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 24307933 226 ESRALAKERQKKDNHNLIERRRRFNINDRIKELGMLIPKANDLDVRWNKGTILKASVDYIRRMQKDLQKSRELENHSRRL 305
Cdd:cd18927   1 EARALAKERQKKDNHNLIERRRRFNINDRIKELGTLIPKTNDLDVRWNKGTILKASVDYIKRMQKDLQRSRELENHSRRL 80

                        90
                ....*....|.
gi 24307933 306 EMTNKQLWLRI 316
Cdd:cd18927  81 EMTNKQLWLRI 91

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 24307933   321 MQARVHGLPTTSPSGMNMAELAQQVVKQELPSEEGPGEALmlgaevpdpeplpalPPQAPLPLPTQPPSPFHHLDFSHSL 400
Cdd:pfam11851   1 MQARAHGLPVASSSGLCTAELAARVIKQEPALPPCPPDLY---------------DMSQPQPPTQAAVSSSSTLDLNDGL 65

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24307933   401 SFGGREDeGPPGYPEPLAPGHG----------SPFpslskkdldlmllddsllpLASDPLLSTMSPEASKASSRRSSFSM 470
Cdd:pfam11851  66 ITFSFGD-LSASFSDALKPGSKlddilmddtlSPL-------------------GPSDPLLSAMSPDASKDSSRRSSFSM 125

                  ...
gi 24307933   471 EEG 473
Cdd:pfam11851 126 EEG 128

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 24307933 226 ESRALAKERQKKDNHNLIERRRRFNINDRIKELGMLIPKANDLDVRWNKGTILKASVDYIRRMQKDLQKSRELENHSRRL 305
Cdd:cd18927   1 EARALAKERQKKDNHNLIERRRRFNINDRIKELGTLIPKTNDLDVRWNKGTILKASVDYIKRMQKDLQRSRELENHSRRL 80

                        90
                ....*....|.
gi 24307933 306 EMTNKQLWLRI 316
Cdd:cd18927  81 EMTNKQLWLRI 91

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 24307933   321 MQARVHGLPTTSPSGMNMAELAQQVVKQELPSEEGPGEALmlgaevpdpeplpalPPQAPLPLPTQPPSPFHHLDFSHSL 400
Cdd:pfam11851   1 MQARAHGLPVASSSGLCTAELAARVIKQEPALPPCPPDLY---------------DMSQPQPPTQAAVSSSSTLDLNDGL 65

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24307933   401 SFGGREDeGPPGYPEPLAPGHG----------SPFpslskkdldlmllddsllpLASDPLLSTMSPEASKASSRRSSFSM 470
Cdd:pfam11851  66 ITFSFGD-LSASFSDALKPGSKlddilmddtlSPL-------------------GPSDPLLSAMSPDASKDSSRRSSFSM 125

                  ...
gi 24307933   471 EEG 473
Cdd:pfam11851 126 EEG 128

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 24307933   236 KKDNHNLIERRRRFNINDRIKELGMLIPKANDlDVRWNKGTILKASVDYIRRMQ 289
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELLPTLPP-DKKLSKAEILRLAIEYIKHLQ 53

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 24307933 226 ESRALAKERQKKDNHNLIERRRRFNINDRIKELGMLIPKANDLDVRWNKGTILKASVDYIRRMQKDLQKSRELENHSRRL 305
Cdd:cd18927   1 EARALAKERQKKDNHNLIERRRRFNINDRIKELGTLIPKTNDLDVRWNKGTILKASVDYIKRMQKDLQRSRELENHSRRL 80

