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 1924574501  319 QSRGEKRTAHNAIEKRYRSSINDKIIELKDLVVGTEAKLNKSAVLRKAIDYIRFLQHSNQKLKQENLSLRTAVHK 393
Cdd:cd18921      1 PSKGEKRTAHNAIEKRYRSSINDKIIELKDLVVGTEAKLNKSAVLRKAIDYIRFLQQSNQKLKQENMALKMAVQK 75

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 1924574501   49 PPYAGSGAGGTdPASPDTSSPGSLSPPPATLSSSLEAFLSGPQAAPSPLSPPQPAPTPLKMYPSMPAFSPGPGIkeeSVP 128
Cdd:pfam05109  476 PTPAGTTSGAS-PVTPSPSPRDNGTESKAPDMTSPTSAVTTPTPNATSPTPAVTTPTPNATSPTLGKTSPTSAV---TTP 551

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924574501  129 LSILQTPTP---QPLPGALLP---QSFPAPA---PPQFSSTPVLGYPSPPGGFSTGSPPGNTQQPLpglpLASPPGVPPV 199
Cdd:pfam05109  552 TPNATSPTPavtTPTPNATIPtlgKTSPTSAvttPTPNATSPTVGETSPQANTTNHTLGGTSSTPV----VTSPPKNATS 627

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924574501  200 SLHT---QVQSVVPQQLLTVTAAPTAAPVTTTVTSQIQQVPVLLQPHFIKADSLL-LTAMKTDGATVKAAGLSPLVSGTT 275
Cdd:pfam05109  628 AVTTgqhNITSSSTSSMSLRPSSISETLSPSTSDNSTSHMPLLTSAHPTGGENITqVTPASTSTHHVSTSSPAPRPGTTS 707

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*
gi 1924574501  276 VQTGPlptlvsGGTILATVPLVVDAEKLPINRLAAGSKAPASAQS 320
Cdd:pfam05109  708 QASGP------GNSSTSTKPGEVNVTKGTPPKNATSPQAPSGQKT 746

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 1924574501  319 QSRGEKRTAHNAIEKRYRSSINDKIIELKDLVVGTEAKLNKSAVLRKAIDYIRFLQHSNQKLKQENLSLRTAVHK 393
Cdd:cd18921      1 PSKGEKRTAHNAIEKRYRSSINDKIIELKDLVVGTEAKLNKSAVLRKAIDYIRFLQQSNQKLKQENMALKMAVQK 75

helix loop helix domain;

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 1924574501   329 NAIEKRYRSSINDKIIELKDLVVG--TEAKLNKSAVLRKAIDYIRFLQHSNQK 379
Cdd:smart00353    1 NARERRRRRKINEAFDELRSLLPTlpKNKKLSKAEILRLAIEYIKSLQEELQK 53

EBNA-3B; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924574501   87 LSGPQAAPSPLSPPQPAPTPLKmypsMPAFSPGPGIKEESVPlsiLQTPTPQPLPGALL-PQSFPAPAPPQfSSTPVLGY 165
Cdd:PHA03378   704 MRPPAAPPGRAQRPAAATGRAR----PPAAAPGRARPPAAAP---GRARPPAAAPGRARpPAAAPGRARPP-AAAPGAPT 775

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1924574501  166 PSPPggfsTGSPPGNTQQPLPGLPLASPPGVPPVSLHTQVQSVVPQQ 212
Cdd:PHA03378   776 PQPP----PQAPPAPQQRPRGAPTPQPPPQAGPTSMQLMPRAAPGQQ 818

Amelogenins, cell adhesion proteins, play a role in the biomineralisation of teeth; They seem to regulate formation of crystallites during the secretory stage of tooth enamel development and are thought to play a major role in the structural organisation and mineralisation of developing enamel. The extracellular matrix of the developing enamel comprises two major classes of protein: the hydrophobic amelogenins and the acidic enamelins. Circular dichroism studies of porcine amelogenin have shown that the protein consists of 3 discrete folding units: the N-terminal region appears to contain beta-strand structures, while the C-terminal region displays characteristics of a random coil conformation. Subsequent studies on the bovine protein have indicated the amelogenin structure to contain a repetitive beta-turn segment and a "beta-spiral" between Gln112 and Leu138, which sequester a (Pro, Leu, Gln) rich region. The beta-spiral offers a probable site for interactions with Ca2+ ions. Muatations in the human amelogenin gene (AMGX) cause X-linked hypoplastic amelogenesis imperfecta, a disease characterised by defective enamel. A 9bp deletion in exon 2 of AMGX results in the loss of codons for Ile5, Leu6, Phe7 and Ala8, and replacement by a new threonine codon, disrupting the 16-residue (Met1-Ala16) amelogenin signal peptide.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924574501    95 SPLSPPQPAPTPLKMYPSMPAFSPGPGiKEESVPLSILQTPTPQPLPGALLPQSFPAPAPPQFSSTPVLGYPSPPGGFST 174
Cdd:smart00818   43 SQQHPPTHTLQPHHHIPVLPAQQPVVP-QQPLMPVPGQHSMTPTQHHQPNLPQPAQQPFQPQPLQPPQPQQPMQPQPPVH 121

