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Aryl hydrocarbon receptor nuclear translocator-like protein 2 (Basic-helix-loop-helix-PAS protein MOP9) (Brain and muscle ARNT-like 2) (CYCLE-like factor) (CLIF) (Class E basic helix-loop-helix protein 6) (bHLHe6) (Member of PAS protein 9) (PAS domain-containing protein 9)

 BMAL2_HUMAN             Reviewed;         636 AA.
Q8WYA1; B7Z429; F5H402; Q8WYA2; Q8WYA3; Q8WYA4; Q96J63; Q9H2M4; Q9NS70;
Q9NYQ4; Q9NYQ5;
23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
23-JAN-2007, sequence version 2.
02-JUN-2021, entry version 167.
RecName: Full=Aryl hydrocarbon receptor nuclear translocator-like protein 2;
AltName: Full=Basic-helix-loop-helix-PAS protein MOP9;
AltName: Full=Brain and muscle ARNT-like 2;
AltName: Full=CYCLE-like factor;
Short=CLIF;
AltName: Full=Class E basic helix-loop-helix protein 6;
Short=bHLHe6;
AltName: Full=Member of PAS protein 9;
AltName: Full=PAS domain-containing protein 9;
Name=ARNTL2; Synonyms=BHLHE6, BMAL2, CLIF, MOP9, PASD9;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6), SUBCELLULAR LOCATION, AND TISSUE
SPECIFICITY.
TISSUE=Brain;
PubMed=10964693; DOI=10.1006/bbrc.2000.3248;
Ikeda M., Yu W., Hirai M., Ebisawa T., Honma S., Yoshimura K., Honma K.,
Nomura M.;
"cDNA cloning of a novel bHLH-PAS transcription factor superfamily gene,
BMAL2; Its mRNA expression, subcellular distribution, and chromosomal
localization.";
Biochem. Biophys. Res. Commun. 275:493-502(2000).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), FUNCTION, INDUCTION, TISSUE
SPECIFICITY, AND INTERACTION WITH CLOCK.
TISSUE=Umbilical vein endothelial cell;
PubMed=11018023; DOI=10.1074/jbc.c000629200;
Maemura K., de La Monte S.M., Chin M.T., Layne M.D., Hsieh C.-M.,
Yet S.-F., Perrella M.A., Lee M.-E.;
"CLIF, a novel cycle-like factor, regulates the circadian oscillation of
plasminogen activator inhibitor-1 gene expression.";
J. Biol. Chem. 275:36847-36851(2000).
[3]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 7 AND 8), TISSUE SPECIFICITY, AND
INTERACTION WITH CLOCK; NPAS2 AND HIF1A.
TISSUE=Brain;
PubMed=10864977; DOI=10.1523/jneurosci.20-13-j0002.2000;
Hogenesch J.B., Gu Y.-Z., Moran S.M., Shimomura K., Radcliffe L.A.,
Takahashi J.S., Bradfield C.A.;
"The basic helix-loop-helix-PAS protein MOP9 is a brain-specific
heterodimeric partner of circadian and hypoxia factors.";
J. Neurosci. 20:RC83-RC83(2000).
[4]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4).
TISSUE=Embryonic kidney;
PubMed=11554928; DOI=10.1046/j.1365-2443.2001.00462.x;
Okano T., Yamamoto K., Okano K., Hirota T., Kasahara T., Sasaki M.,
Takanaka Y., Fukada Y.;
"Chicken pineal clock genes: implication of BMAL2 as a bidirectional
regulator in circadian clock oscillation.";
Genes Cells 6:825-836(2001).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 9).
TISSUE=Tongue;
PubMed=14702039; DOI=10.1038/ng1285;
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.,
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.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=16541075; DOI=10.1038/nature04569;
Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
Gibbs R.A.;
"The finished DNA sequence of human chromosome 12.";
Nature 440:346-351(2006).
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3; 4 AND 5).
TISSUE=Placenta;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project:
the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[8]
FUNCTION.
PubMed=12738229; DOI=10.1016/s0022-2828(03)00051-8;
Schoenhard J.A., Smith L.H., Painter C.A., Eren M., Johnson C.H.,
Vaughan D.E.;
"Regulation of the PAI-1 promoter by circadian clock components:
differential activation by BMAL1 and BMAL2.";
J. Mol. Cell. Cardiol. 35:473-481(2003).
[9]
FUNCTION.
