Reviewed, UniProtKB/Swiss-Prot Q9WTL8 (BMAL1_MOUSE)

Names and origin

Protein names

Recommended name:
    Aryl hydrocarbon receptor nuclear translocator-like protein 1
Alternative name(s):
    Brain and muscle ARNT-like 1
    Arnt3

Gene names

Name:	Arntl
Synonyms:	Bmal1

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	632 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	ARNTL-CLOCK heterodimers activate E-box element (3'-CACGTG-5') 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, ARNTL or ARNTL2, CSNK1D and/or CSNK1E, TIMELESS and the PER proteins. Efficient DNA binding requires dimerization with another bHLH protein. Heterodimerization with CLOCK is required for E-box-dependent transactivation, for CLOCK nuclear translocation and degradation, and, for phosphorylation of both CLOCK and ARNTL. Interaction with PER and CRY proteins requires translocation to the nucleus. Interaction of the CLOCK-ARNTL heterodimer with PER or CRY inhibits transcription activation. Interacts with HSP90; with AHR in vitro, but not in vivo By similarity.
Subcellular location	Nucleus By similarity.
Post-translational modification	Acetylated on Lys-544 upon dimerization with CLOCK. Acetylation facilitates CRY1- mediated repression. Phosphorylated upon dimerization with CLOCK. Ref.5 Ref.6 Sumoylated on Lys-266 upon dimerization with CLOCK. Ref.7
Sequence similarities	Contains 1 basic helix-loop-helix (bHLH) domain. Contains 1 PAC (PAS-associated C-terminal) domain. Contains 2 PAS (PER-ARNT-SIM) domains.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Domain	Repeat
Ligand	DNA-binding
Molecular function	Activator
PTM	Acetylation Isopeptide bond Phosphoprotein Ubl conjugation
Gene Ontology (GO)
Biological process	circadian rhythm Ref.6 Inferred from direct assay. Source: MGI positive regulation of transcription from RNA polymerase II promoter Inferred from genetic interaction. Source: MGI protein import into nucleus, translocation Ref.6 Inferred from direct assay. Source: MGI regulation of protein catabolic process Ref.6 Inferred from direct assay. Source: MGI signal transduction Inferred from electronic annotation. Source: InterPro transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	transcription factor complex Inferred from direct assay. Source: MGI
Molecular function	protein binding Inferred from physical interaction. Source: IntAct signal transducer activity Inferred from electronic annotation. Source: InterPro transcription factor activity Ref.2 Inferred from direct assay. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Clock	O08785	1	EBI-644534,EBI-79859
Cry1	P97784	3	EBI-644534,EBI-1266607
Cry2	Q99JJ1	3	EBI-644534,EBI-1794634
Per2	O54943	3	EBI-644534,EBI-1266779
SIRT1	Q96EB6	1	EBI-644559,EBI-1802965	From a different organism.
Sirt1	Q923E4	1	EBI-644559,EBI-1802585

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9WTL8-1)

Also known as: b';

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: Q9WTL8-2)

Also known as: b;

The sequence of this isoform differs from the canonical sequence as follows:
     48-54: Missing.

Isoform 3 (identifier: Q9WTL8-3)

The sequence of this isoform differs from the canonical sequence as follows:
     49-68: Missing.
     280-280: K → KA

Isoform 4 (identifier: Q9WTL8-4)

The sequence of this isoform differs from the canonical sequence as follows:
     48-54: Missing.
     280-280: K → KA

Isoform 5 (identifier: Q9WTL8-5)

Also known as: g';

