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O00327 (BMAL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 148. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | 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:
Aryl hydrocarbon receptor nuclear translocator-like protein 1
Alternative name(s):
Basic-helix-loop-helix-PAS protein MOP3
Brain and muscle ARNT-like 1
Class E basic helix-loop-helix protein 5
Short name=bHLHe5
Member of PAS protein 3
PAS domain-containing protein 3
bHLH-PAS protein JAP3
Gene names
Name:ARNTL
Synonyms:BHLHE5, BMAL1, MOP3, PASD3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length626 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transcriptional activator which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, ARNTL/BMAL1, ARNTL2/BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and ARNTL/BMAL1 or ARNTL2/BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1, NR1D2, RORA, RORB and RORG, which form a second feedback loop and which activate and repress ARNTL/BMAL1 transcription, respectively. ARNTL/BMAL1 positively regulates myogenesis and negatively regulates adipogenesis via the transcriptional control of the genes of the canonical Wnt signaling pathway. Plays a role in normal pancreatic beta-cell function; regulates glucose-stimulated insulin secretion via the regulation of antioxidant genes NFE2L2/NRF2 and its targets SESN2, PRDX3, CCLC and CCLM. Negatively regulates the mTORC1 signaling pathway; regulates the expression of MTOR and DEPTOR. Controls diurnal oscillations of Ly6C inflammatory monocytes; rhythmic recruitment of the PRC2 complex imparts diurnal variation to chemokine expression that is necessary to sustain Ly6C monocyte rhythms. Regulates the expression of HSD3B2, STAR, PTGS2, CYP11A1, CYP19A1 and LHCGR in the ovary and also the genes involved in hair growth. Plays an important role in adult hippocampal neurogenesis by regulating the timely entry of neural stem/progenitor cells (NSPCs) into the cell cycle and the number of cell divisions that take place prior to cell-cycle exit. The CLOCK-ARNTL/BMAL1 heterodimer regulates the circadian expression of SERPINE1/PAI1, VWF, B3, CCRN4L/NOC, NAMPT, DBP, MYOD1, PPARGC1A, PPARGC1B, SIRT1, GYS2 and also genes implicated in glucose and lipid metabolism. Represses glucocorticoid receptor (GR)-induced transcriptional activity by reducing the association of GR to glucocorticoid response elements (GREs) via the acetylation of multiple lysine residues located in its hinge region. Promotes rhythmic chromatin opening, regulating the DNA accessibility of other transcription factors. Ref.11 Ref.13 Ref.15 Ref.18

Subunit structure

Component of the circadian clock oscillator which includes the CRY1/2 proteins, CLOCK or NPAS2, ARNTL/BMAL1 or ARNTL2/BMAL2, CSNK1D and/or CSNK1E, TIMELESS and the PER1/2/3 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/BMAL1. Interacts with HSP90; with AHR in vitro, but not in vivo. Part of a nuclear complex which also includes GNB2L1/RACK1 and PRKCA; GNB2L1 and PRKCA are recruited to the complex in a circadian manner. Interacts with PER2, CRY1 and CRY2. Interaction with PER and CRY proteins requires translocation to the nucleus. Interaction of the CLOCK-ARNTL/BMAL1 heterodimer with PER or CRY inhibits transcription activation. Interacts with CIART. Interacts with DDX4, SUMO3, OGT, EED, EZH2 and SUZ12. The CLOCK-ARNTL/BMAL1 heterodimer interacts with GSK3B. Ref.2 Ref.10 Ref.17

Subcellular location

Nucleus. Cytoplasm By similarity. NucleusPML body By similarity. Note: Shuttles between the nucleus and the cytoplasm and this nucleocytoplasmic shuttling is essential for the nuclear accumulation of CLOCK, target gene transcription and the degradation of the CLOCK-ARNTL/BMAL1 heterodimer. The sumoylated form localizes in the PML body By similarity. Ref.18

Tissue specificity

Hair follicles (at protein level). Highly expressed in the adult brain, skeletal muscle and heart. Ref.18

Post-translational modification

Ubiquitinated, leading to its proteasomal degradation By similarity.