PubMed=14672706; DOI=10.1016/j.bbrc.2003.11.099;
Kawamoto T., Noshiro M., Sato F., Maemura K., Takeda N., Nagai R.,
Iwata T., Fujimoto K., Furukawa M., Miyazaki K., Honma S., Honma K.I.,
Kato Y.;
"A novel autofeedback loop of Dec1 transcription involved in circadian
rhythm regulation.";
Biochem. Biophys. Res. Commun. 313:117-124(2004).
[10]
SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-294, AND IDENTIFICATION BY MASS
SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=28112733; DOI=10.1038/nsmb.3366;
Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
Nielsen M.L.;
"Site-specific mapping of the human SUMO proteome reveals co-modification
with phosphorylation.";
Nat. Struct. Mol. Biol. 24:325-336(2017).
-!- 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 NR1D1/2 and RORA/B/G,
which form a second feedback loop and which activate and repress
ARNTL/BMAL1 transcription, respectively. The CLOCK-ARNTL2/BMAL2
heterodimer activates the transcription of SERPINE1/PAI1 and
BHLHE40/DEC1. {ECO:0000269|PubMed:11018023,
ECO:0000269|PubMed:12738229, ECO:0000269|PubMed:14672706}.
-!- SUBUNIT: Component of the circadian core oscillator, which includes the
CRY proteins, CLOCK, or NPAS2, ARNTL/BMAL1 or ARNTL2/BMAL2, CSNK1D
and/or CSNK1E, TIMELESS and the PER proteins. Interacts directly with
CLOCK to form the ARNTL2/BMAL2-CLOCK transactivator. Can form
heterodimers or homodimers which interact directly with CLOCK to form
the transcription activator. Interacts with NPAS2 and HIF1A. Interacts
with PER2 (By similarity). {ECO:0000250|UniProtKB:Q2VPD4,
ECO:0000269|PubMed:10864977, ECO:0000269|PubMed:11018023}.
-!- INTERACTION:
Q8WYA1-3; O15516: CLOCK; NbExp=4; IntAct=EBI-12268276, EBI-1794265;
Q8WYA1-3; Q8WZ74: CTTNBP2; NbExp=3; IntAct=EBI-12268276, EBI-1774260;
Q8WYA1-3; Q99814: EPAS1; NbExp=3; IntAct=EBI-12268276, EBI-447470;
Q8WYA1-3; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-12268276, EBI-16439278;
Q8WYA1-3; Q99743: NPAS2; NbExp=10; IntAct=EBI-12268276, EBI-3932727;
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981,
ECO:0000269|PubMed:10964693}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=9;
Name=1; Synonyms=BMAL2a;
IsoId=Q8WYA1-1; Sequence=Displayed;
Name=2; Synonyms=BMAL2b;
IsoId=Q8WYA1-2; Sequence=VSP_022584;
Name=3; Synonyms=BMAL2c;
IsoId=Q8WYA1-3; Sequence=VSP_022585, VSP_022581, VSP_022584;
Name=4; Synonyms=BMAL2d;
IsoId=Q8WYA1-4; Sequence=VSP_022581, VSP_022584;
Name=5; Synonyms=CLIF;
IsoId=Q8WYA1-5; Sequence=VSP_022581;
Name=6;
IsoId=Q8WYA1-6; Sequence=VSP_022580, VSP_022581, VSP_022584;
Name=7; Synonyms=MOP9 long form;
IsoId=Q8WYA1-7; Sequence=VSP_022580, VSP_022584;
Name=8; Synonyms=MOP9 short form;
IsoId=Q8WYA1-8; Sequence=VSP_022580, VSP_022582, VSP_022583,
VSP_022584;
Name=9;
IsoId=Q8WYA1-9; Sequence=VSP_022585, VSP_022581, VSP_022584,
VSP_044773;
-!- TISSUE SPECIFICITY: Expressed in fetal brain. Highly expressed in brain
and placenta. Lower levels in heart, liver, thymus, kidney and lung.
Located to endothelial cells and neuronal cells of the suprachiasmatic
nucleus (SCN). Also detected in endothelial cells of the heart, lung
and kidney. In the brain, specifically expressed in the thalamus,
hippocampus and amygdala. {ECO:0000269|PubMed:10864977,
ECO:0000269|PubMed:10964693, ECO:0000269|PubMed:11018023}.
