NPAS1_HUMAN
ID NPAS1_HUMAN Reviewed; 590 AA.
AC Q99742; B4DR69; Q99632; Q9BY83;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 2.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Neuronal PAS domain-containing protein 1;
DE Short=Neuronal PAS1;
DE AltName: Full=Basic-helix-loop-helix-PAS protein MOP5;
DE AltName: Full=Class E basic helix-loop-helix protein 11;
DE Short=bHLHe11;
DE AltName: Full=Member of PAS protein 5;
DE AltName: Full=PAS domain-containing protein 5;
GN Name=NPAS1; Synonyms=BHLHE11, MOP5, PASD5;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Fetal brain;
RA Ohe N., Saito K., Kaneko H.;
RT "The sequence variation of human neuronal PAS domain protein 1 (NPAS1).";
RL Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 110-590 (ISOFORM 1).
RC TISSUE=Hepatoma;
RX PubMed=9079689; DOI=10.1074/jbc.272.13.8581;
RA Hogenesch J.B., Chan W.K., Jackiw V.H., Brown R.C., Gu Y.-Z.,
RA Pray-Grant M., Perdew G.H., Bradfield C.A.;
RT "Characterization of a subset of the basic-helix-loop-helix-PAS superfamily
RT that interacts with components of the dioxin signaling pathway.";
RL J. Biol. Chem. 272:8581-8593(1997).
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 (By similarity). Forms a heterodimer that binds core DNA sequence
CC 5'-TACGTG-3' within the hypoxia response element (HRE) leading to
CC transcriptional repression on its target gene TH (By similarity).
CC {ECO:0000250, ECO:0000250|UniProtKB:P97459}.
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 (By
CC similarity). {ECO:0000250, ECO:0000250|UniProtKB:P97459}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q99742-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q99742-2; Sequence=VSP_054280, VSP_054281, VSP_054282;
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DR EMBL; U77968; AAB47248.1; -; mRNA.
DR EMBL; AB054002; BAB21098.1; -; mRNA.
DR EMBL; AK299128; BAG61181.1; -; mRNA.
DR EMBL; AC008755; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC039016; AAH39016.1; -; mRNA.
DR EMBL; U51628; AAC51214.1; -; mRNA.
DR CCDS; CCDS12694.1; -. [Q99742-1]
DR CCDS; CCDS82371.1; -. [Q99742-2]
DR RefSeq; NP_001308015.1; NM_001321086.1. [Q99742-2]
DR RefSeq; NP_002508.2; NM_002517.3. [Q99742-1]
DR AlphaFoldDB; Q99742; -.
DR SMR; Q99742; -.
DR BioGRID; 110922; 290.
DR IntAct; Q99742; 15.
DR STRING; 9606.ENSP00000469142; -.
DR iPTMnet; Q99742; -.
DR PhosphoSitePlus; Q99742; -.
DR BioMuta; NPAS1; -.
DR DMDM; 59803108; -.
DR MassIVE; Q99742; -.
DR PaxDb; Q99742; -.
DR PeptideAtlas; Q99742; -.
DR PRIDE; Q99742; -.
DR ProteomicsDB; 78453; -. [Q99742-1]
DR Antibodypedia; 18161; 227 antibodies from 31 providers.
DR DNASU; 4861; -.
DR Ensembl; ENST00000439365.6; ENSP00000398689.2; ENSG00000130751.10. [Q99742-2]
DR Ensembl; ENST00000449844.6; ENSP00000405290.1; ENSG00000130751.10. [Q99742-1]
DR Ensembl; ENST00000602212.6; ENSP00000469142.1; ENSG00000130751.10. [Q99742-1]
DR GeneID; 4861; -.
DR KEGG; hsa:4861; -.
DR MANE-Select; ENST00000602212.6; ENSP00000469142.1; NM_002517.4; NP_002508.2.
DR UCSC; uc002pfw.4; human. [Q99742-1]
DR CTD; 4861; -.
DR DisGeNET; 4861; -.
DR GeneCards; NPAS1; -.
DR HGNC; HGNC:7894; NPAS1.
DR HPA; ENSG00000130751; Tissue enhanced (brain, skin).
DR MIM; 603346; gene.
DR neXtProt; NX_Q99742; -.
DR OpenTargets; ENSG00000130751; -.
DR PharmGKB; PA31695; -.
DR VEuPathDB; HostDB:ENSG00000130751; -.
