basic Helix-Loop-Helix-zipper (bHLHzip) domain found in microphthalmia-associated transcription factor (MITF) and similar proteins; MITF, also termed Class E basic helix-loop-helix protein 32 (bHLHe32), is a bHLHzip transcription factor that is involved in neural crest melanocytes development as well as the pigmented retinal epithelium. It regulates the expression of genes with essential roles in cell differentiation, proliferation and survival. It binds to M-boxes (5'-TCATGTG-3') and symmetrical DNA sequences (E-boxes) (5'-CACGTG-3') found in the promoters of target genes, such as BCL2 and tyrosinase (TYR).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557755  193 ESEARALAKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQREQQRAKELENRQK 272
Cdd:cd18926   1 ESEARALAKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQREQQRAKELENRQK 80

                        90       100
                ....*....|....*....|....
gi 4557755  273 KLEHANRHLLLRIQELEMQARAHG 296
Cdd:cd18926  81 KLEHANRHLLLRIQELEMQARAHG 104

MITF/TFEB/TFEC/TFE3 N-terminus; This domain is found at the N-terminus of several transcription factors including microphthalmia-associated transcription factor, transcription factor EB, transcription factor EC and transcription factor E3.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557755      9 HYQVQTHLENPTKYHIQQAQRQQVKQYLSTTLANKHANQVLSLPCPNQPGDHV-MPP-------VPGSSAPNSPMAMLTL 80
Cdd:pfam15951  59 VLKVQTHLENPTKYHIQQAQRQQVKQYLSTTYGAKQALIPSASPPPPAQSPPPrTSPlmrgnqlPPGNSAPNSPMAMLSI 138

                  ....*..
gi 4557755     81 NSNCEKE 87
Cdd:pfam15951 139 GSSEEKE 145

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in microphthalmia-associated transcription factor (MITF) and similar proteins; MITF, also termed Class E basic helix-loop-helix protein 32 (bHLHe32), is a bHLHzip transcription factor that is involved in neural crest melanocytes development as well as the pigmented retinal epithelium. It regulates the expression of genes with essential roles in cell differentiation, proliferation and survival. It binds to M-boxes (5'-TCATGTG-3') and symmetrical DNA sequences (E-boxes) (5'-CACGTG-3') found in the promoters of target genes, such as BCL2 and tyrosinase (TYR).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557755  193 ESEARALAKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQREQQRAKELENRQK 272
Cdd:cd18926   1 ESEARALAKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQREQQRAKELENRQK 80

                        90       100
                ....*....|....*....|....
gi 4557755  273 KLEHANRHLLLRIQELEMQARAHG 296
Cdd:cd18926  81 KLEHANRHLLLRIQELEMQARAHG 104

MITF/TFEB/TFEC/TFE3 N-terminus; This domain is found at the N-terminus of several transcription factors including microphthalmia-associated transcription factor, transcription factor EB, transcription factor EC and transcription factor E3.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557755      9 HYQVQTHLENPTKYHIQQAQRQQVKQYLSTTLANKHANQVLSLPCPNQPGDHV-MPP-------VPGSSAPNSPMAMLTL 80
Cdd:pfam15951  59 VLKVQTHLENPTKYHIQQAQRQQVKQYLSTTYGAKQALIPSASPPPPAQSPPPrTSPlmrgnqlPPGNSAPNSPMAMLSI 138

                  ....*..
gi 4557755     81 NSNCEKE 87
Cdd:pfam15951 139 GSSEEKE 145

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 4557755     210 NLIERRRRFNINDRIKELGTLIPkSNDPDMRWNKGTILKASVDYIRKLQREQQ 262
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLP-TLPKNKKLSKAEILRLAIEYIKSLQEELQ 52

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in microphthalmia-associated transcription factor (MITF) and similar proteins; MITF, also termed Class E basic helix-loop-helix protein 32 (bHLHe32), is a bHLHzip transcription factor that is involved in neural crest melanocytes development as well as the pigmented retinal epithelium. It regulates the expression of genes with essential roles in cell differentiation, proliferation and survival. It binds to M-boxes (5'-TCATGTG-3') and symmetrical DNA sequences (E-boxes) (5'-CACGTG-3') found in the promoters of target genes, such as BCL2 and tyrosinase (TYR).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557755  193 ESEARALAKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQREQQRAKELENRQK 272
Cdd:cd18926   1 ESEARALAKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQREQQRAKELENRQK 80

                        90       100
                ....*....|....*....|....
gi 4557755  273 KLEHANRHLLLRIQELEMQARAHG 296
Cdd:cd18926  81 KLEHANRHLLLRIQELEMQARAHG 104

