NPAS3_HUMAN
ID NPAS3_HUMAN Reviewed; 933 AA.
AC Q8IXF0; Q86US6; Q86US7; Q8IXF2; Q9BY81; Q9H323; Q9Y4L8;
DT 28-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Neuronal PAS domain-containing protein 3;
DE Short=Neuronal PAS3;
DE AltName: Full=Basic-helix-loop-helix-PAS protein MOP6;
DE AltName: Full=Class E basic helix-loop-helix protein 12;
DE Short=bHLHe12;
DE AltName: Full=Member of PAS protein 6;
DE AltName: Full=PAS domain-containing protein 6;
GN Name=NPAS3; Synonyms=BHLHE12, MOP6, PASD6;
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] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Fetal brain;
RA Ohe N., Saito K., Kaneko H.;
RT "Splicing variants of human NPAS3.";
RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RA Thomas R.S., Bradfield C.A.;
RT "Cloning and chromosomal localization of MOP6.";
RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4 AND 5), SUBCELLULAR LOCATION, AND
RP CHROMOSOMAL TRANSLOCATION.
RC TISSUE=Fetal brain;
RX PubMed=12746393; DOI=10.1136/jmg.40.5.325;
RA Kamnasaran D., Muir W.J., Ferguson-Smith M.A., Cox D.W.;
RT "Disruption of the neuronal PAS3 gene in a family affected with
RT schizophrenia.";
RL J. Med. Genet. 40:325-332(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 58-933 (ISOFORM 6).
RG The European IMAGE consortium;
RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: May play a broad role in neurogenesis. May control regulatory
CC pathways relevant to schizophrenia and to psychotic illness (By
CC similarity). {ECO:0000250}.
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) of
CC target gene promoters (By similarity). {ECO:0000250|UniProtKB:Q9QZQ0}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981,
CC ECO:0000269|PubMed:12746393}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1; Synonyms=long form;
CC IsoId=Q8IXF0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IXF0-2; Sequence=VSP_009085;
CC Name=3; Synonyms=NPAS3v;
CC IsoId=Q8IXF0-3; Sequence=VSP_009085, VSP_009087;
CC Name=4;
CC IsoId=Q8IXF0-4; Sequence=VSP_009085, VSP_009086;
CC Name=5;
CC IsoId=Q8IXF0-5; Sequence=VSP_009084, VSP_009086, VSP_009088,
CC VSP_009089;
CC Name=6;
CC IsoId=Q8IXF0-6; Sequence=VSP_009088, VSP_009089;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed in the adult brain.
CC -!- DISEASE: Note=A chromosomal aberration involving NPAS3 is found in a
CC family with schizophrenia. Translocation t(9;14)(q34;q13).
CC {ECO:0000269|PubMed:12746393}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB055962; BAC53756.1; -; mRNA.
DR EMBL; AB054575; BAB21221.1; -; mRNA.
DR EMBL; AB054576; BAC53754.1; -; mRNA.
DR EMBL; AF164438; AAG35180.1; -; mRNA.
DR EMBL; AY157302; AAO17043.1; -; mRNA.
DR EMBL; AY157303; AAO17044.1; -; mRNA.
DR EMBL; AL079281; CAB45154.1; -; mRNA.
DR CCDS; CCDS53891.1; -. [Q8IXF0-1]
DR CCDS; CCDS53892.1; -. [Q8IXF0-3]
DR CCDS; CCDS55912.1; -. [Q8IXF0-2]
DR CCDS; CCDS9645.1; -. [Q8IXF0-4]
DR RefSeq; NP_001158221.1; NM_001164749.1. [Q8IXF0-1]
DR RefSeq; NP_001159365.1; NM_001165893.1. [Q8IXF0-2]
DR RefSeq; NP_071406.1; NM_022123.2. [Q8IXF0-4]
DR RefSeq; NP_775182.1; NM_173159.2. [Q8IXF0-3]
DR AlphaFoldDB; Q8IXF0; -.
DR SMR; Q8IXF0; -.
