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 2462557118  293 QSRGEKRTAHNAIEKRYRSSINDKIIELKDLVVGTEAKLNKSAVLRKAIDYIRFLQHSNQKLKQENLSLRTAVHK 367
Cdd:cd18921      1 PSKGEKRTAHNAIEKRYRSSINDKIIELKDLVVGTEAKLNKSAVLRKAIDYIRFLQQSNQKLKQENMALKMAVQK 75

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 2462557118  293 QSRGEKRTAHNAIEKRYRSSINDKIIELKDLVVGTEAKLNKSAVLRKAIDYIRFLQHSNQKLKQENLSLRTAVHK 367
Cdd:cd18921      1 PSKGEKRTAHNAIEKRYRSSINDKIIELKDLVVGTEAKLNKSAVLRKAIDYIRFLQQSNQKLKQENMALKMAVQK 75

helix loop helix domain;

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 2462557118   303 NAIEKRYRSSINDKIIELKDLVVG--TEAKLNKSAVLRKAIDYIRFLQHSNQK 353
Cdd:smart00353    1 NARERRRRRKINEAFDELRSLLPTlpKNKKLSKAEILRLAIEYIKSLQEELQK 53

EBNA-3B; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462557118   63 LSGPQAAPSPLSPPQPAPTPLKmypsMPAFSPGPGIKEESVPlsiLQTPTPQPLPGALL-PQSFPAPAPPQfSSTPVLGY 141
Cdd:PHA03378   704 MRPPAAPPGRAQRPAAATGRAR----PPAAAPGRARPPAAAP---GRARPPAAAPGRARpPAAAPGRARPP-AAAPGAPT 775

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 2462557118  142 PSPPggfsTGSPPGNTQQPLPGLPLASPPGVPPVSLHTQVQSVVPQQ 188
Cdd:PHA03378   776 PQPP----PQAPPAPQQRPRGAPTPQPPPQAGPTSMQLMPRAAPGQQ 818

N-terminal domain of Kruppel-like factor 3; Kruppel-like factor 3 (KLF3; also called Krueppel-like factor 3 and originally called Basic Kruppel-like Factor/BKLF), was the third member of the KLF family of zinc finger transcription factors to be discovered. KLF3 possesses a wide range of biological impacts on regulating apoptosis, differentiation, and proliferation in various tissues during the entire progression process. It has been proposed as a tumor suppressor in colorectal cancer. It appears to function predominantly as a repressor of transcription, turning genes off by recruiting the C-terminal Binding Protein co-repressors CtBP1 and CtBP2. CtBP docks onto a short motif (residues 61-65) in the N-terminus of KLF3, through the Proline-X-Aspartate-Leucine-Serine (PXDLS) motif. CtBP in turn recruits histone modifying enzymes to alter chromatin and repress gene expression. KLF3 belongs to a family of proteins, called the Specificity Protein (SP)/KLF family, characterized by a C-terminal DNA-binding domain of 81 amino acids consisting of three Kruppel-like C2H2 zinc fingers. These factors bind to a loose consensus motif, namely NNRCRCCYY (where N is any nucleotide; R is A/G, and Y is C/T), such as the recurring motifs in GC and GT boxes (5'-GGGGCGGGG-3' and 5-GGTGTGGGG-3') that are present in promoters and more distal regulatory elements of mammalian genes. Members of the KLF family can act as activators or repressors of transcription depending on cell and promoter context. KLFs regulate various cellular functions, such as proliferation, differentiation, and apoptosis, as well as the development and homeostasis of several types of tissue. In addition to the C-terminal DNA-binding domain, each KLF also has a unique N-terminal activation/repression domain that confers specificity and allows it to bind specifically to a certain partner, leading to distinct activities in vivo. This model represents the N-terminal domain of KLF3.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462557118   82 PLKMYPSMPaFSPGPGIKEESVPLSILQTPTPqplpgallPQSFPAPAPPQFSSTPVLGYPSPPGGFSTGSPPGNTQQPL 161
Cdd:cd21577      2 PVKTDMETS-FYSPSHSQLEPVDLSLSKRSSP--------PSSSSSSSSSSSSSSSPSSRASPPSPYSKSSPPSPPQQRP 72

