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 1907080803   86 PSVSPFSPGPGIKEEPVPLTILQPAAPQPSPGTLLPPSFPAPPVQ----LSPAPVLGYSSLPSGFSGTLPGNTQQPPSSL 161
Cdd:pfam03154  182 SPPSPPPPGTTQAATAGPTPSAPSVPPQGSPATSQPPNQTQSTAAphtlIQQTPTLHPQRLPSPHPPLQPMTQPPPPSQV 261

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1907080803  162 PLAPapgvLPTPALHTQVQSLasqqPLPASAAP 194
Cdd:pfam03154  262 SPQP----LPQPSLHGQMPPM----PHSLQTGP 286

Helix-loop-helix DNA-binding domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1907080803  295 KRTAHNAIEKRYRSSINDKIVELKDLV--VGTEAKLNKSAVLRKAIDYIRFLQ 345
Cdd:pfam00010    1 RREAHNERERRRRDRINDAFDELRELLptLPPDKKLSKAEILRLAIEYIKHLQ 53

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 1907080803   86 PSVSPFSPGPGIKEEPVPLTILQPAAPQPSPGTLLPPSFPAPPVQ----LSPAPVLGYSSLPSGFSGTLPGNTQQPPSSL 161
Cdd:pfam03154  182 SPPSPPPPGTTQAATAGPTPSAPSVPPQGSPATSQPPNQTQSTAAphtlIQQTPTLHPQRLPSPHPPLQPMTQPPPPSQV 261

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1907080803  162 PLAPapgvLPTPALHTQVQSLasqqPLPASAAP 194
Cdd:pfam03154  262 SPQP----LPQPSLHGQMPPM----PHSLQTGP 286

DNA polymerase III subunit gamma/tau;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907080803   18 SDFPGLFDAPYAGGETGDTGPSSPGANSPESFSSASLASSLEAFLGGPKVTPAPLSPPPSAPAALKMYPSVSPFSPGPGI 97
Cdd:PRK12323   400 AAPPAAPAAAPAAAAAARAVAAAPARRSPAPEALAAARQASARGPGGAPAPAPAPAAAPAAAARPAAAGPRPVAAAAAAA 479

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907080803   98 KEEPVPLTILQPAAPQPSPGTLLPPSFPAP-PVQLSPAPVLGYSSlpsgfSGTLPGNTQQPPSSLPLAPAPGVLPTPALH 176
Cdd:PRK12323   480 PARAAPAAAPAPADDDPPPWEELPPEFASPaPAQPDAAPAGWVAE-----SIPDPATADPDDAFETLAPAPAAAPAPRAA 554

                          170       180
                   ....*....|....*....|...
gi 1907080803  177 TQVQSLASQQPlPASAAPRTNTV 199
Cdd:PRK12323   555 AATEPVVAPRP-PRASASGLPDM 576

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907080803  290 QSRGEKRTAHNAIEKRYRSSINDKIVELKDLVVGTEAKLNKSAVLRKAIDYIRFLQHSNQKLKQENLTLRSA 361
Cdd:cd11394      1 PPKVEKRSAHNAIEKRYRSSINDRIIELKDLVVGPDAKMNKSAVLRKAIDYIRYLQKVNQKLKQENMALKKA 72

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Saccharomyces cerevisiae transcription factor HMS1 and similar proteins; HMS1, also termed high-copy MEP suppressor protein 1, is a putative bHLHzip transcription factor involved in exit from mitosis and pseudohyphal differentiation.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907080803  294 EKRTAHNAIEKRYRSSINDKIVELKDLV----------------------VGTEAKLNKSAVLRKAIDYIRFLQHSNQKL 351
Cdd:cd11399      2 SKKTAHNMIEKRYRSNINDRIAELRDSVpalreayksargededeedlggLTPATKLNKATILSKATEYIRHLEKKNKRL 81

                   ....*...
gi 1907080803  352 KQENLTLR 359
Cdd:cd11399     82 SRENASLR 89

Helix-loop-helix DNA-binding domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1907080803  295 KRTAHNAIEKRYRSSINDKIVELKDLV--VGTEAKLNKSAVLRKAIDYIRFLQ 345
Cdd:pfam00010    1 RREAHNERERRRRDRINDAFDELRELLptLPPDKKLSKAEILRLAIEYIKHLQ 53

helix loop helix domain;

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 1907080803   300 NAIEKRYRSSINDKIVELKDLVVG--TEAKLNKSAVLRKAIDYIRFLQHSNQK 350
Cdd:smart00353    1 NARERRRRRKINEAFDELRSLLPTlpKNKKLSKAEILRLAIEYIKSLQEELQK 53