-!- INDUCTION: Constitutively expressed. Has no circadian rhythm expression
pattern. {ECO:0000269|PubMed:11018023}.
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EMBL; AB039921; BAB01485.1; -; mRNA.
EMBL; AF256215; AAG34652.1; -; mRNA.
EMBL; AF231338; AAF71306.1; -; mRNA.
EMBL; AF231339; AAF71307.1; -; mRNA.
EMBL; AF246960; AAL50339.1; -; mRNA.
EMBL; AF246961; AAL50340.1; -; mRNA.
EMBL; AF246962; AAL50341.1; -; mRNA.
EMBL; AF246963; AAL50342.1; -; mRNA.
EMBL; AK296706; BAH12415.1; -; mRNA.
EMBL; AC068794; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AC092829; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; BC000172; AAH00172.3; -; mRNA.
EMBL; BC125061; AAI25062.1; -; mRNA.
EMBL; BC125062; AAI25063.1; -; mRNA.
CCDS; CCDS58219.1; -. [Q8WYA1-2]
CCDS; CCDS58220.1; -. [Q8WYA1-4]
CCDS; CCDS58221.1; -. [Q8WYA1-3]
CCDS; CCDS58222.1; -. [Q8WYA1-9]
CCDS; CCDS8712.1; -. [Q8WYA1-1]
RefSeq; NP_001234931.1; NM_001248002.1. [Q8WYA1-2]
RefSeq; NP_001234932.1; NM_001248003.1. [Q8WYA1-3]
RefSeq; NP_001234933.1; NM_001248004.1. [Q8WYA1-4]
RefSeq; NP_001234934.1; NM_001248005.1. [Q8WYA1-9]
RefSeq; NP_064568.3; NM_020183.4. [Q8WYA1-1]
PDB; 2KDK; NMR; -; A=360-477.
PDBsum; 2KDK; -.
SMR; Q8WYA1; -.
BioGRID; 121263; 26.
ComplexPortal; CPX-3230; CLOCK-BMAL2 transcription complex.
IntAct; Q8WYA1; 23.
STRING; 9606.ENSP00000266503; -.
iPTMnet; Q8WYA1; -.
PhosphoSitePlus; Q8WYA1; -.
BioMuta; ARNTL2; -.
DMDM; 124007121; -.
EPD; Q8WYA1; -.
jPOST; Q8WYA1; -.
MassIVE; Q8WYA1; -.
MaxQB; Q8WYA1; -.
PaxDb; Q8WYA1; -.
PeptideAtlas; Q8WYA1; -.
PRIDE; Q8WYA1; -.
ProteomicsDB; 26427; -.
ProteomicsDB; 75143; -. [Q8WYA1-1]
ProteomicsDB; 75144; -. [Q8WYA1-2]
ProteomicsDB; 75145; -. [Q8WYA1-3]
ProteomicsDB; 75146; -. [Q8WYA1-4]
ProteomicsDB; 75147; -. [Q8WYA1-5]
ProteomicsDB; 75148; -. [Q8WYA1-6]
ProteomicsDB; 75149; -. [Q8WYA1-7]
ProteomicsDB; 75150; -. [Q8WYA1-8]
Antibodypedia; 12657; 116 antibodies.
DNASU; 56938; -.
Ensembl; ENST00000261178; ENSP00000261178; ENSG00000029153. [Q8WYA1-4]
Ensembl; ENST00000266503; ENSP00000266503; ENSG00000029153. [Q8WYA1-1]
Ensembl; ENST00000311001; ENSP00000312247; ENSG00000029153. [Q8WYA1-2]
Ensembl; ENST00000395901; ENSP00000379238; ENSG00000029153. [Q8WYA1-3]
Ensembl; ENST00000542388; ENSP00000445836; ENSG00000029153. [Q8WYA1-6]
Ensembl; ENST00000544915; ENSP00000442438; ENSG00000029153. [Q8WYA1-5]
Ensembl; ENST00000546179; ENSP00000438545; ENSG00000029153. [Q8WYA1-9]
GeneID; 56938; -.
KEGG; hsa:56938; -.
UCSC; uc001rht.3; human. [Q8WYA1-1]
CTD; 56938; -.
DisGeNET; 56938; -.
GeneCards; ARNTL2; -.
HGNC; HGNC:18984; ARNTL2.
HPA; ENSG00000029153; Tissue enhanced (esophagus).
MIM; 614517; gene.
neXtProt; NX_Q8WYA1; -.
