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 163965354 300 ESEARALAKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQREQQRAKDLENRQK 379
Cdd:cd18926    1 ESEARALAKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQREQQRAKELENRQK 80

                         90       100
                 ....*....|....*....|....
gi 163965354 380 KLEHANRHLLLRVQELEMQARAHG 403
Cdd:cd18926   81 KLEHANRHLLLRIQELEMQARAHG 104

MITF/TFEB/TFEC/TFE3 N-terminus; This domain is found at the N-terminus of several transcription factors including microphthalmia-associated transcription factor, transcription factor EB, transcription factor EC and transcription factor E3.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 163965354   56 RILLRQQLMREQMQEQERREQQQKLQAAQFMQQRVAVSQTPAInvSVPTTLPSATQVPMEVLKVQTHLENPTKYHIQQAQ 135
Cdd:pfam15951   1 RILLRQQLMREQAQQEEQREQQQQQQNHQYMQPAPPPSSTPAI--SVPQSPPSPAQVPVEVLKVQTHLENPTKYHIQQAQ 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 163965354  136 RHQVKQYLSTTLANKHASQVLSSPCPNQPGDHAMPP--------VPGSSAPNSPMAMLTLNSNCEKE 194
Cdd:pfam15951  79 RQQVKQYLSTTYGAKQALIPSASPPPPAQSPPPRTSplmrgnqlPPGNSAPNSPMAMLSIGSSEEKE 145

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 163965354 300 ESEARALAKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQREQQRAKDLENRQK 379
Cdd:cd18926    1 ESEARALAKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQREQQRAKELENRQK 80

                         90       100
                 ....*....|....*....|....
gi 163965354 380 KLEHANRHLLLRVQELEMQARAHG 403
Cdd:cd18926   81 KLEHANRHLLLRIQELEMQARAHG 104

MITF/TFEB/TFEC/TFE3 N-terminus; This domain is found at the N-terminus of several transcription factors including microphthalmia-associated transcription factor, transcription factor EB, transcription factor EC and transcription factor E3.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 163965354   56 RILLRQQLMREQMQEQERREQQQKLQAAQFMQQRVAVSQTPAInvSVPTTLPSATQVPMEVLKVQTHLENPTKYHIQQAQ 135
Cdd:pfam15951   1 RILLRQQLMREQAQQEEQREQQQQQQNHQYMQPAPPPSSTPAI--SVPQSPPSPAQVPVEVLKVQTHLENPTKYHIQQAQ 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 163965354  136 RHQVKQYLSTTLANKHASQVLSSPCPNQPGDHAMPP--------VPGSSAPNSPMAMLTLNSNCEKE 194
Cdd:pfam15951  79 RQQVKQYLSTTYGAKQALIPSASPPPPAQSPPPRTSplmrgnqlPPGNSAPNSPMAMLSIGSSEEKE 145

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 163965354   317 NLIERRRRFNINDRIKELGTLIPkSNDPDMRWNKGTILKASVDYIRKLQREQQ 369
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLP-TLPKNKKLSKAEILRLAIEYIKSLQEELQ 52

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 163965354 300 ESEARALAKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQREQQRAKDLENRQK 379
Cdd:cd18926    1 ESEARALAKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQREQQRAKELENRQK 80

                         90       100
                 ....*....|....*....|....
gi 163965354 380 KLEHANRHLLLRVQELEMQARAHG 403
Cdd:cd18926   81 KLEHANRHLLLRIQELEMQARAHG 104

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 163965354 308 KERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQREQQRAKDLEN 376
Cdd:cd11397    1 KDRQKKDNHNMIERRRRFNINDRIKELGTLLPKSNDPDMRWNKGTILKASVDYIRKLQKEQERLRQLEE 69

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in transcription factor EC (TFEC) and similar proteins; TFEC, also termed Class E basic helix-loop-helix protein 34 (bHLHe34), or transcription factor EC-like (TFEC-L), is a bHLHzip transcriptional regulator that acts as a repressor or an activator and regulates gene expression in macrophages. It plays an important role in the niche to expand hematopoietic progenitors through the modulation of several cytokines.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 163965354 308 KERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQREQQRAKDLENRQKKLEHANRH 387
Cdd:cd18925    1 KERQKKDNHNLIERRRRYNINYRIKELGTLIPKSNDPDMRWNKGTILKASVEYIKWLQKEQQRARELEHRQKKLEQANRR 80