The sequence of this isoform differs from the canonical sequence as follows:
     48-54: Missing.
     161-483: AADGFLFVVG...PSGEGGPKRT → DVTEGRSSLS...PRLDFRLKRI
     484-632: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 632	632	Aryl hydrocarbon receptor nuclear translocator-like protein 1		PRO_0000127158
Regions
	Domain	93 – 133	41	Helix-loop-helix motif
	Domain	150 – 222	73	PAS 1
	Domain	333 – 403	71	PAS 2
	Domain	408 – 451	44	PAC
	DNA binding	80 – 92	13	Basic motif
Amino acid modifications
	Modified residue	544	1	N6-acetyllysine Ref.8
	Cross-link	266		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.7
Natural variations
	Alternative sequence	48 – 54	7	Missing in isoform 2, isoform 4 and isoform 5.		VSP_007992
	Alternative sequence	49 – 68	20	Missing in isoform 3.		VSP_007993
	Alternative sequence	161 – 483	323	AADGF…GPKRT → DVTEGRSSLSPSLSSRSSII ARMTLLARACLTTCIQKILP KLRNSYLPRTLRPGSDSLMP RLDFRLKRI in isoform 5.		VSP_007995
	Alternative sequence	280	1	K → KA in isoform 3 and isoform 4.		VSP_007994
	Alternative sequence	484 – 632	149	Missing in isoform 5.		VSP_007996
Experimental info
	Mutagenesis	230	1	K → R: No effect on sumoylation. Ref.7
	Mutagenesis	236	1	K → R: No effect on sumoylation. Ref.7
	Mutagenesis	266	1	K → R: Abolishes sumoylation. Ref.7
	Mutagenesis	279	1	K → R: No effect on sumoylation. Ref.7
	Sequence conflict	254	1	F → L in BAA76414. Ref.1
	Sequence conflict	254	1	F → L in BAA81898. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (b') [UniParc]. Last modified August 15, 2003. Version 2. Checksum: 9669C3712A95C2DE	FASTA	632	69,452
	10 20 30 40 50 60 MADQRMDISS TISDFMSPGP TDLLSGSLGT SGVDCNRKRK GSATDYQLDD FAFEESMDTD 70 80 90 100 110 120 KDDPHGRLEY AEHQGRIKNA REAHSQIEKR RRDKMNSFID ELASLVPTCN AMSRKLDKLT 130 140 150 160 170 180 VLRMAVQHMK TLRGATNPYT EANYKPTFLS DDELKHLILR AADGFLFVVG CDRGKILFVS 190 200 210 220 230 240 ESVFKILNYS QNDLIGQSLF DYLHPKDIAK VKEQLSSSDT APRERLIDAK TGLPVKTDIT 250 260 270 280 290 300 PGPSRLCSGA RRSFFCRMKC NRPSVKVEDK DFASTCSKKK DRKSFCTIHS TGYLKSWPPT 310 320 330 340 350 360 KMGLDEDNEP DNEGCNLSCL VAIGRLHSHM VPQPANGEIR VKSMEYVSRH AIDGKFVFVD 370 380 390 400 410 420 QRATAILAYL PQELLGTSCY EYFHQDDIGH LAECHRQVLQ TREKITTNCY KFKIKDGSFI 430 440 450 460 470 480 TLRSRWFSFM NPWTKEVEYI VSTNTVVLAN VLEGGDPTFP QLTAPPHSMD SMLPSGEGGP 490 500 510 520 530 540 KRTHPTVPGI PGGTRAGAGK IGRMIAEEIM EIHRIRGSSP SSCGSSPLNI TSTPPPDASS 550 560 570 580 590 600 PGGKKILNGG TPDIPSTGLL PGQAQETPGY PYSDSSSILG ENPHIGIDMI DNDQGSSSPS 610 620 630 NDEAAMAVIM SLLEADAGLG GPVDFSDLPW PL
	Isoform 2 (b). Checksum: 5A99555F851260CF	FASTA	625	68,614
	10 20 30 40 50 60 MADQRMDISS TISDFMSPGP TDLLSGSLGT SGVDCNRKRK GSATDYQESM DTDKDDPHGR 70 80 90 100 110 120 LEYAEHQGRI KNAREAHSQI EKRRRDKMNS FIDELASLVP TCNAMSRKLD KLTVLRMAVQ 130 140 150 160 170 180 HMKTLRGATN PYTEANYKPT FLSDDELKHL ILRAADGFLF VVGCDRGKIL FVSESVFKIL 190 200 210 220 230 240 NYSQNDLIGQ SLFDYLHPKD IAKVKEQLSS SDTAPRERLI DAKTGLPVKT DITPGPSRLC 250 260 270 280 290 300 SGARRSFFCR MKCNRPSVKV EDKDFASTCS KKKDRKSFCT IHSTGYLKSW PPTKMGLDED 310 320 330 340 350 360 NEPDNEGCNL SCLVAIGRLH SHMVPQPANG EIRVKSMEYV SRHAIDGKFV FVDQRATAIL 370 380 390 400 410 420 AYLPQELLGT SCYEYFHQDD IGHLAECHRQ VLQTREKITT NCYKFKIKDG SFITLRSRWF 430 440 450 460 470 480 SFMNPWTKEV EYIVSTNTVV LANVLEGGDP TFPQLTAPPH SMDSMLPSGE GGPKRTHPTV 490 500 510 520 530 540 PGIPGGTRAG AGKIGRMIAE EIMEIHRIRG SSPSSCGSSP LNITSTPPPD ASSPGGKKIL 550 560 570 580 590 600 NGGTPDIPST GLLPGQAQET PGYPYSDSSS ILGENPHIGI DMIDNDQGSS SPSNDEAAMA 610 620 VIMSLLEADA GLGGPVDFSD LPWPL
