basic Helix-Loop-Helix-zipper (bHLHzip) domain found in USF/MITF family; The USF (upstream stimulatory factor)/MITF (microphthalmia-associated transcription factor) family includes two bHLHzip transcription factor subfamilies. USFs are ubiquitously expressed and key regulators of a wide number of gene regulation networks, including the stress and immune responses, cell cycle and proliferation, lipid and glucid metabolism. USFs recruit chromatin remodeling enzymes and interact with co-activators and the members of the transcription pre-initiation complex. USFs interact with high affinity to E-box regulatory elements. The MITF (also known as microphthalmia-TFE, or MiT) subfamily comprises four genes in mammals (MITF, TFE3, TFEB, and TFEC); each gene has different functions. MITF is involved in neural crest melanocytes development as well as the pigmented retinal epithelium. TFEB is required for vascularization of the mouse placenta. TFE3 is involved in B cell function. TFEC regulates gene expression in macrophages. The MITF subfamily proteins can form homodimers or heterodimers with each other but not with other bHLH or bHLHzip proteins.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 6319365  289 FHNAVERRRRELIKQKIKELGQLVPPSLLNYddlgKQIKPNKGIILDRTVEYLQYLAEILE 349
Cdd:cd11387   1 SHNAVERRRRDNINEKIQELGSLVPPSRLET----KDLKPNKGSILSKAVEYIRELQNQNQ 57

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in USF/MITF family; The USF (upstream stimulatory factor)/MITF (microphthalmia-associated transcription factor) family includes two bHLHzip transcription factor subfamilies. USFs are ubiquitously expressed and key regulators of a wide number of gene regulation networks, including the stress and immune responses, cell cycle and proliferation, lipid and glucid metabolism. USFs recruit chromatin remodeling enzymes and interact with co-activators and the members of the transcription pre-initiation complex. USFs interact with high affinity to E-box regulatory elements. The MITF (also known as microphthalmia-TFE, or MiT) subfamily comprises four genes in mammals (MITF, TFE3, TFEB, and TFEC); each gene has different functions. MITF is involved in neural crest melanocytes development as well as the pigmented retinal epithelium. TFEB is required for vascularization of the mouse placenta. TFE3 is involved in B cell function. TFEC regulates gene expression in macrophages. The MITF subfamily proteins can form homodimers or heterodimers with each other but not with other bHLH or bHLHzip proteins.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 6319365  289 FHNAVERRRRELIKQKIKELGQLVPPSLLNYddlgKQIKPNKGIILDRTVEYLQYLAEILE 349
Cdd:cd11387   1 SHNAVERRRRDNINEKIQELGSLVPPSRLET----KDLKPNKGSILSKAVEYIRELQNQNQ 57

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 6319365    286 KREFHNAVERRRRELIKQKIKELGQLVPPsllnyddLGKQIKPNKGIILDRTVEYLQYL 344
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELLPT-------LPPDKKLSKAEILRLAIEYIKHL 52

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in USF/MITF family; The USF (upstream stimulatory factor)/MITF (microphthalmia-associated transcription factor) family includes two bHLHzip transcription factor subfamilies. USFs are ubiquitously expressed and key regulators of a wide number of gene regulation networks, including the stress and immune responses, cell cycle and proliferation, lipid and glucid metabolism. USFs recruit chromatin remodeling enzymes and interact with co-activators and the members of the transcription pre-initiation complex. USFs interact with high affinity to E-box regulatory elements. The MITF (also known as microphthalmia-TFE, or MiT) subfamily comprises four genes in mammals (MITF, TFE3, TFEB, and TFEC); each gene has different functions. MITF is involved in neural crest melanocytes development as well as the pigmented retinal epithelium. TFEB is required for vascularization of the mouse placenta. TFE3 is involved in B cell function. TFEC regulates gene expression in macrophages. The MITF subfamily proteins can form homodimers or heterodimers with each other but not with other bHLH or bHLHzip proteins.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 6319365  289 FHNAVERRRRELIKQKIKELGQLVPPSLLNYddlgKQIKPNKGIILDRTVEYLQYLAEILE 349
Cdd:cd11387   1 SHNAVERRRRDNINEKIQELGSLVPPSRLET----KDLKPNKGSILSKAVEYIRELQNQNQ 57