OpenTargets; ENSG00000029153; -.
PharmGKB; PA134896555; -.
VEuPathDB; HostDB:ENSG00000029153.14; -.
eggNOG; KOG3561; Eukaryota.
GeneTree; ENSGT00940000160423; -.
HOGENOM; CLU_011864_2_2_1; -.
InParanoid; Q8WYA1; -.
OMA; IPQCNPV; -.
OrthoDB; 331262at2759; -.
PhylomeDB; Q8WYA1; -.
TreeFam; TF319983; -.
PathwayCommons; Q8WYA1; -.
Reactome; R-HSA-1368108; BMAL1:CLOCK,NPAS2 activates circadian gene expression.
SIGNOR; Q8WYA1; -.
BioGRID-ORCS; 56938; 13 hits in 1013 CRISPR screens.
ChiTaRS; ARNTL2; human.
GeneWiki; ARNTL2; -.
GenomeRNAi; 56938; -.
Pharos; Q8WYA1; Tbio.
PRO; PR:Q8WYA1; -.
Proteomes; UP000005640; Chromosome 12.
RNAct; Q8WYA1; protein.
Bgee; ENSG00000029153; Expressed in lower esophagus mucosa and 156 other tissues.
ExpressionAtlas; Q8WYA1; baseline and differential.
Genevisible; Q8WYA1; HS.
GO; GO:0034751; C:aryl hydrocarbon receptor complex; IBA:GO_Central.
GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
GO; GO:0005737; C:cytoplasm; IEA:InterPro.
GO; GO:0005730; C:nucleolus; IDA:HPA.
GO; GO:0005654; C:nucleoplasm; IDA:HPA.
GO; GO:0005634; C:nucleus; IDA:MGI.
GO; GO:0005667; C:transcription regulator complex; IEA:InterPro.
GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:BHF-UCL.
GO; GO:0070888; F:E-box binding; IDA:UniProtKB.
GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL.
GO; GO:0007623; P:circadian rhythm; IDA:MGI.
GO; GO:0009649; P:entrainment of circadian clock; NAS:UniProtKB.
GO; GO:0042753; P:positive regulation of circadian rhythm; ISS:UniProtKB.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI.
GO; GO:0006355; P:regulation of transcription, DNA-templated; NAS:UniProtKB.
CDD; cd00130; PAS; 2.
Gene3D; 4.10.280.10; -; 1.
InterPro; IPR011598; bHLH_dom.
InterPro; IPR036638; HLH_DNA-bd_sf.
InterPro; IPR001067; Nuc_translocat.
InterPro; IPR000014; PAS.
InterPro; IPR035965; PAS-like_dom_sf.
InterPro; IPR013767; PAS_fold.
Pfam; PF00010; HLH; 1.
Pfam; PF00989; PAS; 1.
PRINTS; PR00785; NCTRNSLOCATR.
SMART; SM00353; HLH; 1.
SMART; SM00091; PAS; 2.
SUPFAM; SSF47459; SSF47459; 1.
SUPFAM; SSF55785; SSF55785; 2.
TIGRFAMs; TIGR00229; sensory_box; 1.
PROSITE; PS50888; BHLH; 1.
PROSITE; PS50112; PAS; 2.
1: Evidence at protein level;
3D-structure; Activator; Alternative splicing; Biological rhythms;
DNA-binding; Isopeptide bond; Nucleus; Reference proteome; Repeat;
Transcription; Transcription regulation; Ubl conjugation.
