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 226874812  45 RRRRAHTQAEQKRRDAIKRGYDDLQTIVPTCQQQDFsIGSQKLSKAIVLQKTIDYIQFLHKEKKKQEEEVSTLRKDV 121
Cdd:cd19687    1 RRREAHTQAEQKRRDAIKKGYDDLQDIVPTCQQQDD-IGSQKLSKATILQRSIDYIQFLHQQKKKQEEELSALRKEV 76

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 226874812  45 RRRRAHTQAEQKRRDAIKRGYDDLQTIVPTCQQQDFsIGSQKLSKAIVLQKTIDYIQFLHKEKKKQEEEVSTLRKDV 121
Cdd:cd19687    1 RRREAHTQAEQKRRDAIKKGYDDLQDIVPTCQQQDD-IGSQKLSKATILQRSIDYIQFLHQQKKKQEEELSALRKEV 76

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 226874812    53 AEQKRRDAIKRGYDDLQTIVPTCQQqdfsigSQKLSKAIVLQKTIDYIQFL 103
Cdd:smart00353   3 RERRRRRKINEAFDELRSLLPTLPK------NKKLSKAEILRLAIEYIKSL 47

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 226874812  45 RRRRAHTQAEQKRRDAIKRGYDDLQTIVPTCQQQDFsIGSQKLSKAIVLQKTIDYIQFLHKEKKKQEEEVSTLRKDV 121
Cdd:cd19687    1 RRREAHTQAEQKRRDAIKKGYDDLQDIVPTCQQQDD-IGSQKLSKATILQRSIDYIQFLHQQKKKQEEELSALRKEV 76

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 226874812  44 DRRRRAHTQAEQKRRDAIKRGYDDLQTIVPTCQQQDfsigSQKLSKAIVLQKTIDYIQFLH 104
Cdd:cd11405    1 EQRRLSHISAEQKRRFNIKSGFDTLQSLIPSLGQNP----NQKVSKAAMLQKAAEYIKSLK 57

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        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 226874812  54 EQKRRDAIKRGYDDLQTIVPTCQQqdfsigSQKLSKAIVLQKTIDYIQFLH 104
Cdd:cd00083    1 ERRRRDKINDAFEELKRLLPELPD------SKKLSKASILQKAVEYIRELQ 45

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226874812  45 RRRRAHTQAEQKRRDAIKRGYDDLQTIVPTCQQQDF---------SIGSQKLSKAIVLQKTIDYIQFLHKEKKKQEEEVS 115
Cdd:cd11395    2 RKRLPHNAIEKRYRSNLNTKIERLRDAIPSLRSPEGksddgglggLAPTTKLSKATILTKAIEYIRHLEQENERLEEENE 81

                 ....*.
gi 226874812 116 TLRKDV 121
Cdd:cd11395   82 ELRQQV 87

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 226874812  47 RRAHTQA-EQKRRDAIKRGYDDLQTIVPTCQqqdfsigSQKLSKAIVLQKTIDYIQFLHKEKKKQEEEVSTLRK 119
Cdd:cd11406    1 KRAHHNAlERKRRDHIKDSFHSLRDSVPSLQ-------GEKASRAQILKKATEYIQYMRRKNHTHQQDIDDLKR 67

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in MLX-interacting protein-like (MLXIPL) and similar proteins; 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 226874812  44 DRRRRAHTQAEQKRRDAIKRGYDDLQTIVPTCQQQDfsigSQKLSKAIVLQKTIDYIQFLHKEKKKQEEEVSTLRKDV 121
Cdd:cd19689    3 ETRRITHISAEQKRRFNIKLGFDTLHSLVTTLSSQP----SIKISKATTLQKTAEYISKLQQERAQLQEEAQRLRDQI 76

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
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 226874812  46 RRRAHTQAEQKRRDAIKRGYDDLQTIVPTCQqqdfsiGSQKLSKAIVLQKTIDYIQFL 103
Cdd:cd11403    2 KKENHISSEHKRREAIREGFDRLCAIVPALS------SSQSRSEAVVYVKTVEYLKEL 53

basic helix-loop-helix-orange (bHLH-O) domain found in hairy/enhancer-of-split related with YRPW motif-like protein (HEYL) and similar proteins; HEYL, also termed Class B basic helix-loop-helix protein 33 (bHLHb33), or hairy-related transcription factor 3 (HRT-3), is a bHLH-O transcriptional repressor that is strongly expressed in the presomitic mesoderm, the somites, the peripheral nervous system and smooth muscle of all arteries and is a downstream effector of the Notch and transforming growth factor-beta pathways. It promotes neuronal differentiation by activating proneural genes and inhibiting other hairy and enhancer of split (HES) and hairy/enhancer-of-split related with YRPW motif protein (HEY) proteins. HEYL also functions as a tumor suppressor involved in the progression of human cancers.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 226874812  46 RRRAHTQAEQKRRDAIKRGYDDLQTIVPTCQQQDfsiGSQKLSKAIVLQKTIDYIQFLH 104
Cdd:cd11447    9 RKKRRGIIEKRRRDRINSSLSELRRLVPTAFEKQ---GSSKLEKAEILQMTVDHLKMLH 64

