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 302563659  113 RVLLRQQLMRAQAQEQERRERREQAAAAPFPSPAPASpaISVVGVSAGGHtlgRPPPAQVPREVLKVQTHLENPTRYHLQ 192
Cdd:pfam15951   1 RILLRQQLMREQAQQEEQREQQQQQQNHQYMQPAPPP--SSTPAISVPQS---PPSPAQVPVEVLKVQTHLENPTKYHIQ 75

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 302563659  193 QARRQQVKQYLSTTLGPKLASQALTPPPGPTSAqplPAPEAAHTTG-----PTGSAPNSPMALLTIGSSSEKEIDDVID 266
Cdd:pfam15951  76 QAQRQQVKQYLSTTYGAKQALIPSASPPPPAQS---PPPRTSPLMRgnqlpPGNSAPNSPMAMLSIGSSEEKEIDDVID 151

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 302563659  113 RVLLRQQLMRAQAQEQERRERREQAAAAPFPSPAPASpaISVVGVSAGGHtlgRPPPAQVPREVLKVQTHLENPTRYHLQ 192
Cdd:pfam15951   1 RILLRQQLMREQAQQEEQREQQQQQQNHQYMQPAPPP--SSTPAISVPQS---PPSPAQVPVEVLKVQTHLENPTKYHIQ 75

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 302563659  193 QARRQQVKQYLSTTLGPKLASQALTPPPGPTSAqplPAPEAAHTTG-----PTGSAPNSPMALLTIGSSSEKEIDDVID 266
Cdd:pfam15951  76 QAQRQQVKQYLSTTYGAKQALIPSASPPPPAQS---PPPRTSPLMRgnqlpPGNSAPNSPMAMLSIGSSEEKEIDDVID 151

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 302563659  347 KKDNHNLIERRRRFNINDRIKELGTLIPkSSDPEMRWNKGTILKASVDYIRKLQ 400
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELLP-TLPPDKKLSKAEILRLAIEYIKHLQ 53

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 302563659 335 ETEAKALLKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSSDPEMRWNKGTILKASVDYIRKLQKEQQRSKDLESRQR 414
Cdd:cd18926    1 ESEARALAKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQREQQRAKELENRQK 80

                         90       100
                 ....*....|....*....|....
gi 302563659 415 SLEQANRSLQLRIQELELQAQIHG 438
Cdd:cd18926   81 KLEHANRHLLLRIQELEMQARAHG 104

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 302563659 337 EAKALLKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSSDPEMRWNKGTILKASVDYIRKLQKEQQRSKDLESRQRSL 416
Cdd:cd18927    1 EARALAKERQKKDNHNLIERRRRFNINDRIKELGTLIPKTNDLDVRWNKGTILKASVDYIKRMQKDLQRSRELENHSRRL 80

                         90
                 ....*....|.
gi 302563659 417 EQANRSLQLRI 427
Cdd:cd18927   81 EMTNKQLWLRI 91

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 302563659  113 RVLLRQQLMRAQAQEQERRERREQAAAAPFPSPAPASpaISVVGVSAGGHtlgRPPPAQVPREVLKVQTHLENPTRYHLQ 192
Cdd:pfam15951   1 RILLRQQLMREQAQQEEQREQQQQQQNHQYMQPAPPP--SSTPAISVPQS---PPSPAQVPVEVLKVQTHLENPTKYHIQ 75

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 302563659  193 QARRQQVKQYLSTTLGPKLASQALTPPPGPTSAqplPAPEAAHTTG-----PTGSAPNSPMALLTIGSSSEKEIDDVID 266
Cdd:pfam15951  76 QAQRQQVKQYLSTTYGAKQALIPSASPPPPAQS---PPPRTSPLMRgnqlpPGNSAPNSPMAMLSIGSSEEKEIDDVID 151

Domain of unknown function (DUF3371); This domain is functionally uncharacterized. This domain is found in eukaryotes. This presumed domain is typically between 125 to 142 amino acids in length.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 302563659  432 LQAQIHGLPVPPTPGLLSlaTTSASDSLKPEQldIEEEGRPGAATFHVGGGPAQNAPHQQPPAPPSDALLDLHFpsdhlG 511
Cdd:pfam11851   1 MQARAHGLPVASSSGLCT--AELAARVIKQEP--ALPPCPPDLYDMSQPQPPTQAAVSSSSTLDLNDGLITFSF-----G 71

