BMAL2_HUMAN
ID BMAL2_HUMAN Reviewed; 636 AA.
AC Q8WYA1; B7Z429; F5H402; Q8WYA2; Q8WYA3; Q8WYA4; Q96J63; Q9H2M4; Q9NS70;
AC Q9NYQ4; Q9NYQ5;
DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Aryl hydrocarbon receptor nuclear translocator-like protein 2;
DE AltName: Full=Basic-helix-loop-helix-PAS protein MOP9;
DE AltName: Full=Brain and muscle ARNT-like 2;
DE AltName: Full=CYCLE-like factor;
DE Short=CLIF;
DE AltName: Full=Class E basic helix-loop-helix protein 6;
DE Short=bHLHe6;
DE AltName: Full=Member of PAS protein 9;
DE AltName: Full=PAS domain-containing protein 9;
GN Name=ARNTL2; Synonyms=BHLHE6, BMAL2, CLIF, MOP9, PASD9;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6), SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=10964693; DOI=10.1006/bbrc.2000.3248;
RA Ikeda M., Yu W., Hirai M., Ebisawa T., Honma S., Yoshimura K., Honma K.,
RA Nomura M.;
RT "cDNA cloning of a novel bHLH-PAS transcription factor superfamily gene,
RT BMAL2; Its mRNA expression, subcellular distribution, and chromosomal
RT localization.";
RL Biochem. Biophys. Res. Commun. 275:493-502(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), FUNCTION, INDUCTION, TISSUE
RP SPECIFICITY, AND INTERACTION WITH CLOCK.
RC TISSUE=Umbilical vein endothelial cell;
RX PubMed=11018023; DOI=10.1074/jbc.c000629200;
RA Maemura K., de La Monte S.M., Chin M.T., Layne M.D., Hsieh C.-M.,
RA Yet S.-F., Perrella M.A., Lee M.-E.;
RT "CLIF, a novel cycle-like factor, regulates the circadian oscillation of
RT plasminogen activator inhibitor-1 gene expression.";
RL J. Biol. Chem. 275:36847-36851(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 7 AND 8), TISSUE SPECIFICITY, AND
RP INTERACTION WITH CLOCK; NPAS2 AND HIF1A.
RC TISSUE=Brain;
RX PubMed=10864977; DOI=10.1523/jneurosci.20-13-j0002.2000;
RA Hogenesch J.B., Gu Y.-Z., Moran S.M., Shimomura K., Radcliffe L.A.,
RA Takahashi J.S., Bradfield C.A.;
RT "The basic helix-loop-helix-PAS protein MOP9 is a brain-specific
RT heterodimeric partner of circadian and hypoxia factors.";
RL J. Neurosci. 20:RC83-RC83(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4).
RC TISSUE=Embryonic kidney;
RX PubMed=11554928; DOI=10.1046/j.1365-2443.2001.00462.x;
RA Okano T., Yamamoto K., Okano K., Hirota T., Kasahara T., Sasaki M.,
RA Takanaka Y., Fukada Y.;
RT "Chicken pineal clock genes: implication of BMAL2 as a bidirectional
RT regulator in circadian clock oscillation.";
RL Genes Cells 6:825-836(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 9).
RC TISSUE=Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3; 4 AND 5).
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP FUNCTION.
RX PubMed=12738229; DOI=10.1016/s0022-2828(03)00051-8;
RA Schoenhard J.A., Smith L.H., Painter C.A., Eren M., Johnson C.H.,
RA Vaughan D.E.;
RT "Regulation of the PAI-1 promoter by circadian clock components:
RT differential activation by BMAL1 and BMAL2.";
RL J. Mol. Cell. Cardiol. 35:473-481(2003).
RN [9]
RP FUNCTION.
RX PubMed=14672706; DOI=10.1016/j.bbrc.2003.11.099;
RA Kawamoto T., Noshiro M., Sato F., Maemura K., Takeda N., Nagai R.,
RA Iwata T., Fujimoto K., Furukawa M., Miyazaki K., Honma S., Honma K.I.,
RA Kato Y.;
RT "A novel autofeedback loop of Dec1 transcription involved in circadian
RT rhythm regulation.";
RL Biochem. Biophys. Res. Commun. 313:117-124(2004).
RN [10]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-294, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
CC -!- FUNCTION: Transcriptional activator which forms a core component of the
CC circadian clock. The circadian clock, an internal time-keeping system,
CC regulates various physiological processes through the generation of
CC approximately 24 hour circadian rhythms in gene expression, which are
CC translated into rhythms in metabolism and behavior. It is derived from
CC the Latin roots 'circa' (about) and 'diem' (day) and acts as an
CC important regulator of a wide array of physiological functions
CC including metabolism, sleep, body temperature, blood pressure,
CC endocrine, immune, cardiovascular, and renal function. Consists of two
CC major components: the central clock, residing in the suprachiasmatic
CC nucleus (SCN) of the brain, and the peripheral clocks that are present
CC in nearly every tissue and organ system. Both the central and
CC peripheral clocks can be reset by environmental cues, also known as
CC Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the
CC central clock is light, which is sensed by retina and signals directly
CC to the SCN. The central clock entrains the peripheral clocks through
CC neuronal and hormonal signals, body temperature and feeding-related
CC cues, aligning all clocks with the external light/dark cycle. Circadian
CC rhythms allow an organism to achieve temporal homeostasis with its
CC environment at the molecular level by regulating gene expression to
CC create a peak of protein expression once every 24 hours to control when
CC a particular physiological process is most active with respect to the
CC solar day. Transcription and translation of core clock components
CC (CLOCK, NPAS2, ARNTL/BMAL1, ARNTL2/BMAL2, PER1, PER2, PER3, CRY1 and
CC CRY2) plays a critical role in rhythm generation, whereas delays
CC imposed by post-translational modifications (PTMs) are important for
CC determining the period (tau) of the rhythms (tau refers to the period
CC of a rhythm and is the length, in time, of one complete cycle). A
CC diurnal rhythm is synchronized with the day/night cycle, while the
CC ultradian and infradian rhythms have a period shorter and longer than
CC 24 hours, respectively. Disruptions in the circadian rhythms contribute
CC to the pathology of cardiovascular diseases, cancer, metabolic
CC syndromes and aging. A transcription/translation feedback loop (TTFL)
CC forms the core of the molecular circadian clock mechanism.
CC Transcription factors, CLOCK or NPAS2 and ARNTL/BMAL1 or ARNTL2/BMAL2,
CC form the positive limb of the feedback loop, act in the form of a
CC heterodimer and activate the transcription of core clock genes and
CC clock-controlled genes (involved in key metabolic processes), harboring
CC E-box elements (5'-CACGTG-3') within their promoters. The core clock
CC genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form
CC the negative limb of the feedback loop and interact with the
CC CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/BMAL2 heterodimer inhibiting its
CC activity and thereby negatively regulating their own expression. This
CC heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G,
CC which form a second feedback loop and which activate and repress
CC ARNTL/BMAL1 transcription, respectively. The CLOCK-ARNTL2/BMAL2
CC heterodimer activates the transcription of SERPINE1/PAI1 and
CC BHLHE40/DEC1. {ECO:0000269|PubMed:11018023,
CC ECO:0000269|PubMed:12738229, ECO:0000269|PubMed:14672706}.
CC -!- SUBUNIT: Component of the circadian core oscillator, which includes the
CC CRY proteins, CLOCK, or NPAS2, ARNTL/BMAL1 or ARNTL2/BMAL2, CSNK1D
CC and/or CSNK1E, TIMELESS and the PER proteins. Interacts directly with
CC CLOCK to form the ARNTL2/BMAL2-CLOCK transactivator. Can form
CC heterodimers or homodimers which interact directly with CLOCK to form
CC the transcription activator. Interacts with NPAS2 and HIF1A. Interacts
CC with PER2 (By similarity). {ECO:0000250|UniProtKB:Q2VPD4,
CC ECO:0000269|PubMed:10864977, ECO:0000269|PubMed:11018023}.
CC -!- INTERACTION:
CC Q8WYA1-3; O15516: CLOCK; NbExp=4; IntAct=EBI-12268276, EBI-1794265;
CC Q8WYA1-3; Q8WZ74: CTTNBP2; NbExp=3; IntAct=EBI-12268276, EBI-1774260;
CC Q8WYA1-3; Q99814: EPAS1; NbExp=3; IntAct=EBI-12268276, EBI-447470;
CC Q8WYA1-3; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-12268276, EBI-16439278;
CC Q8WYA1-3; Q99743: NPAS2; NbExp=10; IntAct=EBI-12268276, EBI-3932727;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981,
CC ECO:0000269|PubMed:10964693}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=9;
CC Name=1; Synonyms=BMAL2a;
CC IsoId=Q8WYA1-1; Sequence=Displayed;
CC Name=2; Synonyms=BMAL2b;
CC IsoId=Q8WYA1-2; Sequence=VSP_022584;
CC Name=3; Synonyms=BMAL2c;
CC IsoId=Q8WYA1-3; Sequence=VSP_022585, VSP_022581, VSP_022584;
CC Name=4; Synonyms=BMAL2d;
CC IsoId=Q8WYA1-4; Sequence=VSP_022581, VSP_022584;
CC Name=5; Synonyms=CLIF;
CC IsoId=Q8WYA1-5; Sequence=VSP_022581;
CC Name=6;
CC IsoId=Q8WYA1-6; Sequence=VSP_022580, VSP_022581, VSP_022584;
CC Name=7; Synonyms=MOP9 long form;
CC IsoId=Q8WYA1-7; Sequence=VSP_022580, VSP_022584;
CC Name=8; Synonyms=MOP9 short form;
CC IsoId=Q8WYA1-8; Sequence=VSP_022580, VSP_022582, VSP_022583,
CC VSP_022584;
CC Name=9;
CC IsoId=Q8WYA1-9; Sequence=VSP_022585, VSP_022581, VSP_022584,
CC VSP_044773;
CC -!- TISSUE SPECIFICITY: Expressed in fetal brain. Highly expressed in brain
CC and placenta. Lower levels in heart, liver, thymus, kidney and lung.
CC Located to endothelial cells and neuronal cells of the suprachiasmatic
CC nucleus (SCN). Also detected in endothelial cells of the heart, lung
CC and kidney. In the brain, specifically expressed in the thalamus,
CC hippocampus and amygdala. {ECO:0000269|PubMed:10864977,
CC ECO:0000269|PubMed:10964693, ECO:0000269|PubMed:11018023}.
CC -!- INDUCTION: Constitutively expressed. Has no circadian rhythm expression
CC pattern. {ECO:0000269|PubMed:11018023}.
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DR EMBL; AB039921; BAB01485.1; -; mRNA.
DR EMBL; AF256215; AAG34652.1; -; mRNA.
DR EMBL; AF231338; AAF71306.1; -; mRNA.
DR EMBL; AF231339; AAF71307.1; -; mRNA.
DR EMBL; AF246960; AAL50339.1; -; mRNA.
DR EMBL; AF246961; AAL50340.1; -; mRNA.
DR EMBL; AF246962; AAL50341.1; -; mRNA.
DR EMBL; AF246963; AAL50342.1; -; mRNA.
DR EMBL; AK296706; BAH12415.1; -; mRNA.
DR EMBL; AC068794; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC092829; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000172; AAH00172.3; -; mRNA.
DR EMBL; BC125061; AAI25062.1; -; mRNA.
DR EMBL; BC125062; AAI25063.1; -; mRNA.
DR CCDS; CCDS58219.1; -. [Q8WYA1-2]
DR CCDS; CCDS58220.1; -. [Q8WYA1-4]
DR CCDS; CCDS58221.1; -. [Q8WYA1-3]
DR CCDS; CCDS58222.1; -. [Q8WYA1-9]
DR CCDS; CCDS8712.1; -. [Q8WYA1-1]
DR RefSeq; NP_001234931.1; NM_001248002.1. [Q8WYA1-2]
DR RefSeq; NP_001234932.1; NM_001248003.1. [Q8WYA1-3]
DR RefSeq; NP_001234933.1; NM_001248004.1. [Q8WYA1-4]
DR RefSeq; NP_001234934.1; NM_001248005.1. [Q8WYA1-9]
DR RefSeq; NP_064568.3; NM_020183.4. [Q8WYA1-1]
DR PDB; 2KDK; NMR; -; A=360-477.
DR PDBsum; 2KDK; -.
DR AlphaFoldDB; Q8WYA1; -.
DR SMR; Q8WYA1; -.
DR BioGRID; 121263; 33.
DR ComplexPortal; CPX-3230; CLOCK-BMAL2 transcription complex.
DR IntAct; Q8WYA1; 24.
DR STRING; 9606.ENSP00000266503; -.
DR iPTMnet; Q8WYA1; -.
DR PhosphoSitePlus; Q8WYA1; -.
DR BioMuta; ARNTL2; -.
DR DMDM; 124007121; -.
DR EPD; Q8WYA1; -.
DR jPOST; Q8WYA1; -.
DR MassIVE; Q8WYA1; -.
DR MaxQB; Q8WYA1; -.
DR PaxDb; Q8WYA1; -.
DR PeptideAtlas; Q8WYA1; -.
DR PRIDE; Q8WYA1; -.
DR ProteomicsDB; 26427; -.
DR ProteomicsDB; 75143; -. [Q8WYA1-1]
DR ProteomicsDB; 75144; -. [Q8WYA1-2]
DR ProteomicsDB; 75145; -. [Q8WYA1-3]
DR ProteomicsDB; 75146; -. [Q8WYA1-4]
DR ProteomicsDB; 75147; -. [Q8WYA1-5]
DR ProteomicsDB; 75148; -. [Q8WYA1-6]
DR ProteomicsDB; 75149; -. [Q8WYA1-7]
DR ProteomicsDB; 75150; -. [Q8WYA1-8]
DR Antibodypedia; 12657; 118 antibodies from 22 providers.
DR DNASU; 56938; -.
DR Ensembl; ENST00000261178.9; ENSP00000261178.5; ENSG00000029153.15. [Q8WYA1-4]
DR Ensembl; ENST00000266503.10; ENSP00000266503.5; ENSG00000029153.15. [Q8WYA1-1]
DR Ensembl; ENST00000311001.9; ENSP00000312247.5; ENSG00000029153.15. [Q8WYA1-2]
DR Ensembl; ENST00000395901.6; ENSP00000379238.2; ENSG00000029153.15. [Q8WYA1-3]
DR Ensembl; ENST00000542388.1; ENSP00000445836.1; ENSG00000029153.15. [Q8WYA1-6]
DR Ensembl; ENST00000544915.5; ENSP00000442438.1; ENSG00000029153.15. [Q8WYA1-5]
DR Ensembl; ENST00000546179.5; ENSP00000438545.1; ENSG00000029153.15. [Q8WYA1-9]
DR GeneID; 56938; -.
DR KEGG; hsa:56938; -.
DR MANE-Select; ENST00000266503.10; ENSP00000266503.5; NM_020183.6; NP_064568.3.
DR UCSC; uc001rht.3; human. [Q8WYA1-1]
DR CTD; 56938; -.
DR DisGeNET; 56938; -.
DR GeneCards; ARNTL2; -.
DR HGNC; HGNC:18984; ARNTL2.
DR HPA; ENSG00000029153; Tissue enhanced (esophagus, lymphoid tissue).
DR MIM; 614517; gene.
DR neXtProt; NX_Q8WYA1; -.
DR OpenTargets; ENSG00000029153; -.
DR PharmGKB; PA134896555; -.
DR VEuPathDB; HostDB:ENSG00000029153; -.
DR eggNOG; KOG3561; Eukaryota.
DR GeneTree; ENSGT00940000160423; -.
DR HOGENOM; CLU_011864_2_2_1; -.
DR InParanoid; Q8WYA1; -.
DR OMA; YVGDNYR; -.
DR OrthoDB; 331262at2759; -.
DR PhylomeDB; Q8WYA1; -.
DR TreeFam; TF319983; -.
DR PathwayCommons; Q8WYA1; -.
DR Reactome; R-HSA-1368108; BMAL1:CLOCK,NPAS2 activates circadian gene expression.
DR SignaLink; Q8WYA1; -.
DR SIGNOR; Q8WYA1; -.
DR BioGRID-ORCS; 56938; 16 hits in 1096 CRISPR screens.
DR ChiTaRS; ARNTL2; human.
DR GeneWiki; ARNTL2; -.
DR GenomeRNAi; 56938; -.
DR Pharos; Q8WYA1; Tbio.
DR PRO; PR:Q8WYA1; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q8WYA1; protein.
DR Bgee; ENSG00000029153; Expressed in lower esophagus mucosa and 130 other tissues.
DR ExpressionAtlas; Q8WYA1; baseline and differential.
DR Genevisible; Q8WYA1; HS.
DR GO; GO:0034751; C:aryl hydrocarbon receptor complex; IBA:GO_Central.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:1990513; C:CLOCK-BMAL transcription complex; IPI:ComplexPortal.
DR GO; GO:0005737; C:cytoplasm; IEA:InterPro.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:BHF-UCL.
DR GO; GO:0070888; F:E-box binding; IDA:UniProtKB.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL.
DR GO; GO:0032922; P:circadian regulation of gene expression; IDA:ComplexPortal.
DR GO; GO:0007623; P:circadian rhythm; IDA:MGI.
DR GO; GO:0009649; P:entrainment of circadian clock; NAS:UniProtKB.
DR GO; GO:0042753; P:positive regulation of circadian rhythm; IDA:ComplexPortal.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; NAS:UniProtKB.
DR CDD; cd00130; PAS; 2.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR001067; Nuc_translocat.
DR InterPro; IPR000014; PAS.
DR InterPro; IPR035965; PAS-like_dom_sf.
DR InterPro; IPR013767; PAS_fold.
DR Pfam; PF00010; HLH; 1.
DR Pfam; PF00989; PAS; 1.
DR PRINTS; PR00785; NCTRNSLOCATR.
DR SMART; SM00353; HLH; 1.
DR SMART; SM00091; PAS; 2.
DR SUPFAM; SSF47459; SSF47459; 1.
DR SUPFAM; SSF55785; SSF55785; 2.
DR TIGRFAMs; TIGR00229; sensory_box; 1.
DR PROSITE; PS50888; BHLH; 1.
DR PROSITE; PS50112; PAS; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative splicing; Biological rhythms;
KW DNA-binding; Isopeptide bond; Nucleus; Reference proteome; Repeat;
KW Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..636
FT /note="Aryl hydrocarbon receptor nuclear translocator-like
FT protein 2"
FT /id="PRO_0000273631"
FT DOMAIN 107..160
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 178..250
FT /note="PAS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 357..427
FT /note="PAS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 432..475
FT /note="PAC"
FT REGION 25..62
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 46..258
FT /note="Interaction with PER2"
FT /evidence="ECO:0000250|UniProtKB:Q2VPD4"
FT MOTIF 49..54
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:Q9WTL8"
FT MOTIF 177..187
FT /note="Nuclear export signal 1"
FT /evidence="ECO:0000250|UniProtKB:Q9WTL8"
FT MOTIF 392..400
FT /note="Nuclear export signal 2"
FT /evidence="ECO:0000250|UniProtKB:Q9WTL8"
FT COMPBIAS 25..43
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 287
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2 and SUMO3)"
FT /evidence="ECO:0000250|UniProtKB:Q9WTL8"
FT CROSSLNK 294
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..37
FT /note="Missing (in isoform 6, isoform 7 and isoform 8)"
FT /evidence="ECO:0000303|PubMed:10864977,
FT ECO:0000303|PubMed:10964693"
FT /id="VSP_022580"
FT VAR_SEQ 11
FT /note="G -> GEVAGGEATAPG (in isoform 3 and isoform 9)"
FT /evidence="ECO:0000303|PubMed:11554928,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334"
FT /id="VSP_022585"
FT VAR_SEQ 61
FT /note="Q -> H (in isoform 8)"
FT /evidence="ECO:0000303|PubMed:10864977"
FT /id="VSP_022582"
FT VAR_SEQ 62..95
FT /note="Missing (in isoform 3, isoform 4, isoform 5, isoform
FT 6 and isoform 9)"
FT /evidence="ECO:0000303|PubMed:10964693,
FT ECO:0000303|PubMed:11018023, ECO:0000303|PubMed:11554928,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334"
FT /id="VSP_022581"
FT VAR_SEQ 62..74
FT /note="Missing (in isoform 8)"
FT /evidence="ECO:0000303|PubMed:10864977"
FT /id="VSP_022583"
FT VAR_SEQ 96..109
FT /note="Missing (in isoform 2, isoform 3, isoform 4, isoform
FT 6, isoform 7, isoform 8 and isoform 9)"
FT /evidence="ECO:0000303|PubMed:10864977,
FT ECO:0000303|PubMed:10964693, ECO:0000303|PubMed:11554928,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334"
FT /id="VSP_022584"
FT VAR_SEQ 556..635
FT /note="MSNKELFPPSPSEMGELEATRQNQSTVAVHSHEPLLSDGAQLDFDALCDNDD
FT TAMAAFMNYLEAEGGLGDPGDFSDIQWT -> VMVHSWISMPYVTMMTQPWLH (in
FT isoform 9)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044773"
FT VARIANT 340
FT /note="N -> S (in dbSNP:rs1037921)"
FT /id="VAR_030158"
FT VARIANT 574
FT /note="A -> V (in dbSNP:rs11049005)"
FT /id="VAR_030159"
FT CONFLICT 41
FT /note="F -> S (in Ref. 1; BAB01485)"
FT /evidence="ECO:0000305"
FT CONFLICT 173
FT /note="R -> G (in Ref. 5; BAH12415)"
FT /evidence="ECO:0000305"
FT CONFLICT 257
FT /note="A -> T (in Ref. 3; AAF71306/AAF71307)"
FT /evidence="ECO:0000305"
FT CONFLICT 276
FT /note="S -> F (in Ref. 3; AAF71306/AAF71307)"
FT /evidence="ECO:0000305"
FT CONFLICT 304
FT /note="K -> R (in Ref. 5; BAH12415)"
FT /evidence="ECO:0000305"
FT CONFLICT 324
FT /note="P -> R (in Ref. 1; BAB01485)"
FT /evidence="ECO:0000305"
FT CONFLICT 527
FT /note="L -> I (in Ref. 1; BAB01485)"
FT /evidence="ECO:0000305"
FT STRAND 368..375
FT /evidence="ECO:0007829|PDB:2KDK"
FT STRAND 379..384
FT /evidence="ECO:0007829|PDB:2KDK"
FT HELIX 387..391
FT /evidence="ECO:0007829|PDB:2KDK"
FT TURN 396..398
FT /evidence="ECO:0007829|PDB:2KDK"
FT TURN 404..407
FT /evidence="ECO:0007829|PDB:2KDK"
FT STRAND 410..412
FT /evidence="ECO:0007829|PDB:2KDK"
FT HELIX 413..424
FT /evidence="ECO:0007829|PDB:2KDK"
FT STRAND 426..428
FT /evidence="ECO:0007829|PDB:2KDK"
FT STRAND 430..438
FT /evidence="ECO:0007829|PDB:2KDK"
FT STRAND 440..442
FT /evidence="ECO:0007829|PDB:2KDK"
FT STRAND 444..455
FT /evidence="ECO:0007829|PDB:2KDK"
FT STRAND 458..460
FT /evidence="ECO:0007829|PDB:2KDK"
FT STRAND 462..470
FT /evidence="ECO:0007829|PDB:2KDK"
SQ SEQUENCE 636 AA; 70887 MW; 972CE2BC5B05B1F3 CRC64;
MAAEEEAAAG GKVLREENQC IAPVVSSRVS PGTRPTAMGS FSSHMTEFPR KRKGSDSDPS
QSGIMTEKVV EKLSQNPLTY LLSTRIEISA SSGSRVEDGE HQVKMKAFRE AHSQTEKRRR
DKMNNLIEEL SAMIPQCNPM ARKLDKLTVL RMAVQHLRSL KGLTNSYVGS NYRPSFLQDN
ELRHLILKTA EGFLFVVGCE RGKILFVSKS VSKILNYDQA SLTGQSLFDF LHPKDVAKVK
EQLSSFDISP REKLIDAKTG LQVHSNLHAG RTRVYSGSRR SFFCRIKSCK ISVKEEHGCL
PNSKKKEHRK FYTIHCTGYL RSWPPNIVGM EEERNSKKDN SNFTCLVAIG RLQPYIVPQN
SGEINVKPTE FITRFAVNGK FVYVDQRATA ILGYLPQELL GTSCYEYFHQ DDHNNLTDKH
KAVLQSKEKI LTDSYKFRAK DGSFVTLKSQ WFSFTNPWTK ELEYIVSVNT LVLGHSEPGE
ASFLPCSSQS SEESSRQSCM SVPGMSTGTV LGAGSIGTDI ANEILDLQRL QSSSYLDDSS
PTGLMKDTHT VNCRSMSNKE LFPPSPSEMG ELEATRQNQS TVAVHSHEPL LSDGAQLDFD
ALCDNDDTAM AAFMNYLEAE GGLGDPGDFS DIQWTL