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907080803  295 KRTAHNAIEKRYRSSINDKIVELKDLV---VGTEAKLNKSAVLRKAIDYIRFLQHSNQKLKQ 353
Cdd:cd11397      5 KKDNHNMIERRRRFNINDRIKELGTLLpksNDPDMRWNKGTILKASVDYIRKLQKEQERLRQ 66

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 1907080803  303 EKRYRSSINDKIVELKDLV--VGTEAKLNKSAVLRKAIDYIRFLQ 345
Cdd:cd00083      1 ERRRRDKINDAFEELKRLLpeLPDSKKLSKASILQKAVEYIRELQ 45

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 1907080803  294 EKRTAHNAIEKRYRSSINDKIVELKDLVVGT---EAKLNKSAVLRKAIDYIRFLQHSNQKLKQENLTLRSAHKS 364
Cdd:cd18928     10 QKKDNHNLIERRRRFNINDRIKELGTLIPKStdpEMRWNKGTILKASVDYIRKLQKEQQRSKEIEMRQRKLEQA 83

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 1907080803  283 SKALGSAQSRgEKRTAHNAIEKRYRSSINDKIVELKDLVVGT---EAKLNKSAVLRKAIDYIRFLQHSNQKLKQ-ENLTL 358
Cdd:cd18926      2 SEARALAKER-QKKDNHNLIERRRRFNINDRIKELGTLIPKSndpDMRWNKGTILKASVDYIRKLQREQQRAKElENRQK 80

                   ....*....
gi 1907080803  359 RSAHKSKSL 367
Cdd:cd18926     81 KLEHANRHL 89

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 1907080803  292 RGEKRTA-HNAIEKRYRSSINDKIVELKDLVV-----GTEAKLNKSAVLRKAIDYIRFLQHSNQKLkQEN 355
Cdd:cd18923      4 RDERRRAqHNEVERRRRDKINNWIVQLSKIIPdcntdNSKTGASKGGILSKACDYIRELRQTNQRM-QET 72

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 1907080803  299 HNAIEKRYRSSINDKIVELKDLVVGtEAKLNKSAVLRKAIDYIRFLQHSNQKL 351
Cdd:cd11393      1 HSIAERKRREKINERIRALRSLVPN-GGKTDKASILDEAIEYIKFLQEQVKVL 52

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907080803  296 RTAHNAIEKRYRSSINDKIVELKDLVVG-TEAKLNKSAVLRKAIDYIRFLQHSNQKLKQENLTLR 359
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        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907080803  295 KRTAHNAIEKRYRSSINDKIVELKDLV----VGTEAKLNKSAVLRKAIDYIRFLQHSNQKLKQENLTLRS 360
Cdd:cd11405      3 RRLSHISAEQKRRFNIKSGFDTLQSLIpslgQNPNQKVSKAAMLQKAAEYIKSLKRERQQMQEEAEQLRQ 72

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
                   ....*....|....*....|....*....|....*....|....*....
gi 1907080803  302 IEKRYRSSINDKIVELKDLVV-----GTEAKLNKSAVLRKAIDYIRFLQ 345
Cdd:cd19685      1 SEKRRRQRINDKLNQLKELLPpnlskQSRSKLSKAEILEMAITELRRLQ 49

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 1907080803  299 HNAIEKRYRSSINDKIVELKDLV-----VGTEAKLNKSAVLRKAIDYIRFLQ 345
Cdd:cd11389      1 HKVIEKRRRDRINESLAELRRLVpearkSKGSGKLEKAEILEMTLQHLKALQ 52

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 1907080803  294 EKRTAHNAIEKRYRSSINDKIVELKDLVVGTEAKLNKSAVLRKAIDYIRFLQ 345
Cdd:cd19683      1 KSRERHNAKERQRRERIKIACDQLRKLVPGCSRKTDKATVFEFTVAYIKFLR 52

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 1907080803  295 KRTAHNAIEKRYRSSINDKIVELKDLVVGTEAKLNKSAVLRKAIDYIR 342
Cdd:cd19734      7 KRVSRNKSEKKRRDQFNVLIKELGSMLPGNARKMDKSTVLQKSIDFLR 54

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 1907080803  303 EKRYRSSINDKIVELKDLVVGTEAKLNKSAVLRKAIDYIRFLQH 346
Cdd:cd11444      5 RRRGEEAIERRLRALRRLVPGGRESMEVEELLQETADYIMFLEM 48

