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O15055 (PER2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 134. 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·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Period circadian protein homolog 2

Short name=hPER2
Alternative name(s):
Circadian clock protein PERIOD 2
Gene names
Name:PER2
Synonyms:KIAA0347
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1255 AA.
Sequence statusComplete.
Protein existenceEvidence 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 By similarity.

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. Interaction with CSNK1D or CSNK1E promotes nuclear location of PER proteins. Interacts, via its second PAS domain, with TIMELESS in vitro. Interacts with NFIL3 By similarity. Interacts with PML By similarity. Interacts with CIART By similarity. Ref.2 Ref.11

Subcellular location

Nucleus By similarity. Cytoplasm By similarity. Cytoplasmperinuclear region By similarity. 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 By similarity. PML regulates its nuclear localization By similarity.

Tissue specificity

Widely expressed. Found in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. High levels in skeletal muscle and pancreas. Low level in lung. Ref.8

Induction

Serum-induced levels in fibroblasts show circadian oscillations. Maximum levels after 1 hour stimulation, minimum levels after 12 hours. Another peak is then observed after 24 hours. Ref.9

Post-translational modification

Phosphorylated by CSNK1E and CSNK1D. Phosphorylation results in PER2 protein degradation. Ref.2 Ref.11

Involvement in disease

Advanced sleep phase syndrome, familial, 1 (FASPS1) [MIM:604348]: A disorder characterized by very early sleep onset and offset. Individuals are 'morning larks' with a 4 hours advance of the sleep, temperature and melatonin rhythms.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11

Sequence similarities

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

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

Sequence caution

The sequence BAA20804.2 differs from that shown. Reason: Erroneous initiation.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O15055-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O15055-2)

Also known as: PER2S;

The sequence of this isoform differs from the canonical sequence as follows:
     349-404: RAVPLLGYLP...YSPIRFRARN → SPAVRRAAFR...EAQSQGGPFE
     405-1255: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 12551255Period circadian protein homolog 2
PRO_0000162630

Regions

Domain181 – 24868PAS 1
Domain321 – 38767PAS 2
Domain395 – 43844PAC
Region557 – 771215CSNK1E binding domain By similarity
Region1155 – 1255101CRY binding domain By similarity
Motif459 – 47113Nuclear export signal By similarity
Motif789 – 80517Nuclear localization signal By similarity
Compositional bias510 – 5134Poly-Arg
Compositional bias842 – 979138Pro-rich

Amino acid modifications

Modified residue5271Phosphoserine By similarity
Modified residue5301Phosphoserine By similarity
Modified residue5331Phosphoserine By similarity
Modified residue5401Phosphoserine By similarity
Modified residue6621Phosphoserine Ref.11
Modified residue6961Phosphoserine By similarity
Modified residue7001Phosphoserine By similarity
Modified residue7141Phosphoserine By similarity
Modified residue7661Phosphoserine By similarity
Modified residue7711Phosphoserine By similarity
Modified residue9451Phosphoserine By similarity
Modified residue9771Phosphoserine By similarity
Modified residue11241Phosphoserine By similarity

Natural variations

Alternative sequence349 – 40456RAVPL…FRARN → SPAVRRAAFRLFSHSVSRPE RRVHHVGHQLVQLHQPMEQE NLLHHWEAQSQGGPFE in isoform 2.
VSP_021653
Alternative sequence405 – 1255851Missing in isoform 2.
VSP_021654
Natural variant51A → S.
Corresponds to variant rs35572922 [ dbSNP | Ensembl ].
VAR_051575
Natural variant6621S → G in FASPS1; reduced in vitro phosphorylation by CSNK1E. Ref.11
VAR_029080
Natural variant7291V → I.
Corresponds to variant rs4429421 [ dbSNP | Ensembl ].
VAR_051576
Natural variant8231L → V in a breast cancer sample; somatic mutation. Ref.12
VAR_036041
Natural variant9031V → I.
Corresponds to variant rs35333999 [ dbSNP | Ensembl ].
VAR_051577
Natural variant9491F → Y.
Corresponds to variant rs35998480 [ dbSNP | Ensembl ].
VAR_051578
Natural variant12441G → E.
Corresponds to variant rs934945 [ dbSNP | Ensembl ].
VAR_024558

Experimental info

Mutagenesis6621S → D: Restores CSNK1E-dependent phosphorylation of variant G-662. Ref.11