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in the microphthalmia-associated transcription factor family (MITF) family; The MITF (also known as microphthalmia-TFE, or MiT) family is a small family that contain a basic helix loop helix domain associated with a leucine zipper (bHLHZip). The MITF family comprises four genes in mammals (MITF, TFE3, TFEB, and TFEC); each gene has different functions. MITF is involved in neural crest melanocytes development as well as the pigmented retinal epithelium. TFEB is required for vascularization of the mouse placenta. TFE3 is involved in B cell function. TFEC regulates gene expression in macrophages. The MITF family can form homodimers or heterodimers with each other but not with other bHLH or bHLHzip proteins.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 6319365  282 KLRRKREFHNAVERRRRELIKQKIKELGQLVPPSllnYDdlgKQIKPNKGIILDRTVEYLQYL 344
Cdd:cd11397   1 KDRQKKDNHNMIERRRRFNINDRIKELGTLLPKS---ND---PDMRWNKGTILKASVDYIRKL 57

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 6319365     291 NAVERRRRELIKQKIKELGQLVPPSLLNyddlgkqIKPNKGIILDRTVEYLQYLAEILE 349
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPKN-------KKLSKAEILRLAIEYIKSLQEELQ 52

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in sterol regulatory element-binding protein (SREBP) family and similar proteins; The SREBP family includes SREBP1 and SREBP2, which are bHLHzip transcriptional activator of genes encoding proteins essential for cholesterol biosynthesis/uptake and fatty acid biosynthesis. SREBP1 and SREBP2 are principally found in the liver and in adipocytes and made up of an N-terminal transcription factor portion (composed of an activation domain, a bHLHzip domain, and a nuclear localization signal), a hydrophobic region containing two membrane spanning regions, and a C-terminal regulatory segment. They recognize a symmetric sterol regulatory element (TCACNCCAC) instead of E-box. The family also includes Saccharomyces cerevisiae transcription factor HMS1 (also termed high-copy MEP suppressor protein 1) and serine-rich protein TYE7. HMS1 is a putative bHLHzip transcription factor involved in exit from mitosis and pseudohyphal differentiation. TYE7, also termed basic-helix-loop-helix protein SGC1, is a putative bHLHzip transcription activator required for Ty1-mediated glycolytic gene expression. TYE7 N-terminal is extremely rich in serine residues. It binds DNA on E-box motifs, 5'-CANNTG-3'. TYE7 is not essential for growth.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 6319365  284 RRKREFHNAVERRRRELIKQKIKELGQLVPPSLLNY--------DDLGKQIKPNKGIILDRTVEYLQYL 344
Cdd:cd11395   1 PRKRLPHNAIEKRYRSNLNTKIERLRDAIPSLRSPEgksddgglGGLAPTTKLSKATILTKAIEYIRHL 69

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in basic helix-loop-helix domain-containing protein USF3 and similar proteins; USF3, also termed upstream transcription factor 3, is a bHLHzip protein that is involved in the negative regulation of epithelial-mesenchymal transition, the process by which epithelial cells lose their polarity and adhesion properties to become mesenchymal cells with enhanced migration and invasive properties.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 6319365  284 RRKREFHNAVERRRRELIKQKIKELGQLVPPSllnyddlgKQIKPNKGIILDRTVEYLQYLAE 346
Cdd:cd18910   3 EKKRESHNEVERRRKDKINAGINKIGELLPDR--------DAKKQSKNMILEQAYKYIVELKK 57

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in transcription factor EB (TFEB) and similar proteins; TFEB, also termed Class E basic helix-loop-helix protein 35 (bHLHe35), is a bHLHzip transcription factor that is required for vascularization of the mouse placenta. It specifically recognizes and binds E-box sequences (5'-CANNTG-3'). Its efficient DNA-binding requires dimerization with itself or with another MiT/TFE family member such as TFE3 or MITF.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 6319365  282 KLRRKREFHNAVERRRRELIKQKIKELGQLVPPSllnyDDLgkQIKPNKGIILDRTVEYLQYL 344
Cdd:cd18927   7 KERQKKDNHNLIERRRRFNINDRIKELGTLIPKT----NDL--DVRWNKGTILKASVDYIKRM 63