                            90       100
                    ....*....|....*....|....*
gi 1924574501   175 GSPPGNTQQPLPGLPLASPPgvPPV 199
Cdd:smart00818  122 PIPPLPPQPPLPPMFPMQPL--PPL 144

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 1924574501  319 QSRGEKRTAHNAIEKRYRSSINDKIIELKDLVVGTEAKLNKSAVLRKAIDYIRFLQHSNQKLKQENLSLRTAVHK 393
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 1924574501  321 RGEKRTAHNAIEKRYRSSINDKIIELKDLVVGTEAKLNKSAVLRKAIDYIRFLQHSNQKLKQENLSLRTAVHKSK 395
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 1924574501  323 EKRTAHNAIEKRYRSSINDKIIELKDLV-----------------VGTEAKLNKSAVLRKAIDYIRFLQHSNQKLKQENL 385
Cdd:cd11395      2 RKRLPHNAIEKRYRSNLNTKIERLRDAIpslrspegksddgglggLAPTTKLSKATILTKAIEYIRHLEQENERLEEENE 81

                   ....*.
gi 1924574501  386 SLRTAV 391
Cdd:cd11395     82 ELRQQV 87

helix loop helix domain;

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 1924574501   329 NAIEKRYRSSINDKIIELKDLVVG--TEAKLNKSAVLRKAIDYIRFLQHSNQK 379
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 1924574501  323 EKRTAHNAIEKRYRSSINDKIIELKDLVVGTEAKLNKSAVLRKAIDYIRFLQHSNQKLKQE 383
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 1924574501  325 RTAHNAIEKRYRSSINDKIIELKDLVVGTEAKLNKSAVLRKAIDYIRFLQHSNQKL 380
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 1924574501  323 EKRTAHNAIEKRYRSSINDKIIELKDLVVGT---EAKLNKSAVLRKAIDYIRFLQHSNQKLKQENLSLRTAVHKSKSLK 398
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 1924574501  324 KRTAHNAIEKRYRSSINDKIIELKDLVVG-TEAKLNKSAVLRKAIDYIRFLQHSNQKLKQENLSLRTAV 391
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 1924574501  313 KAPASAQSRgEKRTAHNAIEKRYRSSINDKIIELKDLVVGT---EAKLNKSAVLRKAIDYIRFLQHSNQKLKQ-ENLSLR 388
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 1924574501  321 RGEKRTA-HNAIEKRYRSSINDKIIELKDLVV-----GTEAKLNKSAVLRKAIDYIRFLQHSNQKLkQEN 384
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 1924574501  325 RTAHNAIEKRYRSSINDKIIELKDLVVG-TEAKLNKSAVLRKAIDYIRFLQHSNQKLKQENLSLR 388
Cdd:cd19682      1 RLRHKKRERERRSELRELFDKLKQLLGLdSDEKASKLAVLTEAIEEIQQLKREEDELQKEKARLT 65

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in MLX-interacting protein (MLXIP), MLX-interacting protein-like (MLXIPL) and similar proteins; The family includes MLXIP and MLXIPL. MLXIP, also termed Class E basic helix-loop-helix protein 36 (bHLHe36), or transcriptional activator MondoA, is a bHLHZip transcriptional activator that binds DNA as a heterodimer with Mlx. It binds to the canonical E box sequence 5'-CACGTG-3' and plays a role in transcriptional activation of glycolytic target genes. MLXIP is most highly expressed in skeletal muscle and functions as an indirect glucose sensor, by sensing glucose 6-phosphate and shuttling between the nucleus and the cytoplasm. MLXIPL, also termed carbohydrate-responsive element-binding protein (ChREBP), or Class D basic helix-loop-helix protein 14 (bHLHd14), or MLX interactor, or WS basic-helix-loop-helix leucine zipper protein (WS-bHLH), or Williams-Beuren syndrome chromosomal region 14 protein (WBSCR14), is a bHLHZip transcriptional factor integral to the regulation of glycolysis and lipogenesis in the liver. It forms heterodimers with the bHLHZip protein Mlx to bind the DNA sequence 5'-CACGTG-3'.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1924574501  324 KRTAHNAIEKRYRSSINDKIIELKDLV----VGTEAKLNKSAVLRKAIDYIRFLQHSNQKLKQENLSLR 388
Cdd:cd11405      3 RRLSHISAEQKRRFNIKSGFDTLQSLIpslgQNPNQKVSKAAMLQKAAEYIKSLKRERQQMQEEAEQLR 71