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 2462557118  162 PGLPLASPPGVPPVSLHT--------QVQSVVPQQL 189
Cdd:cd21577     73 LSPPLSLPPPVAPPPLSPgsvpgglpVISPVMVQPV 108

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 2462557118  293 QSRGEKRTAHNAIEKRYRSSINDKIIELKDLVVGTEAKLNKSAVLRKAIDYIRFLQHSNQKLKQENLSLRTAVHK 367
Cdd:cd18921      1 PSKGEKRTAHNAIEKRYRSSINDKIIELKDLVVGTEAKLNKSAVLRKAIDYIRFLQQSNQKLKQENMALKMAVQK 75

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 2462557118  295 RGEKRTAHNAIEKRYRSSINDKIIELKDLVVGTEAKLNKSAVLRKAIDYIRFLQHSNQKLKQENLSLRTAVHKSK 369
Cdd:cd18922      3 EGERRTTHNIIEKRYRSSINDKIIELKDLVMGTDAKMHKSGVLRKAIDYIKYLQQVNHKLRQENMALKLANQKNK 77

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 2462557118  297 EKRTAHNAIEKRYRSSINDKIIELKDLV-----------------VGTEAKLNKSAVLRKAIDYIRFLQHSNQKLKQENL 359
Cdd:cd11395      2 RKRLPHNAIEKRYRSNLNTKIERLRDAIpslrspegksddgglggLAPTTKLSKATILTKAIEYIRHLEQENERLEEENE 81

                   ....*.
gi 2462557118  360 SLRTAV 365
Cdd:cd11395     82 ELRQQV 87

helix loop helix domain;

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 2462557118   303 NAIEKRYRSSINDKIIELKDLVVG--TEAKLNKSAVLRKAIDYIRFLQHSNQK 353
Cdd:smart00353    1 NARERRRRRKINEAFDELRSLLPTlpKNKKLSKAEILRLAIEYIKSLQEELQK 53

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 2462557118  297 EKRTAHNAIEKRYRSSINDKIIELKDLVVGTEAKLNKSAVLRKAIDYIRFLQHSNQKLKQE 357
Cdd:cd11398      6 QRRDNHKEVERRRRENINEGINELAALVPGNAREKNKGAILARAVEYIQELQETEAKNIEK 66

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 2462557118  299 RTAHNAIEKRYRSSINDKIIELKDLVVGTEAKLNKSAVLRKAIDYIRFLQHSNQKL 354
Cdd:cd11453      4 RSKHSATEQRRRSKINERLQALRDLIPHSDQKRDKASFLLEVIEYIQALQEKVAKL 59

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462557118  297 EKRTAHNAIEKRYRSSINDKIIELKDLVVGT---EAKLNKSAVLRKAIDYIRFLQHSNQKLKQENLSLRTAVHKSKSLK 372
Cdd:cd18928     10 QKKDNHNLIERRRRFNINDRIKELGTLIPKStdpEMRWNKGTILKASVDYIRKLQKEQQRSKEIEMRQRKLEQANRSLQ 88

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 2462557118  298 KRTAHNAIEKRYRSSINDKIIELKDLVVG-TEAKLNKSAVLRKAIDYIRFLQHSNQKLKQENLSLRTAV 365
Cdd:cd11404      2 RRLNHVRSEKKRRELIKKGYDELCALVPGlDPQKRTKADILQKAADWIQELKEENEKLEEQLDELKEAA 70