	Isoform 3. Checksum: 24B91BA2E81D1A25	FASTA	613	67,200
	10 20 30 40 50 60 MADQRMDISS TISDFMSPGP TDLLSGSLGT SGVDCNRKRK GSATDYQLEY AEHQGRIKNA 70 80 90 100 110 120 REAHSQIEKR RRDKMNSFID ELASLVPTCN AMSRKLDKLT VLRMAVQHMK TLRGATNPYT 130 140 150 160 170 180 EANYKPTFLS DDELKHLILR AADGFLFVVG CDRGKILFVS ESVFKILNYS QNDLIGQSLF 190 200 210 220 230 240 DYLHPKDIAK VKEQLSSSDT APRERLIDAK TGLPVKTDIT PGPSRLCSGA RRSFFCRMKC 250 260 270 280 290 300 NRPSVKVEDK DFASTCSKKK ADRKSFCTIH STGYLKSWPP TKMGLDEDNE PDNEGCNLSC 310 320 330 340 350 360 LVAIGRLHSH MVPQPANGEI RVKSMEYVSR HAIDGKFVFV DQRATAILAY LPQELLGTSC 370 380 390 400 410 420 YEYFHQDDIG HLAECHRQVL QTREKITTNC YKFKIKDGSF ITLRSRWFSF MNPWTKEVEY 430 440 450 460 470 480 IVSTNTVVLA NVLEGGDPTF PQLTAPPHSM DSMLPSGEGG PKRTHPTVPG IPGGTRAGAG 490 500 510 520 530 540 KIGRMIAEEI MEIHRIRGSS PSSCGSSPLN ITSTPPPDAS SPGGKKILNG GTPDIPSTGL 550 560 570 580 590 600 LPGQAQETPG YPYSDSSSIL GENPHIGIDM IDNDQGSSSP SNDEAAMAVI MSLLEADAGL 610 GGPVDFSDLP WPL
	Isoform 4. Checksum: 837330EF65406CE4	FASTA	626	68,685
	10 20 30 40 50 60 MADQRMDISS TISDFMSPGP TDLLSGSLGT SGVDCNRKRK GSATDYQESM DTDKDDPHGR 70 80 90 100 110 120 LEYAEHQGRI KNAREAHSQI EKRRRDKMNS FIDELASLVP TCNAMSRKLD KLTVLRMAVQ 130 140 150 160 170 180 HMKTLRGATN PYTEANYKPT FLSDDELKHL ILRAADGFLF VVGCDRGKIL FVSESVFKIL 190 200 210 220 230 240 NYSQNDLIGQ SLFDYLHPKD IAKVKEQLSS SDTAPRERLI DAKTGLPVKT DITPGPSRLC 250 260 270 280 290 300 SGARRSFFCR MKCNRPSVKV EDKDFASTCS KKKADRKSFC TIHSTGYLKS WPPTKMGLDE 310 320 330 340 350 360 DNEPDNEGCN LSCLVAIGRL HSHMVPQPAN GEIRVKSMEY VSRHAIDGKF VFVDQRATAI 370 380 390 400 410 420 LAYLPQELLG TSCYEYFHQD DIGHLAECHR QVLQTREKIT TNCYKFKIKD GSFITLRSRW 430 440 450 460 470 480 FSFMNPWTKE VEYIVSTNTV VLANVLEGGD PTFPQLTAPP HSMDSMLPSG EGGPKRTHPT 490 500 510 520 530 540 VPGIPGGTRA GAGKIGRMIA EEIMEIHRIR GSSPSSCGSS PLNITSTPPP DASSPGGKKI 550 560 570 580 590 600 LNGGTPDIPS TGLLPGQAQE TPGYPYSDSS SILGENPHIG IDMIDNDQGS SSPSNDEAAM 610 620 AVIMSLLEAD AGLGGPVDFS DLPWPL
	Isoform 5 (g'). Checksum: 9AE175BE7F6A446C	FASTA	222	25,061
	10 20 30 40 50 60 MADQRMDISS TISDFMSPGP TDLLSGSLGT SGVDCNRKRK GSATDYQESM DTDKDDPHGR 70 80 90 100 110 120 LEYAEHQGRI KNAREAHSQI EKRRRDKMNS FIDELASLVP TCNAMSRKLD KLTVLRMAVQ 130 140 150 160 170 180 HMKTLRGATN PYTEANYKPT FLSDDELKHL ILRDVTEGRS SLSPSLSSRS SIIARMTLLA 190 200 210 220 RACLTTCIQK ILPKLRNSYL PRTLRPGSDS LMPRLDFRLK RI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of three splice variants and genomic organization of the mouse BMAL1 gene." Yu W., Ikeda M., Abe H., Honma S., Ebisawa T., Yamauchi T., Honma K., Nomura M. Biochem. Biophys. Res. Commun. 260:760-767(1999) [PubMed: 10403839] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 5). Tissue: Brain.
[2]	"Transcriptionally active heterodimer formation of an Arnt-like PAS protein, Arnt3, with HIF-1a, HLF, and clock." Takahata S., Sogawa K., Kobayashi A., Ema M., Mimura J., Ozaki N., Fujii-Kuriyama Y. Biochem. Biophys. Res. Commun. 248:789-794(1998) [PubMed: 9704006] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4).
[4]	"Role of the CLOCK protein in the mammalian circadian mechanism." Gekakis N., Staknis D., Nguyen H.B., Davis F.C., Wilsbacher L.D., King D.P., Takahashi J.S., Weitz C.J. Science 280:1564-1569(1998) [PubMed: 9616112] [Abstract] Cited for: INTERACTION WITH CLOCK.