                 ....*
gi 163965354 388 LLLRV 392
Cdd:cd18925   81 LLLRI 85

MITF/TFEB/TFEC/TFE3 N-terminus; This domain is found at the N-terminus of several transcription factors including microphthalmia-associated transcription factor, transcription factor EB, transcription factor EC and transcription factor E3.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 163965354   56 RILLRQQLMREQMQEQERREQQQKLQAAQFMQQRVAVSQTPAInvSVPTTLPSATQVPMEVLKVQTHLENPTKYHIQQAQ 135
Cdd:pfam15951   1 RILLRQQLMREQAQQEEQREQQQQQQNHQYMQPAPPPSSTPAI--SVPQSPPSPAQVPVEVLKVQTHLENPTKYHIQQAQ 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 163965354  136 RHQVKQYLSTTLANKHASQVLSSPCPNQPGDHAMPP--------VPGSSAPNSPMAMLTLNSNCEKE 194
Cdd:pfam15951  79 RQQVKQYLSTTYGAKQALIPSASPPPPAQSPPPRTSplmrgnqlPPGNSAPNSPMAMLSIGSSEEKE 145

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Saccharomyces cerevisiae centromere-binding protein 1 (CBP-1) and similar proteins; CBP-1, also termed centromere promoter factor 1 (CPF1), or centromere-binding factor 1 (CBF1), is a bHLHzip protein that is required for chromosome stability and methionine prototrophy. It binds as a homodimer to the centromere DNA elements I (CDEI, GTCACATG) region of the centromere that is required for optimal centromere function.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 163965354 308 KERQKKDNHNLIERRRRFNINDRIKELGTLIPkSNDPDMrwNKGTILKASVDYIRKLQREQQRAKDLENRQKKL-EHANR 386
Cdd:cd11398    3 WHRQRRDNHKEVERRRRENINEGINELAALVP-GNAREK--NKGAILARAVEYIQELQETEAKNIEKWTLEKLLtDQAIA 79

                         90
                 ....*....|
gi 163965354 387 HLLLRVQELE 396
Cdd:cd11398   80 ELAALNEKLR 89

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 163965354   317 NLIERRRRFNINDRIKELGTLIPkSNDPDMRWNKGTILKASVDYIRKLQREQQ 369
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLP-TLPKNKKLSKAEILRLAIEYIKSLQEELQ 52

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in upstream stimulatory factors, USF1, USF2 and similar proteins; Upstream stimulatory factor 1 and 2 (USF-1 and USF-2) are members of bHLHzip transcription factor family. USFs are ubiquitously expressed and key regulators of a wide number of gene regulation networks, including the stress and immune responses, cell cycle and proliferation, lipid and glucid metabolism. USFs recruit chromatin remodeling enzymes and interact with co-activators and the members of the transcription pre-initiation complex. USFs interact with high affinity to E-box regulatory elements.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 163965354 316 HNLIERRRRFNINDRIKELGTLIPKSNDPDMRWN--KGTILKASVDYIRKLQREQQR 370
Cdd:cd11396    2 HNEVERRRRDKINNWIVKLAKIVPDCEKDNSKQGqsKGGILSKACDYIQELRSQNER 58

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 163965354 310 RQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRW--------------NKGTILKASVDYIRKLQREQQRakdLE 375
Cdd:cd11395    1 PRKRLPHNAIEKRYRSNLNTKIERLRDAIPSLRSPEGKSddgglgglapttklSKATILTKAIEYIRHLEQENER---LE 77

                 ....*...
gi 163965354 376 NRQKKLEH 383
Cdd:cd11395   78 EENEELRQ 85

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 163965354 310 RQKKDNHNLIERRRRFNINDRIKELGTLIPKSN-DPDMRWNKGTILKASVDYIRKLQREQQRAKDLENRQKK 380
Cdd:cd11405    1 EQRRLSHISAEQKRRFNIKSGFDTLQSLIPSLGqNPNQKVSKAAMLQKAAEYIKSLKRERQQMQEEAEQLRQ 72

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 163965354 320 ERRRRFNINDRIKELGTLIPKSNDPDmRWNKGTILKASVDYIRKLQR 366
Cdd:cd00083    1 ERRRRDKINDAFEELKRLLPELPDSK-KLSKASILQKAVEYIRELQS 46

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 163965354 312 KKDNHNLIERRRRFNINDRIKELGTLIP--KSNDpdmRWNKGTILKASVDYIRKLQREQQRakdLENRQKKLEHANRHLL 389
Cdd:cd11400    1 KRRLHNVLERQRRNDLKNSFEKLRDLVPelADNE---KASKVVILKKATEYIKQLQQEEKK---LEKEKDKLKARNEQLR 74

