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 71994970 209 RDRRKKDIHNMIERRRRYNINDRIKELGQMLPKNTSEDMKLNKGTILKASCDYIRVLQKDREQAMKTQQ 277
Cdd:cd11397   1 KDRQKKDNHNMIERRRRFNINDRIKELGTLLPKSNDPDMRWNKGTILKASVDYIRKLQKEQERLRQLEE 69

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 71994970 209 RDRRKKDIHNMIERRRRYNINDRIKELGQMLPKNTSEDMKLNKGTILKASCDYIRVLQKDREQAMKTQQ 277
Cdd:cd11397   1 KDRQKKDNHNMIERRRRFNINDRIKELGTLLPKSNDPDMRWNKGTILKASVDYIRKLQKEQERLRQLEE 69

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 71994970    218 NMIERRRRYNINDRIKELGQMLPKNTSeDMKLNKGTILKASCDYIRVLQK 267
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPK-NKKLSKAEILRLAIEYIKSLQE 49

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 71994970 209 RDRRKKDIHNMIERRRRYNINDRIKELGQMLPKNTSEDMKLNKGTILKASCDYIRVLQKDREQAMKTQQ 277
Cdd:cd11397   1 KDRQKKDNHNMIERRRRFNINDRIKELGTLLPKSNDPDMRWNKGTILKASVDYIRKLQKEQERLRQLEE 69

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in transcription factor E3 (TFE3) and similar proteins; TFE3, also termed Class E basic helix-loop-helix protein 33 (bHLHe33), is a bHLHzip transcription factor that is involved in B cell function. It specifically recognizes and binds E-box sequences (5'-CANNTG-3'). Its efficient DNA-binding requires dimerization with itself or with another MiT/TFE family member such as TFEB or MITF.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71994970 207 YYRDRRKKDIHNMIERRRRYNINDRIKELGQMLPKNTSEDMKLNKGTILKASCDYIRVLQKDREQAMKTQQQQKSLESTA 286
Cdd:cd18928   5 FLKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSTDPEMRWNKGTILKASVDYIRKLQKEQQRSKEIEMRQRKLEQAN 84

                ....*..
gi 71994970 287 HKYADRV 293
Cdd:cd18928  85 RSLQLRI 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 71994970 209 RDRRKKDIHNMIERRRRYNINDRIKELGQMLPKNTSEDMKLNKGTILKASCDYIRVLQKDREQAMKTQQQQKSLESTAHK 288
Cdd:cd18925   1 KERQKKDNHNLIERRRRYNINYRIKELGTLIPKSNDPDMRWNKGTILKASVEYIKWLQKEQQRARELEHRQKKLEQANRR 80

                ....*
gi 71994970 289 YADRV 293
Cdd:cd18925  81 LLLRI 85

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 71994970 211 RRKKDIHNMIERRRRYNINDRIKELGQMLPKNTSEDmklNKGTILKASCDYIRVLQKDREQAMKTQQQQKSLestahkya 290
Cdd:cd11398   5 RQRRDNHKEVERRRRENINEGINELAALVPGNAREK---NKGAILARAVEYIQELQETEAKNIEKWTLEKLL-------- 73

                        90
                ....*....|...
gi 71994970 291 drVKELEEMLARQ 303
Cdd:cd11398  74 --TDQAIAELAAL 84

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 71994970   211 RRKKdiHNMIERRRRYNINDRIKELGQMLPKNTSeDMKLNKGTILKASCDYIRVLQ 266
Cdd:pfam00010   1 RREA--HNERERRRRDRINDAFDELRELLPTLPP-DKKLSKAEILRLAIEYIKHLQ 53

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in sterol regulatory element-binding protein (SREBP) family; The SREBP family includes SREBP1 and SREBP2, which are bHLHzip transcriptional activator of genes encoding proteins essential for cholesterol biosynthesis/uptake and fatty acid biosynthesis. SREBP1 and SREBP2 are principally found in the liver and in adipocytes and made up of an N-terminal transcription factor portion (composed of an activation domain, a bHLHzip domain, and a nuclear localization signal), a hydrophobic region containing two membrane spanning regions, and a C-terminal regulatory segment. They recognize a symmetric sterol regulatory element (TCACNCCAC) instead of E-box.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 71994970 213 KKDIHNMIERRRRYNINDRIKELGQMLpknTSEDMKLNKGTILKASCDYIRVLQ------KDREQAMKTQQ 277
Cdd:cd11394   6 KRSAHNAIEKRYRSSINDRIIELKDLV---VGPDAKMNKSAVLRKAIDYIRYLQkvnqklKQENMALKKAL 73

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 71994970 213 KKDIHNMIERRRRYNINDRIKELGQMLpknTSEDMKLNKGTILKASCDYIRVLQkdrEQAMKTQQQQKSLESTAHK 288
Cdd:cd18921   6 KRTAHNAIEKRYRSSINDKIIELKDLV---VGTEAKLNKSAVLRKAIDYIRFLQ---QSNQKLKQENMALKMAVQK 75

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 71994970 221 ERRRRYNINDRIKELGQMLPkNTSEDMKLNKGTILKASCDYIRVLQK 267
Cdd:cd00083   1 ERRRRDKINDAFEELKRLLP-ELPDSKKLSKASILQKAVEYIRELQS 46

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 71994970 209 RDRRKKDIHNMIERRRRYNINDRIKELGQMLPKNTSEDMKLN--KGTILKASCDYIRVLQK 267
Cdd:cd18924   1 RDEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKSGqsKGGILSKACDYIQELRQ 61

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 71994970 211 RRKKDIHNMIERRRRYNINDRIKELGQMLPKNTSEDM--------------KLNKGTILKASCDYIRVLQKDREQ 271
Cdd:cd11395   1 PRKRLPHNAIEKRYRSNLNTKIERLRDAIPSLRSPEGksddgglgglapttKLSKATILTKAIEYIRHLEQENER 75

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 71994970 217 HNMIERRRRYNINDRIKELGQMLPKNTsedmKLNKGTILKASCDYIRVLQKD 268
Cdd:cd11393   1 HSIAERKRREKINERIRALRSLVPNGG----KTDKASILDEAIEYIKFLQEQ 48

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 71994970 217 HNMIERRRRYNINDRIKELGQMLP----KNTSEdmKLNKGTILKASCDYIRVLQ 266
Cdd:cd11408   2 HKVIEKRRRDRINRCLNELGKTVPmalaKQTSG--KLEKAEILEMTVQYLRALH 53

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 71994970 209 RDRRKKDIHNMIERRRRYNINDRIKELGQMLPKNTSedmKLNKGTILKASCDYIR 263
Cdd:cd19734   3 KDKAKRVSRNKSEKKRRDQFNVLIKELGSMLPGNAR---KMDKSTVLQKSIDFLR 54

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 71994970 214 KDIHNMIERRRRYNINDRIKELGQMLPKNTSEDMKLNKGTILKASCDYIRVLQ 266
Cdd:cd11391   1 REKSREAAKKRRDKENAEISELASLLPLPPAVGSKLDKLSVLRLAVAYLRLKK 53

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 71994970 209 RDRRKKDIHNMIERRRRYNINDRIKELGQMLpKNTSEDMKLNKGTILKASCDYirvLQKDREQAMKTQ 276
Cdd:cd19736   6 KDRAKRASRNKSEKKRRDQFNVLIKELCTML-QGHGHPLKMDKSTILQRTIDF---LQKQKEITAQTE 69

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in aryl hydrocarbon receptor nuclear translocator (ARNT) family; The ARNT family of bHLH-PAS transcription regulators includes ARNT, ARNT-like proteins (ARNTL and ARNTL2), and Drosophila melanogaster protein cycle. They act as the heterodimeric partner for bHLH-PAS proteins such as aryl hydrocarbon receptor (AhR), hypoxia-inducible factor (HIF), and single-minded (SIM). These bHLH-PAS transcription complexes are involved in transcriptional responses to xenobiotic, hypoxia, and developmental pathways. Heterodimerization of bHLH-PAS proteins with ARNT is mediated by contacts between both the bHLH and the tandem PAS domains. ARNT use bHLH and/or PAS domains to interact with several transcriptional coactivators. It is required for activity of the aryl hydrocarbon (dioxin) receptor. ARNTL, also termed Basic-helix-loop-helix-PAS protein MOP3, or brain and muscle ARNT-like 1 (BMAL1), or Class E basic helix-loop-helix protein 5 (bHLHe5), or member of PAS protein 3, or PAS domain-containing protein 3 (PASD3), or bHLH-PAS protein JAP3, is a member of the bHLH-PAS transcription factor family that forms heterodimers with another bHLH-PAS protein, CLOCK (circadian locomotor output cycle kaput), which regulates circadian rhythm. ARNTL-CLOCK heterodimer complex activates transcription from E-box (CANNTG) elements found in the promoter of circadian responsive genes. ARNTL is highly homologous to ARNT. ARNTL2, also termed Basic-helix-loop-helix-PAS protein MOP9, or brain and muscle ARNT-like 2 (BMAL2), or CYCLE-like factor (CLIF), or Class E basic helix-loop-helix protein 6 (bHLHe6), or member of PAS protein 9, or PAS domain-containing protein 9 (PASD9), is a neuronal bHLH-PAS transcriptional factor, regulating cell cycle progression and preventing cell death, whose sustained expression might ensure brain neuron survival. It also plays important roles in tumor angiogenesis. Protein cycle, also termed brain and muscle ARNT-like 1 (BMAL1), or MOP3, is a putative bHLH-PAS transcription factor involved in the generation of biological rhythms in Drosophila. It activates cycling transcription of Period (PER) and Timeless (TIM) by binding to the E-box (5'-CACGTG-3') present in their promoters.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 71994970 217 HNMIERRRRYNINDRIKELGQMLPKNTSEDMKLNKGTILKASCDYIRVL 265
Cdd:cd11437   5 HSEIEKRRRDKMNAYIQELSALVPACNAMSRKLDKLTVLRMAVQHLKSL 53

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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 71994970 213 KKDIHNMIERRRRYNINDRIKELGQMLPKNTSedmKLNKGTILKASCDYIRVLQK 267
Cdd:cd19683   2 SRERHNAKERQRRERIKIACDQLRKLVPGCSR---KTDKATVFEFTVAYIKFLRE 53

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 71994970 209 RDRRKKDIHNMIERRRRYNINDRIKELGQMLPKNTSedmKLNKGTILKASCDYirvLQKDREQAMKTQ 276
Cdd:cd19737   6 KDRAKRASRNKSEKKRRDQFNVLIKELSSMLPGNTR---KMDKTTVLEKVIGF---LQKHNEVSAQTE 67

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 71994970 212 RKKDIHNMIERRRRYNINDRIKELGQMLPKNTSEdmKLNKGTILKASCDYIRVLQKDREQAMK 274
Cdd:cd11404   1 QRRLNHVRSEKKRRELIKKGYDELCALVPGLDPQ--KRTKADILQKAADWIQELKEENEKLEE 61

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 71994970 211 RRKKdiHNMIERRRRYNINDRIKELGQMLP----KNTSEdmKLNKGTILKASCDYIRVLQ 266
Cdd:cd11407   1 RKKR--RGIIEKRRRDRINNSLAELRRLVPtafeKQGSA--KLEKAEILQMTVDHLKMLH 56

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 71994970 214 KDIHNMIERRRRYNINDRIKELGQMLPKNTSEDMKLNKGTILKASCDYIRVLQ 266
Cdd:cd11469   2 REAHSQTEKRRRDKMNNLIEELSAMIPQCNPMARKLDKLTVLRMAVQHLKSLK 54

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 71994970 213 KKDIHNMIERRRRYNINDRIKELGQMLPKNTSEdmKLNKGTILKASCDYIRVLQKdreqamKTQQQQKSLE 283
Cdd:cd11406   1 KRAHHNALERKRRDHIKDSFHSLRDSVPSLQGE--KASRAQILKKATEYIQYMRR------KNHTHQQDID 63

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in Drosophila melanogaster protein cycle and similar proteins; 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 71994970 217 HNMIERRRRYNINDRIKELGQMLPKNTSEDMKLNKGTILKASCDYIRVLQ 266
Cdd:cd19726   5 HSEIEKRRRDKMNTYITELSSMIPMCNAMSRKLDKLTVLRMAVQHMKTLR 54

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 71994970 209 RDRRKKdiHNMIERRRRYNINDRIKELGQMLPKNTSEDMKLNKGTiLKASCDYIRVLQKDREQamkTQQQQKSL 282
Cdd:cd19688   1 KNRRMK--HISAEQKRRFNIKICFDTLNSLVSTLKNSKPISNAIT-LQKTVEYIAKLQQERTQ---MQEETKRL 68

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 71994970 217 HNMIERRRRYNINDRIKELGQMLPkntsEDMKLN------KGTILKASCDYIRVLqkdreQAMKTQQQQKSL 282
Cdd:cd11409   8 HRLIEKKRRDRINECIAQLKDLLP----EHLKLTtlghleKAVVLELTLKHLKAL-----TALTEQQQQKII 70

basic helix-loop-helix-orange (bHLH-O) domain found in differentially expressed in chondrocytes protein 1 (DEC1) and similar proteins; DEC1, also termed Class E basic helix-loop-helix protein 40 (bHLHe40), or Class B basic helix-loop-helix protein 2 (bHLHb2), or enhancer-of-split and hairy-related protein 2 (SHARP-2), or stimulated by retinoic acid gene 13 protein (STRA13), is a bHLH-O transcriptional repressor involved in the regulation of the circadian rhythm by negatively regulating the activity of the clock genes and clock-controlled genes.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 71994970 217 HNMIERRRRYNINDRIKELGQMLPkntsEDMKLN------KGTILKASCDYIRVLqkdreQAMKTQQQQKSL 282
Cdd:cd19749  18 HRLIEKKRRDRINECIAQLKDLLP----EHLKLTtlghleKAVVLELTLKHVKAL-----TSLIEQQQQKIL 80

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in Drosophila melanogaster Circadian locomotor output cycles protein kaput (dCLOCK) and similar proteins; dCLOCK, also termed dPAS1, is a bHLH-PAS Circadian regulator that acts as a transcription factor and generates a rhythmic output with a period of about 24 hours.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 71994970 205 EDYYRDRRKKDIHNMIERRRRYNINDRIKELGQMLPKNTSedmKLNKGTILKAScdyIRVLQKDREQAMKTQQQQ 279
Cdd:cd19735   2 EEDEKDTIKRKSRNLSEKKRRDQFNVLINELCSMVSTSNR---KMDKSTVLKST---IAFLKNHNEVTMQSHQQE 70

basic helix-loop-helix-orange (bHLH-O) domain found in transcription factor HES-5 and similar proteins; HES-5, also termed Class B basic helix-loop-helix protein 38 (bHLHb38), or hairy and enhancer of split 5, is a bHLH-O transcription factor that is involved in cell differentiation and proliferation in a variety of tissues. HES-5 is an essential effector for Notch signaling. It acts as a transducer of Notch signals in brain vascular development. It also acts as a key mediator of Wnt-3a-induced neuronal differentiation and plays a crucial role in normal inner ear hair cell development. HES-5 is one mammalian counterpart of the Hairy and Enhancer of split proteins that play a critical role in many physiological processes including cellular differentiation, cell cycle arrest, apoptosis and self-renewal ability.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 71994970 219 MIERRRRYNINDRIKELGQMLPK---NTSEDMKLNKGTILKASCDYIRVLQK 267
Cdd:cd11461   6 VVEKTRRDRINSSIEQLKTLLEKefqRHQPNSKLEKADILEMTVSFLKQSAK 57

basic helix-loop-helix (bHLH) domain found in transcription factor E47 and similar proteins; E47 is a class I bHLH transcriptional regulator that forms heterodimers with class II bHLH proteins to regulate distinct differentiation pathways. Its homodimers regulate B lymphocytes development.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 71994970 209 RDRRKKDIHNMIERRRRYNINDRIKELGQMLPKNTSEDMKLNKGTILKASCDYIRVLQKD-REQAM 273
Cdd:cd18943   6 RDRERRMANNARERVRVRDINEAFKELGRMCQMHLKSDKAQTKLIILQQAVQVILGLEQQvRERNL 71

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 71994970 216 IHNMIERRRRYNINDRIKELGQMLPKNTsedmKLNKGTILKASCDYIRVLQKDREQAMKTQQQQ 279
Cdd:cd11455  10 SHSEAERRRRERINSHLATLRTLLPNLS----KTDKASLLAEVVQHVKELKRQAAEITTPPDVP 69

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 71994970 213 KKDIHNMIERRRRYNINDRIKELGQMLPKNTSE--DMKLNKGTILKASCDYIRVLQ 266
Cdd:cd18920  10 RKKRRGIIEKRRRDRINNSLSELRRLVPTAFEKqgSAKLEKAEILQMTVDHLKMLQ 65

basic helix-loop-helix (bHLH) domain found in Fer3-like protein (FERD3L), pancreas transcription factor 1 subunit alpha (PTF1A) and similar proteins; The family corresponds to a group of bHLH transcription factors, including FERD3L and PTF1A. FERD3L, also termed basic helix-loop-helix protein N-twist, or Class A basic helix-loop-helix protein 31 (bHLHa31), or nephew of atonal 3 (NATO3), or Neuronal twist (NTWIST), is expressed in the developing central nervous system (CNS). It regulates floor plate (FP) cells development. FP is a critical organizing center located at the ventral-most midline of the neural tube. FERD3L binds to the E-box and functions as inhibitor of transcription. PTF1A, also termed Class A basic helix-loop-helix protein 29 (bHLHa29), or pancreas-specific transcription factor 1a, or bHLH transcription factor p48, or p48 DNA-binding subunit of transcription factor PTF1 (PTF1-p48), is implicated in the cell fate determination in various organs. It binds to the E-box consensus sequence 5'-CANNTG-3' and plays a role in early and late pancreas development and differentiation.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 71994970 218 NMIERRRRYNINDRIKELGQMLPKNtSEDMKLNKGTILKASCDYIRVLQK 267
Cdd:cd19686   6 NIRERKRMRSINDAFDGLRRHIPTF-PYEKRLSKVDTLRLAIQYINFLTE 54

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 71994970 209 RDRRKkdihNMIERRRRYNINDRIKELGQMLPKNTSE--DMKLNKGTILKASCDYIRVLQ 266
Cdd:cd19748   9 RKRRR----GIIEKRRRDRINNSLSELRRLVPSAFEKqgSAKLEKAEILQMTVDHLKMLH 64

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 71994970 212 RKKDIHNMIERRRRYNINDRIKELGQML--PKNTSEdMKLNKGTILKASCDYIRVLQKDREQ 271
Cdd:cd11388   2 VKKWKHVEAEKKRRNQIKKGFEDLINLInyPRNNNE-KRISKSELLNKAVDDIRGLLKANEQ 62

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
                ....*....|....*....|....*....|....*....|....*....
gi 71994970 218 NMIERRRRYNINDRIKELGQMLPKNTsEDMKLNKGTILKASCDYIRVLQ 266
Cdd:cd11422   5 NARERERVRNLNSGFSKLRRIVPLIP-RDRKPSKVDTLKGATEYIRLLQ 52

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split HES-1, HES-4 and similar proteins; The family includes two bHLH-O transcriptional repressors, HES-1 and HES-4. HES-1, also termed Class B basic helix-loop-helix protein 39 (bHLHb39), or hairy homolog, or hairy-like protein (HL), plays an essential role in development of both compartment and boundary cells of the central nervous system. It regulates the maintenance of neural stem/progenitor cells by inhibiting proneural gene expression via Notch signaling. HES-4, also termed Class B basic helix-loop-helix protein 42 (bHLHb42), or bHLH factor Hes4, antagonizes the function of Twist-1 to regulate lineage commitment of bone marrow stromal/stem cells (BMSC). Epigenetic dysregulation of HES-4 is associated with striatal degeneration in postmortem Huntington brains. Both HES-1 and HES-4 are mammalian counterparts of the Hairy and Enhancer of split proteins that play a critical role in many physiological processes including cellular differentiation, cell cycle arrest, apoptosis and self-renewal ability.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 71994970 219 MIERRRRYNINDRIKELG----QMLPKNTSEDMKLNKGTILKASCDYIRVLQKD 268
Cdd:cd11459   9 IMEKRRRARINESLSQLKtlilDALKKDSSRHSKLEKADILEMTVKHLRNLQRQ 62

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 71994970 217 HNMIERRRRYNINDRIKELGQMLPKNTSeDMKLNKGTILKASCDYIRVLQK 267
Cdd:cd11390   4 ANARERRRMHDLNDAFEALRKVLPTVPP-DKKLSKIETLRLAINYIAALSD 53