O-glycosylated; contains O-GlcNAc. O-glycosylation by OGT prevents protein degradation by inhibiting ubiquitination. It also stabilizes the CLOCK-ARNTL/BMAL1 heterodimer thereby increasing CLOCK-ARNTL/BMAL1-mediated transcription of genes in the negative loop of the circadian clock such as PER1/2/3 and CRY1/2 By similarity.

Acetylated on Lys-538 upon dimerization with CLOCK. Acetylation facilitates CRY1-mediated repression By similarity.

Phosphorylated upon dimerization with CLOCK. Phosphorylation enhances the transcriptional activity, alters the subcellular localization and decreases the stability of the CLOCK-ARNTL/BMAL1 heterodimer by promoting its degradation. Phosphorylation shows circadian variations in the liver with a peak between CT10 to CT14. Phosphorylation at Ser-90 by CK2 is essential for its nuclear localization, its interaction with CLOCK and controls CLOCK nuclear entry By similarity.

Sumoylated on Lys-259 upon dimerization with CLOCK. Predominantly conjugated to poly-SUMO2/3 rather than SUMO1 and the level of these conjugates undergo rhythmic variation, peaking at CT9-CT12. Sumoylation localizes it exclusively to the PML body and promotes its ubiquitination in the PML body, ubiquitin-dependent proteasomal degradation and the transcriptional activity of the CLOCK-ARNTL/BMAL1 heterodimer By similarity.

Miscellaneous

CLOCK-ARNTL/BMAL1 double mutations within the PAS domains result in syngernistic desensitization to high levels of CRY on repression of CLOCK-ARNTL/BMAL1 transcriptional activity of PER1 and, disrupt circadian rhythmicity.

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 processBiological rhythms
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   DomainRepeat
   LigandDNA-binding
   Molecular functionActivator
   PTMAcetylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcircadian regulation of gene expression

Inferred from direct assay Ref.18. Source: UniProtKB

circadian rhythm

Traceable author statement Ref.10. Source: ProtInc

negative regulation of fat cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

oxidative stress-induced premature senescence

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of canonical Wnt signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of skeletal muscle cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 20093779. Source: BHF-UCL

positive regulation of transcription, DNA-templated

Inferred from direct assay Ref.11. Source: UniProtKB

protein import into nucleus, translocation

Inferred from electronic annotation. Source: Ensembl

regulation of cell cycle

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of cellular senescence

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of hair cycle

Inferred from mutant phenotype Ref.18. Source: UniProtKB

regulation of neurogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of protein catabolic process

Inferred from electronic annotation. Source: Ensembl

regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

spermatogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: GOC

   Cellular_componentchromatoid body

Inferred from sequence or structural similarity. Source: UniProtKB

nuclear body

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay Ref.18. Source: UniProtKB

transcription factor complex

Inferred from physical interaction Ref.4. Source: MGI

   Molecular_functionDNA binding

Inferred from genetic interaction Ref.4. Source: MGI

E-box binding

Inferred from direct assay Ref.11. Source: UniProtKB

Hsp90 protein binding

Inferred from direct assay Ref.2. Source: BHF-UCL

RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity

Inferred from sequence or structural similarity. Source: BHF-UCL

RNA polymerase II transcription factor binding transcription factor activity involved in positive regulation of transcription

Inferred from electronic annotation. Source: Ensembl

aryl hydrocarbon receptor binding

Inferred from physical interaction Ref.2. Source: BHF-UCL

core promoter binding

Inferred from sequence or structural similarity. Source: UniProtKB

signal transducer activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 9 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform BMAL1B (identifier: O00327-2)

Also known as: JAP3;

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 BMAL1A (identifier: O00327-1)

The sequence of this isoform differs from the canonical sequence as follows:
     1-47: MADQRMDISSTISDFMSPGPTDLLSSSLGTSGVDCNRKRKGSSTDYQ → MINI
Isoform BMAL1C (identifier: O00327-3)

The sequence of this isoform differs from the canonical sequence as follows:
     224-224: T → R
     225-626: Missing.
Isoform BMAL1D (identifier: O00327-4)