DR BioGRID; 122040; 7.
DR IntAct; Q8IXF0; 5.
DR MINT; Q8IXF0; -.
DR STRING; 9606.ENSP00000348460; -.
DR GlyGen; Q8IXF0; 3 sites, 1 O-linked glycan (3 sites).
DR iPTMnet; Q8IXF0; -.
DR PhosphoSitePlus; Q8IXF0; -.
DR BioMuta; NPAS3; -.
DR DMDM; 38604888; -.
DR EPD; Q8IXF0; -.
DR MassIVE; Q8IXF0; -.
DR PaxDb; Q8IXF0; -.
DR PeptideAtlas; Q8IXF0; -.
DR PRIDE; Q8IXF0; -.
DR ProteomicsDB; 70984; -. [Q8IXF0-1]
DR ProteomicsDB; 70985; -. [Q8IXF0-2]
DR ProteomicsDB; 70986; -. [Q8IXF0-3]
DR ProteomicsDB; 70987; -. [Q8IXF0-4]
DR ProteomicsDB; 70989; -. [Q8IXF0-6]
DR Antibodypedia; 136; 130 antibodies from 26 providers.
DR DNASU; 64067; -.
DR Ensembl; ENST00000346562.6; ENSP00000319610.5; ENSG00000151322.20. [Q8IXF0-4]
DR Ensembl; ENST00000356141.8; ENSP00000348460.4; ENSG00000151322.20. [Q8IXF0-1]
DR Ensembl; ENST00000357798.9; ENSP00000350446.5; ENSG00000151322.20. [Q8IXF0-3]
DR Ensembl; ENST00000547068.5; ENSP00000449542.1; ENSG00000151322.20. [Q8IXF0-5]
DR Ensembl; ENST00000548645.5; ENSP00000448916.1; ENSG00000151322.20. [Q8IXF0-2]
DR GeneID; 64067; -.
DR KEGG; hsa:64067; -.
DR MANE-Select; ENST00000356141.9; ENSP00000348460.4; NM_001164749.2; NP_001158221.1.
DR UCSC; uc001wrs.4; human. [Q8IXF0-1]
DR CTD; 64067; -.
DR DisGeNET; 64067; -.
DR GeneCards; NPAS3; -.
DR HGNC; HGNC:19311; NPAS3.
DR HPA; ENSG00000151322; Tissue enhanced (brain).
DR MIM; 609430; gene.
DR neXtProt; NX_Q8IXF0; -.
DR OpenTargets; ENSG00000151322; -.
DR PharmGKB; PA134968746; -.
DR VEuPathDB; HostDB:ENSG00000151322; -.
DR eggNOG; KOG3558; Eukaryota.
DR GeneTree; ENSGT00940000158051; -.
DR InParanoid; Q8IXF0; -.
DR OrthoDB; 922461at2759; -.
DR PhylomeDB; Q8IXF0; -.
DR TreeFam; TF317772; -.
DR PathwayCommons; Q8IXF0; -.
DR SignaLink; Q8IXF0; -.
DR BioGRID-ORCS; 64067; 12 hits in 1089 CRISPR screens.
DR ChiTaRS; NPAS3; human.
DR GenomeRNAi; 64067; -.
DR Pharos; Q8IXF0; Tbio.
DR PRO; PR:Q8IXF0; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q8IXF0; protein.
DR Bgee; ENSG00000151322; Expressed in endothelial cell and 164 other tissues.
DR ExpressionAtlas; Q8IXF0; baseline and differential.
DR Genevisible; Q8IXF0; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
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:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
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; 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; 2.
PE 2: Evidence at transcript level;
KW Alternative splicing; Chromosomal rearrangement; DNA-binding; Nucleus;
KW Reference proteome; Repeat; Transcription; Transcription regulation.