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 1924574501  320 SRGEKRTAHNAIEKRYRSSINDKIIELKDLVVGTEA-KLNKSAVLRKAIDYIRFLQHSNQKL 380
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 1924574501  324 KRTAHNAIEKRYRSSINDKIIELKDLVVGTEAKLN--KSAVLRKAIDYIRFLQ---HSNQK----LKQENLSLR 388
Cdd:cd11400      1 KRRLHNVLERQRRNDLKNSFEKLRDLVPELADNEKasKVVILKKATEYIKQLQqeeKKLEKekdkLKARNEQLR 74

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in transcription factor AP-4 (TFAP4) and similar proteins; TFAP4, also termed activating enhancer-binding protein 4, or Class C basic helix-loop-helix protein 41 (bHLHc41), is a bHLHzip transcription factor that activates both viral and cellular genes involved in the regulation of cellular proliferation, stemness, and epithelial-mesenchymal transition by binding to the symmetrical DNA sequence 5'-CAGCTG-3'.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1924574501  324 KRTAHNAIEKRYRSSINDKIIELKDLV-VGTEAKLNKSAVLRKAIDYIRFLQHSNQKL 380
Cdd:cd11419      4 RREIANSNERRRMQSINAGFQSLRTLLpHCDGEKLSKAAILQQTAEYIFSLEQEKTRL 61

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 1924574501  328 HNAIEKRYRSSINDKIIELKDLV-----VGTEAKLNKSAVLRKAIDYIRFLQ 374
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 1924574501  323 EKRTAHNAIEKRYRSSINDKIIELKDLVVGT---EAKLNKSAVLRKAIDYIRFLQHSNQKLKQ 382
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 1924574501  324 KRTAHNAIEKRYRSSINDKIIELKDLVVGTEAKLNKSAVLRKAIDYIR 371
Cdd:cd19734      7 KRVSRNKSEKKRRDQFNVLIKELGSMLPGNARKMDKSTVLQKSIDFLR 54

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924574501   50 PYAGSGAGGTDPASPDTSSPGSLSPPPATLSSSLEAFLSGPQAAPSPLSPPQPAPTPLKMYPSMPAFSPGPGIKEESVPL 129
Cdd:pfam03154  199 PTPSAPSVPPQGSPATSQPPNQTQSTAAPHTLIQQTPTLHPQRLPSPHPPLQPMTQPPPPSQVSPQPLPQPSLHGQMPPM 278

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924574501  130 SILQTPTPQPLPGALLPQSFPAPAPPQFSSTPVLGYPSPPGGFSTGS--PPGNTQ---------QPLPGLPLASPPGVPP 198
Cdd:pfam03154  279 PHSLQTGPSHMQHPVPPQPFPLTPQSSQSQVPPGPSPAAPGQSQQRIhtPPSQSQlqsqqppreQPLPPAPLSMPHIKPP 358

EBNA-3B; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924574501   44 PGLFDPPYAGSGAGGTDPASPDTSSPGSLSPPPATLSSSLEAFLSGPQAAPSPLSPPQPAPTPLKmypsMPAFSPGPGIK 123
Cdd:PHA03378   691 PGTMQPPPRAPTPMRPPAAPPGRAQRPAAATGRARPPAAAPGRARPPAAAPGRARPPAAAPGRAR----PPAAAPGRARP 766

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 1924574501  124 EESVPLSILQTPTPQPLPGALL-PQSFPAPA-PPQFSSTPV-LGYPSPPG 170
Cdd:PHA03378   767 PAAAPGAPTPQPPPQAPPAPQQrPRGAPTPQpPPQAGPTSMqLMPRAAPG 816

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 1924574501  332 EKRYRSSINDKIIELKDLV-VGTEAKLNKSAVLRKAIDYIRFLQHSNQKLKQENLSLRTAVHKSKSLK 398
Cdd:cd11446      5 EKLRRDKLNERFMELSNVLePGRPPKTDKATILGDAIRMLKQLRGEVQKLKEENSSLQEESKELKAEK 72

