O54943 (PER2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Period circadian protein homolog 2
Short name=mPER2

Alternative name(s):
Circadian clock protein PERIOD 2

Gene names

Name:

Per2

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1257 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Component of the circadian clock mechanism which is essential for generating circadian rhythms. Negative element in the circadian transcriptional loop. Influences clock function by interacting with other circadian regulatory proteins and transporting them to the nucleus. Negatively regulates CLOCK|NPAS2-BMAL1|BMAL2-induced transactivation. Ref.5
Subunit structure	Homodimer. Component of the circadian core oscillator, which includes the CRY proteins, CLOCK or NPAS2, BMAL1 or BMAL2, CSNK1D and/or CSNK1E, TIMELESS, and the PER proteins. Interacts directly with PER1 and PER3, and through a C-terminal domain, with CRY1 and CRY2. Interacts with NFIL3. Interaction with CSNK1D or CSNK1E promotes nuclear location of PER proteins. Interacts, via its second PAS domain, with TIMELESS in vitro By similarity. Interacts with PML (isoform PML-1, isoform PML-2, isoform PML-3, isoform PML-4 and isoform PML-5). Ref.4 Ref.5 Ref.6 Ref.8 Ref.9 Ref.10 Ref.12 Ref.13 Ref.15 Ref.16 Ref.17 Ref.18
Subcellular location	Nucleus. Cytoplasm. Cytoplasm › perinuclear region. Note: Mainly nuclear. Nucleocytoplasmic shuttling is effected by interaction with other circadian core oscillator proteins and/or by phosphorylation. Retention of PER1 in the cytoplasm occurs through PER1-PER2 heterodimer formation or by interaction with CSNK1E and/or phosphorylation which appears to mask the PER nuclear localization signal. Also translocated to the nucleus by CRY1 or CRY2. PML regulates its nuclear localization. Ref.5 Ref.6 Ref.7 Ref.8 Ref.15 Ref.17
Tissue specificity	In the brain, high expression in SCN during the subjective day. Constitutive expression in the cornu ammonis and in the dentate gyrus of the hyppocampus. Also expressed in the piriform cortex and the glomeruli of the olfactory bulb, and at a lower extent in the cerebral cortex. Not expressed in the pars tuberalis and the Purkinje neurons. Also found in heart, skeletal muscle, spleen, lung and liver. Highest levels in skeletal muscle and liver. Low level in spleen. Not expressed in kidney nor testis. Ref.1 Ref.2
Developmental stage	Expressed in the SCN during late fetal and early neonatal life. Ref.2
Induction	Exhibits circadian rhythm patterns. Levels alter by light exposure during subjective night, but not during subjective day. Ref.1 Ref.2
Post-translational modification	Phosphorylated by CSNK1E and CSNK1D. Phosphorylation results in PER2 protein degradation. Ref.9 Ref.11 Ref.15
Sequence similarities	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	Cytoplasm Nucleus
Domain	Repeat
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	circadian rhythm Inferred from direct assay PubMed 12843397. Source: MGI negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 9989497. Source: MGI transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	protein binding transcription factor activity Inferred from electronic annotation. Source: Compara signal transducer activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Arntl	Q9WTL8	8	EBI-1266779,EBI-644534
Clock	O08785	10	EBI-1266779,EBI-79859
Cry2	Q9R194	3	EBI-1266779,EBI-1266619