CHAIN 1..636
/note="Aryl hydrocarbon receptor nuclear translocator-like
protein 2"
/id="PRO_0000273631"
DOMAIN 107..160
/note="bHLH"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
DOMAIN 178..250
/note="PAS 1"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
DOMAIN 357..427
/note="PAS 2"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
DOMAIN 432..475
/note="PAC"
REGION 25..62
/note="Disordered"
/evidence="ECO:0000256|SAM:MobiDB-lite"
REGION 46..258
/note="Interaction with PER2"
/evidence="ECO:0000250|UniProtKB:Q2VPD4"
MOTIF 49..54
/note="Nuclear localization signal"
/evidence="ECO:0000250|UniProtKB:Q9WTL8"
MOTIF 177..187
/note="Nuclear export signal 1"
/evidence="ECO:0000250|UniProtKB:Q9WTL8"
MOTIF 392..400
/note="Nuclear export signal 2"
/evidence="ECO:0000250|UniProtKB:Q9WTL8"
COMPBIAS 25..43
/note="Polar residues"
/evidence="ECO:0000256|SAM:MobiDB-lite"
CROSSLNK 287
/note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
G-Cter in SUMO2 and SUMO3)"
/evidence="ECO:0000250|UniProtKB:Q9WTL8"
CROSSLNK 294
/note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
G-Cter in SUMO2)"
/evidence="ECO:0007744|PubMed:28112733"
VAR_SEQ 1..37
/note="Missing (in isoform 6, isoform 7 and isoform 8)"
/evidence="ECO:0000303|PubMed:10864977,
ECO:0000303|PubMed:10964693"
/id="VSP_022580"
VAR_SEQ 11
/note="G -> GEVAGGEATAPG (in isoform 3 and isoform 9)"
/evidence="ECO:0000303|PubMed:11554928,
ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334"
/id="VSP_022585"
VAR_SEQ 61
/note="Q -> H (in isoform 8)"
/evidence="ECO:0000303|PubMed:10864977"
/id="VSP_022582"
VAR_SEQ 62..95
/note="Missing (in isoform 3, isoform 4, isoform 5, isoform
6 and isoform 9)"
/evidence="ECO:0000303|PubMed:10964693,
ECO:0000303|PubMed:11018023, ECO:0000303|PubMed:11554928,
ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334"
/id="VSP_022581"
VAR_SEQ 62..74
/note="Missing (in isoform 8)"
/evidence="ECO:0000303|PubMed:10864977"
/id="VSP_022583"
VAR_SEQ 96..109
/note="Missing (in isoform 2, isoform 3, isoform 4, isoform
6, isoform 7, isoform 8 and isoform 9)"
/evidence="ECO:0000303|PubMed:10864977,
ECO:0000303|PubMed:10964693, ECO:0000303|PubMed:11554928,
ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334"
/id="VSP_022584"
VAR_SEQ 556..635
/note="MSNKELFPPSPSEMGELEATRQNQSTVAVHSHEPLLSDGAQLDFDALCDNDD
TAMAAFMNYLEAEGGLGDPGDFSDIQWT -> VMVHSWISMPYVTMMTQPWLH (in
isoform 9)"
/evidence="ECO:0000303|PubMed:14702039"
/id="VSP_044773"
VARIANT 340
/note="N -> S (in dbSNP:rs1037921)"
/id="VAR_030158"
VARIANT 574
/note="A -> V (in dbSNP:rs11049005)"
/id="VAR_030159"
CONFLICT 41
/note="F -> S (in Ref. 1; BAB01485)"
/evidence="ECO:0000305"
CONFLICT 173
/note="R -> G (in Ref. 5; BAH12415)"
/evidence="ECO:0000305"
CONFLICT 257
/note="A -> T (in Ref. 3; AAF71306/AAF71307)"
/evidence="ECO:0000305"
CONFLICT 276
/note="S -> F (in Ref. 3; AAF71306/AAF71307)"
/evidence="ECO:0000305"
CONFLICT 304
/note="K -> R (in Ref. 5; BAH12415)"
/evidence="ECO:0000305"
CONFLICT 324
/note="P -> R (in Ref. 1; BAB01485)"
/evidence="ECO:0000305"
CONFLICT 527
/note="L -> I (in Ref. 1; BAB01485)"
/evidence="ECO:0000305"
STRAND 368..375
/evidence="ECO:0007829|PDB:2KDK"
STRAND 379..384
/evidence="ECO:0007829|PDB:2KDK"
HELIX 387..391
/evidence="ECO:0007829|PDB:2KDK"
TURN 396..398
/evidence="ECO:0007829|PDB:2KDK"
TURN 404..407
/evidence="ECO:0007829|PDB:2KDK"
STRAND 410..412
/evidence="ECO:0007829|PDB:2KDK"