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924574501   90 PQAAPSPLSPPQPAPTPLKMYPSMPAfsPGPGIKEESVPLSILQTPTPQPLPGALLPQSFPAPAPPQFSSTPVLGYPSPP 169
Cdd:pfam03154  200 TPSAPSVPPQGSPATSQPPNQTQSTA--APHTLIQQTPTLHPQRLPSPHPPLQPMTQPPPPSQVSPQPLPQPSLHGQMPP 277

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1924574501  170 GGFSTGSPPGNTQQPLPGLPLasppGVPPVSLHTQVqSVVPQQLLTVTAAPTAAPVTTTVTSQIQQVP 237
Cdd:pfam03154  278 MPHSLQTGPSHMQHPVPPQPF----PLTPQSSQSQV-PPGPSPAAPGQSQQRIHTPPSQSQLQSQQPP 340

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1924574501  323 EKRTAHNAIEKRYRSSINDKIIELKDLV--VGTEAKLNKSAVLRKAIDYIRFLQHSNQKLKQENLSLR 388
Cdd:cd11456      4 ERRRNHNILERQRRNDLRSSFLTLRDHVpeLVKNEKAAKVVILKKATEYVHSLQAEEQKLLLEKEKLQ 71

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 1924574501  324 KRTAHNAIEKRYRSSINDKIIELKDLV------VGTeAKLNKSAVLRKAIDYIRFLQ 374
Cdd:cd11407      1 RKKRRGIIEKRRRDRINNSLAELRRLVptafekQGS-AKLEKAEILQMTVDHLKMLH 56

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 1924574501  325 RTAHNAIEKRYRSSINDKIIELKDLVVGTEAKLNKSAVLRKAIDyirFLQHSNQ 378
Cdd:cd11441      1 RKSRNLSEKKRRDQFNVLINELASMLPGRGRKMDKSTVLKKTIA---FLRKHKE 51

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 1924574501  324 KRTAHNAIEKRYRSSINDKIIELKDLVVGTEAKLNKSAVLRKAIDyirFLQHSNQKLKQENLS 386
Cdd:cd19737     10 KRASRNKSEKKRRDQFNVLIKELSSMLPGNTRKMDKTTVLEKVIG---FLQKHNEVSAQTEIC 69

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 1924574501  324 KRTAHNAIEKRYRSSINDKIIELKDLVVGTEAKLNKSAVLRKAidyIRFLQHSNQKLKQ 382
Cdd:cd19735     10 KRKSRNLSEKKRRDQFNVLINELCSMVSTSNRKMDKSTVLKST---IAFLKNHNEVTMQ 65

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 1924574501   49 PPYAGSGAGGTdPASPDTSSPGSLSPPPATLSSSLEAFLSGPQAAPSPLSPPQPAPTPLKMYPSMPAFSPGPGIkeeSVP 128
Cdd:pfam05109  476 PTPAGTTSGAS-PVTPSPSPRDNGTESKAPDMTSPTSAVTTPTPNATSPTPAVTTPTPNATSPTLGKTSPTSAV---TTP 551

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924574501  129 LSILQTPTP---QPLPGALLP---QSFPAPA---PPQFSSTPVLGYPSPPGGFSTGSPPGNTQQPLpglpLASPPGVPPV 199
Cdd:pfam05109  552 TPNATSPTPavtTPTPNATIPtlgKTSPTSAvttPTPNATSPTVGETSPQANTTNHTLGGTSSTPV----VTSPPKNATS 627

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924574501  200 SLHT---QVQSVVPQQLLTVTAAPTAAPVTTTVTSQIQQVPVLLQPHFIKADSLL-LTAMKTDGATVKAAGLSPLVSGTT 275
Cdd:pfam05109  628 AVTTgqhNITSSSTSSMSLRPSSISETLSPSTSDNSTSHMPLLTSAHPTGGENITqVTPASTSTHHVSTSSPAPRPGTTS 707

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*
gi 1924574501  276 VQTGPlptlvsGGTILATVPLVVDAEKLPINRLAAGSKAPASAQS 320
Cdd:pfam05109  708 QASGP------GNSSTSTKPGEVNVTKGTPPKNATSPQAPSGQKT 746

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 1924574501  323 EKRtahNAIEKRYRSSINDKIIELKDLV--VGTEAKLNKSAVLRKAIDYIRFLQ 374
Cdd:cd11418      3 ARR---NERERRRVQAVNDAFDRLRQHVpyLKRRKKLSKVKTLRRAIEYIRHLQ 53

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