[5]	"Posttranslational mechanisms regulate the mammalian circadian clock." Lee C., Etchegaray J.-P., Cagampang F.R.A., Loudon A.S.I., Reppert S.M. Cell 107:855-867(2001) [PubMed: 11779462] [Abstract] Cited for: PHOSPHORYLATION, SUBCELLULAR LOCATION.
[6]	"BMAL1-dependent circadian oscillation of nuclear CLOCK: posttranslational events induced by dimerization of transcriptional activators of the mammalian clock system." Kondratov R.V., Chernov M.V., Kondratova A.A., Gorbacheva V.Y., Gudkov A.V., Antoch M.P. Genes Dev. 17:1921-1932(2003) [PubMed: 12897057] [Abstract] Cited for: PHOSPHORYLATION, SUBCELLULAR LOCATION.
[7]	"Circadian clock control by SUMOylation of BMAL1." Cardone L., Hirayama J., Giordano F., Tamaru T., Palvimo J.J., Sassone-Corsi P. Science 309:1390-1394(2005) [PubMed: 16109848] [Abstract] Cited for: SUMOYLATION AT LYS-266, MUTAGENESIS OF LYS-230; LYS-236; LYS-266 AND LYS-279.
[8]	"CLOCK-mediated acetylation of BMAL1 controls circadian function." Hirayama J., Sahar S., Grimaldi B., Tamaru T., Takamatsu K., Nakahata Y., Sassone-Corsi P. Nature 450:1086-1090(2007) [PubMed: 18075593] [Abstract] Cited for: ACETYLATION AT LYS-544.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB012601 mRNA. Translation: BAA76414.1. AB015203 mRNA. Translation: BAA81898.1. AB012602 mRNA. Translation: BAA76415.1. AB014494 mRNA. Translation: BAA32208.1. BC025973 mRNA. Translation: AAH25973.1. BC011080 mRNA. Translation: AAH11080.1.
IPI	IPI00403502. IPI00462286. IPI00474434. IPI00474567. IPI00875930.
PIR	JE0270.
RefSeq	NP_031515.1.
UniGene	Mm.440371
3D structure databases
HSSP	HSSP built from PDB template 1AM9 based on UniProtKB P36956.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9WTL8. 14 interactions.
STRING	Q9WTL8.
PTM databases
PhosphoSite	Q9WTL8.
Proteomic databases
PRIDE	Q9WTL8.
Genome annotation databases
Ensembl	ENSMUST00000047321; ENSMUSP00000046235; ENSMUSG00000055116; Mus musculus. [Genome view] ENSMUST00000084703; ENSMUSP00000081753; ENSMUSG00000055116; Mus musculus. [Genome view] ENSMUST00000106637; ENSMUSP00000102248; ENSMUSG00000055116; Mus musculus. [Genome view]
GeneID	11865.
KEGG	mmu:11865.
UCSC	uc009jhe.1. mouse. uc009jhf.1. mouse. uc009jhi.1. mouse. uc009jhj.1. mouse.
Organism-specific databases
MGI	MGI:1096381. Arntl.
Phylogenomic databases
HOVERGEN	Q9WTL8.
Gene expression databases
ArrayExpress	Q9WTL8.
Bgee	Q9WTL8.
Genevestigator	Q9WTL8.
GermOnline	ENSMUSG00000055116. Mus musculus.
Family and domain databases
InterPro	IPR001092. HLH_basic. IPR011598. HLH_DNA_bd. IPR001067. Nuc_translocat. IPR001610. PAC. IPR000014. PAS. IPR013767. PAS_fold. IPR013655. PAS_fold_3. [Graphical view]
Gene3D	G3DSA:4.10.280.10. HLH_DNA_bd. 1 hit.
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]
PROSITE	PS50888. HLH. 1 hit. PS50113. PAC. False negative. PS50112. PAS. 2 hits. [Graphical view]
ProtoNet	Search...
Other Resources
SOURCE	Search...

Entry information

Entry name

BMAL1_MOUSE

Accession

Primary (citable) accession number: Q9WTL8
Secondary accession number(s): O88295 , Q921S4, Q9R0U2, Q9WTL9

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 15, 2003
Last sequence update:	August 15, 2003
Last modified:	October 13, 2009
This is version 83 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)