basic Helix-Loop-Helix-zipper (bHLHzip) domain found in upstream stimulatory factor 1 (USF1) and similar proteins; USF1, also termed Class B basic helix-loop-helix protein 11 (bHLHb11), or major late transcription factor 1, is a bHLHzip transcription factor that binds to a symmetrical DNA sequence (E-boxes) (5'-CACGTG-3') that is found in a variety of viral and cellular promoters. It is ubiquitously expressed and involved in the transcription activation of various functional genes implicated in lipid and glucose metabolism, stress response, immune response, cell cycle control and tumour suppression. USF-1 recruits chromatin remodeling enzymes and interact with co-activators and the members of the transcription pre-initiation complex. Genetic polymorphisms of USF1 are associated with some metabolic and cardiovascular diseases, like diabetes, atherosclerosis, coronary artery calcifications and familial combined hyperlipidaemia (FCHL).

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 444909174 196 RDEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKSGQSKGGILSKACDYIQELRQSNHR 260
Cdd:cd18924    1 RDEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKSGQSKGGILSKACDYIQELRQSNHR 65

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in upstream stimulatory factor 1 (USF1) and similar proteins; USF1, also termed Class B basic helix-loop-helix protein 11 (bHLHb11), or major late transcription factor 1, is a bHLHzip transcription factor that binds to a symmetrical DNA sequence (E-boxes) (5'-CACGTG-3') that is found in a variety of viral and cellular promoters. It is ubiquitously expressed and involved in the transcription activation of various functional genes implicated in lipid and glucose metabolism, stress response, immune response, cell cycle control and tumour suppression. USF-1 recruits chromatin remodeling enzymes and interact with co-activators and the members of the transcription pre-initiation complex. Genetic polymorphisms of USF1 are associated with some metabolic and cardiovascular diseases, like diabetes, atherosclerosis, coronary artery calcifications and familial combined hyperlipidaemia (FCHL).

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 444909174 196 RDEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKSGQSKGGILSKACDYIQELRQSNHR 260
Cdd:cd18924    1 RDEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKSGQSKGGILSKACDYIQELRQSNHR 65

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 444909174   205 NEVERRRRDKINNWIVQLSKIIPDCSmESTKsgQSKGGILSKACDYIQELRQSNH 259
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLP-KNKK--LSKAEILRLAIEYIKSLQEELQ 52

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in upstream stimulatory factor 1 (USF1) and similar proteins; USF1, also termed Class B basic helix-loop-helix protein 11 (bHLHb11), or major late transcription factor 1, is a bHLHzip transcription factor that binds to a symmetrical DNA sequence (E-boxes) (5'-CACGTG-3') that is found in a variety of viral and cellular promoters. It is ubiquitously expressed and involved in the transcription activation of various functional genes implicated in lipid and glucose metabolism, stress response, immune response, cell cycle control and tumour suppression. USF-1 recruits chromatin remodeling enzymes and interact with co-activators and the members of the transcription pre-initiation complex. Genetic polymorphisms of USF1 are associated with some metabolic and cardiovascular diseases, like diabetes, atherosclerosis, coronary artery calcifications and familial combined hyperlipidaemia (FCHL).

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 444909174 196 RDEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKSGQSKGGILSKACDYIQELRQSNHR 260
Cdd:cd18924    1 RDEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKSGQSKGGILSKACDYIQELRQSNHR 65

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in upstream stimulatory factors, USF1, USF2 and similar proteins; Upstream stimulatory factor 1 and 2 (USF-1 and USF-2) are members of bHLHzip transcription factor family. 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 444909174 203 QHNEVERRRRDKINNWIVQLSKIIPDCSMESTKSGQSKGGILSKACDYIQELRQSNHR 260
Cdd:cd11396    1 THNEVERRRRDKINNWIVKLAKIVPDCEKDNSKQGQSKGGILSKACDYIQELRSQNER 58

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 444909174 196 RDEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCSmestKSGQSKGGILSKACDYIQELRQSNHRL 261
Cdd:cd18910    1 RREKKRESHNEVERRRKDKINAGINKIGELLPDRD----AKKQSKNMILEQAYKYIVELKKKNDKL 62