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in transcription factor EB (TFEB) and similar proteins; TFEB, also termed Class E basic helix-loop-helix protein 35 (bHLHe35), is a bHLHzip transcription factor that is required for vascularization of the mouse placenta. It specifically recognizes and binds E-box sequences (5'-CANNTG-3'). Its efficient DNA-binding requires dimerization with itself or with another MiT/TFE family member such as TFE3 or MITF.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462557118  287 KAPASAQSRgEKRTAHNAIEKRYRSSINDKIIELKDLVVGT---EAKLNKSAVLRKAIDYIRFLQHSNQKLKQ-ENLSLR 362
Cdd:cd18927      1 EARALAKER-QKKDNHNLIERRRRFNINDRIKELGTLIPKTndlDVRWNKGTILKASVDYIKRMQKDLQRSRElENHSRR 79

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in upstream stimulatory factor 2 (USF2) and similar proteins; USF2, also termed Class B basic helix-loop-helix protein 12 (bHLHb12), or major late transcription factor 2, or FOS-interacting protein (FIP), or upstream transcription factor 2, is a bHLHzip transcription factor that binds to a symmetrical DNA sequence (E-boxes) (5'-CACGTG-3') that is found in a variety of viral and cellular promoters.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462557118  295 RGEKRTA-HNAIEKRYRSSINDKIIELKDLVV-----GTEAKLNKSAVLRKAIDYIRFLQHSNQKLkQEN 358
Cdd:cd18923      4 RDERRRAqHNEVERRRRDKINNWIVQLSKIIPdcntdNSKTGASKGGILSKACDYIRELRQTNQRM-QET 72

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462557118  299 RTAHNAIEKRYRSSINDKIIELKDLVVG-TEAKLNKSAVLRKAIDYIRFLQHSNQKLKQENLSLR 362
Cdd:cd19682      1 RLRHKKRERERRSELRELFDKLKQLLGLdSDEKASKLAVLTEAIEEIQQLKREEDELQKEKARLT 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 2462557118  295 RGEKRTA-HNAIEKRYRSSINDKIIELKDLVV-----GTEAKLNKSAVLRKAIDYIRFLQHSNQK 353
Cdd:cd18924      1 RDEKRRAqHNEVERRRRDKINNWIVQLSKIIPdcsmeSTKSGQSKGGILSKACDYIQELRQSNHR 65

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in basic helix-loop-helix domain-containing protein USF3 and similar proteins; USF3, also termed upstream transcription factor 3, is a bHLHzip protein that is involved in the negative regulation of epithelial-mesenchymal transition, the process by which epithelial cells lose their polarity and adhesion properties to become mesenchymal cells with enhanced migration and invasive properties.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462557118  294 SRGEKRTAHNAIEKRYRSSINDKIIELKDLVVGTEA-KLNKSAVLRKAIDYIRFLQHSNQKL 354
Cdd:cd18910      1 RREKKRESHNEVERRRKDKINAGINKIGELLPDRDAkKQSKNMILEQAYKYIVELKKKNDKL 62

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 2462557118  298 KRTAHNAIEKRYRSSINDKIIELKDLVVGTEAKLN--KSAVLRKAIDYIRFLQ---HSNQK----LKQENLSLR 362
Cdd:cd11400      1 KRRLHNVLERQRRNDLKNSFEKLRDLVPELADNEKasKVVILKKATEYIKQLQqeeKKLEKekdkLKARNEQLR 74

EBNA-3B; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462557118   63 LSGPQAAPSPLSPPQPAPTPLKmypsMPAFSPGPGIKEESVPlsiLQTPTPQPLPGALL-PQSFPAPAPPQfSSTPVLGY 141
Cdd:PHA03378   704 MRPPAAPPGRAQRPAAATGRAR----PPAAAPGRARPPAAAP---GRARPPAAAPGRARpPAAAPGRARPP-AAAPGAPT 775

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 2462557118  142 PSPPggfsTGSPPGNTQQPLPGLPLASPPGVPPVSLHTQVQSVVPQQ 188
Cdd:PHA03378   776 PQPP----PQAPPAPQQRPRGAPTPQPPPQAGPTSMQLMPRAAPGQQ 818