HELIX 413..424
/evidence="ECO:0007829|PDB:2KDK"
STRAND 426..428
/evidence="ECO:0007829|PDB:2KDK"
STRAND 430..438
/evidence="ECO:0007829|PDB:2KDK"
STRAND 440..442
/evidence="ECO:0007829|PDB:2KDK"
STRAND 444..455
/evidence="ECO:0007829|PDB:2KDK"
STRAND 458..460
/evidence="ECO:0007829|PDB:2KDK"
STRAND 462..470
/evidence="ECO:0007829|PDB:2KDK"
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


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Pathways :
WP1566: Citrate cycle (TCA cycle)
WP2292: Chemokine signaling pathway
WP1502: Mitochondrial biogenesis
WP2272: Pathogenic Escherichia coli infection
WP1689: Porphyrin and chlorophyll metabolism
WP1493: Carbon assimilation C4 pathway
WP1909: Signal regulatory protein (SIRP) family interactions
WP1675: Nitrogen metabolism
WP211: BMP signaling pathway
WP1685: Peptidoglycan biosynthesis
WP1616: ABC transporters
WP1644: DNA replication
WP731: Sterol regulatory element binding protein related
WP1692: Protein export
WP1165: G Protein Signaling Pathways
WP1657: Glycerolipid metabolism
WP1663: Homologous recombination
WP2218: sGC
WP1714: Tyrosine metabolism
WP1371: G Protein Signaling Pathways
WP1673: Naphthalene and anthracene degradation
WP1678: Nucleotide excision repair
WP2324: AGE/RAGE pathway
WP1613: 1,4-Dichlorobenzene degradation
WP1625: Base excision repair

Related Genes :
[ARNTL2 BHLHE6 BMAL2 CLIF MOP9 PASD9] Aryl hydrocarbon receptor nuclear translocator-like protein 2 (Basic-helix-loop-helix-PAS protein MOP9) (Brain and muscle ARNT-like 2) (CYCLE-like factor) (CLIF) (Class E basic helix-loop-helix protein 6) (bHLHe6) (Member of PAS protein 9) (PAS domain-containing protein 9)
[ARNTL BHLHE5 BMAL1 MOP3 PASD3] Aryl hydrocarbon receptor nuclear translocator-like protein 1 (Basic-helix-loop-helix-PAS protein MOP3) (Brain and muscle ARNT-like 1) (Class E basic helix-loop-helix protein 5) (bHLHe5) (Member of PAS protein 3) (PAS domain-containing protein 3) (bHLH-PAS protein JAP3)
[Arntl BMAL1 MOP3] Aryl hydrocarbon receptor nuclear translocator-like protein 1 (Basic-helix-loop-helix-PAS protein MOP3) (Brain and muscle ARNT-like 1)
[ARNT2 BHLHE1 KIAA0307] Aryl hydrocarbon receptor nuclear translocator 2 (ARNT protein 2) (Class E basic helix-loop-helix protein 1) (bHLHe1)
[HIF1A BHLHE78 MOP1 PASD8] Hypoxia-inducible factor 1-alpha (HIF-1-alpha) (HIF1-alpha) (ARNT-interacting protein) (Basic-helix-loop-helix-PAS protein MOP1) (Class E basic helix-loop-helix protein 78) (bHLHe78) (Member of PAS protein 1) (PAS domain-containing protein 8)
[EPAS1 BHLHE73 HIF2A MOP2 PASD2] Endothelial PAS domain-containing protein 1 (EPAS-1) (Basic-helix-loop-helix-PAS protein MOP2) (Class E basic helix-loop-helix protein 73) (bHLHe73) (HIF-1-alpha-like factor) (HLF) (Hypoxia-inducible factor 2-alpha) (HIF-2-alpha) (HIF2-alpha) (Member of PAS protein 2) (PAS domain-containing protein 2)
[NPAS2 BHLHE9 MOP4 PASD4] Neuronal PAS domain-containing protein 2 (Neuronal PAS2) (Basic-helix-loop-helix-PAS protein MOP4) (Class E basic helix-loop-helix protein 9) (bHLHe9) (Member of PAS protein 4) (PAS domain-containing protein 4)
[AHR BHLHE76] Aryl hydrocarbon receptor (Ah receptor) (AhR) (Class E basic helix-loop-helix protein 76) (bHLHe76)
[NPAS4 BHLHE79 NXF PASD10] Neuronal PAS domain-containing protein 4 (Neuronal PAS4) (Class E basic helix-loop-helix protein 79) (bHLHe79) (HLH-PAS transcription factor NXF) (PAS domain-containing protein 10)