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 11, 2001. Version 2.
Checksum: 2AEF2C6BD4B6CBB0

FASTA1,255136,579
        10         20         30         40         50         60 
MNGYAEFPPS PSNPTKEPVE PQPSQVPLQE DVDMSSGSSG HETNENCSTG RDSQGSDCDD 

        70         80         90        100        110        120 
SGKELGMLVE PPDARQSPDT FSLMMAKSEH NPSTSGCSSD QSSKVDTHKE LIKTLKELKV 

       130        140        150        160        170        180 
HLPADKKAKG KASTLATLKY ALRSVKQVKA NEEYYQLLMS SEGHPCGADV PSYTVEEMES 

       190        200        210        220        230        240 
VTSEHIVKNA DMFAVAVSLV SGKILYISDQ VASIFHCKRD AFSDAKFVEF LAPHDVGVFH 

       250        260        270        280        290        300 
SFTSPYKLPL WSMCSGADSF TQECMEEKSF FCRVSVRKSH ENEIRYHPFR MTPYLVKVRD 

       310        320        330        340        350        360 
QQGAESQLCC LLLAERVHSG YEAPRIPPEK RIFTTTHTPN CLFQDVDERA VPLLGYLPQD 

       370        380        390        400        410        420 
LIETPVLVQL HPSDRPLMLA IHKKILQSGG QPFDYSPIRF RARNGEYITL DTSWSSFINP 

       430        440        450        460        470        480 
WSRKISFIIG RHKVRVGPLN EDVFAAHPCT EEKALHPSIQ ELTEQIHRLL LQPVPHSGSS 

       490        500        510        520        530        540 
GYGSLGSNGS HEHLMSQTSS SDSNGHEDSR RRRAEICKNG NKTKNRSHYS HESGEQKKKS 

       550        560        570        580        590        600 
VTEMQTNPPA EKKAVPAMEK DSLGVSFPEE LACKNQPTCS YQQISCLDSV IRYLESCNEA 

       610        620        630        640        650        660 
ATLKRKCEFP ANVPALRSSD KRKATVSPGP HAGEAEPPSR VNSRTGVGTH LTSLALPGKA 

       670        680        690        700        710        720 
ESVASLTSQC SYSSTIVHVG DKKPQPELEM VEDAASGPES LDCLAGPALA CGLSQEKEPF 

       730        740        750        760        770        780 
KKLGLTKEVL AAHTQKEEQS FLQKFKEIRK LSIFQSHCHY YLQERSKGQP SERTAPGLRN 

       790        800        810        820        830        840 
TSGIDSPWKK TGKNRKLKSK RVKPRDSSES TGSGGPVSAR PPLVGLNATA WSPSDTSQSS 

       850        860        870        880        890        900 
CPAVPFPAPV PAAYSLPVFP APGTVAAPPA PPHASFTVPA VPVDLQHQFA VQPPPFPAPL 

       910        920        930        940        950        960 
APVMAFMLPS YSFPSGTPNL PQAFFPSQPQ FPSHPTLTSE MASASQPEFP SRTSIPRQPC 

       970        980        990       1000       1010       1020 
ACPATRATPP SAMGRASPPL FQSRSSSPLQ LNLLQLEEAP EGGTGAMGTT GATETAAVGA 

      1030       1040       1050       1060       1070       1080 
DCKPGTSRDQ QPKAPLTRDE PSDTQNSDAL STSSGLLNLL LNEDLCSASG SAASESLGSG 

      1090       1100       1110       1120       1130       1140 
SLGCDASPSG AGSSDTSHTS KYFGSIDSSE NNHKAKMNTG MEESEHFIKC VLQDPIWLLM 

      1150       1160       1170       1180       1190       1200 
ADADSSVMMT YQLPSRNLEA VLKEDREKLK LLQKLQPRFT ESQKQELREV HQWMQTGGLP 

      1210       1220       1230       1240       1250 
AAIDVAECVY CENKEKGNIC IPYEEDIPSL GLSEVSDTKE DENGSPLNHR IEEQT 

« Hide

Isoform 2 (PER2S) [UniParc].