FT CHAIN 1..933
FT /note="Neuronal PAS domain-containing protein 3"
FT /id="PRO_0000127408"
FT DOMAIN 51..104
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 147..217
FT /note="PAS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 319..389
FT /note="PAS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 363..406
FT /note="PAC"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 53..64
FT /note="DNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q9QZQ0"
FT REGION 215..253
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 452..549
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 562..641
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 657..725
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 742..780
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 225..253
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 456..506
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 520..541
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 567..592
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 596..612
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 657..690
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..102
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:12746393"
FT /id="VSP_009084"
FT VAR_SEQ 18..47
FT /note="Missing (in isoform 2, isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:12746393, ECO:0000303|Ref.1,
FT ECO:0000303|Ref.2"
FT /id="VSP_009085"
FT VAR_SEQ 128
FT /note="K -> KGIQMWKSELCMRKTPCE (in isoform 3)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_009087"
FT VAR_SEQ 129..130
FT /note="Missing (in isoform 4 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:12746393, ECO:0000303|Ref.2"
FT /id="VSP_009086"
FT VAR_SEQ 246..257
FT /note="ESTSPSLLTTDN -> VCFPPASDQFLL (in isoform 5 and
FT isoform 6)"
FT /evidence="ECO:0000303|PubMed:12746393, ECO:0000303|Ref.4"
FT /id="VSP_009088"
FT VAR_SEQ 258..933
FT /note="Missing (in isoform 5 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:12746393, ECO:0000303|Ref.4"
FT /id="VSP_009089"
FT CONFLICT 65
FT /note="G -> E (in Ref. 4; CAB45154)"
FT /evidence="ECO:0000305"
FT CONFLICT 79..81
FT /note="PLP -> LS (in Ref. 4; CAB45154)"
FT /evidence="ECO:0000305"
FT CONFLICT 552
FT /note="A -> P (in Ref. 3; AAO17043)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 933 AA; 100805 MW; 3215AC657CEDD9A9 CRC64;
MAPTKPSFQQ DPSRRERITA QHPLPNQSEC RKIYRYDGIY CESTYQNLQA LRKEKSRDAA
RSRRGKENFE FYELAKLLPL PAAITSQLDK ASIIRLTISY LKMRDFANQG DPPWNLRMEG
PPPNTSVKVI GAQRRRSPSA LAIEVFEAHL GSHILQSLDG FVFALNQEGK FLYISETVSI
YLGLSQVELT GSSVFDYVHP GDHVEMAEQL GMKLPPGRGL LSQGTAEDGA SSASSSSQSE
TPEPVESTSP SLLTTDNTLE RSFFIRMKST LTKRGVHIKS SGYKVIHITG RLRLRVSLSH
GRTVPSQIMG LVVVAHALPP PTINEVRIDC HMFVTRVNMD LNIIYCENRI SDYMDLTPVD
IVGKRCYHFI HAEDVEGIRH SHLDLLNKGQ CVTKYYRWMQ KNGGYIWIQS SATIAINAKN
ANEKNIIWVN YLLSNPEYKD TPMDIAQLPH LPEKTSESSE TSDSESDSKD TSGITEDNEN
SKSDEKGNQS ENSEDPEPDR KKSGNACDND MNCNDDGHSS SNPDSRDSDD SFEHSDFENP
KAGEDGFGAL GAMQIKVERY VESESDLRLQ NCESLTSDSA KDSDSAGEAG AQASSKHQKR
KKRRKRQKGG SASRRRLSSA SSPGGLDAGL VEPPRLLSSP NSASVLKIKT EISEPINFDN
DSSIWNYPPN REISRNESPY SMTKPPSSEH FPSPQGGGGG GGGGGGLHVA IPDSVLTPPG
ADGAAARKTQ FGASATAALA PVASDPLSPP LSASPRDKHP GNGGGGGGGG GGAGGGGPSA
SNSLLYTGDL EALQRLQAGN VVLPLVHRVT GTLAATSTAA QRVYTTGTIR YAPAEVTLAM
QSNLLPNAHA VNFVDVNSPG FGLDPKTPME MLYHHVHRLN MSGPFGGAVS AASLTQMPAG
NVFTTAEGLF STLPFPVYSN GIHAAQTLER KED