The sequence of this isoform differs from the canonical sequence as follows:
     274-391: Missing.
Isoform BMAL1E (identifier: O00327-5)

The sequence of this isoform differs from the canonical sequence as follows:
     278-301: SFCTIHSTGYLKSWPPTKMGLDED → AFCTIHSTGYFGIFTTRTSRHIVL
     302-626: Missing.
Isoform BMAL1F (identifier: O00327-6)

The sequence of this isoform differs from the canonical sequence as follows:
     443-526: ANVLEGGDPT...CGSSPLNITS → SRVDTGHLGQ...QGEPGLGQEK
     527-626: Missing.
Isoform MOP3 (identifier: O00327-7)

The sequence of this isoform differs from the canonical sequence as follows:
     1-59: MADQRMDISS...MDTDKDDPHG → MSKEAVSLWA...CFYLLLFPPP
Isoform 8 (identifier: O00327-8)

The sequence of this isoform differs from the canonical sequence as follows:
     274-274: Missing.
Isoform 9 (identifier: O00327-9)

The sequence of this isoform differs from the canonical sequence as follows:
     1-47: MADQRMDISSTISDFMSPGPTDLLSSSLGTSGVDCNRKRKGSSTDYQ → MINI
     274-274: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 626626Aryl hydrocarbon receptor nuclear translocator-like protein 1
PRO_0000127156

Regions

Domain72 – 12554bHLH
Domain143 – 21573PAS 1
Domain326 – 39671PAS 2
Domain401 – 44444PAC
Motif36 – 416Nuclear localization signal By similarity
Motif142 – 15211Nuclear export signal 1 By similarity
Motif361 – 3699Nuclear export signal 2 By similarity

Amino acid modifications

Modified residue171Phosphoserine; by GSK3-beta By similarity
Modified residue211Phosphothreonine; by GSK3-beta By similarity
Modified residue901Phosphoserine; by CK2 By similarity
Modified residue5381N6-acetyllysine By similarity
Cross-link252Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2 and SUMO3) By similarity
Cross-link259Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Natural variations

Alternative sequence1 – 5959MADQR…DDPHG → MSKEAVSLWALTVSLQPPVP LCVCREMTGSGRRKQQCVTL PFISRELCFYLLLFPPP in isoform MOP3.
VSP_002095
Alternative sequence1 – 4747MADQR…STDYQ → MINI in isoform BMAL1A and isoform 9.
VSP_002094
Alternative sequence2241T → R in isoform BMAL1C.
VSP_002096
Alternative sequence225 – 626402Missing in isoform BMAL1C.
VSP_002097
Alternative sequence274 – 391118Missing in isoform BMAL1D.
VSP_002098
Alternative sequence2741Missing in isoform 8 and isoform 9.
VSP_035457
Alternative sequence278 – 30124SFCTI…GLDED → AFCTIHSTGYFGIFTTRTSR HIVL in isoform BMAL1E.
VSP_002099
Alternative sequence302 – 626325Missing in isoform BMAL1E.
VSP_002100
Alternative sequence443 – 52684ANVLE…LNITS → SRVDTGHLGQVERCTVLSRP NSRFLIAGMFTEPTSWKAGT QPSHSSQHPPTAWTACCPLE KVAQRGPTPLFQGFQGEPGL GQEK in isoform BMAL1F.
VSP_002101
Alternative sequence527 – 626100Missing in isoform BMAL1F.
VSP_002102

