leucine zipper found in the TSC22 domain leucine zipper transcription factors, c-Myc-binding protein, and similar proteins; The family includes TGF-beta-stimulated clone-22 domain (TSC22D) leucine zipper transcription factors, TSC22D1-4, as well as c-Myc-binding protein (MycBP). TSC22D proteins have diverse physiological functions, including cell growth, development, homeostasis, and immune regulation. MycBP, also called associate of Myc 1 (AMY-1), is a novel c-Myc binding protein that may control the transcriptional activity of Myc. It stimulates the activation of E box-dependent transcription by Myc. Members of this family contain a conserved leucine zipper (ZIP) domain. Its first helix is not basic and does not contain the consensus sequence, NXX(A)(A)XX(C/S)R, found in most basic region/leucine zipper (bZIP) proteins. In the bZIP family of transcription factors, the leucine zipper acts as a dimerization domain and the upstream basic region as a DNA-binding domain. However, DNA-binding capability of TSC22D family proteins is not obvious, due to the lack of the basic region found in the original bZIP DNA-binding domains. Similar to bZIP, ZIP forms homo- and heterodimers, resulting in many dimers that may have different effects on transcription.

                          10        20        30
                  ....*....|....*....|....*....|....
gi 1007384330 172 EAERLQMDNELLRQQIEELKNENALLRAQLQQHN 205
Cdd:cd21937    20 DVEALRLENEELKQKNEELEEENKELKAKLQQYE 53

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1007384330  110 NEVERRRRDKINNWIVQLSKIIPDCNaDNSKTgaSKGGILSKACDYIRELRQTNQ 164
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLP-KNKKL--SKAEILRLAIEYIKSLQEELQ 52

leucine zipper domain found in c-Myc-binding protein and similar proteins; MycBP, also called associate of Myc 1 (AMY-1), is a novel c-Myc binding protein that may control the transcriptional activity of Myc. It stimulates the activation of E box-dependent transcription by Myc. This model corresponds to the conserved region that shows high sequence similarity with the leucine zipper (ZIP) domain located at the C-terminus of TGF-beta-stimulated clone-22 domain (TSC22D) family transcription factors. The first helix of ZIP is not basic and does not contain the consensus sequence, NXX(A)(A)XX(C/S)R, found in most basic region/leucine zipper (bZIP) proteins. Thus, the DNA-binding capability of the ZIP domain is not obvious. Similar to bZIP, ZIP forms homo- and heterodimers, resulting in many dimers that may have different effects on transcription.

                          10        20        30
                  ....*....|....*....|....*....|....
gi 1007384330 172 EAERLQMDNELLRQQIEELKNENALLRAQLQQHN 205
Cdd:cd21937    20 DVEALRLENEELKQKNEELEEENKELKAKLQQYE 53

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 1007384330 101 RDERRRAQHNEVERRRRDKINNWIVQLSKIIPDCNADNSKTGASKGGILSKACDYIRELRQTNQR 165
Cdd:cd18924     1 RDEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKSGQSKGGILSKACDYIQELRQSNHR 65

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 1007384330 108 QHNEVERRRRDKINNWIVQLSKIIPDCNADNSKTGASKGGILSKACDYIRELRQTNQR 165
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 1007384330 104 RRRAQHNEVERRRRDKINNWIVQLSKIIPDCNADNsktgaSKGGILSKACDYIRELRQTNQRMQETFkEAERLQMDnell 183
Cdd:cd11398     6 QRRDNHKEVERRRRENINEGINELAALVPGNAREK-----NKGAILARAVEYIQELQETEAKNIEKW-TLEKLLTD---- 75

                          90
                  ....*....|....*
gi 1007384330 184 rQQIEELKNENALLR 198
Cdd:cd11398    76 -QAIAELAALNEKLR 89

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1007384330  110 NEVERRRRDKINNWIVQLSKIIPDCNaDNSKTgaSKGGILSKACDYIRELRQTNQ 164
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLP-KNKKL--SKAEILRLAIEYIKSLQEELQ 52