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 444909174 200 RRAQHNEVERRRRDKINNWIVQLSKII--PDCSMestksgqSKGGILSKACDYIQELRQSNHRLSEELQGL 268
Cdd:cd11394    6 KRSAHNAIEKRYRSSINDRIIELKDLVvgPDAKM-------NKSAVLRKAIDYIRYLQKVNQKLKQENMAL 69

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 444909174  200 RRAQHNEVERRRRDKINNWIVQLSKIIPdCSMESTKsgQSKGGILSKACDYIQELR 255
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELLP-TLPPDKK--LSKAEILRLAIEYIKHLQ 53

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 444909174 200 RRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTksgqSKGGILSKACDYIQELRQSNHRLSEEL 265
Cdd:cd11404    2 RRLNHVRSEKKRRELIKKGYDELCALVPGLDPQKR----TKADILQKAADWIQELKEENEKLEEQL 63

basic Helix Loop Helix (bHLH) domain superfamily; bHLH proteins are transcriptional regulators that are found in organisms from yeast to humans. Members of the bHLH superfamily have two highly conserved and functionally distinct regions. The basic part is at the amino end of the bHLH that may bind DNA to a consensus hexanucleotide sequence known as the E box (CANNTG). Different families of bHLH proteins recognize different E-box consensus sequences. At the carboxyl-terminal end of the region is the HLH region that interacts with other proteins to form homo- and heterodimers. bHLH proteins function as a diverse set of regulatory factors because they recognize different DNA sequences and dimerize with different proteins. The bHLH proteins can be divided to cell-type specific and widely expressed proteins. The cell-type specific members of bHLH superfamily are involved in cell-fate determination and act in neurogenesis, cardiogenesis, myogenesis, and hematopoiesis.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 444909174 208 ERRRRDKINNWIVQLSKIIPDCsmeSTKSGQSKGGILSKACDYIQELRQ 256
Cdd:cd00083    1 ERRRRDKINDAFEELKRLLPEL---PDSKKLSKASILQKAVEYIRELQS 46

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in protein Max and similar proteins; Max, also termed Class D basic helix-loop-helix protein 4 (bHLHd4), or Myc-associated factor X, is a bHLHZip transcription regulator that forms a sequence-specific DNA-binding protein complex with MYC or MAD which recognizes the core sequence 5'-CAC[GA]TG-3'. The MYC:MAX complex is a transcriptional activator, whereas the MAD:MAX complex is a transcriptional repressor. Max homodimer bind DNA but is transcriptionally inactive. Targeted deletion of max results in early embryonic lethality in mice.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444909174 200 RRAQHNEVERRRRDKINNWIVQLSKIIPdcSMESTKsgQSKGGILSKACDYIQELRQSNHrlseelqgldqlqldndVLR 279
Cdd:cd11406    1 KRAHHNALERKRRDHIKDSFHSLRDSVP--SLQGEK--ASRAQILKKATEYIQYMRRKNH-----------------THQ 59

                         90
                 ....*....|
gi 444909174 280 QQVEDLKNKN 289
Cdd:cd11406   60 QDIDDLKRQN 69

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 444909174 196 RDEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKsgQSKGGILSKACDYIQELR--QSNHRLSEE 264
Cdd:cd11397    1 KDRQKKDNHNMIERRRRFNINDRIKELGTLLPKSNDPDMR--WNKGTILKASVDYIRKLQkeQERLRQLEE 69