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split (HES)-related repressor protein (HERP)-like family; The HERP-like family includes bHLH-O transcriptional regulators that are related to the Drosophila hairy and Enhancer-of-split proteins. They contain a basic helix-loop-helix (bHLH) domain with an invariant glycine residue in its basic region, an orange domain in the central region and YXXW sequence motif at its C-terminal region. HERP proteins (HEY1, HEY2 and HEYL) act as downstream effectors of Notch signaling. They are involved in cardiovascular development and have roles in somitogenesis, myogenesis and gliogenesis. Hairy and enhancer of split-related protein HELT is a transcriptional repressor expressed in the developing central nervous system. It binds preferentially to the canonical E box sequence 5'-CACGCG-3' and regulates neuronal differentiation and/or identity. Differentially expressed in chondrocytes proteins, DEC1 and DEC2, are widely expressed in both embryonic and adult tissues and have been implicated in apoptosis, cell proliferation, and circadian rhythms, as well as malignancy in various cancers. Drosophila melanogaster protein clockwork orange (Cwo) is also included in this family. It is involved in the regulation of Drosophila circadian rhythms. It functions as both an activator and a repressor of clock gene expression.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2462557118  302 HNAIEKRYRSSINDKIIELKDLV-----VGTEAKLNKSAVLRKAIDYIRFLQ 348
Cdd:cd11389      1 HKVIEKRRRDRINESLAELRRLVpearkSKGSGKLEKAEILEMTLQHLKALQ 52

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462557118  297 EKRTAHNAIEKRYRSSINDKIIELKDLVVGT---EAKLNKSAVLRKAIDYIRFLQHSNQKLKQ 356
Cdd:cd18925      4 QKKDNHNLIERRRRYNINYRIKELGTLIPKSndpDMRWNKGTILKASVEYIKWLQKEQQRARE 66

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
                   ....*....|....*....|....*....|....*....|....*...
gi 2462557118  298 KRTAHNAIEKRYRSSINDKIIELKDLVVGTEAKLNKSAVLRKAIDYIR 345
Cdd:cd19734      7 KRVSRNKSEKKRRDQFNVLIKELGSMLPGNARKMDKSTVLQKSIDFLR 54

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2462557118  299 RTAHNAIEKRYRSSINDKIIELKDLVV---GTEAklNKSAVLRKAIDYIRFLQHSNQKLKQENLSLR 362
Cdd:cd19690      1 RVSHKLAERKRRKEMKELFEDLRDALPqerGTKA--SKWEILTKAISYIQQLKRHIRELRSEVNDLR 65

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana ILI1-BINDING BHLH 1 (IBH1) and similar proteins; The family includes several bHLH transcription factors from Arabidopsis thaliana, such as IBH1, UPBEAT1, PAR1 and PAR2. IBH1, also termed bHLH zeta, or AtbHLH158, is an atypical and probable non DNA-binding bHLH transcription factor that acts as transcriptional repressor that negatively regulates cell and organ elongation in response to gibberellin (GA) and brassinosteroid (BR) signaling. IBH1 forms heterodimer with BHLH49, thus inhibiting DNA binding of BHLH49, which is a transcriptional activator that regulates the expression of a subset of genes involved in cell expansion by binding to the G-box motif. UPBEAT1, also termed AtbHLH151, or EN 146, is a bHLH transcription factor that modulates the balance between cellular proliferation and differentiation in root growth. It does not act through cytokinin and auxin signaling, but by repressing peroxidase expression in the elongation zone. PAR1 (also termed AtbHLH165, or protein helix-loop-helix 1, or protein phytochrome rapidly regulated 1) and PAR2 (also termed AtbHLH166, or protein helix-loop-helix 2, or protein phytochrome rapidly regulated 2) are two atypical bHLH transcription factors that act as negative regulators of a variety of shade avoidance syndrome (SAS) responses, including seedling elongation and photosynthetic pigment accumulation. They act as direct transcriptional repressor of two auxin-responsive genes, SAUR15 and SAUR68. They may function in integrating shade and hormone transcriptional networks in response to light and auxin changes.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 2462557118  306 EKRYRSSINDKIIELKDLVVGTEAKLNKSAVLRKAIDYIRFLQH 349
Cdd:cd11444      5 RRRGEEAIERRLRALRRLVPGGRESMEVEELLQETADYIMFLEM 48