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557755  195 EARALAKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQREQQRAKELENRQKKL 274
Cdd:cd18927   1 EARALAKERQKKDNHNLIERRRRFNINDRIKELGTLIPKTNDLDVRWNKGTILKASVDYIKRMQKDLQRSRELENHSRRL 80

                        90
                ....*....|.
gi 4557755  275 EHANRHLLLRI 285
Cdd:cd18927  81 EMTNKQLWLRI 91

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 4557755  201 KERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQREQQRAKELENRQKKLEHANRH 280
Cdd:cd18925   1 KERQKKDNHNLIERRRRYNINYRIKELGTLIPKSNDPDMRWNKGTILKASVEYIKWLQKEQQRARELEHRQKKLEQANRR 80

                ....*
gi 4557755  281 LLLRI 285
Cdd:cd18925  81 LLLRI 85

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 4557755  208 NHNLIERRRRFNINDRIKELGTLIPKSND--PDMRWNKGTILKASVDYIRKLQREQQR 263
Cdd:cd11387   1 SHNAVERRRRDNINEKIQELGSLVPPSRLetKDLKPNKGSILSKAVEYIRELQNQNQE 58

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Saccharomyces cerevisiae centromere-binding protein 1 (CBP-1) and similar proteins; CBP-1, also termed centromere promoter factor 1 (CPF1), or centromere-binding factor 1 (CBF1), is a bHLHzip protein that is required for chromosome stability and methionine prototrophy. It binds as a homodimer to the centromere DNA elements I (CDEI, GTCACATG) region of the centromere that is required for optimal centromere function.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557755  201 KERQKKDNHNLIERRRRFNINDRIKELGTLIPkSNDPDMrwNKGTILKASVDYIRKLQREQQRAKELENRQKKLEHANRH 280
Cdd:cd11398   3 WHRQRRDNHKEVERRRRENINEGINELAALVP-GNAREK--NKGAILARAVEYIQELQETEAKNIEKWTLEKLLTDQAIA 79

                ....*..
gi 4557755  281 LLLRIQE 287
Cdd:cd11398  80 ELAALNE 86

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 4557755     210 NLIERRRRFNINDRIKELGTLIPkSNDPDMRWNKGTILKASVDYIRKLQREQQ 262
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLP-TLPKNKKLSKAEILRLAIEYIKSLQEELQ 52

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 4557755  209 HNLIERRRRFNINDRIKELGTLIPKSNDPDMRWN--KGTILKASVDYIRKLQREQQR 263
Cdd:cd11396   2 HNEVERRRRDKINNWIVKLAKIVPDCEKDNSKQGqsKGGILSKACDYIQELRSQNER 58

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        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 4557755  204 QKKDNHNLIERRRRFNINDRIKELGTLIPksnDPDMRWNKGTILKASVDYIRKLQREQQRAKElENRQKKL 274
Cdd:cd18921   5 EKRTAHNAIEKRYRSSINDKIIELKDLVV---GTEAKLNKSAVLRKAIDYIRFLQQSNQKLKQ-ENMALKM 71

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 4557755  203 RQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRW--------------NKGTILKASVDYIRKLQREQQRakeLE 268
Cdd:cd11395   1 PRKRLPHNAIEKRYRSNLNTKIERLRDAIPSLRSPEGKSddgglgglapttklSKATILTKAIEYIRHLEQENER---LE 77

                ....*...
gi 4557755  269 NRQKKLEH 276
Cdd:cd11395  78 EENEELRQ 85

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 4557755  213 ERRRRFNINDRIKELGTLIPKSNDPDmRWNKGTILKASVDYIRKLQR 259
Cdd:cd00083   1 ERRRRDKINDAFEELKRLLPELPDSK-KLSKASILQKAVEYIRELQS 46

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in the Myc family; The Myc family is a member of the bHLHzip family of transcription factors that play important roles in the control of normal cell proliferation, growth, survival and differentiation. All Myc isoforms contain two independently functioning polypeptide chain regions: N-terminal transactivating residues and a C-terminal bHLHzip segment. The bHLHzip family of bHLH transcription factors are characterized by a highly conserved N-terminal basic region that may bind DNA at a consensus hexanucleotide sequence known as the E-box (CANNTG) followed by HLH and leucine zipper motifs that may interact with other proteins to form homo- and heterodimers. Myc heterodimerizes with Max enabling specific binding to E-box DNA sequences in the promoters of target genes. The Myc proto-oncoprotein family includes at least five different functional members: c-, N-, L-, S- and B-Myc (which is lacking the bHLH domain).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557755  205 KKDNHNLIERRRRFNINDRIKELGTLIP--KSNDpdmRWNKGTILKASVDYIRKLQREQqraKELENRQKKLEHANRHLL 282
Cdd:cd11400   1 KRRLHNVLERQRRNDLKNSFEKLRDLVPelADNE---KASKVVILKKATEYIKQLQQEE---KKLEKEKDKLKARNEQLR 74

