Reviewed, UniProtKB/Swiss-Prot O15534 (PER1_HUMAN)

Names and origin

Protein names

Recommended name:
    Period circadian protein homolog 1
Alternative name(s):
    Circadian clock protein PERIOD 1
    Circadian pacemaker protein Rigui
      Short name=hPER1

Gene names

Name:	PER1
Synonyms:	KIAA0482, PER, RIGUI

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1290 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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 By similarity.
Subunit structure	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 TIMELESS, PER2, PER3 and, through a C-terminal domain, with CRY1 and CRY2. Interaction with CSNK1D or CSNK1E promotes nuclear location of PER proteins. Interacts with GPRASP1 By similarity.
Subcellular location	NucleusBy similarity. CytoplasmBy 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 PER1 nuclear localization signal. Also translocated to the nucleus by CRY1 or CRY2 By similarity.
Tissue specificity	Widely expressed. Found in heart, brain, placenta, lung, liver, skeletal muscle, pancreas, kidney, spleen, thymus, prostate, testis, ovary and small intestine. Highest level in skeletal muscle. Low level in kidney.
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 20 hours. Protein levels show maximum levels at 6 hours, decrease to reach minimum levels at 20 hours, and increase again to reach a second peak after 26 hours. Levels then decrease slightly and then increase to maximum levels at 32 hours. Levels of phosphorylated form increase between 3 hours and 12 hours.
Post-translational modification	Phosphorylated on serine residues by CSNK1E. Also can be phosphorylated by the delta isoform. Phosphorylation by CSNK1 retains PER1 in the cytoplasm and leads to its ubiquitination and subsequent degradation. Phosphorylated upon DNA damage, probably by ATM or ATR. Ubiquitinated By similarity.
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
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure
Gene Ontology (GO)
Biological process	entrainment of circadian clock Ref.1 Traceable author statement. Source: ProtInc negative regulation of transcription Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	protein binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Select]

Notes: Additional isoforms seem to exist.

Isoform Rigui 4.7 (identifier: O15534-1)

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 Rigui 3.0 (identifier: O15534-2)

The sequence of this isoform is not available.

Isoform Rigui 6.6 (identifier: O15534-3)

Also known as: Truncated;

The sequence of this isoform is not available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 1290	1290	Period circadian protein homolog 1
Regions
	Domain	208 – 275	68	PAS 1
	Domain	348 – 414	67	PAS 2
	Domain	422 – 465	44	PAC
	Region	596 – 815	220	CSNK1E binding domain By similarity
	Region	1149 – 1290	142	CRY binding domain By similarity
	Motif	486 – 498	13	Nuclear export signal By similarity
	Motif	827 – 843	17	Nuclear localization signal By similarity
	Compositional bias	49 – 129	81	Ser-rich
	Compositional bias	653 – 656	4	Poly-Ser
	Compositional bias	848 – 1013	166	Pro-rich
	Compositional bias	1030 – 1104	75	Ser-rich
	Compositional bias	1269 – 1273	5	Poly-Glu
	Compositional bias	1276 – 1279	4	Poly-Ser
Amino acid modifications
	Modified residue	979	1	Phosphoserine
	Modified residue	980	1	Phosphoserine
	Modified residue	1100	1	Phosphoserine
	Modified residue	1103	1	Phosphoserine
	Modified residue	1104	1	Phosphoserine
	Modified residue	1262	1	Phosphoserine
	Modified residue	1263	1	Phosphoserine
Natural variations
	Natural variant	696	1	E → Q in a breast cancer sample; somatic mutation.
	Natural variant	985	1	N → S in a breast cancer sample; somatic mutation.
	Natural variant	1060	1	S → L in a colorectal cancer sample; somatic mutation.

