helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 50286411    478 AEQERRNRLNNALSDLNSLLPQDWKDavTVPSKAITAELACKYIRTLLEELEQ 530
Cdd:smart00353   3 RERRRRRKINEAFDELRSLLPTLPKN--KKLSKAEILRLAIEYIKSLQEELQK 53

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 50286411    478 AEQERRNRLNNALSDLNSLLPQDWKDavTVPSKAITAELACKYIRTLLEELEQ 530
Cdd:smart00353   3 RERRRRRKINEAFDELRSLLPTLPKN--KKLSKAEILRLAIEYIKSLQEELQK 53

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 50286411 470 RKKEVHKYAEQERRNRLNNALSDLNSLLPQ-DWKDAVTVpSKAITAELACKYIRTL-------LEELEQYKK 533
Cdd:cd11405   2 QRRLSHISAEQKRRFNIKSGFDTLQSLIPSlGQNPNQKV-SKAAMLQKAAEYIKSLkrerqqmQEEAEQLRQ 72

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 50286411 470 RKKEVHKYAEQERRNRLNNALSDLNSLLP---QDWKDAVTVPSKAITAELACKYIRTLL-------EELEQYKK 533
Cdd:cd19687   1 RRREAHTQAEQKRRDAIKKGYDDLQDIVPtcqQQDDIGSQKLSKATILQRSIDYIQFLHqqkkkqeEELSALRK 74

basic helix-loop-helix-orange (bHLH-O) domain found in differentially expressed in chondrocytes protein (DEC) family; The DEC family includes two bHLH-O transcriptional repressors, DEC1 and DEC2, which 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. They mediate the circadian rhythm by negatively regulating the activity of the clock genes and clock-controlled genes. They are induced by CLOCK:BMAL1 heterodimer via the CACGTG E-box in the promoter.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 50286411 475 HKYAEQERRNRLNNALSDLNSLLPQDWK-DAVTVPSKAITAELACKYIRTLLEELEQYKK 533
Cdd:cd11409   8 HRLIEKKRRDRINECIAQLKDLLPEHLKlTTLGHLEKAVVLELTLKHLKALTALTEQQQQ 67

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 50286411 479 EQERRNRLNNALSDLNSLLPQDWKDavTVPSKAITAELACKYIRTLLEELE 529
Cdd:cd11422   8 ERERVRNLNSGFSKLRRIVPLIPRD--RKPSKVDTLKGATEYIRLLQRILE 56

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 50286411 474 VHKYAEQERRNRLNNALSDLNSLLPQDWKDAVT-VPSKAITAELACKYIRTLLEELEQ 530
Cdd:cd11396   1 THNEVERRRRDKINNWIVKLAKIVPDCEKDNSKqGQSKGGILSKACDYIQELRSQNER 58

basic helix-loop-helix (bHLH) domain found in Saccharomyces cerevisiae protein INO2 and similar proteins; INO2 is a positive regulatory factor required for depression of the co-regulated phospholipid biosynthetic enzymes in Saccharomyces cerevisiae. It is also involved in the expression of ITR1.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 50286411 470 RKKEVHKYAEQERRNRLNNALSDLNSLLPQDWKDAVTVPSKAITAELACKYIRTLLEELEQ 530
Cdd:cd11388   2 VKKWKHVEAEKKRRNQIKKGFEDLINLINYPRNNNEKRISKSELLNKAVDDIRGLLKANEQ 62

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 50286411 475 HKYAEQERRNRLNNALSDLNSLLPQDWKDAV-TVPSKAITAELACKYIRTLLEELE 529
Cdd:cd11387   2 HNAVERRRRDNINEKIQELGSLVPPSRLETKdLKPNKGSILSKAVEYIRELQNQNQ 57

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
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 50286411 469 QRKKEVHKYAEQERRNRLNNALSDLNSLLPQ-DWKDAVTVPSKAITAELACKYIRTL 524
Cdd:cd18923   6 ERRRAQHNEVERRRRDKINNWIVQLSKIIPDcNTDNSKTGASKGGILSKACDYIREL 62

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 50286411 475 HKYAEQERRNRLNNALSDLNSLLPQDWKDAVTVP-SKAITAELACKYIRTL 524
Cdd:cd11389   1 HKVIEKRRRDRINESLAELRRLVPEARKSKGSGKlEKAEILEMTLQHLKAL 51