                 ....*.
gi 163965354 390 LRVQEL 395
Cdd:cd11400   75 KKLERL 80

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 163965354 308 KERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKgtILKASVDYIRKLQRE 367
Cdd:cd18910    1 RREKKRESHNEVERRRKDKINAGINKIGELLPDRDAKKQSKNM--ILEQAYKYIVELKKK 58

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 163965354 308 KERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWN--KGTILKASVDYIRKLQREQQR 370
Cdd:cd18924    1 RDEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKSGqsKGGILSKACDYIQELRQSNHR 65

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 163965354 319 IERRRRFNINDRIKELGTLIPKSNDPDMRW--NKGTILKASVDYIRKLQREQ 368
Cdd:cd19685    1 SEKRRRQRINDKLNQLKELLPPNLSKQSRSklSKAEILEMAITELRRLQQEV 52

basic Helix-Loop-Helix (bHLH) domain found in Arabidopsis thaliana MYC1 and similar proteins; MYC1, also termed AtbHLH12, or EN 58, acts as a transcription activator, when associated with MYB75/PAP1 or MYB90/PAP2.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 163965354 316 HNLIERRRRFNINDRIKELGTLIPKSNDPDmrwnKGTILKASVDYIRKLQReqqRAKDLENRQKKLEHANRH 387
Cdd:cd18918    1 LFATERERREKLNEKFSDLRNLIPNPTKND----RASILSDAIKYINELQR---TVEELKSLVEKKRCGERD 65

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 163965354 316 HNLIERRRRFNINDRIKELGTLIPKSndpDMRWNKGTILKASVDYIrklQREQQRAKDLENRQKKLEH 383
Cdd:cd11453    7 HSATEQRRRSKINERLQALRDLIPHS---DQKRDKASFLLEVIEYI---QALQEKVAKLEEQVQGWGG 68

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in aryl hydrocarbon receptor nuclear translocator (ARNT) and similar proteins; ARNT, also termed Class E basic helix-loop-helix protein 2 (bHLHe2), or Dioxin receptor, nuclear translocator, or hypoxia-inducible factor 1-beta (HIF1b), or HIF-1-beta, or HIF1-beta, is a member of bHLH-PAS transcription regulators that acts 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 163965354 308 KERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQ 365
Cdd:cd18947    1 KERFARENHSEIERRRRNKMTAYITELSDMVPTCSALARKPDKLTILRMAVSHMKSLR 58

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL) and similar proteins; ARNTL, also termed Basic-helix-loop-helix-PAS protein MOP3, or brain and muscle ARNT-like 1 (BMAL1), or Class E basic helix-loop-helix protein 5 (bHLHe5), or member of PAS protein 3, or PAS domain-containing protein 3 (PASD3), or bHLH-PAS protein JAP3, is a member of the bHLH-PAS transcription factor family that forms heterodimers with another bHLH-PAS protein, CLOCK (circadian locomotor output cycle kaput), which regulates circadian rhythm. ARNTL-CLOCK heterodimer complex activates transcription from E-box (CANNTG) elements found in the promoter of circadian responsive genes. ARNTL is highly homologous to ARNT.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 163965354 310 RQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQ 365
Cdd:cd11438    5 KNAREAHSQIEKRRRDKMNSFIDELASLVPTCNAMSRKLDKLTVLRMAVQHMKTLR 60

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in Drosophila melanogaster protein cycle and similar proteins; Protein cycle, also termed brain and muscle ARNT-like 1 (BMAL1), or MOP3, is a putative bHLH-PAS transcription factor involved in the generation of biological rhythms in Drosophila. It activates cycling transcription of Period (PER) and Timeless (TIM) by binding to the E-box (5'-CACGTG-3') present in their promoters.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 163965354 312 KKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQ 365
Cdd:cd19726    1 RRQNHSEIEKRRRDKMNTYITELSSMIPMCNAMSRKLDKLTVLRMAVQHMKTLR 54

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 163965354 313 KDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQ 365
Cdd:cd11391    1 REKSREAAKKRRDKENAEISELASLLPLPPAVGSKLDKLSVLRLAVAYLRLKK 53

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana BIG PETAL (BPE) and similar proteins; The family includes several bHLH transcription factors from Arabidopsis thaliana, such as BPE, HBI1 and BEE proteins (BEE1-3). BPE, also termed AtbHLH31, or EN 88, is involved in the control of Arabidopsis petal size, by interfering with postmitotic cell expansion to limit final petal cell size. HBI1, also termed AtbHLH64, or homolog of bee2 interacting with IBH1, or EN 79, is an atypical bHLH transcription factor that acts as positive regulator of cell elongation downstream of multiple external and endogenous signals by direct binding to the promoters and activation of the two expansin genes EXPA1 and EXPA8, encoding cell wall loosening enzymes. BEEs, also termed protein Brassinosteroid enhanced expression, are positive regulators of brassinosteroid signaling.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 163965354 307 AKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDmrwNKGTILKASVDYIRKLQRE 367
Cdd:cd18919    7 ARRGQATDSHSLAERVRREKISERMKLLQDLVPGCNKVT---GKALMLDEIINYVQSLQRQ 64