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 302563659  512 DLGDPFHL------GLEDILMEEeegvvgglsggALSPLRAaSDPLLSSVSPAVSKASSRRSSFSMEE 573
Cdd:pfam11851  72 DLSASFSDalkpgsKLDDILMDD-----------TLSPLGP-SDPLLSAMSPDASKDSSRRSSFSMEE 127

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 302563659 343 KERQKKDNHNLIERRRRFNINDRIKELGTLIpksSDPEMRWNKGTILKASVDYIRKLQKEQQRskdlesrqrsLEQANRS 422
Cdd:cd11394    2 PKVEKRSAHNAIEKRYRSSINDRIIELKDLV---VGPDAKMNKSAVLRKAIDYIRYLQKVNQK----------LKQENMA 68

                 ....
gi 302563659 423 LQLR 426
Cdd:cd11394   69 LKKA 72

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 302563659   352 NLIERRRRFNINDRIKELGTLIPKSSDPEmRWNKGTILKASVDYIRKLQKEQQ 404
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPKNK-KLSKAEILRLAIEYIKSLQEELQ 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 302563659 351 HNLIERRRRFNINDRIKELGTLIPKSSDPEMRWN--KGTILKASVDYIRKLQKEQQR 405
Cdd:cd11396    2 HNEVERRRRDKINNWIVKLAKIVPDCEKDNSKQGqsKGGILSKACDYIQELRSQNER 58

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 302563659 342 LKERQKKDNHNLIERRRRFNINDRIKELGTLIpKSSDPEMrwNKGTILKASVDYIRKLQKEQQRskdlesrqrsLEQANR 421
Cdd:cd18922    1 PKEGERRTTHNIIEKRYRSSINDKIIELKDLV-MGTDAKM--HKSGVLRKAIDYIKYLQQVNHK----------LRQENM 67

                 ....*...
gi 302563659 422 SLQLRIQE 429
Cdd:cd18922   68 ALKLANQK 75

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 302563659 355 ERRRRFNINDRIKELGTLIPKSSDPEmRWNKGTILKASVDYIRKLQK 401
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 302563659 347 KKDNHNLIERRRRFNINDRIKELGTLIPKSSDPEmRWNKGTILKASVDYIRKLQKEQQRskdLESRQRSLEQANRSLQLR 426
Cdd:cd11400    1 KRRLHNVLERQRRNDLKNSFEKLRDLVPELADNE-KASKVVILKKATEYIKQLQQEEKK---LEKEKDKLKARNEQLRKK 76

                 ....
gi 302563659 427 IQEL 430
Cdd:cd11400   77 LERL 80

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 302563659 343 KERQKKDNHNLIERRRRFNINDRIKELGTLIPKSSDPEMRWN--KGTILKASVDYIRKLQKEQQR 405
Cdd:cd18924    1 RDEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKSGqsKGGILSKACDYIQELRQSNHR 65

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 302563659 351 HNLIERRRRFNINDRIKELGTLIP--KSSDPEMRWNKGTILKASVDYIRKLQKEQ 403
Cdd:cd11389    1 HKVIEKRRRDRINESLAELRRLVPeaRKSKGSGKLEKAEILEMTLQHLKALQSST 55

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 302563659 343 KERQKKDNHNLIERRRRFNINDRIKELGTLIPKSSDPEMRWNKGTILKASVDYIRKLQKEQQRS 406
Cdd:cd18947    1 KERFARENHSEIERRRRNKMTAYITELSDMVPTCSALARKPDKLTILRMAVSHMKSLRGTGNTS 64

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        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 302563659 350 NHNLIERRRRFNINDRIKELGTLIPKSSdpemRWNKGTILKASVDYIRKLQKeqqRSKDLESRQRSLEQANRSLQLR 426
Cdd:cd11451    5 SHAMAERRRREKLNERFITLRSMVPFVT----KMDKVSILGDAIEYLKQLQR---RVEELESRRKSSDTETRPTMER 74

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 302563659 351 HNLIERRRRFNINDRIKELGTLIPKSsdPEMrwNKGTILKASVDYIRKLQK 401
Cdd:cd11393    1 HSIAERKRREKINERIRALRSLVPNG--GKT--DKASILDEAIEYIKFLQE 47

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 302563659 347 KKDNHNLIERRRRFNINDRIKELGTLIPKSSDPEMRWNKGTILKASVDYIRKL 399
Cdd:cd11437    1 SRSNHSEIEKRRRDKMNAYIQELSALVPACNAMSRKLDKLTVLRMAVQHLKSL 53

