervous system.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:713-718(1997).
RN [2]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=15347806; DOI=10.1073/pnas.0405310101;
RA Erbel-Sieler C., Dudley C., Zhou Y., Wu X., Estill S.J., Han T.,
RA Diaz-Arrastia R., Brunskill E.W., Potter S.S., McKnight S.L.;
RT "Behavioral and regulatory abnormalities in mice deficient in the NPAS1 and
RT NPAS3 transcription factors.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:13648-13653(2004).
RN [3]
RP FUNCTION, AND INTERACTION WITH ARNT.
RX PubMed=15635607; DOI=10.1002/jnr.20365;
RA Ohsawa S., Hamada S., Kakinuma Y., Yagi T., Miura M.;
RT "Novel function of neuronal PAS domain protein 1 in erythropoietin
RT expression in neuronal cells.";
RL J. Neurosci. Res. 79:451-458(2005).
RN [4] {ECO:0007744|PDB:5SY5}
RP X-RAY CRYSTALLOGRAPHY (3.20 ANGSTROMS) OF 43-423 IN COMPLEX WITH ARNT,
RP MUTAGENESIS OF PHE-249; ARG-251; VAL-270 AND HIS-272, INTERACTION WITH
RP ARNT, AND FUNCTION.
RX PubMed=27782878; DOI=10.7554/elife.18790;
RA Wu D., Su X., Potluri N., Kim Y., Rastinejad F.;
RT "NPAS1-ARNT and NPAS3-ARNT crystal structures implicate the bHLH-PAS family
RT as multi-ligand binding transcription factors.";
RL Elife 5:0-0(2016).
CC -!- FUNCTION: May control regulatory pathways relevant to schizophrenia and
CC to psychotic illness. May play a role in late central nervous system
CC development by modulating EPO expression in response to cellular oxygen
CC level. Forms a heterodimer that binds core DNA sequence 5'-TACGTG-3'
CC within the hypoxia response element (HRE) leading to transcriptional
CC repression on its target gene TH (PubMed:27782878).
CC {ECO:0000269|PubMed:15347806, ECO:0000269|PubMed:15635607,
CC ECO:0000269|PubMed:27782878}.
CC -!- SUBUNIT: Efficient DNA binding requires dimerization with another bHLH
CC protein. Interacts with ARNT; forms a heterodimer that binds core DNA
CC sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE)
CC leading to a transcriptional repressor on its target gene TH.
CC {ECO:0000269|PubMed:15635607, ECO:0000269|PubMed:27782878}.
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- TISSUE SPECIFICITY: Expressed in brain in inhibitory interneurons. Also
CC found in spinal cord. {ECO:0000269|PubMed:15347806}.
CC -!- DEVELOPMENTAL STAGE: First detected between embryonic day 15 and day
CC 16.
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DR EMBL; U77967; AAB47247.1; -; mRNA.
DR CCDS; CCDS20850.1; -.
DR RefSeq; NP_032744.1; NM_008718.2.
DR RefSeq; XP_017177510.1; XM_017322021.1.
DR PDB; 5SY5; X-ray; 3.20 A; B/D/F=43-423.
DR PDBsum; 5SY5; -.
DR AlphaFoldDB; P97459; -.
DR SMR; P97459; -.
DR BioGRID; 201818; 1.
DR STRING; 10090.ENSMUSP00000002053; -.
DR PhosphoSitePlus; P97459; -.
DR PaxDb; P97459; -.
DR PRIDE; P97459; -.
DR ProteomicsDB; 253003; -.
DR Antibodypedia; 18161; 227 antibodies from 31 providers.
DR DNASU; 18142; -.
DR Ensembl; ENSMUST00000002053; ENSMUSP00000002053; ENSMUSG00000001988.
DR Ensembl; ENSMUST00000210748; ENSMUSP00000147412; ENSMUSG00000001988.
DR GeneID; 18142; -.
DR KEGG; mmu:18142; -.
DR UCSC; uc009fhv.2; mouse.
DR CTD; 4861; -.
DR MGI; MGI:109205; Npas1.
DR VEuPathDB; HostDB:ENSMUSG00000001988; -.
DR eggNOG; KOG3558; Eukaryota.
DR GeneTree; ENSGT00940000161295; -.
DR HOGENOM; CLU_010044_6_3_1; -.
DR InParanoid; P97459; -.
DR OMA; VCQTKNM; -.
DR OrthoDB; 922461at2759; -.
DR PhylomeDB; P97459; -.
DR TreeFam; TF317772; -.
DR BioGRID-ORCS; 18142; 3 hits in 75 CRISPR screens.
DR PRO; PR:P97459; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P97459; protein.
DR Bgee; ENSMUSG00000001988; Expressed in urethra and 57 other tissues.
DR ExpressionAtlas; P97459; baseline and differential.
DR Genevisible; P97459; MM.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0042711; P:maternal behavior; IGI:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0001964; P:startle response; IGI:MGI.
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; IPR000014; PAS.
DR InterPro; IPR035965; PAS-like_dom_sf.
DR InterPro; IPR013767; PAS_fold.
DR InterPro; IPR013655; PAS_fold_3.
DR Pfam; PF00010; HLH; 1.
DR Pfam; PF00989; PAS; 1.
DR Pfam; PF08447; PAS_3; 1.
DR SMART; SM00353; HLH; 1.
DR SMART; SM00091; PAS; 2.
DR SUPFAM; SSF47459; SSF47459; 1.
DR SUPFAM; SSF55785; SSF55785; 2.
DR TIGRFAMs; TIGR00229; sensory_box; 1.