[Arntl Bmal1] Aryl hydrocarbon receptor nuclear translocator-like protein 1 (Arnt3) (Brain and muscle ARNT-like 1)
[AHRR BHLHE77 KIAA1234] Aryl hydrocarbon receptor repressor (AhR repressor) (AhRR) (Class E basic helix-loop-helix protein 77) (bHLHe77)
[NCOA2 BHLHE75 SRC2 TIF2] Nuclear receptor coactivator 2 (NCoA-2) (Class E basic helix-loop-helix protein 75) (bHLHe75) (Transcriptional intermediary factor 2) (hTIF2)
[Arntl Bmal1 Tic] Aryl hydrocarbon receptor nuclear translocator-like protein 1 (Brain and muscle ARNT-like 1) (Tic)
[Arnt2 Kiaa0307] Aryl hydrocarbon receptor nuclear translocator 2 (ARNT protein 2)
[ARNTL BMAL1] Aryl hydrocarbon receptor nuclear translocator-like protein 1 (Brain and muscle ARNT-like 1)
[Arntl2 Bmal2] Aryl hydrocarbon receptor nuclear translocator-like protein 2 (Brain and muscle ARNT-like 2)
[ARNTL BMAL1] Aryl hydrocarbon receptor nuclear translocator-like protein 1 (Brain and muscle ARNT-like 1)
[ARNTL BMAL1] Aryl hydrocarbon receptor nuclear translocator-like protein 1 (Brain and muscle ARNT-like 1)
[NCOA3 AIB1 BHLHE42 RAC3 TRAM1] Nuclear receptor coactivator 3 (NCoA-3) (EC 2.3.1.48) (ACTR) (Amplified in breast cancer 1 protein) (AIB-1) (CBP-interacting protein) (pCIP) (Class E basic helix-loop-helix protein 42) (bHLHe42) (Receptor-associated coactivator 3) (RAC-3) (Steroid receptor coactivator protein 3) (SRC-3) (Thyroid hormone receptor activator molecule 1) (TRAM-1)
[CLOCK BHLHE8 KIAA0334] Circadian locomoter output cycles protein kaput (hCLOCK) (EC 2.3.1.48) (Class E basic helix-loop-helix protein 8) (bHLHe8)
[ARNTL BMAL1] Aryl hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1b') (Brain and muscle ARNT-like 1) (cBMAL1)
[BHLHE40 BHLHB2 DEC1 SHARP2 STRA13] Class E basic helix-loop-helix protein 40 (bHLHe40) (Class B basic helix-loop-helix protein 2) (bHLHb2) (Differentially expressed in chondrocytes protein 1) (DEC1) (Enhancer-of-split and hairy-related protein 2) (SHARP-2) (Stimulated by retinoic acid gene 13 protein)
[BHLHA9 BHLHF42] Class A basic helix-loop-helix protein 9 (bHLHa9) (Class F basic helix-loop-helix factor 42) (bHLHf42)
[TCF3 BHLHB21 E2A ITF1] Transcription factor E2-alpha (Class B basic helix-loop-helix protein 21) (bHLHb21) (Immunoglobulin enhancer-binding factor E12/E47) (Immunoglobulin transcription factor 1) (Kappa-E2-binding factor) (Transcription factor 3) (TCF-3) (Transcription factor ITF-1)
[Bhlhe22 Bhlhb5] Class E basic helix-loop-helix protein 22 (bHLHe22) (Class B basic helix-loop-helix protein 5) (bHLHb5) (Protein BETA3)
[arnt2] Aryl hydrocarbon receptor nuclear translocator 2 (ARNT protein 2) (zfARNT2)
[Bhlha15 Bhlhb8 Mist1] Class A basic helix-loop-helix protein 15 (bHLHa15) (Class B basic helix-loop-helix protein 8) (bHLHb8) (Muscle, intestine and stomach expression 1) (MIST-1)
[TCF12 BHLHB20 HEB HTF4] Transcription factor 12 (TCF-12) (Class B basic helix-loop-helix protein 20) (bHLHb20) (DNA-binding protein HTF4) (E-box-binding protein) (Transcription factor HTF-4)
[TCF4 BHLHB19 ITF2 SEF2] Transcription factor 4 (TCF-4) (Class B basic helix-loop-helix protein 19) (bHLHb19) (Immunoglobulin transcription factor 2) (ITF-2) (SL3-3 enhancer factor 2) (SEF-2)
[Bhlha15 Bhlhb8 Mist1] Class A basic helix-loop-helix protein 15 (bHLHa15) (Class B basic helix-loop-helix protein 8) (bHLHb8) (Muscle, intestine and stomach expression 1) (MIST-1)

Bibliography :