                        90
                ....*....|.
gi 24307933 306 EMTNKQLWLRI 316
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 24307933     4 RIGLRMQLMREQAQQEEQRERMQQQAVMHYMQQQQQqqqqqlgGPPTPAINTPVHFQSPPPVPGEVLKVQSYLENPTSYH 83
Cdd:pfam15951   1 RILLRQQLMREQAQQEEQREQQQQQQNHQYMQPAPP-------PSSTPAISVPQSPPSPAQVPVEVLKVQTHLENPTKYH 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24307933    84 LQQSQHQKVREYLSETYGNKFA--AHISPAQGSPKPPPAASPGVRAghvLSSSAGNSAPNSPMAMLHIGSNPERELDDVI 161
Cdd:pfam15951  74 IQQAQRQQVKQYLSTTYGAKQAliPSASPPPPAQSPPPRTSPLMRG---NQLPPGNSAPNSPMAMLSIGSSEEKEIDDVI 150

                  .
gi 24307933   162 D 162
Cdd:pfam15951 151 D 151

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24307933 226 ESRALAKERQKKDNHNLIERRRRFNINDRIKELGMLIPKANDLDVRWNKGTILKASVDYIRRMQKDLQKSRELENHSRRL 305
Cdd:cd18928   1 EAKAFLKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSTDPEMRWNKGTILKASVDYIRKLQKEQQRSKEIEMRQRKL 80

                        90
                ....*....|.
gi 24307933 306 EMTNKQLWLRI 316
Cdd:cd18928  81 EQANRSLQLRI 91

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in USF/MITF family; The USF (upstream stimulatory factor)/MITF (microphthalmia-associated transcription factor) family includes two bHLHzip transcription factor subfamilies. 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. The MITF (also known as microphthalmia-TFE, or MiT) subfamily 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 subfamily proteins can form homodimers or heterodimers with each other but not with other bHLH or bHLHzip proteins.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 24307933 239 NHNLIERRRRFNINDRIKELGMLIPKANDL--DVRWNKGTILKASVDYIRRMQKDLQ 293
Cdd:cd11387   1 SHNAVERRRRDNINEKIQELGSLVPPSRLEtkDLKPNKGSILSKAVEYIRELQNQNQ 57

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24307933 232 KERQKKDNHNLIERRRRFNINDRIKELGMLIPKANDldvRWNKGTILKASVDYIRRMQKDLQKSRE 297
Cdd:cd11398   3 WHRQRRDNHKEVERRRRENINEGINELAALVPGNAR---EKNKGAILARAVEYIQELQETEAKNIE 65

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 24307933   236 KKDNHNLIERRRRFNINDRIKELGMLIPKANDlDVRWNKGTILKASVDYIRRMQ 289
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELLPTLPP-DKKLSKAEILRLAIEYIKHLQ 53

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 24307933 234 RQKKDNHNLIERRRRFNINDRIKELGMLIP-------KANDLD------------VRWNKGTILKASVDYIRRMQKDLQK 294
Cdd:cd11399   1 PSKKTAHNMIEKRYRSNINDRIAELRDSVPalreaykSARGEDedeedlggltpaTKLNKATILSKATEYIRHLEKKNKR 80

                        90
                ....*....|....
gi 24307933 295 SRELENH-SRRLEM 307
Cdd:cd11399  81 LSRENASlRERLAA 94

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 24307933 232 KERQKKDNHNLIERRRRFNINDRIKELGMLIPKAndlDVRWNKGTILKASVDYIRRMQKDLQKSRElENHSrrLEMTNKQ 311
Cdd:cd18922   2 KEGERRTTHNIIEKRYRSSINDKIIELKDLVMGT---DAKMHKSGVLRKAIDYIKYLQQVNHKLRQ-ENMA--LKLANQK 75

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 24307933 234 RQKKDNHNLIERRRRFNINDRIKELGMLIPKANDLDVRW--------------NKGTILKASVDYIrrmqkdlqksRELE 299
Cdd:cd11395   1 PRKRLPHNAIEKRYRSNLNTKIERLRDAIPSLRSPEGKSddgglgglapttklSKATILTKAIEYI----------RHLE 70