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1257

1257

Period circadian protein homolog 2

PRO_0000162631

Regions

Domain

179 – 246

68

PAS 1

Domain

319 – 385

67

PAS 2

Domain

393 – 436

44

PAC

Region

555 – 763

209

CSNK1E binding domain By similarity

Region

1157 – 1257

101

CRY binding domain By similarity

Motif

457 – 469

13

Nuclear export signal

Motif

778 – 794

17

Nuclear localization signal By similarity

Compositional bias

831 – 961

131

Pro-rich

Compositional bias

1061 – 1111

51

Ser-rich

Amino acid modifications

Modified residue

525

1

Phosphoserine Ref.11

Modified residue

528

1

Phosphoserine Ref.11

Modified residue

531

1

Phosphoserine Ref.11

Modified residue

538

1

Phosphoserine Ref.11

Modified residue

544

1

Phosphoserine Ref.11

Modified residue

554

1

Phosphothreonine Ref.11

Modified residue

659

1

Phosphoserine By similarity

Modified residue

693

1

Phosphoserine Ref.14

Modified residue

697

1

Phosphoserine Ref.14

Modified residue

706

1

Phosphoserine Ref.11

Modified residue

758

1

Phosphoserine Ref.11

Modified residue

763

1

Phosphoserine Ref.11

Modified residue

858

1

Phosphothreonine Ref.11

Modified residue

939

1

Phosphoserine Ref.11

Modified residue

964

1

Phosphothreonine Ref.11

Modified residue

971

1

Phosphoserine Ref.11

Modified residue

1126

1

Phosphoserine Ref.11

Experimental info

Mutagenesis

415

1

F → E: Abolishes dimerization. Ref.18

Mutagenesis

419

1

W → E: Abolishes dimerization. Ref.18

Mutagenesis

427

1

I → E: Abolishes dimerization. Ref.18

Sequence conflict

445

1

P → S in AAC53592. Ref.2

Sequence conflict

728

1

K → R in AAC53592. Ref.2

Secondary structure

1

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1257

Helix Strand Turn

Details...