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 1907080803  294 EKRTAHNAIEKRYRSSINDKIVELKDLVVGTEA----KLNKSAVLRKAIDYIRFLQHSNQKLKQEN 355
Cdd:cd11388      2 VKKWKHVEAEKKRRNQIKKGFEDLINLINYPRNnnekRISKSELLNKAVDDIRGLLKANEQLQEEI 67

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split (HES)-related repressor protein (HERP) family; HERP (also called Hey/Hesr/HRT/CHF/gridlock) proteins corresponds to a family of bHLH-O transcriptional repressors that are related to the Drosophila hairy and Enhancer-of-split proteins and act as downstream effectors of Notch signaling. They contain a basic helix-loop-helix (bHLH) domain with an invariant glycine residue in its basic region, an orange domain in the central region and YXXW sequence motif at its C-terminal region. HERP proteins are involved in cardiovascular development and have roles in somitogenesis, myogenesis and gliogenesis.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1907080803  295 KRTAHNAIEKRYRSSINDKIVELKDLV------VGTeAKLNKSAVLRKAIDYIRFLQ 345
Cdd:cd11407      1 RKKRRGIIEKRRRDRINNSLAELRRLVptafekQGS-AKLEKAEILQMTVDHLKMLH 56

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in the Mad family; Members of the Mad family (Mad1, Mxi, Mad3, and Mad4) bear the bHLHzip domain (also known as basic-helix-loop-helix-leucine-zipper or bHLH-LZ domain), which mediates heterodimerization to Max and the sequence-specific DNA binding ability to E-box DNA. Mad family proteins can repress transcription at the E-box through their interaction with co-repressors. Mad family proteins antagonize Myc function in transactivation and transformation and they are growth/tumor suppressors. The developmental phenotypes of the individual Mad family member knockout mice are relatively mild- all these mice have been shown to be viable and normal.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907080803  296 RTAHNAIEKRYRSSINDKIVELKDLV-VGTEA-KLNKSAVLRKAIDYIRFLQHSNQKLKQENLTLRSAH 362
Cdd:cd11401      1 RSTHNELEKNRRAHLRLCLERLKELVpLGPDAtRHTTLSLLTKAKAYIKNLEDKEKRQRQQKEQLRREQ 69

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 1907080803  296 RTAHNAIEKRYRSSINDKIVELKDLVVGTEAKLNKSAVLRKAIDyirFLQHSNQ 349
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 1907080803  295 KRTAHNAIEKRYRSSINDKIVELKDLVVGTEA---KLNKSAVLRKAIDYIRFL 344
Cdd:cd11437      1 SRSNHSEIEKRRRDKMNAYIQELSALVPACNAmsrKLDKLTVLRMAVQHLKSL 53

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 1907080803  299 HNAIEKRYRSSINDKIVELKDLVVGTEA---KLNKSAVLRKAIDYIRFLQ 345
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 1907080803  294 EKRtahNAIEKRYRSSINDKIVELKDLV--VGTEAKLNKSAVLRKAIDYIRFLQ 345
Cdd:cd11418      3 ARR---NERERRRVQAVNDAFDRLRQHVpyLKRRKKLSKVKTLRRAIEYIRHLQ 53

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in L-Myc and similar proteins; L-Myc, also termed Class E basic helix-loop-helix protein 38 (bHLHe38), or protein L-Myc-1, or V-myc myelocytomatosis viral oncogene homolog, is a bHLHZip oncoprotein belonging to the Myc oncogene protein family. It binds DNA as a heterodimer with MAX. L-Myc is co-expressed with another Myc family member and has weaker transformation/transactivation activities. L-Myc knockout mouse did not exhibit any phenotypic abnormalities.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907080803  295 KRTAHNAIEKRYRSSINDKIVELKDLVVG--TEAKLNKSAVLRKAIDYIRFLQHSNQKLKQENLTLRSAHK 363
Cdd:cd11457      7 KRKNHNFLERKRRNDLRSRFLALRDEVPGlaSCSKTPKVVILSKATEYLRGLVSAERRMAAEKRQLKSRQQ 77

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.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1907080803  297 TAHNAIEKRYRSSINDKIVELKDLVVGTeAKLNKSAVLRKAIDYIRFLQHSNQKLKQEN 355
Cdd:cd11451      4 GSHAMAERRRREKLNERFITLRSMVPFV-TKMDKVSILGDAIEYLKQLQRRVEELESRR 61