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in transcription factor EC (TFEC) and similar proteins; TFEC, also termed Class E basic helix-loop-helix protein 34 (bHLHe34), or transcription factor EC-like (TFEC-L), is a bHLHzip transcriptional regulator that acts as a repressor or an activator and regulates gene expression in macrophages. It plays an important role in the niche to expand hematopoietic progenitors through the modulation of several cytokines.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 6319365  282 KLRRKREFHNAVERRRRELIKQKIKELGQLVPPSllNYDDLgkqiKPNKGIILDRTVEYLQYL 344
Cdd:cd18925   1 KERQKKDNHNLIERRRRYNINYRIKELGTLIPKS--NDPDM----RWNKGTILKASVEYIKWL 57

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-like protein X (Mlx) family; Mlx, also termed Class D basic helix-loop-helix protein 13 (bHLHd13), or Max-like bHLHZip protein, or protein BigMax, or transcription factor-like protein 4, is a Max-like bHLHZip transcription regulator that interacts with the Max network of transcription factors. It forms a sequence-specific DNA-binding protein complex with some member of Mad family (Mad1 and Mad4) and Mondo family but not the Myc family and bind the E-box DNA to control transcription. The family also includes Saccharomyces cerevisiae INO4, which is a bHLH transcriptional activator of phospholipid synthetic genes (such as INO1, CHO1/PSS, CHO2/PEM1, OPI3/PEM2, etc.). It is required for de-repression of phospholipid biosynthetic gene expression in response to inositol deprivation in yeast.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 6319365  285 RKREFHNAVERRRRELIKQKIKELGQLVPpsllnydDLgKQIKPNKGIILDRTVEYLQYLAE 346
Cdd:cd11404   1 QRRLNHVRSEKKRRELIKKGYDELCALVP-------GL-DPQKRTKADILQKAADWIQELKE 54

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in sterol regulatory element-binding protein 1 (SREBP1) and similar proteins; SREBP1, also termed Class D basic helix-loop-helix protein 1 (bHLHd1), or sterol regulatory element-binding transcription factor 1 (SREBF1), is a member of a family of bHLHzip transcription factors that recognize sterol regulatory element 1 (SRE-1). It acts as a transcriptional activator required for lipid homeostasis. It may control transcription of the low-density lipoprotein receptor gene as well as the fatty acid. SREBP1 has dual sequence specificity binding to both an E-box motif (5'-ATCACGTGA-3') and to SRE-1 (5'-ATCACCCCAC-3').

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 6319365  286 KREFHNAVERRRRELIKQKIKELGQLVppsllnyddLGKQIKPNKGIILDRTVEYLQYL 344
Cdd:cd18921   6 KRTAHNAIEKRYRSSINDKIIELKDLV---------VGTEAKLNKSAVLRKAIDYIRFL 55

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in sterol regulatory element-binding protein (SREBP) family; The SREBP family includes SREBP1 and SREBP2, which are bHLHzip transcriptional activator of genes encoding proteins essential for cholesterol biosynthesis/uptake and fatty acid biosynthesis. SREBP1 and SREBP2 are principally found in the liver and in adipocytes and made up of an N-terminal transcription factor portion (composed of an activation domain, a bHLHzip domain, and a nuclear localization signal), a hydrophobic region containing two membrane spanning regions, and a C-terminal regulatory segment. They recognize a symmetric sterol regulatory element (TCACNCCAC) instead of E-box.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 6319365  286 KREFHNAVERRRRELIKQKIKELGQLVppsllnyddLGKQIKPNKGIILDRTVEYLQYLAEI 347
Cdd:cd11394   6 KRSAHNAIEKRYRSSINDRIIELKDLV---------VGPDAKMNKSAVLRKAIDYIRYLQKV 58

