Q99743 (NPAS2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	824 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Biological rhythms Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Domain	Repeat
Ligand	DNA-binding
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular 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: Compara locomotor rhythm Inferred from electronic annotation. Source: Compara 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-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Traceable author statement. Source: Reactome transcription factor complex Inferred from physical interaction PubMed 9576906. Source: MGI
Molecular_function	DNA 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 824	824	Neuronal PAS domain-containing protein 2		PRO_0000127406
Regions
	Domain	9 – 59	51	bHLH
	Domain	82 – 152	71	PAS 1
	Domain	237 – 307	71	PAS 2
	Domain	311 – 354	44	PAC
Natural variations
	Natural variant	394	1	T → A. Ref.1 Ref.3 Ref.4 Corresponds to variant rs2305160 [ dbSNP | Ensembl ].		VAR_029078
	Natural variant	471	1	S → 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 conflict	51	1	K → E in AAC51211. Ref.4
	Sequence conflict	164	1	S → G in AAC51211. Ref.4
	Sequence conflict	308	1	K → T in AAB47250. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q99743 [UniParc]. Last modified November 2, 2010. Version 3. Checksum: 679919FCDD3AFDEB	FASTA	824	91,791
	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

References

	« Hide 'large scale' referencesShow '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. , 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.
IPI	IPI00956556.
RefSeq	NP_002509.2. NM_002518.3.
UniGene	Hs.156832. Hs.705895.
3D structure databases
ProteinModelPortal	Q99743.
SMR	Q99743. Positions 6-359.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q99743. 8 interactions.
STRING	9606.ENSP00000338283.
PTM databases
PhosphoSite	Q99743.
Polymorphism databases
DMDM	311033423.
Proteomic databases
PaxDb	Q99743.
PRIDE	Q99743.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000335681; ENSP00000338283; ENSG00000170485.
GeneID	4862.
KEGG	hsa:4862.
UCSC	uc002tap.1. human.
Organism-specific databases
CTD	4862.
GeneCards	GC02P101436.
H-InvDB	HIX0200274.
HGNC	HGNC:7895. NPAS2.
HPA	HPA019674.
MIM	603347. gene. 608516. phenotype.
neXtProt	NX_Q99743.
PharmGKB	PA31696.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG300360.
HOVERGEN	HBG050997.
InParanoid	Q99743.
KO	K09026.
OrthoDB	EOG444KJQ.
PhylomeDB	Q99743.
Enzyme and pathway databases
Pathway_Interaction_DB	circadianpathway. Circadian rhythm pathway.
Reactome	REACT_111217. Metabolism. REACT_24941. Circadian Clock.
Gene expression databases
ArrayExpress	Q99743.
Bgee	Q99743.
CleanEx	HS_NPAS2.
Genevestigator	Q99743.
GermOnline	ENSG00000170485. Homo sapiens.
Family and domain databases
Gene3D	4.10.280.10. 1 hit.
InterPro	IPR011598. bHLH_dom. IPR001067. Nuc_translocat. IPR001610. PAC. IPR000014. PAS. IPR013767. PAS_fold. IPR013655. PAS_fold_3. [Graphical view]
Pfam	PF00010. HLH. 1 hit. PF00989. PAS. 1 hit. PF08447. PAS_3. 1 hit. [Graphical view]
PRINTS	PR00785. NCTRNSLOCATR.
SMART	SM00353. HLH. 1 hit. SM00086. PAC. 1 hit. SM00091. PAS. 2 hits. [Graphical view]
SUPFAM	SSF47459. HLH_basic. 1 hit.
TIGRFAMs	TIGR00229. sensory_box. 1 hit.
PROSITE	PS50888. BHLH. 1 hit. PS50113. PAC. False negative. PS50112. PAS. 2 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	NPAS2. human.
GenomeRNAi	4862.
NextBio	18730.
SOURCE	Search...

Entry information

Entry name

NPAS2_HUMAN

Accession

Primary (citable) accession number: Q99743
Secondary accession number(s): Q4ZFV9 , Q53SQ3, Q86V96, Q99629

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	November 2, 2010
Last modified:	May 1, 2013
This is version 130 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.