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in aryl hydrocarbon receptor nuclear translocator (ARNT) family; The ARNT family of bHLH-PAS transcription regulators includes ARNT, ARNT-like proteins (ARNTL and ARNTL2), and Drosophila melanogaster protein cycle. They act 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. 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. ARNTL2, also termed Basic-helix-loop-helix-PAS protein MOP9, or brain and muscle ARNT-like 2 (BMAL2), or CYCLE-like factor (CLIF), or Class E basic helix-loop-helix protein 6 (bHLHe6), or member of PAS protein 9, or PAS domain-containing protein 9 (PASD9), is a neuronal bHLH-PAS transcriptional factor, regulating cell cycle progression and preventing cell death, whose sustained expression might ensure brain neuron survival. It also plays important roles in tumor angiogenesis. Protein cycle, also termed brain and muscle ARNT-like 1 (BMAL1), or MOP3, is a putative bHLH-PAS transcription factor involved in the generation of biological rhythms in Drosophila. It activates cycling transcription of Period (PER) and Timeless (TIM) by binding to the E-box (5'-CACGTG-3') present in their promoters.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 444909174 200 RRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKsgQSKGGILSKACDYIQELRQSNH 259
Cdd:cd11437    1 SRSNHSEIEKRRRDKMNAYIQELSALVPACNAMSRK--LDKLTVLRMAVQHLKSLRGTGS 58

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-like protein X (Mlx) and similar proteins; 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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 444909174 199 KRRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKSGQ--SKGGILSKACDYIQELRQSNHRLSEELQGL 268
Cdd:cd19687    1 RRREAHTQAEQKRRDAIKKGYDDLQDIVPTCQQQDDIGSQklSKATILQRSIDYIQFLHQQKKKQEEELSAL 72

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in MLX-interacting protein (MLXIP), MLX-interacting protein-like (MLXIPL) and similar proteins; The family includes MLXIP and MLXIPL. MLXIP, also termed Class E basic helix-loop-helix protein 36 (bHLHe36), or transcriptional activator MondoA, is a bHLHZip transcriptional activator that binds DNA as a heterodimer with Mlx. It binds to the canonical E box sequence 5'-CACGTG-3' and plays a role in transcriptional activation of glycolytic target genes. MLXIP is most highly expressed in skeletal muscle and functions as an indirect glucose sensor, by sensing glucose 6-phosphate and shuttling between the nucleus and the cytoplasm. MLXIPL, also termed carbohydrate-responsive element-binding protein (ChREBP), or Class D basic helix-loop-helix protein 14 (bHLHd14), or MLX interactor, or WS basic-helix-loop-helix leucine zipper protein (WS-bHLH), or Williams-Beuren syndrome chromosomal region 14 protein (WBSCR14), is a bHLHZip transcriptional factor integral to the regulation of glycolysis and lipogenesis in the liver. It forms heterodimers with the bHLHZip protein Mlx to bind the DNA sequence 5'-CACGTG-3'.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 444909174 198 EKRRAQHNEVERRRRDKINNWIVQLSKIIPdcSMESTKSGQ-SKGGILSKACDYIQELRQSNHRLSEELQGLDQ 270
Cdd:cd11405    1 EQRRLSHISAEQKRRFNIKSGFDTLQSLIP--SLGQNPNQKvSKAAMLQKAAEYIKSLKRERQQMQEEAEQLRQ 72

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in transcription factor E3 (TFE3) and similar proteins; TFE3, also termed Class E basic helix-loop-helix protein 33 (bHLHe33), is a bHLHzip transcription factor that is involved in B cell function. 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 TFEB or MITF.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444909174 190 EAPRTTRDEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKsgQSKGGILSKACDYIQELRQSNHRlSEELQgld 269
Cdd:cd18928    1 EAKAFLKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSTDPEMR--WNKGTILKASVDYIRKLQKEQQR-SKEIE--- 74

                         90       100
                 ....*....|....*....|....
gi 444909174 270 qlqldndvLRQQVEDLKNKNLLLR 293
Cdd:cd18928   75 --------MRQRKLEQANRSLQLR 90

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 444909174 204 HNEVERRRRDKINNWIVQLSKIIPDCSMESTKSGQSKGGILSKACDYIQELRQS 257
Cdd:cd11389    1 HKVIEKRRRDRINESLAELRRLVPEARKSKGSGKLEKAEILEMTLQHLKALQSS 54