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split (HES)-related repressor protein (HERP)-like family; The HERP-like family includes bHLH-O transcriptional regulators that are related to the Drosophila hairy and Enhancer-of-split proteins. They contain a basic helix-loop-helix (bHLH) domain with an invariant glycine residue in its basic region, an orange domain in the central region and YXXW sequence motif at its C-terminal region. HERP proteins (HEY1, HEY2 and HEYL) act as downstream effectors of Notch signaling. They are involved in cardiovascular development and have roles in somitogenesis, myogenesis and gliogenesis. Hairy and enhancer of split-related protein HELT is a transcriptional repressor expressed in the developing central nervous system. It binds preferentially to the canonical E box sequence 5'-CACGCG-3' and regulates neuronal differentiation and/or identity. Differentially expressed in chondrocytes proteins, DEC1 and DEC2, are widely expressed in both embryonic and adult tissues and have been implicated in apoptosis, cell proliferation, and circadian rhythms, as well as malignancy in various cancers. Drosophila melanogaster protein clockwork orange (Cwo) is also included in this family. It is involved in the regulation of Drosophila circadian rhythms. It functions as both an activator and a repressor of clock gene expression.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 6319365  290 HNAVERRRRELIKQKIKELGQLVPPSlLNYDDLGKQikpNKGIILDRTVEYLQYL 344
Cdd:cd11389   1 HKVIEKRRRDRINESLAELRRLVPEA-RKSKGSGKL---EKAEILEMTLQHLKAL 51

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in sterol regulatory element-binding protein 2 (SREBP2) and similar proteins; SREBP2, also termed Class D basic helix-loop-helix protein 2 (bHLHd2), or sterol regulatory element-binding transcription factor 2 (SREBF2), is a member of a family of bHLHzip transcription factors that recognize sterol regulatory element 1 (SRE-1). It acts as a transcription activator of cholesterol biosynthesis.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 6319365  286 KREFHNAVERRRRELIKQKIKELGQLVppsllnyddLGKQIKPNKGIILDRTVEYLQYLAEI 347
Cdd:cd18922   6 RRTTHNIIEKRYRSSINDKIIELKDLV---------MGTDAKMHKSGVLRKAIDYIKYLQQV 58

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana phytochrome interacting factors (PIFs) and similar proteins; The family includes several bHLH transcription factors from Arabidopsis thaliana, such as PIFs, ALC, PIL1, SPATULA, and UNE10. PIFs (PIF1, PIF3, PIF4, PIF5, PIF6 and PIF7) have been shown to control light-regulated gene expression. They directly bind to the photoactivated phytochromes and are degraded in response to light signals. ALC, also termed AtbHLH73, or protein ALCATRAZ, or EN 98, is required for the dehiscence of fruit, especially for the separation of the valve cells from the replum. It promotes the differentiation of a strip of labile non-lignified cells sandwiched between layers of lignified cells. PIL1, also termed AtbHLH124, or protein phytochrome interacting factor 3-like 1, or EN 110, is involved in responses to transient and long-term shade. It is required for the light-mediated inhibition of hypocotyl elongation and necessary for rapid light-induced expression of the photomorphogenesis- and circadian-related gene APRR9. PIL1 seems to play a role in multiple PHYB responses, such as flowering transition and petiole elongation. SPATULA, also termed AtbHLH24, or EN 99, plays a role in floral organogenesis. It promotes the growth of carpel margins and of pollen tract tissues derived from them. UNE10, also termed AtbHLH16, or protein UNFERTILIZED EMBRYO SAC 10, or EN 99, is required during the fertilization of ovules by pollen.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 6319365  285 RKREFHNAVERRRRELIKQKIKELGQLVPPSLlnyddlgkqiKPNKGIILDRTVEYLQYLAeiLEIQ 351
Cdd:cd11445   1 RAAEVHNLSERRRRDRINEKMKALQELIPNCN----------KTDKASMLDEAIEYLKSLQ--LQVQ 55

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in circadian clock protein PASD1; PASD1, also termed PAS domain-containing protein 1, is evolutionarily related to Circadian locomotor output cycles protein kaput (CLOCK)and functions as a suppressor of the biological clock that drives the daily circadian rhythms of cells throughout the body. Mammalian PASD1 doesn't harbor the bHLH-PAS domain and is not included in this family.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 6319365  277 LTSDEKLRRKREFHNAVERRRRELIKQKIKELGQLVPPSllnyddlGKQIKPNKGIILDRTVEYLQYLAEI 347
Cdd:cd19736   1 MDEDEKDRAKRASRNKSEKKRRDQFNVLIKELCTMLQGH-------GHPLKMDKSTILQRTIDFLQKQKEI 64