Experimental info

Mutagenesis91S → A or E: Enhanced PER1 reporter activity by CLOCK-ARNTL/BMAL1. Ref.12
Mutagenesis91S → F: 2-2.5-fold increase in CLOCK-BMAL1 transcriptional activity in the absence of CRY1. No change in repression activity in the presence of CRY1. Ref.12
Mutagenesis101S → A or E: Enhanced PER1 reporter activity by CLOCK-ARNTL/BMAL1. Ref.12
Mutagenesis101S → L: 2-2.5-fold increase in CLOCK-ARNTL/BMAL1 transcriptional activity in the absence of CRY1. No change in repression activity in the presence of CRY1. Ref.12
Mutagenesis6111A → S or T: Increased desensitization to CRY1, in the presence of CLOCK. Approximately 2-fold increase in CLOCK-ARNTL/BMAL1 transcriptional activity in the absence of CRY1; when associated with E-407. Ref.12
Mutagenesis6121G → E: Increased desensitization to CRY1, in the presence of CLOCK. Approximately 2-fold increase in CLOCK-ARNTL/BMAL1 transcriptional activity in the absence of CRY1. Ref.12
Sequence conflict691R → G in AAC51213. Ref.2
Sequence conflict1231K → R in BAA19935. Ref.1
Sequence conflict1731S → P in BAA19939. Ref.1
Sequence conflict2591K → N in BAA19938. Ref.1
Sequence conflict2641D → N in BAA19938. Ref.1
Sequence conflict4181S → N in BAA19937. Ref.1
Sequence conflict513 – 5142SP → LR in AAC51213. Ref.2

Secondary structure

....... 626
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform BMAL1B (JAP3) [UniParc].

Last modified August 15, 2003. Version 2.
Checksum: 820F0E07DC6265A6

FASTA62668,762
        10         20         30         40         50         60 
MADQRMDISS TISDFMSPGP TDLLSSSLGT SGVDCNRKRK GSSTDYQESM DTDKDDPHGR 

        70         80         90        100        110        120 
LEYTEHQGRI 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 EDKDFPSTCS KKKADRKSFC TIHSTGYLKS WPPTKMGLDE 

       310        320        330        340        350        360 
DNEPDNEGCN LSCLVAIGRL HSHVVPQPVN GEIRVKSMEY VSRHAIDGKF VFVDQRATAI 

       370        380        390        400        410        420 
LAYLPQELLG TSCYEYFHQD DIGHLAECHR QVLQTREKIT TNCYKFKIKD GSFITLRSRW 

       430        440        450        460        470        480 
FSFMNPWTKE VEYIVSTNTV VLANVLEGGD PTFPQLTASP HSMDSMLPSG EGGPKRTHPT 

       490        500        510        520        530        540 
VPGIPGGTRA GAGKIGRMIA EEIMEIHRIR GSSPSSCGSS PLNITSTPPP DASSPGGKKI 

       550        560        570        580        590        600 
LNGGTPDIPS SGLLSGQAQE NPGYPYSDSS SILGENPHIG IDMIDNDQGS SSPSNDEAAM 

       610        620 
AVIMSLLEAD AGLGGPVDFS DLPWPL 

« Hide

Isoform BMAL1A [UniParc].

Checksum: 2AA8E7EEB4A71119
Show »

FASTA58364,207
Isoform BMAL1C [UniParc].

Checksum: 0A0580AEDC5A45A0
Show »

FASTA22425,353
Isoform BMAL1D [UniParc].

Checksum: 5FAB2403FD8AAB32
Show »

FASTA50855,462
Isoform BMAL1E [UniParc].

Checksum: EC942D8A9C9219B3
Show »

FASTA30133,922
Isoform BMAL1F [UniParc].

Checksum: ED01AF63A26CE4E0
Show »

FASTA52659,242
Isoform MOP3 [UniParc].

Checksum: 7A3FD8FAE5E496D7
Show »

FASTA62468,828
Isoform 8 [UniParc].

Checksum: 3F3F7D5688A6FFE2
Show »

FASTA62568,691
Isoform 9 [UniParc].

Checksum: E8D6943E4DD24037
Show »