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2462557118  306 EKRYRSSINDKIIELKDLV-VGTEAKLNKSAVLRKAIDYIRFLQHSNQKLKQENLSLRTAVHKSKSLK 372
Cdd:cd11446      5 EKLRRDKLNERFMELSNVLePGRPPKTDKATILGDAIRMLKQLRGEVQKLKEENSSLQEESKELKAEK 72

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.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2462557118  302 HNAIEKRYRSSINDKIIELKDLVVGTEAKLNKSAVLRKAIDYIRFLQHSNQKLKQE 357
Cdd:cd19698      1 HNLLEKKRRERIKDKIEILKGLTPNCTPKSDIASILSCVIDYIKSLLLQVEKLSMG 56

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 2462557118  297 EKRTAHNAIEKRYRSSINDKIIELKDLVVGTEA----KLNKSAVLRKAIDYIRFLQHSNQKLKQEN 358
Cdd:cd11388      2 VKKWKHVEAEKKRRNQIKKGFEDLINLINYPRNnnekRISKSELLNKAVDDIRGLLKANEQLQEEI 67

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 2462557118  299 RTAHNAIEKRYRSSINDKIIELKDLVVGTEAKLNKSAVLRKAIDyirFLQHSNQ 352
Cdd:cd11441      1 RKSRNLSEKKRRDQFNVLINELASMLPGRGRKMDKSTVLKKTIA---FLRKHKE 51

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 2462557118  298 KRTAHNAIEKRYRSSINDKIIELKDLVVGTEA---KLNKSAVLRKAIDYIRFL 347
Cdd:cd11437      1 SRSNHSEIEKRRRDKMNAYIQELSALVPACNAmsrKLDKLTVLRMAVQHLKSL 53

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 2462557118  298 KRTAHNAIEKRYRSSINDKIIELKDLVVGTEAKLNKSAVLRKAidyIRFLQHSNQKLKQ 356
Cdd:cd19735     10 KRKSRNLSEKKRRDQFNVLINELCSMVSTSNRKMDKSTVLKST---IAFLKNHNEVTMQ 65

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain family; bHLH-PAS domain has been found in a large group of bHLH transcription regulators that are involved in gene expression responding to environmental change and controlling aspects of neural development, including proteins from aryl hydrocarbon receptor nuclear translocator (ARNT) family, hypoxia-inducible factor (HIF) family, aryl hydrocarbon receptor (AhR) family, neuronal PAS domain-containing protein (NPAS) family, Circadian locomotor output cycles protein kaput (CLOCK)-like family, and single-minded (SIM) family. bHLH-PAS transcriptional regulatory factors have a bHLH DNA-binding domain followed by two PAS domains and a C-terminal activation or repression domain. bHLH-PAS family members can be divided into class I and class II based on their dimerization partner. bHLH-PAS class I factors include AhR, HIF and SIM. The best characterized bHLH-PAS Class II protein is the ubiquitous ARNT. Some members of bHLH-PAS family act as transcriptional coactivators (such as NCoA) that lack the ability to dimerize and bind DNA.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2462557118  302 HNAIEKRYRSSINDKIIELKDLVVGTEA---KLNKSAVLRKAIDYIRFLQ 348
Cdd:cd11391      4 SREAAKKRRDKENAEISELASLLPLPPAvgsKLDKLSVLRLAVAYLRLKK 53

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 2462557118  297 EKRtahNAIEKRYRSSINDKIIELKDLV--VGTEAKLNKSAVLRKAIDYIRFLQ 348
Cdd:cd11418      3 ARR---NERERRRVQAVNDAFDRLRQHVpyLKRRKKLSKVKTLRRAIEYIRHLQ 53