Turn

173 – 176

4

Beta strand

190 – 195

6

Turn

197 – 199

3

Beta strand

201 – 205

5

Turn

207 – 212

6

Helix

225 – 228

4

Turn

231 – 233

3

Helix

234 – 240

7

Beta strand

268 – 272

5

Beta strand

285 – 295

11

Beta strand

306 – 314

9

Beta strand

320 – 322

3

Helix

326 – 328

3

Beta strand

330 – 335

6

Beta strand

340 – 344

5

Helix

348 – 352

5

Helix

356 – 359

4

Helix

364 – 367

4

Helix

373 – 385

13

Turn

386 – 388

3

Beta strand

391 – 399

9

Beta strand

405 – 416

12

Turn

418 – 420

3

Beta strand

423 – 434

12

Beta strand

437 – 439

3

Helix

455 – 467

13

Sequences

	Sequence		Length	Mass (Da)
	O54943 [UniParc]. Last modified July 15, 1999. Version 3. Checksum: 554B8AFF036CF7FB	FASTA	1,257	135,881
	10 20 30 40 50 60 MNGYVDFSPS PTSPTKEPGA PQPTQAVLQE DVDMSSGSSG NENCSTGRDS QGSDCDDNGK 70 80 90 100 110 120 ELRMLVESSN THPSPDDAFR LMMTEAEHNP STSGCSSEQS AKADAHKELI RTLKELKVHL 130 140 150 160 170 180 PADKKAKGKA STLATLKYAL RSVKQVKANE EYYQLLMSSE SQPCSVDVPS YSMEQVEGIT 190 200 210 220 230 240 SEYIVKNADM FAVAVSLVSG KILYISNQVA SIFHCKKDAF SDAKFVEFLA PHDVSVFHSY 250 260 270 280 290 300 TTPYKLPPWS VCSGLDSFTQ ECMEEKSFFC RVSVGKHHEN EIRYQPFRMT PYLVKVQEQQ 310 320 330 340 350 360 GAESQLCCLL LAERVHSGYE APRIPPEKRI FTTTHTPNCL FQAVDERAVP LLGYLPQDLI 370 380 390 400 410 420 ETPVLVQLHP SDRPLMLAIH KKILQAGGQP FDYSPIRFRT RNGEYITLDT SWSSFINPWS 430 440 450 460 470 480 RKISFIIGRH KVRVGPLNED VFAAPPCPEE KTPHPSVQEL TEQIHRLLMQ PVPHSGSSGY 490 500 510 520 530 540 GSLGSNGSHE HLMSQTSSSD SNGQEESHRR RSGIFKTSGK IQTKSHVSHE SGGQKEASVA 550 560 570 580 590 600 EMQSSPPAQV KAVTTIERDS SGASLPKASF PEELAYKNQP PCSYQQISCL DSVIRYLESC 610 620 630 640 650 660 SEAATLKRKC EFPANIPSRK ATVSPGLHSG EAARPSKVTS HTEVSAHLSS LTLPGKAESV 670 680 690 700 710 720 VSLTSQCSYS STIVHVGDKK PQPELETVED MASGPESLDG AAGGLSQEKG PLQKLGLTKE 730 740 750 760 770 780 VLAAHTQKEE QGFLQRFREV SRLSALQAHC QNYLQERSRA QASDRGLRNT SGLESSWKKT 790 800 810 820 830 840 GKNRKLKSKR VKTRDSSEST GSGGPVSHRP PLMGLNATAW SPSDTSQSSC PSAPFPTAVP 850 860 870 880 890 900 AYPLPVFQAP GIVSTPGTVV APPAATHTGF TMPVVPMGTQ PEFAVQPLPF AAPLAPVMAF 910 920 930 940 950 960 MLPSYPFPPA TPNLPQAFLP SQPHFPAHPT LASEITPASQ AEFPSRTSTL RQPCACPVTP 970 980 990 1000 1010 1020 PAGTVALGRA SPPLFQSRGS SPLQLNLLQL EEAPEGSTGA AGTLGTTGTA ASGLDCTSGT 1030 1040 1050 1060 1070 1080 SRDRQPKAPP TCNEPSDTQN SDAISTSSDL LNLLLGEDLC SATGSALSRS GASATSDSLG 1090 1100 1110 1120 1130 1140 SSSLGFGTSQ SGAGSSDTSH TSKYFGSIDS SENNHKAKMI PDTEESEQFI KYVLQDPIWL 1150 1160 1170 1180 1190 1200 LMANTDDSIM MTYQLPSRDL QAVLKEDQEK LKLLQRSQPR FTEGQRRELR EVHPWVHTGG 1210 1220 1230 1240 1250 LPTAIDVTGC VYCESEEKGN ICLPYEEDSP SPGLCDTSEA KEEEGEQLTG PRIEAQT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A differential response of two putative mammalian circadian regulators, mper1 and mper2, to light." Albrecht U., Sun Z.S., Eichele G., Lee C.C. Cell 91:1055-1064(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INDUCTION. Tissue: Brain.
[2]	"Two period homologs: circadian expression and photic regulation in the suprachiasmatic nuclei." Shearman L.P., Zylka M.J., Weaver D.R., Kolakowski L.F. Jr., Reppert S.M. Neuron 19:1261-1269(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INDUCTION, DEVELOPMENTAL STAGE. Tissue: Brain.
[3]	Zylka M.J., Reppert S.M. Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO 172 AND 501.
[4]	"Mammalian circadian autoregulatory loop: a timeless ortholog and mPer1 interact and negatively regulate CLOCK-BMAL1-induced transcription." Sangoram A.M., Saez L., Antoch M.P., Gekakis N., Staknis D., Whiteley A., Fruechte E.M., Vitaterna M.H., Shimomura K., King D.P., Young M.W., Weitz C.J., Takahashi J.S. Neuron 21:1101-1113(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TIMELESS.
[5]	"mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop." Kume K., Zylka M.J., Sriram S., Shearman L.P., Weaver D.R., Jin X., Maywood E.S., Hastings M.H., Reppert S.M. Cell 98:193-205(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PER3; CRY1 AND CRY2, FUNCTION, SUBCELLULAR LOCATION.
[6]	"Nuclear entry of the circadian regulator mPER1 is controlled by mammalian casein kinase I epsilon." Vielhaber E., Eide E., Rivers A., Gao Z.-H., Virshup D.M. Mol. Cell. Biol. 20:4888-4899(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PER1; CKSN1D AND CKSN1E, SUBCELLULAR LOCATION.
[7]	"Nuclear export of mammalian PERIOD proteins." Vielhaber E.L., Duricka D., Ullman K.S., Virshup D.M. J. Biol. Chem. 276:45921-45927(2001) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, NUCLEAR EXPORT SIGNAL.
[8]	"Nucleocytoplasmic shuttling and mCRY-dependent inhibition of ubiquitylation of the mPER2 clock protein." Yagita K., Tamanini F., Yasuda M., Hoeijmakers J.H., van der Horst G.T., Okamura H. EMBO J. 21:1301-1314(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CRY1 AND CRY2, SUBCELLULAR LOCATION.
[9]	"Control of intracellular dynamics of mammalian period proteins by casein kinase I epsilon (CKIepsilon) and CKIdelta in cultured cells." Akashi M., Tsuchiya Y., Yoshino T., Nishida E. Mol. Cell. Biol. 22:1693-1703(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CSNK1D AND CKSN1E, PHOSPHORYLATION.
[10]	"Direct association between mouse PERIOD and CKIepsilon is critical for a functioning circadian clock." Lee C., Weaver D.R., Reppert S.M. Mol. Cell. Biol. 24:584-594(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CKSN1E; PER1; PER3; CRY1 AND CRY2.
[11]	"Mapping of phosphorylation sites by a multi-protease approach with specific phosphopeptide enrichment and NanoLC-MS/MS analysis." Schlosser A., Vanselow J.T., Kramer A. Anal. Chem. 77:5243-5250(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-525; SER-528; SER-531; SER-538; SER-544; THR-554; SER-706; SER-758; SER-763; THR-858; SER-939; THR-964; SER-971 AND SER-1126.
[12]	"Functional evolution of the photolyase/cryptochrome protein family: importance of the C terminus of mammalian CRY1 for circadian core oscillator performance." Chaves I., Yagita K., Barnhoorn S., Okamura H., van der Horst G.T.J., Tamanini F. Mol. Cell. Biol. 26:1743-1753(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CRY1 AND CRY2.
[13]	"The negative transcription factor E4BP4 is associated with circadian clock protein PERIOD2." Ohno T., Onishi Y., Ishida N. Biochem. Biophys. Res. Commun. 354:1010-1015(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NFIL3.
[14]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-693 AND SER-697, MASS SPECTROMETRY. Tissue: Liver.
[15]	"Casein kinase 1 delta regulates the pace of the mammalian circadian clock." Etchegaray J.P., Machida K.K., Noton E., Constance C.M., Dallmann R., Di Napoli M.N., DeBruyne J.P., Lambert C.M., Yu E.A., Reppert S.M., Weaver D.R. Mol. Cell. Biol. 29:3853-3866(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CSNK1D AND CSNK1E, SUBCELLULAR LOCATION, PHOSPHORYLATION.
[16]	"Identification of two amino acids in the C-terminal domain of mouse CRY2 essential for PER2 interaction." Ozber N., Baris I., Tatlici G., Gur I., Kilinc S., Unal E.B., Kavakli I.H. BMC Mol. Biol. 11:69-69(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CRY2.
[17]	"PML regulates PER2 nuclear localization and circadian function." Miki T., Xu Z., Chen-Goodspeed M., Liu M., Van Oort-Jansen A., Rea M.A., Zhao Z., Lee C.C., Chang K.S. EMBO J. 31:1427-1439(2012) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH PML.
[18]	"Structural and functional analyses of PAS domain interactions of the clock proteins Drosophila PERIOD and mouse PERIOD2." Hennig S., Strauss H.M., Vanselow K., Yildiz O., Schulze S., Arens J., Kramer A., Wolf E. PLoS Biol. 7:E94-E94(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 170-473, MUTAGENESIS OF PHE-415; TRP-419 AND ILE-427, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF036893 mRNA. Translation: AAC39942.1.
AF035830 mRNA. Translation: AAC53592.1.