                        90
                ....*....|...
gi 24307933 300 NHSRRLEMTNKQL 312
Cdd:cd11395  71 QENERLEEENEEL 83

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 24307933 244 ERRRRFNINDRIKELGMLIPkANDLDVRWNKGTILKASVDYIRRMQK 290
Cdd:cd00083   1 ERRRRDKINDAFEELKRLLP-ELPDSKKLSKASILQKAVEYIRELQS 46

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 24307933 234 RQKKDNHNLIERRRRFNINDRIKELGMLIPK-ANDLDVRWNKGTILKASVDYIRRMQKDLQKSRELENHSRR 304
Cdd:cd11405   1 EQRRLSHISAEQKRRFNIKSGFDTLQSLIPSlGQNPNQKVSKAAMLQKAAEYIKSLKRERQQMQEEAEQLRQ 72

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 24307933 236 KKDNHNLIERRRRFNINDRIKELGMLIPKANDLDVRWNKGTILKASVDYIRRM 288
Cdd:cd11437   1 SRSNHSEIEKRRRDKMNAYIQELSALVPACNAMSRKLDKLTVLRMAVQHLKSL 53

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 24307933 232 KERQKKDNHNLIERRRRFNINDRIKELGMLIPKANDLDVRWNKGTILKASVDYIRRMQKDLQKSR 296
Cdd:cd18947   1 KERFARENHSEIERRRRNKMTAYITELSDMVPTCSALARKPDKLTILRMAVSHMKSLRGTGNTST 65

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 24307933 239 NHNLIERRRRFNINDRIKELGMLIPKANDLDvrwnKGTILKASVDYIRRMQK---DLQKSRELENHSRRLEMTNK 310
Cdd:cd11451   5 SHAMAERRRREKLNERFITLRSMVPFVTKMD----KVSILGDAIEYLKQLQRrveELESRRKSSDTETRPTMERK 75

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
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 24307933 232 KERQKKDNHNLIERRRRFNINDRIKELGMLIPKANDLdvRWNKGTILKASVDYIRRMQK 290
Cdd:cd18910   1 RREKKRESHNEVERRRKDKINAGINKIGELLPDRDAK--KQSKNMILEQAYKYIVELKK 57

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 24307933 240 HNLIERRRRFNINDRIKELGMLIPKANDLD--VRWNKGTILKASVDYIRRMQK 290
Cdd:cd11389   1 HKVIEKRRRDRINESLAELRRLVPEARKSKgsGKLEKAEILEMTLQHLKALQS 53

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        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 24307933 232 KERQKKDNHNLIERRRRFNINDRIKELGMLIPKANDldvRWNKGTILKASVDYIRR 287
Cdd:cd19734   3 KDKAKRVSRNKSEKKRRDQFNVLIKELGSMLPGNAR---KMDKSTVLQKSIDFLRK 55

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 24307933 237 KDNHNLIERRRRFNINDRIKELGMLIPKANDLDVRWNKGTILKASVDYIrRMQKDL 292
Cdd:cd11391   1 REKSREAAKKRRDKENAEISELASLLPLPPAVGSKLDKLSVLRLAVAYL-RLKKFL 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 24307933 236 KKDNHNLIERRRRFNINDRIKELGMLIPKA-NDLDVRWNKGTILKASVDYIRRMQKDLQKSRELEN 300
Cdd:cd11388   3 KKWKHVEAEKKRRNQIKKGFEDLINLINYPrNNNEKRISKSELLNKAVDDIRGLLKANEQLQEEIN 68

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 24307933 242 LIERRRRFNINDRIKELGMLIPKANDLD--VRWNKGTILKASVDYIRRMQ 289
Cdd:cd18916   6 MLERQRRARINKCLSELKTLVAECSGDDgcLRMDKAEMLETAVAFMRQQQ 55

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24307933 231 AKERQKKDNHNLIERRRRFNINDRIKELGMLIPKANDLDvrwNKGTILKASVDYIRRMQkdlqksRELENHSRRLEMTNK 310
Cdd:cd18919   7 ARRGQATDSHSLAERVRREKISERMKLLQDLVPGCNKVT---GKALMLDEIINYVQSLQ------RQVEFLSMKLAAVNP 77