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 302563659 346 QKKDNHNLIERRRRFNINDRIKELGTLIPKSSDPEMRwnKGTILKASVDYIRKLqkeQQRSKDLESRQRSLEQAN 420
Cdd:cd11404    1 QRRLNHVRSEKKRRELIKKGYDELCALVPGLDPQKRT--KADILQKAADWIQEL---KEENEKLEEQLDELKEAA 70

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        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 302563659 351 HNLIERRRRFNINDRIKELGTLIPKSSdpemRWNKGTILKASVDYIRKLQKEQQ 404
Cdd:cd11445    6 HNLSERRRRDRINEKMKALQELIPNCN----KTDKASMLDEAIEYLKSLQLQVQ 55

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 302563659 347 KKDNHNLIERRRRFNINDRIKELGTLIPK-SSDPEMRWNKGTILKASVDYIRKLQKEQQRS 406
Cdd:cd11388    3 KKWKHVEAEKKRRNQIKKGFEDLINLINYpRNNNEKRISKSELLNKAVDDIRGLLKANEQL 63

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 302563659 353 LIERRRRFNINDRIKELGTLIPKSSDPE--MRWNKGTILKASVDYIRKLQKEQQ 404
Cdd:cd18916    6 MLERQRRARINKCLSELKTLVAECSGDDgcLRMDKAEMLETAVAFMRQQQTAKN 59

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 302563659 345 RQKKDNHNLIERRRRFNINDRIKELGTLIPKSSDPEMRWNKGTILKASVDYIRKLQ 400
Cdd:cd11438    5 KNAREAHSQIEKRRRDKMNSFIDELASLVPTCNAMSRKLDKLTVLRMAVQHMKTLR 60

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 302563659 346 QKKDNHNLIERRRRFNINDRIKELGTLIPKSSdPEMrwNKGTILKASVDYIRKLQK 401
Cdd:cd19683    1 KSRERHNAKERQRRERIKIACDQLRKLVPGCS-RKT--DKATVFEFTVAYIKFLRE 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 302563659 348 KDNHNLIERRRRFNINDRIKELGTLIPKSSDPEMRWNKGTILKASVDYIRKLQ 400
Cdd:cd11391    1 REKSREAAKKRRDKENAEISELASLLPLPPAVGSKLDKLSVLRLAVAYLRLKK 53

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 302563659 351 HNLIERRRRFNINDRIKELGTLIPKSSDPEmrwnKGTILKASVDYIRKLQKeqqRSKDLES 411
Cdd:cd18918    1 LFATERERREKLNEKFSDLRNLIPNPTKND----RASILSDAIKYINELQR---TVEELKS 54

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 302563659 347 KKDNHNLIERRRRFNINDRIKELGTLIPKSSDPEmRWNKGTILKASVDYIRKLQkEQQRSKDLESRQrsLEQANRSLQLR 426
Cdd:cd11457    7 KRKNHNFLERKRRNDLRSRFLALRDEVPGLASCS-KTPKVVILSKATEYLRGLV-SAERRMAAEKRQ--LKSRQQQLLRR 82

                 ....*
gi 302563659 427 IQELE 431
Cdd:cd11457   83 IAQLK 87

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 302563659 355 ERRRRFNINDRIKELGTLIPKSSdpemRWNKGTILKASVDYIRKLqkeQQRSKDLESRQRSLEQANRSLQL 425
Cdd:cd11443    7 ERRRRKKLNDRLYMLRSVVPKIT----KMDRASILGDAIDYVKEL---LQEINELQDELEGLPESESGETL 70

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 302563659 346 QKKDNHNLIERRRRFNINDRIKELGTLI----PKSSDPEMRWNKGTILKASVDYIRKLQKEQ 403
Cdd:cd11459    2 HRKSSKPIMEKRRRARINESLSQLKTLIldalKKDSSRHSKLEKADILEMTVKHLRNLQRQQ 63

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 302563659 355 ERRRRFNINDRIKELGTLIPKS-SDPE---MRWNKGTILKASVDYIRKLQKEQ 403
Cdd:cd11439    6 EKRRREQENKYIEELAELISASiSDMDslsVKPDKCAILQETVKQIRQIKEQE 58

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in MLX-interacting protein-like (MLXIPL) and similar proteins; 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 302563659 343 KERQKKDNHNLIERRRRFNINDRIKELGTLIPK-SSDPEMRWNKGTILKASVDYIRKLQKEQQRSKDLESRQRS 415
Cdd:cd19689    1 KTETRRITHISAEQKRRFNIKLGFDTLHSLVTTlSSQPSIKISKATTLQKTAEYISKLQQERAQLQEEAQRLRD 74