Sequences

	Sequence		Length	Mass (Da)
	Isoform Rigui 4.7 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 24B53042869A4562	FASTA	1,290	136,238
	10 20 30 40 50 60 MSGPLEGADG GGDPRPGESF CPGGVPSPGP PQHRPCPGPS LADDTDANSN GSSGNESNGH 70 80 90 100 110 120 ESRGASQRSS HSSSSGNGKD SALLETTESS KSTNSQSPSP PSSSIAYSLL SASSEQDNPS 130 140 150 160 170 180 TSGCSSEQSA RARTQKELMT ALRELKLRLP PERRGKGRSG TLATLQYALA CVKQVQANQE 190 200 210 220 230 240 YYQQWSLEEG EPCSMDMSTY TLEELEHITS EYTLQNQDTF SVAVSFLTGR IVYISEQAAV 250 260 270 280 290 300 LLRCKRDVFR GTRFSELLAP QDVGVFYGST APSRLPTWGT GASAGSGLRD FTQEKSVFCR 310 320 330 340 350 360 IRGGPDRDPG PRYQPFRLTP YVTKIRVSDG APAQPCCLLI AERIHSGYEA PRIPPDKRIF 370 380 390 400 410 420 TTRHTPSCLF QDVDERAAPL LGYLPQDLLG APVLLFLHPE DRPLMLAIHK KILQLAGQPF 430 440 450 460 470 480 DHSPIRFCAR NGEYVTMDTS WAGFVHPWSR KVAFVLGRHK VRTAPLNEDV FTPPAPSPAP 490 500 510 520 530 540 SLDTDIQELS EQIHRLLLQP VHSPSPTGLC GVGAVTSPGP LHSPGSSSDS NGGDAEGPGP 550 560 570 580 590 600 PAPVTFQQIC KDVHLVKHQG QQLFIESRAR PQSRPRLPAT GTFKAKALPC QSPDPELEAG 610 620 630 640 650 660 SAPVQAPLAL VPEEAERKEA SSCSYQQINC LDSILRYLES CNLPSTTKRK CASSSSYTTS 670 680 690 700 710 720 SASDDDRQRT GPVSVGTKKD PPSAALSGEG ATPRKEPVVG GTLSPLALAN KAESVVSVTS 730 740 750 760 770 780 QCSFSSTIVH VGDKKPPESD IIMMEDLPGL APGPAPSPAP SPTVAPDPAP DAYRPVGLTK 790 800 810 820 830 840 AVLSLHTQKE EQAFLSRFRD LGRLRGLDSS STAPSALGER GCHHGPAPPS RRHHCRSKAK 850 860 870 880 890 900 RSRHHQNPRA EAPCYVSHPS PVPPSTPWPT PPATTPFPAV VQPYPLPVFS PRGGPQPLPP 910 920 930 940 950 960 APTSVPPAAF PAPLVTPMVA LVLPNYLFPT PSSYPYGALQ TPAEGPPTPA SHSPSPSLPA 970 980 990 1000 1010 1020 LPPSPPHRPD SPLFNSRCSS PLQLNLLQLE ELPRAEGAAV AGGPGSSAGP PPPSAEAAEP 1030 1040 1050 1060 1070 1080 EARLAEVTES SNQDALSGSS DLLELLLQED SRSGTGSAAS GSLGSGLGSG SGSGSHEGGS 1090 1100 1110 1120 1130 1140 TSASITRSSQ SSHTSKYFGS IDSSEAEAGA ARGGAEPGDQ VIKYVLQDPI WLLMANADQR 1150 1160 1170 1180 1190 1200 VMMTYQVPSR DMTSVLKQDR ERLRAMQKQQ PRFSEDQRRE LGAVHSWVRK GQLPRALDVM 1210 1220 1230 1240 1250 1260 ACVDCGSSTQ DPGHPDDPLF SELDGLGLEP MEEGGGEQGS SGGGSGEGEG CEEAQGGAKA 1270 1280 1290 SSSQDLAMEE EEEGRSSSSP ALPTAGNCTS
	Isoform Rigui 3.0 (Sequence not available).		–	–
	Isoform Rigui 6.6 (Truncated) (Sequence not available).		–	–