DR PROSITE; PS50888; BHLH; 1.
DR PROSITE; PS50112; PAS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; DNA-binding; Nucleus; Reference proteome; Repeat;
KW Transcription; Transcription regulation.
FT CHAIN 1..594
FT /note="Neuronal PAS domain-containing protein 1"
FT /id="PRO_0000127405"
FT DOMAIN 45..98
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 135..205
FT /note="PAS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 294..360
FT /note="PAS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 366..409
FT /note="PAC"
FT REGION 206..237
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 427..498
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 208..229
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 450..491
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 249
FT /note="F->D: Destabilizes heterodimerization with ARNT.
FT Compromises the transcriptional repression activity of
FT heterodimer ARNT:NPAS1."
FT /evidence="ECO:0000269|PubMed:27782878"
FT MUTAGEN 251
FT /note="R->A: Destabilizes heterodimerization with ARNT.
FT Compromises the transcriptional repression activity of
FT heterodimer ARNT:NPAS1."
FT /evidence="ECO:0000269|PubMed:27782878"
FT MUTAGEN 270
FT /note="V->D: Destabilizes heterodimerization with ARNT.
FT Compromises the transcriptional repression activity of
FT heterodimer ARNT:NPAS1."
FT /evidence="ECO:0000269|PubMed:27782878"
FT MUTAGEN 272
FT /note="H->A: Destabilizes heterodimerization with ARNT.
FT Compromises the transcriptional repression activity of
FT heterodimer ARNT:NPAS1."
FT /evidence="ECO:0000269|PubMed:27782878"
FT HELIX 53..71
FT /evidence="ECO:0007829|PDB:5SY5"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:5SY5"
FT HELIX 76..79
FT /evidence="ECO:0007829|PDB:5SY5"
FT HELIX 84..102
FT /evidence="ECO:0007829|PDB:5SY5"
FT STRAND 103..106
FT /evidence="ECO:0007829|PDB:5SY5"
FT TURN 130..134
FT /evidence="ECO:0007829|PDB:5SY5"
FT HELIX 138..145
FT /evidence="ECO:0007829|PDB:5SY5"
FT STRAND 146..153
FT /evidence="ECO:0007829|PDB:5SY5"
FT STRAND 158..162
FT /evidence="ECO:0007829|PDB:5SY5"
FT HELIX 166..169
FT /evidence="ECO:0007829|PDB:5SY5"
FT HELIX 174..177
FT /evidence="ECO:0007829|PDB:5SY5"
FT HELIX 182..184
FT /evidence="ECO:0007829|PDB:5SY5"
FT HELIX 191..198
FT /evidence="ECO:0007829|PDB:5SY5"
FT STRAND 245..253
FT /evidence="ECO:0007829|PDB:5SY5"
FT STRAND 268..276
FT /evidence="ECO:0007829|PDB:5SY5"
FT STRAND 285..290
FT /evidence="ECO:0007829|PDB:5SY5"
FT STRAND 305..310
FT /evidence="ECO:0007829|PDB:5SY5"
FT STRAND 315..319
FT /evidence="ECO:0007829|PDB:5SY5"
FT HELIX 321..325
FT /evidence="ECO:0007829|PDB:5SY5"
FT HELIX 331..334
FT /evidence="ECO:0007829|PDB:5SY5"
FT HELIX 339..342
FT /evidence="ECO:0007829|PDB:5SY5"
FT TURN 345..347
FT /evidence="ECO:0007829|PDB:5SY5"
FT HELIX 348..361
FT /evidence="ECO:0007829|PDB:5SY5"
FT STRAND 362..365
FT /evidence="ECO:0007829|PDB:5SY5"
FT STRAND 368..372
FT /evidence="ECO:0007829|PDB:5SY5"
FT STRAND 374..376
FT /evidence="ECO:0007829|PDB:5SY5"
FT STRAND 378..387
FT /evidence="ECO:0007829|PDB:5SY5"
FT STRAND 399..405
FT /evidence="ECO:0007829|PDB:5SY5"
SQ SEQUENCE 594 AA; 63737 MW; D6477696DF69A4B3 CRC64;
MATPYPRSGG RGEVKCGGGR GAGVPWDFLP GLMVKAPPGP CLQAQRKEKS RNAARWRRGK
ENLEFFELAK LLPLPGAISS QLDKASIVRL SVTYLRLRRF AALGAPPWGL RAVGPPAGLA
PGRRGPVALV SEVFEQHLGG HILQSLDGFV FALNQEGKFL YISETVSIYL GLSQVELTGS
SVFDYIHPGD HSEVLEQLGL RAASIGPPTP PSVSSSSSSS SSSLVDTPEI EASPTEASPA
FRAQERSFFV RMKSTLTKRG LNVKASGYKV IHVTGRLRAR ALGLVALGHT LPPAPLAELP
LHGHMIVFRL SLGLTILACE SRVSDHMDMG PSELVGRSCY QFVHGQDATR IRQSHLDLLD
KGQVVTGYYR WLQRAGGFVW LQSVATVAGN GKSTGEHHVL WVSHVLSNAE GSQTPLDAFQ
LPAIVSQEEP SRPGPEPTEE EPPVDGKQAV PADQDKDKDP QARGKRIKVE ASPKEARGSE
DSGEEELSDP PAPPRPEFTS VIRAGALKHD PVLPWGLTTP GDPSPALLHA GFLPPVVRGL
CTPGTIRYGP AELSLMYPHL HRLGAGPSLP EAFYPTLGLP YPGPTGTRVQ RKGD