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
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 444909174 201 RAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKSgqSKGGILSKACDYIQELR 255
Cdd:cd18947    6 RENHSEIERRRRNKMTAYITELSDMVPTCSALARKP--DKLTILRMAVSHMKSLR 58

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein aborted microspores (AMS) and similar proteins; The family includes several bHLH transcription factors from Arabidopsis thaliana, such as AMS, ICE1 and SCREAM2. AMS, also termed AtbHLH21, or EN 48, plays a crucial role in tapetum development and it is required for male fertility and pollen differentiation. ICE1, also termed inducer of CBF expression 1, or AtbHLH116, or EN 45, or SCREAM, acts as a transcriptional activator that regulates the cold-induced transcription of CBF/DREB1 genes. It binds specifically to the MYC recognition sites (5'-CANNTG-3') found in the CBF3/DREB1A promoter. SCREAM2, also termed AtbHLH33, or EN 44, mediates stomatal differentiation in the epidermis probably by controlling successive roles of SPCH, MUTE, and FAMA.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 444909174 208 ERRRRDKINNWIVQLSKIIPdcsmESTKsgQSKGGILSKACDYIQELRQSNHRLSEELQGL 268
Cdd:cd11443    7 ERRRRKKLNDRLYMLRSVVP----KITK--MDRASILGDAIDYVKELLQEINELQDELEGL 61

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in the Mad family; Members of the Mad family (Mad1, Mxi, Mad3, and Mad4) bear the bHLHzip domain (also known as basic-helix-loop-helix-leucine-zipper or bHLH-LZ domain), which mediates heterodimerization to Max and the sequence-specific DNA binding ability to E-box DNA. Mad family proteins can repress transcription at the E-box through their interaction with co-repressors. Mad family proteins antagonize Myc function in transactivation and transformation and they are growth/tumor suppressors. The developmental phenotypes of the individual Mad family member knockout mice are relatively mild- all these mice have been shown to be viable and normal.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444909174 201 RAQHNEVERRRRDKINNWIVQLSKIIP---DCSMESTKSgqskggILSKACDYIQELRQSNHRLSEElqgLDQLQLDNDV 277
Cdd:cd11401    1 RSTHNELEKNRRAHLRLCLERLKELVPlgpDATRHTTLS------LLTKAKAYIKNLEDKEKRQRQQ---KEQLRREQRE 71

                 ....*
gi 444909174 278 LRQQV 282
Cdd:cd11401   72 LKRRL 76

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        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 444909174 196 RDEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKsgQSKGGILSKACDYIQELR 255
Cdd:cd11438    3 RIKNAREAHSQIEKRRRDKMNSFIDELASLVPTCNAMSRK--LDKLTVLRMAVQHMKTLR 60

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 444909174 207 VERRRRDKINNWIVQLSKIIPDCSMESTKSGQSKGGILSKACDYIQELRQSN 258
Cdd:cd19685    1 SEKRRRQRINDKLNQLKELLPPNLSKQSRSKLSKAEILEMAITELRRLQQEV 52

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in L-Myc and similar proteins; L-Myc, also termed Class E basic helix-loop-helix protein 38 (bHLHe38), or protein L-Myc-1, or V-myc myelocytomatosis viral oncogene homolog, is a bHLHZip oncoprotein belonging to the Myc oncogene protein family. It binds DNA as a heterodimer with MAX. L-Myc is co-expressed with another Myc family member and has weaker transformation/transactivation activities. L-Myc knockout mouse did not exhibit any phenotypic abnormalities.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444909174 195 TRDEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCSmESTKSgqSKGGILSKACDYIQELRQSNHRLSEELQgldQLQLD 274
Cdd:cd11457    2 TEDVAKRKNHNFLERKRRNDLRSRFLALRDEVPGLA-SCSKT--PKVVILSKATEYLRGLVSAERRMAAEKR---QLKSR 75

                         90
                 ....*....|...
gi 444909174 275 NDVLRQQVEDLKN 287
Cdd:cd11457   76 QQQLLRRIAQLKG 88

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444909174 196 RDEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKsgQSKGGILSKACDYIQELRQSNHRLSEelqgldqlqLDN 275
Cdd:cd18925    1 KERQKKDNHNLIERRRRYNINYRIKELGTLIPKSNDPDMR--WNKGTILKASVEYIKWLQKEQQRARE---------LEH 69