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in nuclear receptor coactivator 3 (NCoA-3) and similar proteins; NCoA-3, also termed ACTR, or amplified in breast cancer 1 protein (AIB-1), or CBP-interacting protein (pCIP), or Class E basic helix-loop-helix protein 42 (bHLHe42), or receptor-associated coactivator 3 (RAC-3), or steroid receptor coactivator protein 3 (SRC-3), or thyroid hormone receptor activator molecule 1 (TRAM-1), is a bHLH-PAS steroid/nuclear receptor-associated coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. It also plays a central role in creating a multisubunit coactivator complex, which probably acts via remodeling of chromatin.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 6319365  292 AVERRRRELIKQKIKELGQLVPPSLLNYDDLgkQIKPNKGIILDRTVEYLQYLAE 346
Cdd:cd18949   4 SGEKRRREQESKYIEELAELISANLSDIDNF--NVKPDKCAILKETVRQIRQIKE 56

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana BES1-interacting Myc-like proteins (BIMs) and similar proteins; The family includes Arabidopsis thaliana BIM1 and its homologs (BIM2 and BIM3), which are bHLH transcription factors that interact with BES1 to regulate transcription of Brassinosteroid (BR)-induced gene. BR regulates many growth and developmental processes such as cell elongation, vascular development, senescence stress responses, and photomorphogenesis. BIM1 heterodimerize with BES1 and bind to E-box sequences present in many BR-induced promoters to regulated BR-induced genes.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 6319365  287 REFHNAVERRRRELIKQKIKELGQLVPpsllnyddlGKQIKPNKGIILDRTVEYLQYLAE---ILEIQ 351
Cdd:cd11453   4 RSKHSATEQRRRSKINERLQALRDLIP---------HSDQKRDKASFLLEVIEYIQALQEkvaKLEEQ 62

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein maternal effect embryo arrest 8 (AtMEE8) and similar proteins; AtMEE8, also termed AtbHLH108, or EN 132, is a bHLH transcription factor required during early embryo development, for the endosperm formation.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 6319365  290 HNAVERRRRELIKQKIKELGQLVPpsllnyddlGKQIKPNKGIILDRTVEYLQYL 344
Cdd:cd19698   1 HNLLEKKRRERIKDKIEILKGLTP---------NCTPKSDIASILSCVIDYIKSL 46

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split (HES)-related repressor protein (HERP) family; HERP (also called Hey/Hesr/HRT/CHF/gridlock) proteins corresponds to a family of bHLH-O transcriptional repressors that are related to the Drosophila hairy and Enhancer-of-split proteins and act as downstream effectors of Notch signaling. They contain a basic helix-loop-helix (bHLH) domain with an invariant glycine residue in its basic region, an orange domain in the central region and YXXW sequence motif at its C-terminal region. HERP proteins are involved in cardiovascular development and have roles in somitogenesis, myogenesis and gliogenesis.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 6319365  284 RRKREfhNAVERRRRELIKQKIKELGQLVPPSllnYDDLGKQiKPNKGIILDRTVEYLQYL 344
Cdd:cd11407   1 RKKRR--GIIEKRRRDRINNSLAELRRLVPTA---FEKQGSA-KLEKAEILQMTVDHLKML 55

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in steroid receptor coactivator (SRC) family; The SRC family of coactivators includes SRC-1 (NcoA-1/p160), SRC-2(TIF2/GRIP1/NcoA-2) and SRC-3(NcoA-3/pCIP/RAC3/ACTR/pCIP/AIB1/TRAM1), which are critical mediators of steroid receptor action. They contain bHLH-PAS domain at the N-terminal that is followed by receptor interacting domain and C-terminal transcriptional activation domain. SRC coactivators interact with nuclear receptors in a ligand-dependent manner and enhance transcriptional activation by the receptor via histone acetylation/methylation.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 6319365  294 ERRRRELIKQKIKELGQLVPPSLLNYDDLgkQIKPNKGIILDRTVEYLQYLAE 346
Cdd:cd11439   6 EKRRREQENKYIEELAELISASISDMDSL--SVKPDKCAILQETVKQIRQIKE 56