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Rigui, a putative mammalian ortholog of the Drosophila period gene." Sun Z.S., Albrecht U., Zhuchenko O., Bailey J., Eichele G., Lee C.C. Cell 90:1003-1011(1997) [PubMed: 9323128] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING. Tissue: Heart.
[2]	"Circadian oscillation of a mammalian homologue of the Drosophila period gene." Tei H., Okamura H., Shigeyoshi Y., Fukuhara C., Ozawa R., Hirose M., Sakaki Y. Nature 389:512-516(1997) [PubMed: 9333243] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Brain.
[3]	"The human Per1 gene: genomic organization and promoter analysis of the first human orthologue of the Drosophila period gene." Taruscio D., Zoraqi G.K., Falchi M., Iosi F., Paradisi S., Di Fiore B., Lavia P., Falbo V. Gene 253:161-170(2000) [PubMed: 10940553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"The human and mouse Period1 genes: five well-conserved E-boxes additively contribute to the enhancement of mPer1 transcription." Hida A., Koike N., Hirose M., Hattori M., Sakaki Y., Tei H. Genomics 65:224-233(2000) [PubMed: 10857746] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"Characterization of cDNA clones in size-fractionated cDNA libraries from human brain." Seki N., Ohira M., Nagase T., Ishikawa K., Miyajima N., Nakajima D., Nomura N., Ohara O. DNA Res. 4:345-349(1997) [PubMed: 9455484] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[6]	Nagase T., Kikuno R., Ohara O. Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[7]	"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: 9427249] [Abstract] Cited for: TISSUE SPECIFICITY.
[8]	"Phosphorylation and destabilization of human period I clock protein by human casein kinase I epsilon." Keesler G.A., Camacho F., Guo Y., Virshup D., Mondadori C., Yao Z. NeuroReport 11:951-955(2000) [PubMed: 10790862] [Abstract] Cited for: PHOSPHORYLATION, INTERACTION WITH CSNK1E.
[9]	"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: 11165242] [Abstract] Cited for: PHOSPHORYLATION, INTERACTION WITH CSNK1D.
[10]	"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: 14750904] [Abstract] Cited for: PHOSPHORYLATION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INDUCTION.
[11]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-979; SER-980; SER-1100; SER-1103 AND SER-1104, MASS SPECTROMETRY. Tissue: Epithelium.
[12]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1262 AND SER-1263, MASS SPECTROMETRY.
[13]	"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. , 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: 16959974] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLN-696; SER-985 AND LEU-1060.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF022991 mRNA. Translation: AAC51765.1.
AB002107 mRNA. Translation: BAA22633.1.
AF102137 Genomic DNA. Translation: AAF15544.1.
AB030817 Genomic DNA. Translation: BAA94085.1.
AB088477 mRNA. Translation: BAC06326.2. Different initiation.

PIR

T00018.

UniGene

Hs.445534

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1UL6	model	-	A	830-845	[»]

ModBase

Search...

PTM databases

PhosphoSite

O15534.

Genome annotation databases

Ensembl

ENSG00000179094. Homo sapiens. [Contig view]

KEGG

hsa:5187.

Organism-specific databases

H-InvDB

HIX0019808.

HGNC

HGNC:8845. PER1.

MIM

602260. gene.

PharmGKB

PA38438.

HUGE

Search...

GenAtlas

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GeneCards

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Phylogenomic databases

HOGENOM

O15534.

HOVERGEN

O15534.

Gene expression databases

ArrayExpress

O15534.

CleanEx

HS_PER1.

GermOnline

ENSG00000179094. Homo sapiens.

Family and domain databases

InterPro

IPR001610. PAC.
IPR000014. PAS.
IPR000700. PAS-assoc_C.
IPR013655. PAS_3.
[Graphical view]

Pfam

PF08447. PAS_3. 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]

ProDom

O15534.
[Graphical view] [Entries sharing at least one domain]

BLOCKS

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Other Resources

SOURCE

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ProtoNet

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Entry information

Entry name

PER1_HUMAN

Accession

Primary (citable) accession number: O15534

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	January 1, 1998
Last modified:	September 23, 2008
This is version 80 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)