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Q99743 (NPAS2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 137. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Neuronal PAS domain-containing protein 2

Short name=Neuronal PAS2
Alternative name(s):
Basic-helix-loop-helix-PAS protein MOP4
Class E basic helix-loop-helix protein 9
Short name=bHLHe9
Member of PAS protein 4
PAS domain-containing protein 4
Gene names
Name:NPAS2
Synonyms:BHLHE9, MOP4, PASD4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length824 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

BMAL1-NPAS2 heterodimers activate E-box element (5'-CACGTG-3') transcription of a number of proteins of the circadian clock. This transcription is inhibited in a feedback loop by PER, and also by CRY proteins By similarity.

Subunit structure

Component of the circadian clock oscillator which includes the CRY proteins, CLOCK or NPAS2, BMAL1 or BMAL2, CSNK1D and/or CSNK1E, TIMELESS and the PER proteins. Efficient DNA binding requires dimerization with another bHLH protein. Heterodimerization with CLOCK or NPAS2 is required for E-box-dependent transactivation.

Subcellular location

Nucleus By similarity.

Polymorphism

Variants in NPAS2 show a susceptibility to seasonal affective disorder (SAD) [MIM:608516]. SAD is a depressive condition resulting from seasonal changes, and with diurnal preference.

Sequence similarities

Contains 1 bHLH (basic helix-loop-helix) domain.

Contains 1 PAC (PAS-associated C-terminal) domain.

Contains 2 PAS (PER-ARNT-SIM) domains.

Ontologies

Keywords
   Biological processBiological rhythms
Transcription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityPolymorphism
   DomainRepeat
   LigandDNA-binding
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular lipid metabolic process

Traceable author statement. Source: Reactome

central nervous system development

Traceable author statement Ref.1. Source: ProtInc

circadian sleep/wake cycle

Inferred from electronic annotation. Source: Ensembl

locomotor rhythm

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from genetic interaction PubMed 9576906. Source: MGI

small molecule metabolic process

Traceable author statement. Source: Reactome

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

transcription factor complex

Inferred from physical interaction PubMed 9576906. Source: MGI

   Molecular_functionDNA binding

Inferred from physical interaction PubMed 9576906. Source: MGI

Hsp90 protein binding

Inferred from direct assay Ref.4. Source: BHF-UCL

sequence-specific DNA binding transcription factor activity

Traceable author statement Ref.1. Source: ProtInc

signal transducer activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 824824Neuronal PAS domain-containing protein 2
PRO_0000127406

Regions

Domain9 – 5951bHLH
Domain82 – 15271PAS 1
Domain237 – 30771PAS 2
Domain311 – 35444PAC

Natural variations

Natural variant3941T → A. Ref.1 Ref.3 Ref.4
Corresponds to variant rs2305160 [ dbSNP | Ensembl ].
VAR_029078
Natural variant4711S → L Susceptibility to seasonal affective disorder (SAD) and diurnal preference. Ref.1 Ref.5
Corresponds to variant rs11541353 [ dbSNP | Ensembl ].
VAR_029079

Experimental info

Sequence conflict511K → E in AAC51211. Ref.4
Sequence conflict1641S → G in AAC51211. Ref.4
Sequence conflict3081K → T in AAB47250. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q99743 [UniParc].

Last modified November 2, 2010. Version 3.
Checksum: 679919FCDD3AFDEB

FASTA82491,791
        10         20         30         40         50         60 
MDEDEKDRAK RASRNKSEKK RRDQFNVLIK ELSSMLPGNT RKMDKTTVLE KVIGFLQKHN 

        70         80         90        100        110        120 
EVSAQTEICD IQQDWKPSFL SNEEFTQLML EALDGFIIAV TTDGSIIYVS DSITPLLGHL 

       130        140        150        160        170        180 
PSDVMDQNLL NFLPEQEHSE VYKILSSHML VTDSPSPEYL KSDSDLEFYC HLLRGSLNPK 

       190        200        210        220        230        240 
EFPTYEYIKF VGNFRSYNNV PSPSCNGFDN TLSRPCRVPL GKEVCFIATV RLATPQFLKE 

       250        260        270        280        290        300 
MCIVDEPLEE FTSRHSLEWK FLFLDHRAPP IIGYLPFEVL GTSGYDYYHI DDLELLARCH 

       310        320        330        340        350        360 
QHLMQFGKGK SCCYRFLTKG QQWIWLQTHY YITYHQWNSK PEFIVCTHSV VSYADVRVER 

       370        380        390        400        410        420 
RQELALEDPP SEALHSSALK DKGSSLEPRQ HFNTLDVGAS GLNTSHSPSA SSRSSHKSSH 

       430        440        450        460        470        480 
TAMSEPTSTP TKLMAEASTP ALPRSATLPQ ELPVPGLSQA ATMPAPLPSP SSCDLTQQLL 

       490        500        510        520        530        540 
PQTVLQSTPA PMAQFSAQFS MFQTIKDQLE QRTRILQANI RWQQEELHKI QEQLCLVQDS 

       550        560        570        580        590        600 
NVQMFLQQPA VSLSFSSTQR PEAQQQLQQR SAAVTQPQLG AGPQLPGQIS SAQVTSQHLL 