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
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 226874812  50 HTQAEQKRRDAIKRGYDDLQTIVPTCQqqdFSIGSQKLSKAIVLQKTIDYIQFLH 104
Cdd:cd11387    2 HNAVERRRRDNINEKIQELGSLVPPSR---LETKDLKPNKGSILSKAVEYIRELQ 53

basic helix-loop-helix-orange (bHLH-O) domain found in hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1) and similar proteins; HEY1, also termed cardiovascular helix-loop-helix factor 2 (CHF-2), or Class B basic helix-loop-helix protein 31 (bHLHb31), or HES-related repressor protein 1, or hairy and enhancer of split-related protein 1 (HESR-1), or hairy-related transcription factor 1 (HRT-1), is a bHLH-O transcriptional repressor that acts as an essential downstream effector of the Notch signaling pathway and may play a fundamental role in vascular development. HEY1 also participates several cancer-related pathways. It acts as a positive regulator of the tumor suppressor p53.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 226874812  46 RRRAHTQAEQKRRDAIKRGYDDLQTIVPTCQQQDfsiGSQKLSKAIVLQKTIDYIQFLH 104
Cdd:cd19748    9 RKRRRGIIEKRRRDRINNSLSELRRLVPSAFEKQ---GSAKLEKAEILQMTVDHLKMLH 64

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 226874812  50 HTQAEQKRRDAIKRGYDDLQTIVPTCQQqdfSIGSQKLSKAIVLQKTIDYIQFL 103
Cdd:cd11396    2 HNEVERRRRDKINNWIVKLAKIVPDCEK---DNSKQGQSKGGILSKACDYIQEL 52

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in transcription factor AP-4 (TFAP4) and similar proteins; TFAP4, also termed activating enhancer-binding protein 4, or Class C basic helix-loop-helix protein 41 (bHLHc41), is a bHLHzip transcription factor that activates both viral and cellular genes involved in the regulation of cellular proliferation, stemness, and epithelial-mesenchymal transition by binding to the symmetrical DNA sequence 5'-CAGCTG-3'.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 226874812  43 KDRRRRAHTQAEQKRRDAIKRGYDDLQTIVPTCQqqdfsigSQKLSKAIVLQKTIDYIQFL 103
Cdd:cd11419    1 RRIRREIANSNERRRMQSINAGFQSLRTLLPHCD-------GEKLSKAAILQQTAEYIFSL 54

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
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 226874812  46 RRRAHTQAEQKRRDAIKRGYDDLQTIVPTcqqqdfsiGSQKLSKAIVLQKTIDYIQFL 103
Cdd:cd11453    3 PRSKHSATEQRRRSKINERLQALRDLIPH--------SDQKRDKASFLLEVIEYIQAL 52

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in upstream stimulatory factor 2 (USF2) and similar proteins; USF2, also termed Class B basic helix-loop-helix protein 12 (bHLHb12), or major late transcription factor 2, or FOS-interacting protein (FIP), or upstream transcription factor 2, 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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 226874812  43 KDRRRRA-HTQAEQKRRDAIKRGYDDLQTIVPTCQQQDFSIGSqklSKAIVLQKTIDYIQFL 103
Cdd:cd18923    4 RDERRRAqHNEVERRRRDKINNWIVQLSKIIPDCNTDNSKTGA---SKGGILSKACDYIREL 62

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
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 226874812  46 RRRAHTQAEQKRRDAIKRGYDDLQTIVPTCQQQDfsiGSQKLSKAIVLQKTIDYIQFLH 104
Cdd:cd18920   10 RKKRRGIIEKRRRDRINNSLSELRRLVPTAFEKQ---GSAKLEKAEILQMTVDHLKMLQ 65

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226874812  46 RRRAHTQAEQKRRDAIKRGYDDLQTIVptcqqqdfsIGSQ-KLSKAIVLQKTIDYIQFLHKEKKkqeeevsTLRKDVTAL 124
Cdd:cd11394    6 KRSAHNAIEKRYRSSINDRIIELKDLV---------VGPDaKMNKSAVLRKAIDYIRYLQKVNQ-------KLKQENMAL 69

                 .
gi 226874812 125 K 125
Cdd:cd11394   70 K 70

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in aryl hydrocarbon receptor nuclear translocator-like protein 2 (ARNTL2) and similar proteins; 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. ARNT-2 heterodimerize with other bHLH-PAS proteins such as aryl hydrocarbon receptor (AhR), hypoxia-inducible factor (HIF), and single-minded (SIM).