FASTA58264,136

References

« Hide 'large scale' references
[1]"cDNA cloning and tissue-specific expression of a novel basic helix-loop-helix/PAS protein (BMAL1) and identification of alternatively spliced variants with alternative translation initiation site usage."
Ikeda M., Nomura M.
Biochem. Biophys. Res. Commun. 233:258-264(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], ALTERNATIVE SPLICING (ISOFORMS BMAL1A; BMAL1B; BMAL1C; BMAL1D; BMAL1E AND BMAL1F).
Tissue: Brain.
[2]"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] (ISOFORM MOP3), INTERACTION WITH HSP90 AND AHR.
Tissue: Fetal brain.
[3]"JAP3: a novel ARNT-like bHLH-PAS protein."
Tian H., Russell D.W., McKnight S.L.
Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BMAL1B).
[4]"The basic-helix-loop-helix-PAS orphan MOP3 forms transcriptionally active complexes with circadian and hypoxia factors."
Hogenesch J.B., Gu Y.Z., Jain S., Bradfield C.A.
Proc. Natl. Acad. Sci. U.S.A. 95:5474-5479(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BMAL1B).
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS BMAL1B AND 9).
Tissue: Brain.
[6]"ARNTL resequence."
Kripke D.F., Klimecki W.
Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]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 (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"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] (ISOFORMS 8 AND BMAL1A).
Tissue: Brain and Skin.
[10]"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CLOCK.
[11]"Regulation of the PAI-1 promoter by circadian clock components: differential activation by BMAL1 and BMAL2."
Schoenhard J.A., Smith L.H., Painter C.A., Eren M., Johnson C.H., Vaughan D.E.
J. Mol. Cell. Cardiol. 35:473-481(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[12]"Feedback repression is required for mammalian circadian clock function."
Sato T.K., Yamada R.G., Ukai H., Baggs J.E., Miraglia L.J., Kobayashi T.J., Welsh D.K., Kay S.A., Ueda H.R., Hogenesch J.B.
Nat. Genet. 38:312-319(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF SER-9; SER-10; ALA-611 AND GLY-612.
[13]"CLOCK/BMAL1 regulates human nocturnin transcription through binding to the E-box of nocturnin promoter."
Li R., Yue J., Zhang Y., Zhou L., Hao W., Yuan J., Qiang B., Ding J.M., Peng X., Cao J.M.
Mol. Cell. Biochem. 317:169-177(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[14]"Mechanism of the circadian clock in physiology."
Richards J., Gumz M.L.
Am. J. Physiol. 304:R1053-R1064(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[15]"The clock gene brain and muscle Arnt-like protein-1 (BMAL1) is involved in hair growth."
Watabe Y., Tomioka M., Watabe A., Aihara M., Shimba S., Inoue H.
Arch. Dermatol. Res. 305:755-761(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[16]"Metabolism and the circadian clock converge."
Eckel-Mahan K., Sassone-Corsi P.
Physiol. Rev. 93:107-135(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[17]"Gene model 129 (Gm129) encodes a novel transcriptional repressor that modulates circadian gene expression."
Annayev Y., Adar S., Chiou Y.Y., Lieb J., Sancar A., Ye R.
J. Biol. Chem. 289:5013-5024(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CIART.
[18]"A meeting of two chronobiological systems: circadian proteins Period1 and BMAL1 modulate the human hair cycle clock."
Al-Nuaimi Y., Hardman J.A., Biro T., Haslam I.S., Philpott M.P., Toth B.I., Farjo N., Farjo B., Baier G., Watson R.E., Grimaldi B., Kloepper J.E., Paus R.
J. Invest. Dermatol. 134:610-619(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[19]"Molecular architecture of the mammalian circadian clock."
Partch C.L., Green C.B., Takahashi J.S.
Trends Cell Biol. 24:90-99(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D89722 mRNA. Translation: BAA19968.1.
AB000812 mRNA. Translation: BAA19935.1.
AB000813 Genomic DNA. Translation: BAA19936.1.
AB000814 mRNA. Translation: BAA19937.1.
AB000815 mRNA. Translation: BAA19938.1.
AB000816 mRNA. Translation: BAA19939.1.
U51627 mRNA. Translation: AAC51213.1.
U60415 mRNA. Translation: AAB37248.1.
AF044288 mRNA. Translation: AAC24353.1.
AK095749 mRNA. Translation: BAG53120.1.
AK291510 mRNA. Translation: BAF84199.1.
EF015894 Genomic DNA. Translation: ABM64205.1.
AC016884 Genomic DNA. No translation available.
AC022878 Genomic DNA. No translation available.
CH471064 Genomic DNA. Translation: EAW68504.1.
CH471064 Genomic DNA. Translation: EAW68505.1.
CH471064 Genomic DNA. Translation: EAW68510.1.
CH471064 Genomic DNA. Translation: EAW68511.1.
CH471064 Genomic DNA. Translation: EAW68513.1.
BC016674 mRNA. Translation: AAH16674.1.
BC031214 mRNA. Translation: AAH31214.1.
BC041129 mRNA. Translation: AAH41129.2.
PIRJC5405.
JC5407.
PC4288.
PC4289.
RefSeqNP_001025443.1. NM_001030272.1.
NP_001025444.1. NM_001030273.1.
NP_001169.3. NM_001178.4.
XP_005252986.1. XM_005252929.2.
XP_005252987.1. XM_005252930.1.
UniGeneHs.65734.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4H10X-ray2.40A66-128[»]
ProteinModelPortalO00327.
SMRO00327. Positions 69-442.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106899. 24 interactions.
DIPDIP-46008N.
IntActO00327. 3 interactions.