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-interacting protein 1 (MXI1) and similar proteins; MXI1, also termed Max interactor 1, or Class C basic helix-loop-helix protein 11 (bHLHc11), is a bHLHZip transcriptional repressor that binds with MAX to form a sequence-specific DNA-binding protein complex which recognizes the core sequence 5'-CAC[GA]TG-3'. It thus antagonizes MYC transcriptional activity by competing for MAX. It plays an important role in the regulation of cell proliferation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 302563659 348 KDNHNLIERRRRFNINDRIKELGTLIPKSSDPEMRWNKGTILKASVdYIRKLQKEQQRSKdleSRQRSLEQANRSLQLRI 427
Cdd:cd18930    2 RSTHNELEKNRRAHLRLCLERLKVLIPLGPDCTRHTTLGLLNKAKA-HIKKLEEADRKSQ---HQLENLEREQRFLKRRL 77

                 ...
gi 302563659 428 QEL 430
Cdd:cd18930   78 EQL 80

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in c-Myc and similar proteins; c-Myc, also termed Myc proto-oncogene protein, or Class E basic helix-loop-helix protein 39 (bHLHe39), or transcription factor p64, a bHLHZip proto-oncogene protein that functions as a transcription factor, which binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. It activates the transcription of growth-related genes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 302563659 343 KERQKKDNHNLIERRRRFNINDRIKELGTLIPKSSDPEmRWNKGTILKASVDYIRKLQKEQQRskdLESRQRSLEQANRS 422
Cdd:cd11458    1 EENDKRRTHNVLERQRRNELKLSFFALRDQIPEVANNE-KAPKVVILKKATEYILSMQADEQR---LISEKEQLRRRREQ 76

                 ....*...
gi 302563659 423 LQLRIQEL 430
Cdd:cd11458   77 LKHRLEQL 84

basic helix-loop-helix-orange (bHLH-O) domain found in Drosophila melanogaster protein hairy, protein deadpan and similar proteins; Protein hairy is a bHLH transcriptional repressor of genes that require a bHLH-O protein for their transcription. It acts as a pair-rule protein that regulates embryonic segmentation and adult bristle patterning. Protein deadpan is closely related to the product of the segmentation gene hairy. It is a direct target of Notch signaling and regulates neuroblast self-renewal in Drosophila.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 302563659 347 KKDNHNLIERRRRFNINDRIKELGTLI----PKSSDPEMRWNKGTILKASVDYIRKLQKEQ 403
Cdd:cd18913    3 RKSSKPIMEKRRRARINASLNELKSLLldalKKDGTRHSKLEKADILEMTVKHLRQVQRQQ 63

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 302563659 353 LIERRRRFNINDRIKELGTLIPK---SSDPEMRWNKGTILKASVDYIRKLQKEQ 403
Cdd:cd11461    6 VVEKTRRDRINSSIEQLKTLLEKefqRHQPNSKLEKADILEMTVSFLKQSAKLS 59

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 302563659 348 KDNHNLIERRRRFNINDRIKELGTLIPKSSDpEMRWNKGTILKASVDYIRKLQKEQQRSKDLESRqrsLEQANRSLQLRI 427
Cdd:cd18929    3 RSSHNELEKHRRAKLRLYLEQLKQLVPLGPD-STRHTTLSLLKRAKMHIKKLEEQDRKALNIKEQ---LQREHRYLKRRL 78

                 ....*..
gi 302563659 428 QELELQA 434
Cdd:cd18929   79 EQLSVQG 85

basic helix-loop-helix-orange (bHLH-O) domain found in hairy/enhancer-of-split related with YRPW motif-like protein (HEYL) and similar proteins; HEYL, also termed Class B basic helix-loop-helix protein 33 (bHLHb33), or hairy-related transcription factor 3 (HRT-3), is a bHLH-O transcriptional repressor that is strongly expressed in the presomitic mesoderm, the somites, the peripheral nervous system and smooth muscle of all arteries and is a downstream effector of the Notch and transforming growth factor-beta pathways. It promotes neuronal differentiation by activating proneural genes and inhibiting other hairy and enhancer of split (HES) and hairy/enhancer-of-split related with YRPW motif protein (HEY) proteins. HEYL also functions as a tumor suppressor involved in the progression of human cancers.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 302563659 347 KKDNHNLIERRRRFNINDRIKELGTLIPKSSDPE--MRWNKGTILKASVDYIRKLQ 400
Cdd:cd11447    9 RKKRRGIIEKRRRDRINSSLSELRRLVPTAFEKQgsSKLEKAEILQMTVDHLKMLH 64