                         90
                 ....*....|....*...
gi 444909174 276 dvlRQQVEDLKNKNLLLR 293
Cdd:cd18925   70 ---RQKKLEQANRRLLLR 84

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain family; bHLH-PAS domain has been found in a large group of bHLH transcription regulators that are involved in gene expression responding to environmental change and controlling aspects of neural development, including proteins from aryl hydrocarbon receptor nuclear translocator (ARNT) family, hypoxia-inducible factor (HIF) family, aryl hydrocarbon receptor (AhR) family, neuronal PAS domain-containing protein (NPAS) family, Circadian locomotor output cycles protein kaput (CLOCK)-like family, and single-minded (SIM) family. bHLH-PAS transcriptional regulatory factors have a bHLH DNA-binding domain followed by two PAS domains and a C-terminal activation or repression domain. bHLH-PAS family members can be divided into class I and class II based on their dimerization partner. bHLH-PAS class I factors include AhR, HIF and SIM. The best characterized bHLH-PAS Class II protein is the ubiquitous ARNT. Some members of bHLH-PAS family act as transcriptional coactivators (such as NCoA) that lack the ability to dimerize and bind DNA.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 444909174 201 RAQHNEVERRRRDKINNWIVQLSKIIPDCsmESTKSGQSKGGILSKACDYIQ 252
Cdd:cd11391    1 REKSREAAKKRRDKENAEISELASLLPLP--PAVGSKLDKLSVLRLAVAYLR 50

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in N-Myc and similar proteins; N-Myc, also termed Class E basic helix-loop-helix protein 37 (bHLHe37), is a bHLHZip proto-oncogene protein that positively regulates the transcription of MYCNOS in neuroblastoma cells. It is also essential during embryonic development. N-Myc has a critical role in regulating the switch between proliferation and differentiation of progenitor cells. It binds DNA as a heterodimer with MAX. The family also includes S-Myc, encoded by rat or mouse intronless myc gene, which has apoptosis-inducing activity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444909174 197 DEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCsMESTKSgqSKGGILSKACDYIQELRQSNHRLseeLQGLDQLQLDND 276
Cdd:cd11456    2 DSERRRNHNILERQRRNDLRSSFLTLRDHVPEL-VKNEKA--AKVVILKKATEYVHSLQAEEQKL---LLEKEKLQARQQ 75

                         90
                 ....*....|
gi 444909174 277 VLRQQVEDLK 286
Cdd:cd11456   76 QLLKKIEQAR 85

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
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 444909174 200 RRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKSGQSKGGILSKACDYIQELRQSN 258
Cdd:cd11407    1 RKKRRGIIEKRRRDRINNSLAELRRLVPTAFEKQGSAKLEKAEILQMTVDHLKMLHSKG 59

basic Helix-Loop-Helix (bHLH) domain found in Arabidopsis thaliana MYC1 and similar proteins; MYC1, also termed AtbHLH12, or EN 58, acts as a transcription activator, when associated with MYB75/PAP1 or MYB90/PAP2.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 444909174 204 HNEVERRRRDKINNWIVQLSKIIPDCSMESTKSgqskggILSKACDYIQELRqsnhRLSEELQGL 268
Cdd:cd18918    1 LFATERERREKLNEKFSDLRNLIPNPTKNDRAS------ILSDAIKYINELQ----RTVEELKSL 55

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 444909174 204 HNEVERRRRDKINNWIVQLSKIIPDCsmeSTKSGQSkgGILSKACDYIQELRQSNHRLSEE 264
Cdd:cd19698    1 HNLLEKKRRERIKDKIEILKGLTPNC---TPKSDIA--SILSCVIDYIKSLLLQVEKLSMG 56