       610        620        630        640        650        660 
RESSVISTQG PKPMRSSQLM QSSGRSGSSL VSPFSSATAA LPPSLNLTTP ASTSQDASQC 

       670        680        690        700        710        720 
QPSPDFSHDR QLRLLLSQPI QPMMPGSCDA RQPSEVSRTG RQVKYAQSQT VFQNPDAHPA 

       730        740        750        760        770        780 
NSSSAPMPVL LMGQAVLHPS FPASQPSPLQ PAQARQQPPQ HYLQVQAPTS LHSEQQDSLL 

       790        800        810        820 
LSTYSQQPGT LGYPQPPPAQ PQPLRPPRRV SSLSESSGLQ QPPR 

« Hide

References

« Hide 'large scale' references
[1]"Molecular characterization of two mammalian bHLH-PAS domain proteins selectively expressed in the central nervous system."
Zhou Y.-D., Barnard M., Tian H., Li X., Ring H.Z., Francke U., Shelton J., Richardson J., Russell D.W., McKnight S.L.
Proc. Natl. Acad. Sci. U.S.A. 94:713-718(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ALA-394 AND LEU-471.
[2]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-394.
Tissue: Lung.
[4]"Characterization of a subset of the basic-helix-loop-helix-PAS superfamily that interacts with components of the dioxin signaling pathway."
Hogenesch J.B., Chan W.K., Jackiw V.H., Brown R.C., Gu Y.-Z., Pray-Grant M., Perdew G.H., Bradfield C.A.
J. Biol. Chem. 272:8581-8593(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-626, VARIANT ALA-394.
[5]"Circadian clock-related polymorphisms in seasonal affective disorder and their relevance to diurnal preference."
Johansson C., Willeit M., Smedh C., Ekholm J., Paunio T., Kieseppa T., Lichtermann D., Praschak-Rieder N., Neumeister A., Nilsson L.G., Kasper S., Peltonen L., Adolfsson R., Schalling M., Partonen T.
Neuropsychopharmacology 28:734-739(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: ASSOCIATION OF VARIANT LEU-471 WITH SAD.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U77970 mRNA. Translation: AAB47250.1.
AC016738 Genomic DNA. Translation: AAY14822.1.
AC092168 Genomic DNA. No translation available.
AC106891 Genomic DNA. Translation: AAX88966.1.
BC051351 mRNA. Translation: AAH51351.2.
BC072383 mRNA. Translation: AAH72383.1.
U51625 mRNA. Translation: AAC51211.1.
RefSeqNP_002509.2. NM_002518.3.
UniGeneHs.156832.
Hs.705895.

3D structure databases

ProteinModelPortalQ99743.
SMRQ99743. Positions 6-359.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110923. 13 interactions.
IntActQ99743. 8 interactions.
STRING9606.ENSP00000338283.

PTM databases

PhosphoSiteQ99743.

Polymorphism databases

DMDM311033423.

Proteomic databases

PaxDbQ99743.
PRIDEQ99743.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000335681; ENSP00000338283; ENSG00000170485.
GeneID4862.
KEGGhsa:4862.
UCSCuc002tap.1. human.

Organism-specific databases

CTD4862.
GeneCardsGC02P101436.
H-InvDBHIX0200274.
HGNCHGNC:7895. NPAS2.
HPAHPA019674.
MIM603347. gene.
608516. phenotype.
neXtProtNX_Q99743.
PharmGKBPA31696.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG300360.
HOVERGENHBG050997.
InParanoidQ99743.
KOK09026.
PhylomeDBQ99743.
TreeFamTF324568.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
REACT_24941. Circadian Clock.

Gene expression databases

ArrayExpressQ99743.
BgeeQ99743.
CleanExHS_NPAS2.
GenevestigatorQ99743.

Family and domain databases

Gene3D4.10.280.10. 1 hit.
InterProIPR011598. bHLH_dom.
IPR001067. Nuc_translocat.
IPR001610. PAC.
IPR000014. PAS.
IPR013767. PAS_fold.
[Graphical view]
PfamPF00010. HLH. 1 hit.
PF00989. PAS. 1 hit.
[Graphical view]
PRINTSPR00785. NCTRNSLOCATR.
SMARTSM00353. HLH. 1 hit.
SM00086. PAC. 1 hit.
SM00091. PAS. 2 hits.
[Graphical view]
SUPFAMSSF47459. SSF47459. 1 hit.
SSF55785. SSF55785. 2 hits.
TIGRFAMsTIGR00229. sensory_box. 1 hit.
PROSITEPS50888. BHLH. 1 hit.
PS50112. PAS. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSNPAS2. human.
GeneWikiNPAS2.
GenomeRNAi4862.
NextBio18730.
PROQ99743.
SOURCESearch...

Entry information

Entry nameNPAS2_HUMAN
AccessionPrimary (citable) accession number: Q99743
Secondary accession number(s): Q4ZFV9 expand/collapse secondary AC list , Q53SQ3, Q86V96, Q99629
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: November 2, 2010
Last modified: February 19, 2014
This is version 137 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM