basic Helix-Loop-Helix-zipper (bHLHzip) domain found in sterol regulatory element-binding protein 2 (SREBP2) and similar proteins; SREBP2, also termed Class D basic helix-loop-helix protein 2 (bHLHd2), or sterol regulatory element-binding transcription factor 2 (SREBF2), is a member of a family of bHLHzip transcription factors that recognize sterol regulatory element 1 (SRE-1). It acts as a transcription activator of cholesterol biosynthesis.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 73661204  315 PKEGERRTTHNIIEKRYRSSINDKIIELKDLVMGTDAKMHKSGVLRKAIDYIKYLQQVNHKLRQENMVLKLANQKNK 391
Cdd:cd18922    1 PKEGERRTTHNIIEKRYRSSINDKIIELKDLVMGTDAKMHKSGVLRKAIDYIKYLQQVNHKLRQENMALKLANQKNK 77

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in sterol regulatory element-binding protein 2 (SREBP2) and similar proteins; SREBP2, also termed Class D basic helix-loop-helix protein 2 (bHLHd2), or sterol regulatory element-binding transcription factor 2 (SREBF2), is a member of a family of bHLHzip transcription factors that recognize sterol regulatory element 1 (SRE-1). It acts as a transcription activator of cholesterol biosynthesis.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 73661204  315 PKEGERRTTHNIIEKRYRSSINDKIIELKDLVMGTDAKMHKSGVLRKAIDYIKYLQQVNHKLRQENMVLKLANQKNK 391
Cdd:cd18922    1 PKEGERRTTHNIIEKRYRSSINDKIIELKDLVMGTDAKMHKSGVLRKAIDYIKYLQQVNHKLRQENMALKLANQKNK 77

helix loop helix domain;

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 73661204     325 NIIEKRYRSSINDKIIELKDLVMG--TDAKMHKSGVLRKAIDYIKYLQQVNHK 375
Cdd:smart00353    1 NARERRRRRKINEAFDELRSLLPTlpKNKKLSKAEILRLAIEYIKSLQEELQK 53

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in sterol regulatory element-binding protein 2 (SREBP2) and similar proteins; SREBP2, also termed Class D basic helix-loop-helix protein 2 (bHLHd2), or sterol regulatory element-binding transcription factor 2 (SREBF2), is a member of a family of bHLHzip transcription factors that recognize sterol regulatory element 1 (SRE-1). It acts as a transcription activator of cholesterol biosynthesis.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 73661204  315 PKEGERRTTHNIIEKRYRSSINDKIIELKDLVMGTDAKMHKSGVLRKAIDYIKYLQQVNHKLRQENMVLKLANQKNK 391
Cdd:cd18922    1 PKEGERRTTHNIIEKRYRSSINDKIIELKDLVMGTDAKMHKSGVLRKAIDYIKYLQQVNHKLRQENMALKLANQKNK 77

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 73661204  315 PKEGERRTTHNIIEKRYRSSINDKIIELKDLVMGTDAKMHKSGVLRKAIDYIKYLQQVNHKLRQENMVLKLANQK 389
Cdd:cd18921    1 PSKGEKRTAHNAIEKRYRSSINDKIIELKDLVVGTEAKLNKSAVLRKAIDYIRFLQQSNQKLKQENMALKMAVQK 75

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 73661204  319 ERRTTHNIIEKRYRSSINDKIIELKDLV-----------------MGTDAKMHKSGVLRKAIDYIKYLQQVNHKLRQENM 381
Cdd:cd11395    2 RKRLPHNAIEKRYRSNLNTKIERLRDAIpslrspegksddgglggLAPTTKLSKATILTKAIEYIRHLEQENERLEEENE 81

                 ...
gi 73661204  382 VLK 384
Cdd:cd11395   82 ELR 84

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 73661204  316 KEGERRTTHNIIEKRYRSSINDKIIELKDLVMGTDAKMHKSGVLRKAIDYIKYLQQVNHKLRQE 379
Cdd:cd11398    3 WHRQRRDNHKEVERRRRENINEGINELAALVPGNAREKNKGAILARAVEYIQELQETEAKNIEK 66

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 73661204  323 THNIIEKRYRSSINDKIIELKDLV-----MGTDAKMHKSGVLRKAIDYIKYLQQVNH 374
Cdd:cd11387    1 SHNAVERRRRDNINEKIQELGSLVppsrlETKDLKPNKGSILSKAVEYIRELQNQNQ 57

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana BES1-interacting Myc-like proteins (BIMs) and similar proteins; The family includes Arabidopsis thaliana BIM1 and its homologs (BIM2 and BIM3), which are bHLH transcription factors that interact with BES1 to regulate transcription of Brassinosteroid (BR)-induced gene. BR regulates many growth and developmental processes such as cell elongation, vascular development, senescence stress responses, and photomorphogenesis. BIM1 heterodimerize with BES1 and bind to E-box sequences present in many BR-induced promoters to regulated BR-induced genes.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 73661204  320 RRTTHNIIEKRYRSSINDKIIELKDLVMGTDAKMHKSGVLRKAIDYIKYLQQVNHKLR 377
Cdd:cd11453    3 PRSKHSATEQRRRSKINERLQALRDLIPHSDQKRDKASFLLEVIEYIQALQEKVAKLE 60

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 73661204  328 EKRYRSSINDKIIELKDLV--MGTDAKMHKSGVLRKAIDYIKYLQQ 371
Cdd:cd00083    1 ERRRRDKINDAFEELKRLLpeLPDSKKLSKASILQKAVEYIRELQS 46

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 73661204  316 KEGERRTTHNIIEKRYRSSINDKIIELKDLVMGT---DAKMHKSGVLRKAIDYIKYLQQVNHKLRQ-ENMVLKLANQKNK 391
Cdd:cd18926    9 KERQKKDNHNLIERRRRFNINDRIKELGTLIPKSndpDMRWNKGTILKASVDYIRKLQREQQRAKElENRQKKLEHANRH 88

                 ..
gi 73661204  392 LL 393
Cdd:cd18926   89 LL 90

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 73661204  321 RTTHNIIEKRYRSSINDKIIELKDLV-MGTDAKMHKSGVLRKAIDYIKYLQqvnhklRQENmvlKLANQKNKLL 393
Cdd:cd19682    1 RLRHKKRERERRSELRELFDKLKQLLgLDSDEKASKLAVLTEAIEEIQQLK------REED---ELQKEKARLT 65

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 73661204  316 KEGERRTTHNIIEKRYRSSINDKIIELKDLV-----MGTDAKMHKSGVLRKAIDYIKYLQQVNHK 375
Cdd:cd18924    1 RDEKRRAQHNEVERRRRDKINNWIVQLSKIIpdcsmESTKSGQSKGGILSKACDYIQELRQSNHR 65

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 73661204  320 RRTTHNIIEKRYRSSINDKIIELKDLVMGTDA-KMHKSGVLRKAIDYIKYLQQVNHKLRQENMVLKLAN 387
Cdd:cd11406    1 KRAHHNALERKRRDHIKDSFHSLRDSVPSLQGeKASRAQILKKATEYIQYMRRKNHTHQQDIDDLKRQN 69

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 73661204  324 HNIIEKRYRSSINDKIIELKDLVMGTdAKMHKSGVLRKAIDYIKYLQQVNHKLR 377
Cdd:cd11393    1 HSIAERKRREKINERIRALRSLVPNG-GKTDKASILDEAIEYIKFLQEQVKVLS 53

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 73661204  319 ERRTTHNIIEKRYRSSINDKIIELKDLV--MGTDAKMHKSGVLRKAIDYIKYLQQVNHKLRQENMVLKLANQknKLLKGI 396
Cdd:cd11456    4 ERRRNHNILERQRRNDLRSSFLTLRDHVpeLVKNEKAAKVVILKKATEYVHSLQAEEQKLLLEKEKLQARQQ--QLLKKI 81

                 .
gi 73661204  397 D 397
Cdd:cd11456   82 E 82

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 73661204  319 ERRTTHNIIEKRYRSSINDKIIELKDLVMGTDAKMHKSGVLRKAIDYIKYLQ 370
Cdd:cd19683    1 KSRERHNAKERQRRERIKIACDQLRKLVPGCSRKTDKATVFEFTVAYIKFLR 52

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 73661204  320 RRTTHNIIEKRYRSSINDKIIELKDLV--MGTDAKMHKSGVLRKAIDYIKYLQQVNHKLRQENMvlKLANQKNKLLK 394
Cdd:cd11400    1 KRRLHNVLERQRRNDLKNSFEKLRDLVpeLADNEKASKVVILKKATEYIKQLQQEEKKLEKEKD--KLKARNEQLRK 75

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 73661204  327 IEKRYRSSINDKIIELKDLV-----MGTDAKMHKSGVLRKAIDYIKYLQQ 371
Cdd:cd19685    1 SEKRRRQRINDKLNQLKELLppnlsKQSRSKLSKAEILEMAITELRRLQQ 50

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 73661204  320 RRTTHNIIEKRYRSSINDKIIELKDLV------MGTdAKMHKSGVLRKAIDYIKYLQQ 371
Cdd:cd11407    1 RKKRRGIIEKRRRDRINNSLAELRRLVptafekQGS-AKLEKAEILQMTVDHLKMLHS 57

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 73661204  316 KEGERRTTHNIIEKRYRSSINDKIIELKDLVMGTDAKMHKSGVLRKAIDYIKYLQQV 372
Cdd:cd19734    3 KDKAKRVSRNKSEKKRRDQFNVLIKELGSMLPGNARKMDKSTVLQKSIDFLRKHKEI 59

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
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 73661204  316 KEGERRTTHNIIEKRYRSSINDKIIELKDLVMGTDAKMHKSGVLRKAIDYIKYLQQV 372
Cdd:cd19735    6 KDTIKRKSRNLSEKKRRDQFNVLINELCSMVSTSNRKMDKSTVLKSTIAFLKNHNEV 62

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in Circadian locomotor output cycles protein kaput (CLOCK) and similar proteins; The family includes CLOCK, neuronal PAS domain-containing protein 2 (NPAS2) and non-mammalian circadian clock protein PASD1. CLOCK, also termed Class E basic helix-loop-helix protein 8 (bHLHe8), is a transcriptional activator which forms a core component of the circadian clock. NPAS2, also termed neuronal PAS2, or basic-helix-loop-helix-PAS protein MOP4, or Class E basic helix-loop-helix protein 9 (bHLHe9), or member of PAS protein 4, or PAS domain-containing protein 4, is a transcriptional activator which forms a core component of the circadian clock. PASD1 is evolutionarily related to Circadian locomotor output cycles protein kaput (CLOCK)and functions as a suppressor of the biological clock that drives the daily circadian rhythms of cells throughout the body.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 73661204  321 RTTHNIIEKRYRSSINDKIIELKDLVMGTDAKMHKSGVLRKAIDYIKYLQQV 372
Cdd:cd11441    1 RKSRNLSEKKRRDQFNVLINELASMLPGRGRKMDKSTVLKKTIAFLRKHKEL 52

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein IAA-leucine resistant 3 (ILR3) and similar proteins; ILR3, also termed AtbHLH105, or EN 133, is a bHLH transcription factor that plays a role in resistance to amide-linked indole-3-acetic acid (IAA) conjugates such as IAA-Leu and IAA-Phe. It may regulate gene expression in response to metal homeostasis changes.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 73661204  328 EKRYRSSINDKIIELKDLV-MGTDAKMHKSGVLRKAIDYIKYLQQVNHKLRQENMVLK-----LANQKNKL 392
Cdd:cd11446    5 EKLRRDKLNERFMELSNVLePGRPPKTDKATILGDAIRMLKQLRGEVQKLKEENSSLQeeskeLKAEKNEL 75

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein aborted microspores (AMS) and similar proteins; The family includes several bHLH transcription factors from Arabidopsis thaliana, such as AMS, ICE1 and SCREAM2. AMS, also termed AtbHLH21, or EN 48, plays a crucial role in tapetum development and it is required for male fertility and pollen differentiation. ICE1, also termed inducer of CBF expression 1, or AtbHLH116, or EN 45, or SCREAM, acts as a transcriptional activator that regulates the cold-induced transcription of CBF/DREB1 genes. It binds specifically to the MYC recognition sites (5'-CANNTG-3') found in the CBF3/DREB1A promoter. SCREAM2, also termed AtbHLH33, or EN 44, mediates stomatal differentiation in the epidermis probably by controlling successive roles of SPCH, MUTE, and FAMA.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 73661204  328 EKRYRSSINDKIIELKDLVMGTdAKMHKSGVLRKAIDYIKYLQQVNHKLRQE 379
Cdd:cd11443    7 ERRRRKKLNDRLYMLRSVVPKI-TKMDRASILGDAIDYVKELLQEINELQDE 57

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
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 73661204  316 KEGERRTTHNIIEKRYRSSINDKIIELKDLVMGTDAKMHKSGVLRKAIDYIKYLQQ 371
Cdd:cd18919    8 RRGQATDSHSLAERVRREKISERMKLLQDLVPGCNKVTGKALMLDEIINYVQSLQR 63

basic helix-loop-helix (bHLH) domain found in heart- and neural crest derivatives-expressed protein 2 (HAND2) and similar proteins; HAND2, also termed Class A basic helix-loop-helix protein 26 (bHLHa26), or deciduum, heart, autonomic nervous system and neural crest derivatives-expressed protein 2 (dHAND), is a bHLH transcription factor that is essential for cardiac morphogenesis, particularly for the formation of the right ventricle and of the aortic arch arteries.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 73661204  320 RRTTHNIIEKRYRSSINDKIIELKDLV--MGTDAKMHKSGVLRKAIDYIKYLQQV 372
Cdd:cd11471    1 RRGTANRKERRRTQSINSAFAELRECIpnVPADTKLSKIKTLRLATSYIAYLMDL 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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 73661204  320 RRTTHNIIEKRYRSSINDKIIELKDLVMGT-----DAKMHKSGVLRKAIDYIKYLQQVNHK 375
Cdd:cd18920   10 RKKRRGIIEKRRRDRINNSLSELRRLVPTAfekqgSAKLEKAEILQMTVDHLKMLQATGGK 70

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 73661204  320 RRTTHNIIEKRYRSSINDKIIELKDLVMGT-----DAKMHKSGVLRKAIDYIKYLQ 370
Cdd:cd19748    9 RKRRRGIIEKRRRDRINNSLSELRRLVPSAfekqgSAKLEKAEILQMTVDHLKMLH 64

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 73661204  320 RRTTHNIIEKRYRSSINDKIIELKDLVMGTDA---KMHKSGVLRKAIDYIKYLQ 370
Cdd:cd19726    1 RRQNHSEIEKRRRDKMNTYITELSSMIPMCNAmsrKLDKLTVLRMAVQHMKTLR 54

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
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 73661204  316 KEGERRTTHNIIEKRYRSSINDKIIELKDLVMGTDAKMHKSGVLRKAIDYIKYLQQV 372
Cdd:cd19737    6 KDRAKRASRNKSEKKRRDQFNVLIKELSSMLPGNTRKMDKTTVLEKVIGFLQKHNEV 62

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
                 ....*....|....*....|....*....|....*....|....*....|...
gi 73661204  321 RTTHNIIEKRYRSSINDKIIELKDLVMGTDA---KMHKSGVLRKAIDYIKYLQ 370
Cdd:cd11438    8 REAHSQIEKRRRDKMNSFIDELASLVPTCNAmsrKLDKLTVLRMAVQHMKTLR 60

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 73661204  319 ERRtthNIIEKRYRSSINDKIIELKDLV--MGTDAKMHKSGVLRKAIDYIKYLQQV 372
Cdd:cd11418    3 ARR---NERERRRVQAVNDAFDRLRQHVpyLKRRKKLSKVKTLRRAIEYIRHLQKL 55

basic helix-loop-helix (bHLH) domain found in heart- and neural crest derivatives-expressed protein (HAND) family; The HAND family includes two bHLH transcription factors, HAND1 and HAND2. HAND1, also termed Class A basic helix-loop-helix protein 27 (bHLHa27), or extraembryonic tissues, heart, autonomic nervous system and neural crest derivatives-expressed protein 1 (eHAND), plays an essential role in both trophoblast-giant cells differentiation and in cardiac morphogenesis. HAND2, also termed Class A basic helix-loop-helix protein 26 (bHLHa26), or deciduum, heart, autonomic nervous system and neural crest derivatives-expressed protein 2 (dHAND), is essential for cardiac morphogenesis, particularly for the formation of the right ventricle and of the aortic arch arteries.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 73661204  320 RRTTHNIIEKRYRSSINDKIIELKDLV--MGTDAKMHKSGVLRKAIDYIKYLQQV 372
Cdd:cd11466    1 RRGSANKKERRRTQSINSAFADLRECIpnVPADTKLSKIKTLRLATSYIAYLMDV 55

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-binding protein Mnt and similar proteins; Mnt, also termed Class D basic helix-loop-helix protein 3 (bHLHd3), or Myc antagonist MNT, or protein ROX, is a bHLHZip transcriptional repressor that binds DNA as a heterodimer with MAX. It binds to the canonical E box sequence 5'-CACGTG-3' and, with higher affinity, to 5'-CACGCG-3'. Mnt has an important role as an antagonist and regulator of Myc activities and it is a potential tumor suppressor. Mnt is ubiquitously expressed. Mnt-deficient mice shown to exhibit early postnatal lethality.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 73661204  321 RTTHNIIEKRYRSSINDKIIELKD-LVMGTDAKMHKSGVLRKAIDYIKYLQQVNHklRQENMVLKLANQK 389
Cdd:cd11402    3 REVHNKLEKNRRAHLKECFETLKRqIPNLDDKKTSNLNILRSALRYIQILKRKEK--EYEHEMERLAREK 70