Sine oculis-binding protein; SOBP is associated with syndromic and nonsyndromic intellectual disability. It carries a zinc-finger of the zf-C2H2 type at the N-terminus, and a highly characteriztic C-terminal PhPhPhPhPhPh motif. The deduced 873-amino acid protein contains an N-terminal nuclear localization signal (NLS), followed by 2 FCS-type zinc finger motifs, a proline-rich region (PR1), a putative RNA-binding motif region, and a C-terminal NLS embedded in a second proline-rich motif. SOBP is expressed in various human tissues, including developing mouse brain at embryonic day 14. In postnatal and adult mouse brain SOBP is expressed in all neurons, with intense staining in the limbic system. Highest expression is in layer V cortical neurons, hippocampus, pyriform cortex, dorsomedial nucleus of thalamus, amygdala, and hypothalamus. Postnatal expression of SOBP in the limbic system corresponds to a time of active synaptogenesis. the family is also referred to as Jackson circler, JXC1. In seven affected siblings from a consanguineous Israeli Arab family with mental retardation, anterior maxillary protrusion, and strabismus mutations were found in this protein.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462557118   70 PSPLSPPQPAPTPLKMYPSMpaFSPGPgikeESVPLSILQTPTPQPLPgaLLPQSFPAPAPPQF---SSTPVLGYP---- 142
Cdd:pfam15279  175 GKPQQHPPPSPLPAFMEPSS--MPPPF----LRPPPSIPQPNSPLSNP--MLPGIGPPPKPPRNlgpPSNPMHRPPfsph 246

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 2462557118  143 -SPPGGFSTGSPPGNTQQPLPGLPLASPPGVPPVS 176
Cdd:pfam15279  247 hPPPPPTPPGPPPGLPPPPPRGFTPPFGPPFPPVN 281

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 2462557118  306 EKRYRSSINDKIIELKDlVVGTEAKLNKSAVLRKAIDYIRFLQHSNQKLKQE 357
Cdd:cd11443      7 ERRRRKKLNDRLYMLRS-VVPKITKMDRASILGDAIDYVKELLQEINELQDE 57

putative scaffolding protein

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462557118   63 LSGPQAAPSPLSPPQPAPTPLkMYPSMPAFSPGPGIKEEsvplsiLQTPTPQPLP---GALLPQSFP-APAPPQFSSTPV 138
Cdd:PHA01929    12 LAGLVANVPPAAAPTPQPNPV-IQPQAPVQPGQPGAPQQ------LAIPTQQPQPvptSAMTPHVVQqAPAQPAPAAPPA 84

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 2462557118  139 LGYPSP----PGGFSTGSPPGNTQQPLPGLPLASPPGVPPVS 176
Cdd:PHA01929    85 AGAALPealeVPPPPAFTPNGEIVGTLAGNLEGDPQLAPSVS 126

Herpes virus major outer envelope glycoprotein (BLLF1); This family consists of the BLLF1 viral late glycoprotein, also termed gp350/220. It is the most abundantly expressed glycoprotein in the viral envelope of the Herpesviruses and is the major antigen responsible for stimulating the production of neutralising antibodies in vivo.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462557118   25 PPYAGSGAGGTdPASPDTSSPGSLSPPPATLSSSLEAFLSGPQAAPSPLSPPQPAPTPLKMYPSMPAFSPGPGIkeeSVP 104
Cdd:pfam05109  476 PTPAGTTSGAS-PVTPSPSPRDNGTESKAPDMTSPTSAVTTPTPNATSPTPAVTTPTPNATSPTLGKTSPTSAV---TTP 551

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462557118  105 LSILQTPTP---QPLPGALLP---QSFPAPA---PPQFSSTPVLGYPSPPGGFSTGSPPGNTQQPLpglpLASPP 170
Cdd:pfam05109  552 TPNATSPTPavtTPTPNATIPtlgKTSPTSAvttPTPNATSPTVGETSPQANTTNHTLGGTSSTPV----VTSPP 622