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 226874812  47 RRAHTQAEQKRRDAIKRGYDDLQTIVPTCQQQdfsigSQKLSKAIVLQKTIDYIQFL 103
Cdd:cd11469    2 REAHSQTEKRRRDKMNNLIEELSAMIPQCNPM-----ARKLDKLTVLRMAVQHLKSL 53

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split-related protein HELT and similar proteins; HELT, also termed HES/HEY-like transcription factor, is a bHLH-O 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. HELT could homodimerize and heterodimerize with other bHLH-O protein such as HES-5 or HEY-2 and bound to E box to repress gene transcription.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 226874812  49 AHTQAEQKRRDAIKRGYDDL-QTIVPTCQQQDfsigSQKLSKAIVLQKTIDYIQFLH 104
Cdd:cd11408    1 SHKVIEKRRRDRINRCLNELgKTVPMALAKQT----SGKLEKAEILEMTVQYLRALH 53

basic helix-loop-helix (bHLH) domain found in factor in the germline alpha (FIGLA) and similar proteins; FIGLA, also termed FIGalpha, or Class C basic helix-loop-helix protein 8 (bHLHc8), or folliculogenesis-specific basic helix-loop-helix protein, or transcription factor FIGa, is a germ-cell-specific bHLH transcription factor expressed abundantly in female and less so in male germ cells. It is essential for primordial follicle formation and expression of many genes required for folliculogenesis, fertilization and early embryonic survival. FIGLA knockout mice cannot form primordial follicles and lose oocytes rapidly after birth, whereas male gonads are unaffected.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 226874812  46 RRRAHTQaEQKRRDAIKRGYDDLQTIVPTcQQQDFsigsqKLSKAIVLQKTIDYIQFLH 104
Cdd:cd11422    1 RRVANAR-ERERVRNLNSGFSKLRRIVPL-IPRDR-----KPSKVDTLKGATEYIRLLQ 52

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 226874812  54 EQKRRDAIKRGYDDLQTIVPTCQQQDfsiGSQKLSKAIVLQKTIDYIQFLH 104
Cdd:cd19685    2 EKRRRQRINDKLNQLKELLPPNLSKQ---SRSKLSKAEILEMAITELRRLQ 49

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in Circadian locomotor output cycles protein kaput (CLOCK) and similar proteins; The family includes CLOCK, neuronal PAS domain-containing protein 2 (NPAS2) and non-mammalian circadian clock protein PASD1. CLOCK, also termed Class E basic helix-loop-helix protein 8 (bHLHe8), is a transcriptional activator which forms a core component of the circadian clock. 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, is a transcriptional activator which forms a core component of the circadian clock. PASD1 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 226874812  47 RRAHTQAEQKRRDAIKRGYDDLQTIVPTcqqqdfsiGSQKLSKAIVLQKTIDYIQ 101
Cdd:cd11441    1 RKSRNLSEKKRRDQFNVLINELASMLPG--------RGRKMDKSTVLKKTIAFLR 47

basic helix-loop-helix (bHLH) domain found in protein atonal homologs ATOH1, ATOH7 and similar proteins; The family includes ATOH1 and ATOH7. ATOH1, also termed Class A basic helix-loop-helix protein 14 (bHLHa14), or helix-loop-helix protein hATH-1 (hATH1), or Math1, or Cath1, is a proneural bHLH transcription factor that is essential for inner ear hair cell differentiation. It dimerizes with E47 and activates E-box (CANNTG) dependent transcription. ATOH1 is a mammalian homolog of the Drosophila melanogaster gene atonal and mouse atonal homolog 1 (Math1). ATOH7, also termed Class A basic helix-loop-helix protein 13 (bHLHa13), or helix-loop-helix protein hATH-5 (hATH5), or Math5, is a bHLH transcription factor involved in the differentiation of retinal ganglion cells. The family also includes protein Amos (also termed absent MD neurons and olfactory sensilla protein, or reduced olfactory organs protein, or rough eye protein). It is a bHLH transcription factor that promotes multiple dendritic neuron formation in the Drosophila peripheral nervous system.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 226874812  46 RRRAHTQAEQKRRDAIKRGYDDLQTIVPTCQQQdfsigsQKLSKAIVLQKTIDYIQFL 103
Cdd:cd11430    1 RRLAANARERRRMNGLNRAFDQLRSVVPSIGND------KKLSKYETLQMAQIYIETL 52

basic helix-loop-helix (bHLH) domain found in protein atonal homolog 7 (ATOH7) and similar proteins; ATOH7, also termed Class A basic helix-loop-helix protein 13 (bHLHa13), or helix-loop-helix protein hATH-5 (hATH5), or Math5, is a bHLH transcription factor involved in the differentiation of retinal ganglion cells.