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL) and similar proteins; ARNTL, also termed Basic-helix-loop-helix-PAS protein MOP3, or brain and muscle ARNT-like 1 (BMAL1), or Class E basic helix-loop-helix protein 5 (bHLHe5), or member of PAS protein 3, or PAS domain-containing protein 3 (PASD3), or bHLH-PAS protein JAP3, is a member of the bHLH-PAS transcription factor family that forms heterodimers with another bHLH-PAS protein, CLOCK (circadian locomotor output cycle kaput), which regulates circadian rhythm. ARNTL-CLOCK heterodimer complex activates transcription from E-box (CANNTG) elements found in the promoter of circadian responsive genes. ARNTL is highly homologous to ARNT.

                        10        20        30
                ....*....|....*....|....*....|....
gi 6319365  280 DEKLRRKREFHNAVERRRRELIKQKIKELGQLVP 313
Cdd:cd11438   1 QGRIKNAREAHSQIEKRRRDKMNSFIDELASLVP 34

basic helix-loop-helix-orange (bHLH-O) domain found in HERP/HES-like family; The HERP/HES-like family includes bHLH-O transcriptional regulators that are related to the Drosophila hairy and Enhancer-of-split (HES) proteins. The HERP (HES-related repressor protein) subfamily proteins contain a basic helix-loop-helix (bHLH) domain with an invariant glycine residue in its basic region, an orange domain in the central region and YXXW sequence motif at its C-terminal region. Hairy and enhancer of split (HES)-related repressor protein (HERP) proteins (HEY1, HEY2 and HEYL) act as downstream effectors of Notch signaling. They are involved in cardiovascular development and have roles in somitogenesis, myogenesis and gliogenesis. Hairy and enhancer of split-related protein HELT is a transcriptional repressor expressed in the developing central nervous system. It binds preferentially to the canonical E box sequence 5'-CACGCG-3' and regulates neuronal differentiation and/or identity. Differentially expressed in chondrocytes proteins, DEC1 and DEC2, are widely expressed in both embryonic and adult tissues and have been implicated in apoptosis, cell proliferation, and circadian rhythms, as well as malignancy in various cancers. Drosophila melanogaster protein clockwork orange (Cwo) is also included in this subfamily. It is involved in the regulation of Drosophila circadian rhythms. It functions as both an activator and a repressor of clock gene expression. The HES subfamily proteins contain a basic helix-loop-helix (bHLH) domain with an invariant proline residue in its basic region, an orange domain in the central region and a conserved tetrapeptide motif, WRPW, at its C-terminal region. They form heterodimers or homodimers via their HLH domain and bind DNA to repress gene transcription that play an essential role in development of both compartment and boundary cells of the central nervous system.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 6319365  293 VERRRRELIKQKIKELGQLVPPSLlnydDLGKQIKPNKGIILDRTVEYLQYL 344
Cdd:cd19685   1 SEKRRRQRINDKLNQLKELLPPNL----SKQSRSKLSKAEILEMAITELRRL 48

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in aryl hydrocarbon receptor nuclear translocator (ARNT) and similar proteins; ARNT, also termed Class E basic helix-loop-helix protein 2 (bHLHe2), or Dioxin receptor, nuclear translocator, or hypoxia-inducible factor 1-beta (HIF1b), or HIF-1-beta, or HIF1-beta, is a member of bHLH-PAS transcription regulators that acts as the heterodimeric partner for bHLH-PAS proteins such as aryl hydrocarbon receptor (AhR), hypoxia-inducible factor (HIF), and single-minded (SIM). These bHLH-PAS transcription complexes are involved in transcriptional responses to xenobiotic, hypoxia, and developmental pathways. Heterodimerization of bHLH-PAS proteins with ARNT is mediated by contacts between both the bHLH and the tandem PAS domains. ARNT use bHLH and/or PAS domains to interact with several transcriptional coactivators. It is required for activity of the aryl hydrocarbon (dioxin) receptor.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 6319365  282 KLRRKREFHNAVERRRRELIKQKIKELGQLVPpsllNYDDLGKqiKPNKGIILDRTVEYLQYL 344
Cdd:cd18947   1 KERFARENHSEIERRRRNKMTAYITELSDMVP----TCSALAR--KPDKLTILRMAVSHMKSL 57