Checksum: B6DED6DD2AC3F971
Show »

FASTA40445,175

References

« Hide 'large scale' references
[1]"cDNA cloning and characterization of Per2S, an alternatively spliced human Per2 variant."
Ikeda M., Takehara N., Ebisawa T., Yamauchi T., Nomura M.
Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Brain.
[2]"Human casein kinase Idelta phosphorylation of human circadian clock proteins period 1 and 2."
Camacho F., Cilio M., Guo Y., Virshup D.M., Patel K., Khorkova O., Styren S., Morse B., Yao Z., Keesler G.A.
FEBS Lett. 489:159-165(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PHOSPHORYLATION, INTERACTION WITH CSNK1D.
Tissue: Brain.
[3]NHLBI resequencing and genotyping service (RS&G)
Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro."
Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 4:141-150(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[5]Nagase T., Ishikawa K., Seki N., Nakajima D., Ohira M., Miyajima N., Kotani H., Nomura N., Ohara O.
Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION TO C-TERMINUS.
[6]"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].
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"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: TISSUE SPECIFICITY.
[9]"Phosphorylation of clock protein PER1 regulates its circadian degradation in normal human fibroblasts."
Miyazaki K., Nagase T., Mesaki M., Narukawa J., Ohara O., Ishida N.
Biochem. J. 380:95-103(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[10]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"An hPer2 phosphorylation site mutation in familial advanced sleep phase syndrome."
Toh K.L., Jones C.R., He Y., Eide E.J., Hinz W.A., Virshup D.M., Ptacek L.J., Fu Y.-H.
Science 291:1040-1043(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT FASPS1 GLY-662, INTERACTION WITH CSNK1E, PHOSPHORYLATION AT SER-662, MUTAGENESIS OF SER-662.
[12]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] VAL-823.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB012614 mRNA. Translation: BAA83709.1.
EF015905 Genomic DNA. Translation: ABM64216.1.
AB002345 mRNA. Translation: BAA20804.2. Different initiation.
AC012485 Genomic DNA. Translation: AAX88976.1.
CH471063 Genomic DNA. Translation: EAW71155.1.
RefSeqNP_073728.1. NM_022817.2.
XP_005246168.1. XM_005246111.2.
UniGeneHs.58756.

3D structure databases

ProteinModelPortalO15055.
SMRO15055. Positions 115-525.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114387. 10 interactions.
DIPDIP-38051N.
IntActO15055. 2 interactions.
STRING9606.ENSP00000254657.

PTM databases

PhosphoSiteO15055.

Proteomic databases

PaxDbO15055.
PRIDEO15055.

Protocols and materials databases

DNASU8864.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000254657; ENSP00000254657; ENSG00000132326. [O15055-1]
ENST00000254658; ENSP00000254658; ENSG00000132326. [O15055-2]
ENST00000355768; ENSP00000348013; ENSG00000132326. [O15055-2]
GeneID8864.
KEGGhsa:8864.
UCSCuc002vyc.3. human. [O15055-1]
uc010fyx.1. human. [O15055-2]

Organism-specific databases

CTD8864.
GeneCardsGC02M239188.
H-InvDBHIX0030280.
HGNCHGNC:8846. PER2.
HPAHPA053136.
MIM603426. gene.
604348. phenotype.
neXtProtNX_O15055.
Orphanet164736. Familial advanced sleep-phase syndrome.
PharmGKBPA33185.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG253593.
HOGENOMHOG000231111.
HOVERGENHBG008167.
InParanoidO15055.
KOK02633.
OMANATAWSP.
OrthoDBEOG78SQH2.
PhylomeDBO15055.
TreeFamTF318445.

Enzyme and pathway databases

ReactomeREACT_24941. Circadian Clock.

Gene expression databases

ArrayExpressO15055.
BgeeO15055.
CleanExHS_PER2.
GenevestigatorO15055.

Family and domain databases

InterProIPR001610. PAC.
IPR000014. PAS.
IPR022728. Period_circadian-like_C.
[Graphical view]
PfamPF12114. Period_C. 1 hit.
[Graphical view]
SMARTSM00086. PAC. 1 hit.
SM00091. PAS. 2 hits.
[Graphical view]
SUPFAMSSF55785. SSF55785. 1 hit.
PROSITEPS50112. PAS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiPER2.
GenomeRNAi8864.
NextBio33285.
PROO15055.
SOURCESearch...

Entry information

Entry namePER2_HUMAN
AccessionPrimary (citable) accession number: O15055
Secondary accession number(s): A2I2P7, Q4ZG49, Q9UQ45
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: July 11, 2001
Last modified: April 16, 2014
This is version 134 of the entry and version 2 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