                ....*.
gi 4557755  283 LRIQEL 288
Cdd:cd11400  75 KKLERL 80

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana genes coding transcription factors and similar proteins; bHLH proteins are the second largest class of plant transcription factors that regulate transcription of genes that are involve in many essential physiological and developmental process. bHLH proteins are transcriptional regulators that are found in organisms from yeast to humans. The Arabidopsis bHLH proteins that have been characterized so far have roles in regulation of fruit dehiscence, cell development (carpel, anther and epidermal), phytochrome signaling, flavonoid biosynthesis, hormone signaling and stress responses.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557755  209 HNLIERRRRFNINDRIKELGTLIPKSNDPDmrwnKGTILKASVDYIRKLQReqqRAKELE 268
Cdd:cd11393   1 HSIAERKRREKINERIRALRSLVPNGGKTD----KASILDEAIEYIKFLQE---QVKVLS 53

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 4557755  201 KERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKgtILKASVDYIRKLQRE 260
Cdd:cd18910   1 RREKKRESHNEVERRRKDKINAGINKIGELLPDRDAKKQSKNM--ILEQAYKYIVELKKK 58

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 4557755  209 HNLIERRRRFNINDRIKELGTLIPKSNDPDmrwnKGTILKASVDYIRKLQReqqRAKELENRQKKLEHANRH 280
Cdd:cd18918   1 LFATERERREKLNEKFSDLRNLIPNPTKND----RASILSDAIKYINELQR---TVEELKSLVEKKRCGERD 65

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
                ....*....|....*....|....*....|....*....|....*....|....
gi 4557755  209 HNLIERRRRFNINDRIKELGTLIPKSNDPDmrwnKGTILKASVDYIRKLQREQQ 262
Cdd:cd11445   6 HNLSERRRRDRINEKMKALQELIPNCNKTD----KASMLDEAIEYLKSLQLQVQ 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 4557755  201 KERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPdMRWNKGTILKASVDYirkLQREQQRAKELE 268
Cdd:cd19736   6 KDRAKRASRNKSEKKRRDQFNVLIKELCTMLQGHGHP-LKMDKSTILQRTIDF---LQKQKEITAQTE 69

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 4557755  204 QKKDNHNLIERRRRFNINDRIKELGTLIpksndPDMRWNKGT---ILKASVDYIRKLQREQQRAKE 266
Cdd:cd11404   1 QRRLNHVRSEKKRRELIKKGYDELCALV-----PGLDPQKRTkadILQKAADWIQELKEENEKLEE 61

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4557755  205 KKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKAsVDYIRKLQREQQRAKELENRQKKLEHANRH 280
Cdd:cd18914   1 KKLLHNDVERQRRQEMASLFSSLRSLLPLQYIKGKLSVSDHVDEA-VNYIKELQEKIKELSEKRDELLKLISGVRS 75

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 4557755  209 HNLIERRRRFNINDRIKELGTLIP--KSNDPDMRWNKGTILKASVDYIRKLQ 258
Cdd:cd11389   1 HKVIEKRRRDRINESLAELRRLVPeaRKSKGSGKLEKAEILEMTLQHLKALQ 52

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in MAX gene-associated protein (MGA) family; The MGA family includes MGA, Schizosaccharomyces pombe ESC1 (spESC1) and similar proteins. MGA, also termed MAX dimerization protein 5 (MAD5), is a dual specificity T-box/ bHLHzip transcription factor that regulates the expression of both Max-network and T-box family target genes. It contains a Myc-like bHLHZip motif and requires heterodimerization with Max for binding to the preferred Myc-Max-binding site CACGTG. In addition to the bHLHZip domain, MGA harbors a second DNA-binding domain, the T-box or T-domain. It thus binds the preferred Brachyury-binding sequence and represses transcription of reporter genes containing promoter-proximal Brachyury-binding sites. spESC1 is a bHLHzip protein with homology to human MyoD and Myf-5 myogenic differentiation inducers. It is involved in the sexual differentiation process.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 4557755  208 NHNLIERRRRFNINDRIKELGTLIPKSNDPDMrwNKGTILKASVDYIRKLQREQqraKELENRQKKLE 275
Cdd:cd19682   3 RHKKRERERRSELRELFDKLKQLLGLDSDEKA--SKLAVLTEAIEEIQQLKREE---DELQKEKARLT 65

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 4557755  206 KDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQ 258
Cdd:cd11391   1 REKSREAAKKRRDKENAEISELASLLPLPPAVGSKLDKLSVLRLAVAYLRLKK 53

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in MLX-interacting protein (MLXIP) and similar proteins; 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.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 4557755  208 NHNLIERRRRFNINDRIKELGTLIPkSNDPDMRWNKGTILKASVDYIRKLQREQQRAKELENR 270
Cdd:cd19688   6 KHISAEQKRRFNIKICFDTLNSLVS-TLKNSKPISNAITLQKTVEYIAKLQQERTQMQEETKR 67

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 4557755  200 AKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDmrwNKGTILKASVDYIRKLQRE 260
Cdd:cd18919   7 ARRGQATDSHSLAERVRREKISERMKLLQDLVPGCNKVT---GKALMLDEIINYVQSLQRQ 64

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
                ....*....|....*....|....*....|....*....|....*....|.
gi 4557755  213 ERRRRFNINDRIKELGTLIPKSNDPDMrwNKGTILKASVDYIRKLQREQQR 263
Cdd:cd11419  12 ERRRMQSINAGFQSLRTLLPHCDGEKL--SKAAILQQTAEYIFSLEQEKTR 60

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 4557755  204 QKKDNHNLIERRRRFNINDRIKELGTLIPK--SNDpdmRWNKGTILKASVDYIRKLQREQQRakeLENRQKKLEHANRHL 281
Cdd:cd11456   4 ERRRNHNILERQRRNDLRSSFLTLRDHVPElvKNE---KAAKVVILKKATEYVHSLQAEEQK---LLLEKEKLQARQQQL 77

                ....*..
gi 4557755  282 LLRIQEL 288
Cdd:cd11456  78 LKKIEQA 84

basic helix-loop-helix (bHLH) domain found in Saccharomyces cerevisiae phosphate system positive regulatory protein PHO4 and similar proteins; PHO4 is a transcriptional activator that regulates the expression of repressible phosphatase under phosphate starvation conditions in Saccharomyces cerevisiae. The PHO4 protein has four functional domains with the bHLH domain at its carboxyl-terminal region. It regulates transcription by binding to promoter of the genes as a homodimer.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 4557755  204 QKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPD--------------------MRWNKGTILKASVDYIRKLQRE 260
Cdd:cd11392   1 SKRTAHKVAERGRRDRLNAALKELASLMPAEFVEGkmgadgsasdsndkekaaasAAGSKAATVEMAIDYIKHLQKE 77

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 4557755  206 KDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQ 258
Cdd:cd11469   2 REAHSQTEKRRRDKMNNLIEELSAMIPQCNPMARKLDKLTVLRMAVQHLKSLK 54

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 4557755  210 NLI-ERRRRFNINDRIKELGTLIPKSNDPDmrwnKGTILKASVDYIRKLQREQQRAK----ELENRQKKLE 275
Cdd:cd11450   7 NLVsERNRRQKLNQRLFALRSVVPNITKMD----KASIIKDAISYIQELQYQEKKLEaeirELESRPPSTL 73

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        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557755  191 PTESEARALAKERqkkdnhNLIERRRRFNINDRIKELGTLIPKS--NDPDMRWNKGTILKASVDYIRKLQ 258
Cdd:cd11447   1 TTSSQIQARKKRR------GIIEKRRRDRINSSLSELRRLVPTAfeKQGSSKLEKAEILQMTVDHLKMLH 64

basic helix-loop-helix-orange (bHLH-O) domain found in Drosophila melanogaster protein hairy, protein deadpan and similar proteins; Protein hairy is a bHLH transcriptional repressor of genes that require a bHLH-O protein for their transcription. It acts as a pair-rule protein that regulates embryonic segmentation and adult bristle patterning. Protein deadpan is closely related to the product of the segmentation gene hairy. It is a direct target of Notch signaling and regulates neuroblast self-renewal in Drosophila.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 4557755  205 KKDNHNLIERRRRFNINDRIKELGTLI----PKSNDPDMRWNKGTILKASVDYIRKLQREQ 261
Cdd:cd18913   3 RKSSKPIMEKRRRARINASLNELKSLLldalKKDGTRHSKLEKADILEMTVKHLRQVQRQQ 63

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-associated protein 4 (Mad4) and similar proteins; Mad4, also termed Max dimerization protein 4, or Max dimerizer 4 (MXD4), or Class C basic helix-loop-helix protein 12 (bHLHc12), or Max-interacting transcriptional repressor MAD4, is a bHLHZip Max-interacting transcriptional repressor that suppresses c-myc dependent transformation and is expressed during neural and epidermal differentiation. It is regulated by a transcriptional repressor complex that contains Miz-1 and c-Myc.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557755  206 KDNHNLIERRRRFNINDRIKELGTLIPKSNDPDmRWNKGTILKASVDYIRKLQREQQRAKeleNRQKKLEHANRHLLLRI 285
Cdd:cd18929   3 RSSHNELEKHRRAKLRLYLEQLKQLVPLGPDST-RHTTLSLLKRAKMHIKKLEEQDRKAL---NIKEQLQREHRYLKRRL 78

                ....*..
gi 4557755  286 QELEMQA 292
Cdd:cd18929  79 EQLSVQG 85

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Schizosaccharomyces pombe ESC1 (spESC1) and similar proteins; spESC1 is a bHLHzip protein with homology to human MyoD and Myf-5 myogenic differentiation inducers. It is involved in the sexual differentiation process.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 4557755  209 HNLIERRRRFNINDRIKELGTLIPKsnDPDMRWNKGTILKASVDYIRKLQREQQ 262
Cdd:cd19690   4 HKLAERKRRKEMKELFEDLRDALPQ--ERGTKASKWEILTKAISYIQQLKRHIR 55

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 4557755  201 KERQKKDNHNLIERRRRFNINDRIKELGTLIPK-SNDPDMRWNKGTILKASVDYIRKLQreQQRAKELENRQK 272
Cdd:cd19689   1 KTETRRITHISAEQKRRFNIKLGFDTLHSLVTTlSSQPSIKISKATTLQKTAEYISKLQ--QERAQLQEEAQR 71

basic helix-loop-helix (bHLH) domain found in the spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein (SOHLH) family; The SOHLH family includes two bHLH transcription factors, SOHLH1 and SOHLH2. They are specifically in spermatogonia and oocytes and essential for early spermatogonial and oocyte differentiation.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 4557755  209 HNLIERRRRfninDRIKE----LGTLIP--KSNDPDMrwnkGTILKASVDYIRKLQR 259
Cdd:cd18908   6 HSLKERLRR----ERIKSscdqLRDLLPyiKGRKLDM----ASVLEMTVKYIRYIQE 54

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein NAI1 and similar proteins; NAI1, also termed AtbHLH20, or EN 27, is a bHLH transcription activator that regulates the expression of at least NAI2, PYK10 and PBP1. It is required for and mediates the formation of endoplasmic reticulum bodies (ER bodies). It plays a role in the symbiotic interactions with the endophytes of the Sebacinaceae fungus family, such as Piriformospora indica and Sebacina.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4557755  208 NHNLIERRRRFNINDRIKELGTLIPKSNDPDmrwnKGTILKASVDYIRKLqreQQRAKELENRQKK 273
Cdd:cd11452   5 DHILAERKRREKLSQRFIALSALVPGLKKMD----KASVLGDAIKHIKQL---QERVKELEEEKKE 63

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-interacting protein 1 (MXI1) and similar proteins; MXI1, also termed Max interactor 1, or Class C basic helix-loop-helix protein 11 (bHLHc11), 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. It plays an important role in the regulation of cell proliferation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557755  206 KDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVdYIRKLQREQQRAK-ELENrqkkLEHANRHLLLR 284
Cdd:cd18930   2 RSTHNELEKNRRAHLRLCLERLKVLIPLGPDCTRHTTLGLLNKAKA-HIKKLEEADRKSQhQLEN----LEREQRFLKRR 76

                ....
gi 4557755  285 IQEL 288
Cdd:cd18930  77 LEQL 80

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in c-Myc and similar proteins; c-Myc, also termed Myc proto-oncogene protein, or Class E basic helix-loop-helix protein 39 (bHLHe39), or transcription factor p64, a bHLHZip proto-oncogene protein that functions as a transcription factor, which binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. It activates the transcription of growth-related genes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557755  201 KERQKKDNHNLIERRRR-------FNINDRIKELgtlipKSNDpdmRWNKGTILKASVDYIRKLQREQQRakeLENRQKK 273
Cdd:cd11458   1 EENDKRRTHNVLERQRRnelklsfFALRDQIPEV-----ANNE---KAPKVVILKKATEYILSMQADEQR---LISEKEQ 69

                        90
                ....*....|....*
gi 4557755  274 LEHANRHLLLRIQEL 288
Cdd:cd11458  70 LRRRREQLKHRLEQL 84