DR eggNOG; KOG3558; Eukaryota.
DR GeneTree; ENSGT00940000161295; -.
DR HOGENOM; CLU_010044_6_3_1; -.
DR InParanoid; Q99742; -.
DR OMA; VCQTKNM; -.
DR OrthoDB; 922461at2759; -.
DR PhylomeDB; Q99742; -.
DR TreeFam; TF317772; -.
DR PathwayCommons; Q99742; -.
DR SignaLink; Q99742; -.
DR SIGNOR; Q99742; -.
DR BioGRID-ORCS; 4861; 18 hits in 1091 CRISPR screens.
DR ChiTaRS; NPAS1; human.
DR GenomeRNAi; 4861; -.
DR Pharos; Q99742; Tbio.
DR PRO; PR:Q99742; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q99742; protein.
DR Bgee; ENSG00000130751; Expressed in right frontal lobe and 119 other tissues.
DR ExpressionAtlas; Q99742; baseline and differential.
DR Genevisible; Q99742; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; TAS:ProtInc.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0007417; P:central nervous system development; TAS:ProtInc.
DR GO; GO:0042711; P:maternal behavior; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0001964; P:startle response; IEA:Ensembl.
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 PROSITE; PS50888; BHLH; 1.
DR PROSITE; PS50112; PAS; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; DNA-binding; Nucleus; Reference proteome; Repeat;
KW Transcription; Transcription regulation.
FT CHAIN 1..590
FT /note="Neuronal PAS domain-containing protein 1"
FT /id="PRO_0000127404"
FT DOMAIN 45..98
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 135..207
FT /note="PAS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 293..359
FT /note="PAS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 365..408
FT /note="PAC"
FT REGION 198..229
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 425..494
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 213..228
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 464..487
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..176
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054280"
FT VAR_SEQ 357..410
FT /note="LLDKGQVMTGYYRWLQRAGGFVWLQSVATVAGSGKSPGEHHVLWVSHVLSQA
FT EG -> SCRGLRVAAVCGHSGWEREEPRGAPCALGQPRAQPSRGWPNSFGCLPASSQRG
FT L (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054281"
FT VAR_SEQ 411..590
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054282"
FT CONFLICT 80
FT /note="S -> I (in Ref. 1; AAB47248)"
FT /evidence="ECO:0000305"
FT CONFLICT 110..134
FT /note="LRAAGPPAGLAPGRRGPAALVSEVF -> NSRRPALRAAAAGARPAGGPGSQ
FT PP (in Ref. 6)"
FT /evidence="ECO:0000305"
FT CONFLICT 203
FT /note="P -> T (in Ref. 1; AAB47248)"
FT /evidence="ECO:0000305"
FT CONFLICT 211
FT /note="P -> S (in Ref. 1; AAB47248)"
FT /evidence="ECO:0000305"
FT CONFLICT 449
FT /note="A -> V (in Ref. 1; AAB47248)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 590 AA; 62702 MW; CE893A0C7CEEDB09 CRC64;
MAAPYPGSGG GSEVKCVGGR GASVPWDFLP GLMVKAPSGP CLQAQRKEKS RNAARSRRGK
ENLEFFELAK LLPLPGAISS QLDKASIVRL SVTYLRLRRF AALGAPPWGL RAAGPPAGLA
PGRRGPAALV SEVFEQHLGG HILQSLDGFV FALNQEGKFL YISETVSIYL GLSQVEMTGS
SVFDYIHPGD HSEVLEQLGL RTPTPGPPTP PSVSSSSSSS SSLADTPEIE ASLTKVPPSS
LVQERSFFVR MKSTLTKRGL HVKASGYKVI HVTGRLRAHA LGLVALGHTL PPAPLAELPL
HGHMIVFRLS LGLTILACES RVSDHMDLGP SELVGRSCYQ FVHGQDATRI RQSHVDLLDK
GQVMTGYYRW LQRAGGFVWL QSVATVAGSG KSPGEHHVLW VSHVLSQAEG GQTPLDAFQL
PASVACEEAS SPGPEPTEPE PPTEGKQAAP AENEAPQTQG KRIKVEPGPR ETKGSEDSGD
EDPSSHPATP RPEFTSVIRA GVLKQDPVRP WGLAPPGDPP PTLLHAGFLP PVVRGLCTPG
TIRYGPAELG LVYPHLQRLG PGPALPEAFY PPLGLPYPGP AGTRLPRKGD