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein AIG1 and similar proteins; AIG1, also termed AtbHLH32, or EN 54, or protein target of MOOPTEROS 5, is a transcription factor required for MONOPTEROS-dependent root initiation in embryo.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 444909174 204 HNEVERRRRDKINNWIVQLSKIIPDcsmeSTKsgQSKGGILSKACDYIQELRQ 256
Cdd:cd11455   11 HSEAERRRRERINSHLATLRTLLPN----LSK--TDKASLLAEVVQHVKELKR 57

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in Circadian locomotor output cycles protein kaput (CLOCK) and similar proteins; CLOCK, also termed Class E basic helix-loop-helix protein 8 (bHLHe8), is a bHLH-PAS transcriptional activator which forms a core component of the circadian clock. It forms heterodimers with another bHLH-PAS protein, Brain-Muscle-Arnt-Like (also known as BMAL or ARNT3 or mop3), which regulates circadian rhythm. BMAL1-CLOCK heterodimer complex activates transcription from E-box (CANNTG) elements found in the promoter of circadian responsive genes.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 444909174 196 RDEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKSgqskgGILSKACDYIQELRQ 256
Cdd:cd19734    3 KDKAKRVSRNKSEKKRRDQFNVLIKELGSMLPGNARKMDKS-----TVLQKSIDFLRKHKE 58

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana Fe-deficiency induced transcription factor 1 (FIT) and similar proteins; The family includes bHLH transcription factors from Arabidopsis thaliana, such as FIT and DYT1. FIT, also termed FER-like iron deficiency-induced transcription factor, or FER-like regulator of iron uptake, or AtbHLH29, or EN 43, is a bHLH transcription factor that is required for the iron deficiency response in plant. It regulates FRO2 at the level of mRNA accumulation and IRT1 at the level of protein accumulation. DYT1, also termed AtbHLH22, or protein dysfunctional tapetum 1, or EN 49, is a bHLH transcription factor involved in the control of tapetum development. It is required for male fertility and pollen differentiation, especially during callose deposition.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 444909174 206 EVERRRRDKINNWIVQLSKIIPDCSmestksGQSKGGILSKACDYIQELRQSNHRLSEELQGLD 269
Cdd:cd11450    9 VSERNRRQKLNQRLFALRSVVPNIT------KMDKASIIKDAISYIQELQYQEKKLEAEIRELE 66

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in protein Max-associated protein 1 (Mad1) and similar proteins; Mad1, also termed Max dimerization protein 1 (MXD1), or Max dimerizer 1, or protein MAD, is a bHLHZip transcriptional repressor that binds with MAX to form a sequence-specific DNA-binding protein complex which recognizes the core sequence 5'-CAC[GA]TG-3'. It thus antagonizes MYC transcriptional activity by competing for MAX.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444909174 201 RAQHNEVERRRRDKINNWIVQLSKII---PDCSMESTKSgqskggILSKACDYIQELRQSNHRlseELQGLDQLQLDNDV 277
Cdd:cd18931    2 RSTHNEMEKNRRAHLRLCLEKLKMLVplgPESNRHTTLS------LLMKAKLHIKKLEDSDRK---AVHQIDQLQREQRH 72

                 ....*...
gi 444909174 278 LRQQVEDL 285
Cdd:cd18931   73 LKRQLEKL 80

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in neuronal PAS domain-containing protein 4 (NPAS4) and similar proteins; NPAS4, also termed neuronal Per-Arnt-Sim homology (PAS) factor 4, or neuronal PAS4, or Class E basic helix-loop-helix protein 79 (bHLHe79), or HLH-PAS transcription factor NXF, or PAS domain-containing protein 10 (PASD10), is a bHLH-PAS neuronal activity-dependent transcription factor which heterodimerizes with ARNT2 to regulate genes involved in inhibitory synapse formation.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 444909174 211 RRDKINNWIVQLSKIIPDCsmESTKSGQSKGGILSKACDYIqelRQSNH 259
Cdd:cd19697   11 RRDLINAEIRELRDLLPLP--ESTRQRLSQLQIMSLACVYI---RKSNF 54