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                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 226874812  45 RRRRAHTQAEQKRRDAIKRGYDDLQTIVPTCQQQdfsigsQKLSKAIVLQKTIDYIQFL 103
Cdd:cd19714    7 RRRLAANARERRRMQGLNTAFDRLRKVVPQWGQD------KKLSKYETLQMALSYIMAL 59

tissue specific basic helix-loop-helix (bHLH-TS) domain family; Tissue specific bHLH domain family includes transcription regulators whose expression are restricted to certain tissues. They are involved in cell-fate determination and process in neurogenesis, cardiogenesis, myogenesis, and hematopoiesis and include proteins from myogenic regulatory factor (MRF) family, twist-related protein (TWIST) family, scleraxis-like family, heart- and neural crest derivatives-expressed protein (HAND) family, helix-loop-helix protein (HEN) family, musculin-like family, germline alpha (FIGLA) family, T-cell acute lymphocytic leukemia protein/ lymphoblastic leukemia-derived sequence (TAL/LYL) family, ovary, uterus and testis protein (OUT) family, mesoderm posterior protein (Mesp) family, muscle, intestine and stomach expression 1 (MIST-1) family, protein atonal homologs (ATOH) family, neurogenin (NGN) family, neurogenic differentiation factor (NeuroD) family, achaete-scute complex-like (ASCL) family, Fer3-like protein (FERD3L)-like family, and Oligodendrocyte lineage genes (OLIG) family of transcription factors.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 226874812  47 RRAHTQAEQKRRDAIKRGYDDLQTIVPTCQQqdfsigSQKLSKAIVLQKTIDYIQFL 103
Cdd:cd11390    1 RNAANARERRRMHDLNDAFEALRKVLPTVPP------DKKLSKIETLRLAINYIAAL 51

basic helix-loop-helix (bHLH) domain found in pancreas transcription factor 1 subunit alpha (PTF1A) and similar proteins; PTF1A, also termed Class A basic helix-loop-helix protein 29 (bHLHa29), or pancreas-specific transcription factor 1a, or bHLH transcription factor p48, or p48 DNA-binding subunit of transcription factor PTF1 (PTF1-p48), is a bHLH transcription factor implicated in the cell fate determination in various organs. It binds to the E-box consensus sequence 5'-CANNTG-3' and plays a role in early and late pancreas development and differentiation.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 226874812  46 RRRAHTQAEQKRRDAIKRGYDDLQTIVPTCQQQdfsigsQKLSKAIVLQKTIDYIQFL 103
Cdd:cd11417    1 QRQAANLRERRRMQSINDAFEGLRSHIPTLPYE------KRLSKVDTLRLAIGYINFL 52

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 226874812  43 KDRRRRA-HTQAEQKRRDAIKRGYDDLQTIVPTcqqqdfsiGSQKLSKAIVLQKTIDYIQ 101
Cdd:cd19734    3 KDKAKRVsRNKSEKKRRDQFNVLIKELGSMLPG--------NARKMDKSTVLQKSIDFLR 54

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana BIG PETAL (BPE) and similar proteins; The family includes several bHLH transcription factors from Arabidopsis thaliana, such as BPE, HBI1 and BEE proteins (BEE1-3). BPE, also termed AtbHLH31, or EN 88, is involved in the control of Arabidopsis petal size, by interfering with postmitotic cell expansion to limit final petal cell size. HBI1, also termed AtbHLH64, or homolog of bee2 interacting with IBH1, or EN 79, is an atypical bHLH transcription factor that acts as positive regulator of cell elongation downstream of multiple external and endogenous signals by direct binding to the promoters and activation of the two expansin genes EXPA1 and EXPA8, encoding cell wall loosening enzymes. BEEs, also termed protein Brassinosteroid enhanced expression, are positive regulators of brassinosteroid signaling.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 226874812  45 RRRR-----AHTQAEQKRRDAIKRGYDDLQTIVPTCqqqdfsigSQKLSKAIVLQKTIDYIQFL 103
Cdd:cd18919    6 RARRgqatdSHSLAERVRREKISERMKLLQDLVPGC--------NKVTGKALMLDEIINYVQSL 61