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007384330 103 ERRRAQHNEVERRRRDKINNWIVQLSKIIPDCNADNSKTG------------ASKGGILSKACDYIRELRQTNQrmqetf 170
Cdd:cd11395     1 PRKRLPHNAIEKRYRSNLNTKIERLRDAIPSLRSPEGKSDdgglgglapttkLSKATILTKAIEYIRHLEQENE------ 74

                          90
                  ....*....|....*..
gi 1007384330 171 keaeRLQMDNELLRQQI 187
Cdd:cd11395    75 ----RLEEENEELRQQV 87

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
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1007384330 105 RRAQHNEVERRRRDKINNWIVQLSKIIPDCNADNSKTgaSKGGILSKACDYIRELRQTN 163
Cdd:cd11437     1 SRSNHSEIEKRRRDKMNAYIQELSALVPACNAMSRKL--DKLTVLRMAVQHLKSLRGTG 57

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007384330 103 ERRRAQHNEVERRRRDKINNWIVQLSKIIPDCNA-DNSKTgaSKGGILSKACDYIRELRQTNQRMQEtfkEAERlqmdne 181
Cdd:cd11405     1 EQRRLSHISAEQKRRFNIKSGFDTLQSLIPSLGQnPNQKV--SKAAMLQKAAEYIKSLKRERQQMQE---EAEQ------ 69

                  ....*.
gi 1007384330 182 lLRQQI 187
Cdd:cd11405    70 -LRQEI 74

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1007384330 101 RDERRRAQHNEVERRRRDKINNWIVQLSKIIPDCNADNSKTgaSKGGILSKACDYIRELRQTNQRMQET 169
Cdd:cd11397     1 KDRQKKDNHNMIERRRRFNINDRIKELGTLLPKSNDPDMRW--NKGTILKASVDYIRKLQKEQERLRQL 67

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1007384330 100 PRDERRRAqHNEVERRRRDKINNWIVQLSKIIPDCNADnsktgASKGGILSKACDYIRELRQTNQRMQE 168
Cdd:cd18921     2 SKGEKRTA-HNAIEKRYRSSINDKIIELKDLVVGTEAK-----LNKSAVLRKAIDYIRFLQQSNQKLKQ 64

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 1007384330 105 RRAQHNEVERRRRDKINNWIVQLSKIIPDCNADNsktgASKGGILSKACDYIRELRQTNQRMQetfkeaerlqmdnellr 184
Cdd:cd11406     1 KRAHHNALERKRRDHIKDSFHSLRDSVPSLQGEK----ASRAQILKKATEYIQYMRRKNHTHQ----------------- 59

                          90
                  ....*....|
gi 1007384330 185 QQIEELKNEN 194
Cdd:cd11406    60 QDIDDLKRQN 69

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 1007384330 101 RDERRRAQHNEVERRRRDKINNWIVQLSKIIPDCNADNSKTgaSKGGILSKACDYIRELRQTNQRMQETFKEAERLQMDN 180
Cdd:cd18926     9 KERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRW--NKGTILKASVDYIRKLQREQQRAKELENRQKKLEHAN 86

                          90
                  ....*....|.
gi 1007384330 181 ELLRQQIEELK 191
Cdd:cd18926    87 RHLLLRIQELE 97

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 1007384330 103 ERRRAQHNEVERRRRDKINNWIVQLSKIIPDCNADNSKTgASKGGILSKACDYIRELRQTNQRMQE 168
Cdd:cd11388     1 PVKKWKHVEAEKKRRNQIKKGFEDLINLINYPRNNNEKR-ISKSELLNKAVDDIRGLLKANEQLQE 65

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 1007384330 112 VERRRRDKINNWIVQLSKIIPDCNADNSKTGASKGGILSKACDYIRELRQTN 163
Cdd:cd19685     1 SEKRRRQRINDKLNQLKELLPPNLSKQSRSKLSKAEILEMAITELRRLQQEV 52

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 1007384330 101 RDERRRAQHNEVERRRRDKINNWIVQLSKIIPDCNADNSKTgaSKGGILSKACDYIRELR 160
Cdd:cd11438     3 RIKNAREAHSQIEKRRRDKMNSFIDELASLVPTCNAMSRKL--DKLTVLRMAVQHMKTLR 60

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 1007384330 109 HNEVERRRRDKINNWIVQLSKIIPDCNADNSKTGASKGGILSKACDYIRELRQTN 163
Cdd:cd11408     2 HKVIEKRRRDRINRCLNELGKTVPMALAKQTSGKLEKAEILEMTVQYLRALHSAD 56

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
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1007384330 109 HNEVERRRRDKINNWIVQLSKIIPDCnadnskTGASKGGILSKACDYIRELRQTNQRMQ 167
Cdd:cd11393     1 HSIAERKRREKINERIRALRSLVPNG------GKTDKASILDEAIEYIKFLQEQVKVLS 53

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 1007384330 109 HNEVERRRRDKINNWIVQLSKIIPDCNADNsktgasKGGILSKACDYIRELRQTNQRM 166
Cdd:cd11445     6 HNLSERRRRDRINEKMKALQELIPNCNKTD------KASMLDEAIEYLKSLQLQVQMM 57

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 1007384330 102 DERRRAQHNEVERRRRDKINNWIVQLSKIIPDCnADNSKtgASKGGILSKACDYIRELRQTNQRMQEtfkEAERLQMDNE 181
Cdd:cd11456     2 DSERRRNHNILERQRRNDLRSSFLTLRDHVPEL-VKNEK--AAKVVILKKATEYVHSLQAEEQKLLL---EKEKLQARQQ 75

                          90
                  ....*....|
gi 1007384330 182 LLRQQIEELK 191
Cdd:cd11456    76 QLLKKIEQAR 85

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1007384330 104 RRRAQHNEVERRRRDKINNWIVQLSKIIPDC--NADNSKTGASKGGILSKACDYIRELRQTNQRMQE 168
Cdd:cd19687     1 RRREAHTQAEQKRRDAIKKGYDDLQDIVPTCqqQDDIGSQKLSKATILQRSIDYIQFLHQQKKKQEE 67

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 1007384330 105 RRAQHNEVERRRRDKINNWIVQLSKIIPDCNADNSKTGASKGGILSKACDYIRELRQTN 163
Cdd:cd11407     1 RKKRRGIIEKRRRDRINNSLAELRRLVPTAFEKQGSAKLEKAEILQMTVDHLKMLHSKG 59

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007384330 106 RAQHNEVERRRRDKINNWIVQLSKIIPdCNADNSKtgASKGGILSKACDYIRELRQTNQRmqetfkeaerlqmdnelLRQ 185
Cdd:cd11401     1 RSTHNELEKNRRAHLRLCLERLKELVP-LGPDATR--HTTLSLLTKAKAYIKNLEDKEKR-----------------QRQ 60

                          90
                  ....*....|....*.
gi 1007384330 186 QIEELKNENALLRAQL 201
Cdd:cd11401    61 QKEQLRREQRELKRRL 76

basic helix-loop-helix (bHLH) domain found in the spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein (SOHLH) family and similar proteins; 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. The family also includes transcription factor-like 5 protein (TCFL5) and similar proteins. TCFL5, also termed Cha transcription factor, or HPV-16 E2-binding protein 1 (E2BP-1), is a bHLH transcription factor that plays a crucial role in spermatogenesis. It regulates cell proliferation or differentiation of cells through binding to a specific DNA sequence like other bHLH molecules.

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                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1007384330 105 RRAQHNEVERRRRDKINNWIVQLSKIIPDCNADNSKtgASkggILSKACDYIRELR 160
Cdd:cd19683     2 SRERHNAKERQRRERIKIACDQLRKLVPGCSRKTDK--AT---VFEFTVAYIKFLR 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'.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1007384330 104 RRRAQHNEVERRRRDKINNWIVQLSKIIPDCNADNsktgASKGGILSKACDYIRELRQTNQRM 166
Cdd:cd11419     3 IRREIANSNERRRMQSINAGFQSLRTLLPHCDGEK----LSKAAILQQTAEYIFSLEQEKTRL 61

basic helix-loop-helix (bHLH) domain found in muscle, intestine and stomach expression 1 (MIST-1) and similar proteins; MIST-1, also termed Class A basic helix-loop-helix protein 15 (bHLHa15), or Class B basic helix-loop-helix protein 8 (bHLHb8), is a bHLH transcription factor expressed in pancreatic acinar cells and other serous exocrine cells. It is essential for cytoskeletal organization and secretory activity. It also functions as a potent endoplasmic reticulum (ER) stress-inducible transcriptional regulator. MIST-1 is capable of binding to E-box (CANNTG) motifs as a homodimer or a heterodimer with E-proteins (E12 and E47) to regulate transcription.

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                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1007384330 105 RRAQHNEVERRRRDKINNWIVQLSKIIPDCNADNSktgASKGGILSKACDYIRELRQT 162
Cdd:cd19711     1 RRLESNERERQRMHKLNNAFQALREVIPHVRAEKK---LSKIETLTLAKNYIKSLTTT 55

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007384330  97 TRTPRDERRRAQHNEVERRRRDKINNWIVQLSKIIPDCNADNSKTGASKGGILSKACDYIRELRQTNQRmqeTFKEAERL 176
Cdd:cd18920     2 TTTSQIMARKKRRGIIEKRRRDRINNSLSELRRLVPTAFEKQGSAKLEKAEILQMTVDHLKMLQATGGK---GYFDAHAL 78

                  ...
gi 1007384330 177 QMD 179
Cdd:cd18920    79 AMD 81

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 1007384330 105 RRAQHNEVERRRRDKINNWIVQLSKIIPDCNADNSKtgaSKGGILSKACDYIRELRQTNQRMQE 168
Cdd:cd11403     2 KKENHISSEHKRREAIREGFDRLCAIVPALSSSQSR---SEAVVYVKTVEYLKELYERRAKLRS 62

basic helix-loop-helix (bHLH) domain found in achaete-scute complex-like (ASCL) family; The achaete-scute complex-like (ASCL, also known as achaete-scute complex homolog or ASH) family of bHLH transcription factors, ASCL1-5, have been implicated in cell fate specification and differentiation. They are critical for proper development of the nervous system. The deregulation of ASCL plays a key role in psychiatric and neurological disorders. ASCL-1, also termed Class A basic helix-loop-helix protein 46 (bHLHa46), or achaete-scute homolog 1 (ASH-1), or mammalian achaete-scute homolog 1 (Mash1), is a neural-specific bHLH transcription factor that is expressed in subsets of neural progenitors in both the central and peripheral nervous system. It plays a key role in neuronal differentiation and specification in the nervous system. ASCL-2, also termed achaete-scute homolog 2 (ASH-2), or Class A basic helix-loop-helix protein 45 (bHLHa45), or mammalian achaete-scute homolog 2 (Mash2), is a bHLH transcription factor that is involved in Schwann cell differentiation and control of proliferation in adult peripheral nerves. ASCL-3, also termed Class A basic helix-loop-helix protein 42 (bHLHa42), or bHLH transcriptional regulator Sgn-1, or achaete-scute homolog 3 (ASH-3), is a bHLH transcription factor specifically localized in the duct cells of the salivary glands. It may act as transcriptional repressor that inhibits myogenesis. The family also includes Drosophila melanogaster achaete-scute complex (AS-C) proteins, which consists of lethal of scute (also known as achaete-scute complex protein T3 or AST3), scute (also known as achaete-scute complex protein T4 or AST4), achaete (also known as achaete-scute complex protein T5 or AST5), and asense (also known as achaete-scute complex protein T8 or AST8). They are involved in the determination of the neuronal precursors in the peripheral nervous system and the central nervous system, as well as in sex determination and dosage compensation.

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                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1007384330 105 RRAQHNEVERRRRDKINNWIVQLSKIIPDCNADNSktgASKGGILSKACDYIRELRQ 161
Cdd:cd11418     1 RVARRNERERRRVQAVNDAFDRLRQHVPYLKRRKK---LSKVKTLRRAIEYIRHLQK 54

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein transparent testa 8 (TT8) and similar proteins; The family includes several bHLH transcription factors from Arabidopsis thaliana, such as TT8, EGL1, and GL3. TT8, also termed AtbHLH42, or EN 32, is involved in the control of flavonoid pigmentation and plays a key role in regulating leucoanthocyanidin reductase (BANYULS) and dihydroflavonol-4-reductase (DFR). EGL1, also termed AtbHLH2, or EN 30, or AtMYC146, or protein enhancer of GLABRA 3, is involved in epidermal cell fate specification and regulates negatively stomata formation but promotes trichome formation. GL3, also termed AtbHLH1, or AtMYC6, or protein shapeshifter, or EN 31, is involved in epidermal cell fate specification. It regulates negatively stomata formation, but, in association with TTG1 and MYB0/GL1, promotes trichome formation, branching and endoreplication.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1007384330 109 HNEVERRRRDKINNWIVQLSKIIPdcnadnSKTGASKGGILSKACDYIRELRQTNQRMQETFKEAE 174
Cdd:cd11451     6 HAMAERRRREKLNERFITLRSMVP------FVTKMDKVSILGDAIEYLKQLQRRVEELESRRKSSD 65

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1007384330 109 HNEVERRRRDKINNWIVQLSKIIPDCNadnskTGASKGGILSKACDYIRELRQTNQRMQETFKEAERLQMDN 180
Cdd:cd19698     1 HNLLEKKRRERIKDKIEILKGLTPNCT-----PKSDIASILSCVIDYIKSLLLQVEKLSMGICDDWRLFTPF 67

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1007384330 105 RRAQHNEVERRRRDKINNWIVQLSKIIPdcNADNSKTgASKGGILSKACDYIRELRQTNQRMQEtfkEAERLQ 177
Cdd:cd19688     3 RRMKHISAEQKRRFNIKICFDTLNSLVS--TLKNSKP-ISNAITLQKTVEYIAKLQQERTQMQE---ETKRLR 69

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1007384330 101 RDERRRAQHNEVERRRRDKINNWIVQLSKIIPdcnaDNSKTgASKGGILSKACDYIRELRQT 162
Cdd:cd19734     3 KDKAKRVSRNKSEKKRRDQFNVLIKELGSMLP----GNARK-MDKSTVLQKSIDFLRKHKEI 59

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007384330 106 RAQHNEVERRRRDKINNWIVQLSKIIPdcnADNSKTGASKGGILSKACDYIRELRQTNQRMQETFKEAERLQmdnELLRQ 185
Cdd:cd18930     2 RSTHNELEKNRRAHLRLCLERLKVLIP---LGPDCTRHTTLGLLNKAKAHIKKLEEADRKSQHQLENLEREQ---RFLKR 75

                  ....*
gi 1007384330 186 QIEEL 190
Cdd:cd18930    76 RLEQL 80

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split (HES) family; The HES family includes bHLH-O transcriptional regulators that are related to the Drosophila hairy and Enhancer-of-split (HES) proteins. They 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. HES family proteins 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.

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                  ....*....|....*....|....*....|....*....|....*....|...
gi 1007384330 112 VERRRRDKINNWIVQLSKIIPDCNADNsKTGAS---KGGILSKACDYIRELRQ 161
Cdd:cd11410     1 MEKKRRARINKSLEQLKTLVLEALNKD-NTRYSkleKADILEMTVKYLKQLQR 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1007384330 106 RAQHNEVERRRRDKINNWIVQLSKIIPDcnadNSKTGASKGGILSKACDYIRELRQTNQRMQET 169
Cdd:cd19682     1 RLRHKKRERERRSELRELFDKLKQLLGL----DSDEKASKLAVLTEAIEEIQQLKREEDELQKE 60