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana OBP3-responsive gene 2 (ORG2), 3 (ORG3) and similar proteins; The family includes ORG2 (also termed AtbHLH38, or EN 8) and ORG3 (also termed AtbHLH39, or EN 9), both of which act as bHLH transcription factors.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 444909174 200 RRAQHNEVERRRRDKINNWIVQLSKIIPdcsMESTKSGQSKGGILSKACDYIQELRQSNHRLSEE 264
Cdd:cd18914    1 KKLLHNDVERQRRQEMASLFSSLRSLLP---LQYIKGKLSVSDHVDEAVNYIKELQEKIKELSEK 62

basic Helix-Loop-Helix (bHLH) domain found in Saccharomyces cerevisiae INO4 and similar proteins; INO4 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. INO4 dimerizes with INO2 and binds to an UAS DNA element to control expression of the genes whose expression is inositol-responsive.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 444909174 200 RRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKsgqSKGGILSKACDYIQELRQSNHRLSEEL 265
Cdd:cd11403    2 KKENHISSEHKRREAIREGFDRLCAIVPALSSSQSR---SEAVVYVKTVEYLKELYERRAKLRSQL 64

basic helix-loop-helix-orange (bHLH-O) domain found in hairy/enhancer-of-split related with YRPW motif protein 2 (HEY2) and similar proteins; HEY2, also termed cardiovascular helix-loop-helix factor 1 (CHF-1), or Class B basic helix-loop-helix protein 32 (bHLHb32), or HES-related repressor protein 2, or hairy and enhancer of split-related protein 2 (HESR-2), or hairy-related transcription factor 2 (HRT-2), or protein gridlock homolog, is a bHLH-O transcriptional repressor expressed preferentially in the developing and adult cardiovascular system. As a downstream effector of Notch signaling, HEY2 may be required for cardiovascular development. It also plays an important role in neurologic development, as well as in the progression of human cancers.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 444909174 194 TTRDEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKSGQSKGGILSKACDYIQELRQS 257
Cdd:cd18920    4 TSQIMARKKRRGIIEKRRRDRINNSLSELRRLVPTAFEKQGSAKLEKAEILQMTVDHLKMLQAT 67

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein IAA-leucine resistant 3 (ILR3) and similar proteins; ILR3, also termed AtbHLH105, or EN 133, is a bHLH transcription factor that plays a role in resistance to amide-linked indole-3-acetic acid (IAA) conjugates such as IAA-Leu and IAA-Phe. It may regulate gene expression in response to metal homeostasis changes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444909174 208 ERRRRDKINNWIVQLSKII-PDcsmESTKSGqsKGGILSKACDYIQELRQSNHRLSEElqgldqlqldNDVLRQQVEDLK 286
Cdd:cd11446    5 EKLRRDKLNERFMELSNVLePG---RPPKTD--KATILGDAIRMLKQLRGEVQKLKEE----------NSSLQEESKELK 69

                         90
                 ....*....|.
gi 444909174 287 nknlLLRAQLR 297
Cdd:cd11446   70 ----AEKNELR 76

transcription factor ATBS1; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 444909174 200 RRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKSGQSKGGILSKACDYIQELRQSNHRLSEELQGL 268
Cdd:PLN03217   7 RSRQSSGTSRISEDQINDLIIKLQQLLPELRDSRRSDKVSAARVLQDTCNYIRNLHREVDDLSERLSEL 75

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in neuronal PAS domain-containing protein 2 (NPAS2) and similar proteins; NPAS2, also termed neuronal PAS2, or basic-helix-loop-helix-PAS protein MOP4, or Class E basic helix-loop-helix protein 9 (bHLHe9), or member of PAS protein 4, or PAS domain-containing protein 4 (PASD4), is a bHLH-PAS transcriptional activator which forms a core component of the circadian clock.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 444909174 196 RDEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKSgqskgGILSKACDYIQE 253
Cdd:cd19737    6 KDRAKRASRNKSEKKRRDQFNVLIKELSSMLPGNTRKMDKT-----TVLEKVIGFLQK 58