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana OBP3-responsive gene 2 (ORG2), 3 (ORG3) and similar proteins; The family includes ORG2 (also termed AtbHLH38, or EN 8) and ORG3 (also termed AtbHLH39, or EN 9), both of which act as bHLH transcription factors.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 163965354 312 KKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKAsVDYIRKLQREQQRAKDLENRQKKLEHANRH 387
Cdd:cd18914    1 KKLLHNDVERQRRQEMASLFSSLRSLLPLQYIKGKLSVSDHVDEA-VNYIKELQEKIKELSEKRDELLKLISGVRS 75

basic helix-loop-helix-orange (bHLH-O) domain found in Drosophila melanogaster Enhancer of split proteins, E(spl)m5, E(spl)m8 and similar proteins; The family includes two bHLH-O transcriptional repressors, E(spl)m5 and E(spl)m8, which participate in the control of cell fate choice by uncommitted neuroectodermal cells in the embryo. They bind DNA on N-box motifs, 5'-CACNAG-3'.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 163965354 318 LIERRRRFNINDRIKELGTLIPKSNDPD--MRWNKGTILKASVDYIRKLQREQQ 369
Cdd:cd18916    6 MLERQRRARINKCLSELKTLVAECSGDDgcLRMDKAEMLETAVAFMRQQQTAKN 59

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 163965354 320 ERRRRFNINDRIKELGTLIPKSNDPDMrwNKGTILKASVDYIRKLQREQQR 370
Cdd:cd11419   12 ERRRMQSINAGFQSLRTLLPHCDGEKL--SKAAILQQTAEYIFSLEQEKTR 60

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
                 ....*....|....*....|....*....|....*....|....*....
gi 163965354 315 NHNLIERRRRFNINDRIKELGTLIPKSNdpdMRWNKGTILKASVDYIRK 363
Cdd:cd11441    3 SRNLSEKKRRDQFNVLINELASMLPGRG---RKMDKSTVLKKTIAFLRK 48

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in MLX-interacting protein (MLXIP) and similar proteins; MLXIP, also termed Class E basic helix-loop-helix protein 36 (bHLHe36), or transcriptional activator MondoA, is a bHLHZip transcriptional activator that binds DNA as a heterodimer with Mlx. It binds to the canonical E box sequence 5'-CACGTG-3' and plays a role in transcriptional activation of glycolytic target genes. MLXIP is most highly expressed in skeletal muscle and functions as an indirect glucose sensor, by sensing glucose 6-phosphate and shuttling between the nucleus and the cytoplasm.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 163965354 315 NHNLIERRRRFNINDRIKELGTLIPkSNDPDMRWNKGTILKASVDYIRKLQREQQRAKDLENR 377
Cdd:cd19688    6 KHISAEQKRRFNIKICFDTLNSLVS-TLKNSKPISNAITLQKTVEYIAKLQQERTQMQEETKR 67

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in N-Myc and similar proteins; N-Myc, also termed Class E basic helix-loop-helix protein 37 (bHLHe37), is a bHLHZip proto-oncogene protein that positively regulates the transcription of MYCNOS in neuroblastoma cells. It is also essential during embryonic development. N-Myc has a critical role in regulating the switch between proliferation and differentiation of progenitor cells. It binds DNA as a heterodimer with MAX. The family also includes S-Myc, encoded by rat or mouse intronless myc gene, which has apoptosis-inducing activity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 163965354 311 QKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDmRWNKGTILKASVDYIRKLQREQQRakdLENRQKKLEHANRHLLL 390
Cdd:cd11456    4 ERRRNHNILERQRRNDLRSSFLTLRDHVPELVKNE-KAAKVVILKKATEYVHSLQAEEQK---LLLEKEKLQARQQQLLK 79