PTM databases

PhosphoSiteO00327.

Proteomic databases

PaxDbO00327.
PRIDEO00327.

Protocols and materials databases

DNASU406.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000361003; ENSP00000354278; ENSG00000133794. [O00327-4]
ENST00000389707; ENSP00000374357; ENSG00000133794. [O00327-8]
ENST00000396441; ENSP00000379718; ENSG00000133794. [O00327-8]
ENST00000401424; ENSP00000385915; ENSG00000133794. [O00327-1]
ENST00000403290; ENSP00000384517; ENSG00000133794. [O00327-2]
ENST00000403482; ENSP00000385897; ENSG00000133794. [O00327-7]
ENST00000403510; ENSP00000385581; ENSG00000133794. [O00327-9]
GeneID406.
KEGGhsa:406.
UCSCuc001mko.3. human. [O00327-9]
uc001mkp.3. human. [O00327-8]
uc001mkr.3. human. [O00327-2]
uc001mks.3. human. [O00327-1]
uc001mkx.3. human. [O00327-7]
uc009ygm.1. human. [O00327-4]

Organism-specific databases

CTD406.
GeneCardsGC11P013299.
HGNCHGNC:701. ARNTL.
HPACAB045962.
HPA050938.
HPA054172.
MIM602550. gene.
neXtProtNX_O00327.
PharmGKBPA24996.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG293303.
HOGENOMHOG000234379.
HOVERGENHBG107503.
InParanoidO00327.
KOK02296.
OMAEKINTNC.
OrthoDBEOG7V1FQ8.
PhylomeDBO00327.
TreeFamTF319983.

Enzyme and pathway databases

ReactomeREACT_24941. Circadian Clock.

Gene expression databases

ArrayExpressO00327.
BgeeO00327.
GenevestigatorO00327.

Family and domain databases

Gene3D4.10.280.10. 1 hit.
InterProIPR011598. bHLH_dom.
IPR001067. Nuc_translocat.
IPR001610. PAC.
IPR000014. PAS.
IPR013767. PAS_fold.
[Graphical view]
PfamPF00010. HLH. 1 hit.
PF00989. PAS. 1 hit.
[Graphical view]
PRINTSPR00785. NCTRNSLOCATR.
SMARTSM00353. HLH. 1 hit.
SM00086. PAC. 1 hit.
SM00091. PAS. 2 hits.
[Graphical view]
SUPFAMSSF47459. SSF47459. 1 hit.
SSF55785. SSF55785. 3 hits.
TIGRFAMsTIGR00229. sensory_box. 1 hit.
PROSITEPS50888. BHLH. 1 hit.
PS50112. PAS. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiARNTL.
GenomeRNAi406.
NextBio1701.
PROO00327.
SOURCESearch...

Entry information

Entry nameBMAL1_HUMAN
AccessionPrimary (citable) accession number: O00327
Secondary accession number(s): A2I2N6 expand/collapse secondary AC list , A8K645, B5ME11, B7WPG7, D3DQW6, O00313, O00314, O00315, O00316, O00317, Q4G136, Q8IUT4, Q99631, Q99649
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: August 15, 2003
Last modified: April 16, 2014
This is version 148 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM