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 24-JAN-2024, entry version 179. DE RecName: Full=Basic helix-loop-helix ARNT-like protein 2 {ECO:0000312|HGNC:HGNC:18984}; DE AltName: 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=BMAL2 {ECO:0000312|HGNC:HGNC:18984}; GN Synonyms=ARNTL2, BHLHE6, 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, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a CC critical role in rhythm generation, whereas delays imposed by post- CC translational modifications (PTMs) are important for determining the CC period (tau) of the rhythms (tau refers to the period of a rhythm and CC is the length, in time, of one complete cycle). A diurnal rhythm is CC synchronized with the day/night cycle, while the ultradian and CC infradian rhythms have a period shorter and longer than 24 hours, CC respectively. Disruptions in the circadian rhythms contribute to the CC pathology of cardiovascular diseases, cancer, metabolic syndromes and CC aging. A transcription/translation feedback loop (TTFL) forms the core CC of the molecular circadian clock mechanism. Transcription factors, CC CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the CC feedback loop, act in the form of a heterodimer and activate the CC transcription of core clock genes and clock-controlled genes (involved CC in key metabolic processes), harboring E-box elements (5'-CACGTG-3') CC within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which CC are transcriptional repressors form the negative limb of the feedback CC loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer CC inhibiting its activity and thereby negatively regulating their own CC expression. This heterodimer also activates nuclear receptors NR1D1/2 CC and RORA/B/G, which form a second feedback loop and which activate and CC repress BMAL1 transcription, respectively. The CLOCK-BMAL2 heterodimer CC activates the transcription of SERPINE1/PAI1 and BHLHE40/DEC1. CC {ECO:0000269|PubMed:11018023, ECO:0000269|PubMed:12738229, CC ECO:0000269|PubMed:14672706}. CC -!- SUBUNIT: Component of the circadian core oscillator, which includes the CC CRY proteins, CLOCK, or NPAS2, BMAL1 or BMAL2, CSNK1D and/or CSNK1E, CC TIMELESS and the PER proteins. Interacts directly with CLOCK to form CC the BMAL2-CLOCK transactivator. Can form heterodimers or homodimers CC which interact directly with CLOCK to form the transcription activator. CC Interacts with NPAS2 and HIF1A. Interacts with PER2 (By similarity). CC {ECO:0000250|UniProtKB:Q2VPD4, ECO:0000269|PubMed:10864977, CC 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 CCDS; CCDS91666.1; -. [Q8WYA1-5] 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; 34. DR ComplexPortal; CPX-3230; CLOCK-BMAL2 transcription complex. DR IntAct; Q8WYA1; 23. 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; 9606-ENSP00000266503; -. DR PeptideAtlas; 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; 159 antibodies from 23 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 AGR; HGNC:18984; -. DR CTD; 56938; -. DR DisGeNET; 56938; -. DR GeneCards; BMAL2; -. DR HGNC; HGNC:18984; BMAL2. 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; RIKCSRI; -. DR OrthoDB; 2872674at2759; -. 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; 17 hits in 1173 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 131 other cell types or tissues. DR ExpressionAtlas; Q8WYA1; baseline and differential. 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:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:0006355; P:regulation of DNA-templated transcription; NAS:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI. DR CDD; cd11469; bHLH-PAS_ARNTL2_PASD9; 1. DR CDD; cd00130; PAS; 2. DR Gene3D; 4.10.280.10; Helix-loop-helix DNA-binding domain; 1. DR Gene3D; 3.30.450.20; PAS domain; 2. 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 NCBIfam; TIGR00229; sensory_box; 1. DR PANTHER; PTHR23042:SF48; ARYL HYDROCARBON RECEPTOR NUCLEAR TRANSLOCATOR-LIKE PROTEIN 2; 1. DR PANTHER; PTHR23042; CIRCADIAN PROTEIN CLOCK/ARNT/BMAL/PAS; 1. DR Pfam; PF00010; HLH; 1. DR Pfam; PF00989; PAS; 1. DR Pfam; PF14598; PAS_11; 1. DR PRINTS; PR00785; NCTRNSLOCATR. DR SMART; SM00353; HLH; 1. DR SMART; SM00091; PAS; 2. DR SUPFAM; SSF47459; HLH, helix-loop-helix DNA-binding domain; 1. DR SUPFAM; SSF55785; PYP-like sensor domain (PAS domain); 2. DR PROSITE; PS50888; BHLH; 1. DR PROSITE; PS50112; PAS; 2. DR Genevisible; Q8WYA1; HS. 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="Basic helix-loop-helix ARNT-like 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 //