IPI

IPI00469179.

PIR

T09493.

RefSeq

NP_035196.2. NM_011066.3.

UniGene

Mm.482463.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3GDI	X-ray	2.40	A/B	170-473	[»]

ProteinModelPortal

O54943.

SMR

O54943. Positions 113-473.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-38518N.

IntAct

O54943. 13 interactions.

PTM databases

PhosphoSite

O54943.

Proteomic databases

PRIDE

O54943.

Protocols and materials databases

DNASU

18627.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000069620; ENSMUSP00000066620; ENSMUSG00000055866.

GeneID

18627.

KEGG

mmu:18627.

Organism-specific databases

CTD

8864.

MGI

MGI:1195265. Per2.

Phylogenomic databases

eggNOG

NOG253593.

GeneTree

ENSGT00510000046467.

HOVERGEN

HBG008167.

InParanoid

O54943.

KO

K02633.

OrthoDB

EOG48D0TV.

Enzyme and pathway databases

Reactome

REACT_109335. Circadian Clock.
REACT_24972. Circadian Clock (mouse).

Gene expression databases

ArrayExpress

O54943.

Bgee

O54943.

CleanEx

MM_PER2.

Genevestigator

O54943.

GermOnline

ENSMUSG00000055866. Mus musculus.

Family and domain databases

InterPro

IPR001610. PAC.
IPR000014. PAS.
IPR013655. PAS_fold_3.
IPR022728. Period_circadian-like_C.
[Graphical view]

Pfam

PF08447. PAS_3. 1 hit.
PF12114. Period_C. 1 hit.
[Graphical view]

SMART

SM00086. PAC. 1 hit.
SM00091. PAS. 2 hits.
[Graphical view]

PROSITE

PS50113. PAC. False negative.
PS50112. PAS. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

PER2. mouse.

EvolutionaryTrace

O54943.

NextBio

294580.

SOURCE

Search...

Entry information

Entry name

PER2_MOUSE

Accession

Primary (citable) accession number: O54943
Secondary accession number(s): O54954

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	July 15, 1999
Last modified:	May 1, 2013
This is version 105 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program