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split-related protein HELT and similar proteins; HELT, also termed HES/HEY-like transcription factor, is a bHLH-O transcriptional repressor expressed in the developing central nervous system. It binds preferentially to the canonical E box sequence 5'-CACGCG-3' and regulates neuronal differentiation and/or identity. HELT could homodimerize and heterodimerize with other bHLH-O protein such as HES-5 or HEY-2 and bound to E box to repress gene transcription.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1907080803  298 AHNAIEKRYRSSINDKIVELKDLVVG-----TEAKLNKSAVLRKAIDYIRFLQHSN 348
Cdd:cd11408      1 SHKVIEKRRRDRINRCLNELGKTVPMalakqTSGKLEKAEILEMTVQYLRALHSAD 56

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana phytochrome interacting factors (PIFs) and similar proteins; The family includes several bHLH transcription factors from Arabidopsis thaliana, such as PIFs, ALC, PIL1, SPATULA, and UNE10. PIFs (PIF1, PIF3, PIF4, PIF5, PIF6 and PIF7) have been shown to control light-regulated gene expression. They directly bind to the photoactivated phytochromes and are degraded in response to light signals. ALC, also termed AtbHLH73, or protein ALCATRAZ, or EN 98, is required for the dehiscence of fruit, especially for the separation of the valve cells from the replum. It promotes the differentiation of a strip of labile non-lignified cells sandwiched between layers of lignified cells. PIL1, also termed AtbHLH124, or protein phytochrome interacting factor 3-like 1, or EN 110, is involved in responses to transient and long-term shade. It is required for the light-mediated inhibition of hypocotyl elongation and necessary for rapid light-induced expression of the photomorphogenesis- and circadian-related gene APRR9. PIL1 seems to play a role in multiple PHYB responses, such as flowering transition and petiole elongation. SPATULA, also termed AtbHLH24, or EN 99, plays a role in floral organogenesis. It promotes the growth of carpel margins and of pollen tract tissues derived from them. UNE10, also termed AtbHLH16, or protein UNFERTILIZED EMBRYO SAC 10, or EN 99, is required during the fertilization of ovules by pollen.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1907080803  297 TAHNAIEKRYRSSINDKIVELKDLvVGTEAKLNKSAVLRKAIDYIRFLQ 345
Cdd:cd11445      4 EVHNLSERRRRDRINEKMKALQEL-IPNCNKTDKASMLDEAIEYLKSLQ 51

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1907080803  296 RTAHNAIEKRYRSSINDKIVELKDLV--VGTEAKLNKSAVLRKAIDYIRFLQHS 347
Cdd:cd11390      1 RNAANARERRRMHDLNDAFEALRKVLptVPPDKKLSKIETLRLAINYIAALSDL 54

DNA polymerase III subunit gamma/tau;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907080803   18 SDFPGLFDAPYAGGETGDTGPSSPGANSPESFSSASLASSLEAFLGGPKVTPAPLSPPPSAPAALKMYPSVSPFSPGPGI 97
Cdd:PRK12323   400 AAPPAAPAAAPAAAAAARAVAAAPARRSPAPEALAAARQASARGPGGAPAPAPAPAAAPAAAARPAAAGPRPVAAAAAAA 479

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907080803   98 KEEPVPLTILQPAAPQPSPGTLLPPSFPAP-PVQLSPAPVLGYSSlpsgfSGTLPGNTQQPPSSLPLAPAPGVLPTPALH 176
Cdd:PRK12323   480 PARAAPAAAPAPADDDPPPWEELPPEFASPaPAQPDAAPAGWVAE-----SIPDPATADPDDAFETLAPAPAAAPAPRAA 554

                          170       180
                   ....*....|....*....|...
gi 1907080803  177 TQVQSLASQQPlPASAAPRTNTV 199
Cdd:PRK12323   555 AATEPVVAPRP-PRASASGLPDM 576

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 1907080803   86 PSVSPFSPGPGIKEEPVPLTILQPAAPQPSPGTLLPPSfPAPPVQLSPAPVLGYSSLPSGFSGTLPGNTQQP-----PSS 160
Cdd:pfam03154  311 PGPSPAAPGQSQQRIHTPPSQSQLQSQQPPREQPLPPA-PLSMPHIKPPPTTPIPQLPNPQSHKHPPHLSGPspfqmNSN 389

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1907080803  161 LPlaPAPGVLPTPALHTQ---------VQSLASQQPLPASAA 193
Cdd:pfam03154  390 LP--PPPALKPLSSLSTHhppsahpppLQLMPQSQQLPPPPA 429