                 ....*
gi 163965354 391 RVQEL 395
Cdd:cd11456   80 KIEQA 84

basic helix-loop-helix (bHLH) domain found in Saccharomyces cerevisiae phosphate system positive regulatory protein PHO4 and similar proteins; PHO4 is a transcriptional activator that regulates the expression of repressible phosphatase under phosphate starvation conditions in Saccharomyces cerevisiae. The PHO4 protein has four functional domains with the bHLH domain at its carboxyl-terminal region. It regulates transcription by binding to promoter of the genes as a homodimer.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 163965354 311 QKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPD--------------------MRWNKGTILKASVDYIRKLQRE 367
Cdd:cd11392    1 SKRTAHKVAERGRRDRLNAALKELASLMPAEFVEGkmgadgsasdsndkekaaasAAGSKAATVEMAIDYIKHLQKE 77

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 163965354 311 QKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPD----MRWNKGTILKASVDYIRKLQREQ 368
Cdd:cd11459    2 HRKSSKPIMEKRRRARINESLSQLKTLILDALKKDssrhSKLEKADILEMTVKHLRNLQRQQ 63

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana Fe-deficiency induced transcription factor 1 (FIT) and similar proteins; The family includes bHLH transcription factors from Arabidopsis thaliana, such as FIT and DYT1. FIT, also termed FER-like iron deficiency-induced transcription factor, or FER-like regulator of iron uptake, or AtbHLH29, or EN 43, is a bHLH transcription factor that is required for the iron deficiency response in plant. It regulates FRO2 at the level of mRNA accumulation and IRT1 at the level of protein accumulation. DYT1, also termed AtbHLH22, or protein dysfunctional tapetum 1, or EN 49, is a bHLH transcription factor involved in the control of tapetum development. It is required for male fertility and pollen differentiation, especially during callose deposition.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 163965354 317 NLI-ERRRRFNINDRIKELGTLIPKSNDPDmrwnKGTILKASVDYIRKLQreqqrakdleNRQKKLEHANRHLLLRVQEL 395
Cdd:cd11450    7 NLVsERNRRQKLNQRLFALRSVVPNITKMD----KASIIKDAISYIQELQ----------YQEKKLEAEIRELESRPPST 72

                 .
gi 163965354 396 E 396
Cdd:cd11450   73 L 73

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-associated protein 4 (Mad4) and similar proteins; Mad4, also termed Max dimerization protein 4, or Max dimerizer 4 (MXD4), or Class C basic helix-loop-helix protein 12 (bHLHc12), or Max-interacting transcriptional repressor MAD4, is a bHLHZip Max-interacting transcriptional repressor that suppresses c-myc dependent transformation and is expressed during neural and epidermal differentiation. It is regulated by a transcriptional repressor complex that contains Miz-1 and c-Myc.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 163965354 313 KDNHNLIERRRRFNINDRIKELGTLIPKSNDPDmRWNKGTILKASVDYIRKLQREQQRAKdleNRQKKLEHANRHLLLRV 392
Cdd:cd18929    3 RSSHNELEKHRRAKLRLYLEQLKQLVPLGPDST-RHTTLSLLKRAKMHIKKLEEQDRKAL---NIKEQLQREHRYLKRRL 78

                 ....*..
gi 163965354 393 QELEMQA 399
Cdd:cd18929   79 EQLSVQG 85

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in steroid receptor coactivator (SRC) family; The SRC family of coactivators includes SRC-1 (NcoA-1/p160), SRC-2(TIF2/GRIP1/NcoA-2) and SRC-3(NcoA-3/pCIP/RAC3/ACTR/pCIP/AIB1/TRAM1), which are critical mediators of steroid receptor action. They contain bHLH-PAS domain at the N-terminal that is followed by receptor interacting domain and C-terminal transcriptional activation domain. SRC coactivators interact with nuclear receptors in a ligand-dependent manner and enhance transcriptional activation by the receptor via histone acetylation/methylation.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 163965354 320 ERRRRFNINDRIKELGTLIPKS-NDPD---MRWNKGTILKASVDYIRKLQREQ 368
Cdd:cd11439    6 EKRRREQENKYIEELAELISASiSDMDslsVKPDKCAILQETVKQIRQIKEQE 58

basic helix-loop-helix (bHLH) domain found in the spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein (SOHLH) family; 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 163965354 316 HNLIERRRRfninDRIKE----LGTLIP--KSNDPDMrwnkGTILKASVDYIRKLQR 366
Cdd:cd18908    6 HSLKERLRR----ERIKSscdqLRDLLPyiKGRKLDM----ASVLEMTVKYIRYIQE 54

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 163965354 318 LIERRRRFNINDRIKELGTLIPK---SNDPDMRWNKGTILKASVDYirkLQREQQRA 371
Cdd:cd11461    6 VVEKTRRDRINSSIEQLKTLLEKefqRHQPNSKLEKADILEMTVSF---LKQSAKLS 59