                ..
gi 24307933 311 QL 312
Cdd:cd18919  78 RL 79

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 24307933 241 NLI-ERRRRFNINDRIKELGMLIPKANDLDvrwnKGTILKASVDYIrrmqkdlqksRELENHSRRLEMTNKQLWLRIQEL 319
Cdd:cd11450   7 NLVsERNRRQKLNQRLFALRSVVPNITKMD----KASIIKDAISYI----------QELQYQEKKLEAEIRELESRPPST 72

                .
gi 24307933 320 E 320
Cdd:cd11450  73 L 73

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in protein Max and similar proteins; Max, also termed Class D basic helix-loop-helix protein 4 (bHLHd4), or Myc-associated factor X, is a bHLHZip transcription regulator that forms a sequence-specific DNA-binding protein complex with MYC or MAD which recognizes the core sequence 5'-CAC[GA]TG-3'. The MYC:MAX complex is a transcriptional activator, whereas the MAD:MAX complex is a transcriptional repressor. Max homodimer bind DNA but is transcriptionally inactive. Targeted deletion of max results in early embryonic lethality in mice.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24307933 236 KKDNHNLIERRRRFNINDRIKELGMLIPKANDLDVrwNKGTILKASVDYIRRMQKDLQKSRE 297
Cdd:cd11406   1 KRAHHNALERKRRDHIKDSFHSLRDSVPSLQGEKA--SRAQILKKATEYIQYMRRKNHTHQQ 60

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 24307933 236 KKDNHNLIERRRRFNINDRIKELGMLIPKANDLD--VRWNKGTILKASVDYIRRMQ 289
Cdd:cd11407   1 RKKRRGIIEKRRRDRINNSLAELRRLVPTAFEKQgsAKLEKAEILQMTVDHLKMLH 56

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 24307933 235 QKKDNHNLIERRRRFNINDRIKELGMLIPKANDldvRWNKGTILKASVDYIRRMQKDL 292
Cdd:cd19683   1 KSRERHNAKERQRRERIKIACDQLRKLVPGCSR---KTDKATVFEFTVAYIKFLREKL 55

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 24307933 244 ERRRRFNINDRIKELGMLIPKANdlDVRWNKGTILKASVDYIRRMQKDLQK 294
Cdd:cd11419  12 ERRRMQSINAGFQSLRTLLPHCD--GEKLSKAAILQQTAEYIFSLEQEKTR 60

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 24307933 235 QKKDNHNLIERRRRFNINDRIKELGMLIPK--ANDldvRWNKGTILKASVDYIRRMQKDLQKsreLENHSRRLEMTNKQL 312
Cdd:cd11456   4 ERRRNHNILERQRRNDLRSSFLTLRDHVPElvKNE---KAAKVVILKKATEYVHSLQAEEQK---LLLEKEKLQARQQQL 77

                ....*..
gi 24307933 313 WLRIQEL 319
Cdd:cd11456  78 LKKIEQA 84

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 24307933 236 KKDNHNLIERRRRFNINDRIKELGMLIPKANDlDVRWNKGTILKASVDYIrrmqkdlqksRELENHSRRLEMTNKQLWLR 315
Cdd:cd11457   7 KRKNHNFLERKRRNDLRSRFLALRDEVPGLAS-CSKTPKVVILSKATEYL----------RGLVSAERRMAAEKRQLKSR 75

                ....
gi 24307933 316 IQEL 319
Cdd:cd11457  76 QQQL 79

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 24307933 235 QKKDNHNLIERRRRFNINDRIKELGMLIPKANDLDV----RWNKGTILKASVDYIRRMQKD 291
Cdd:cd11459   2 HRKSSKPIMEKRRRARINESLSQLKTLILDALKKDSsrhsKLEKADILEMTVKHLRNLQRQ 62

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 24307933 232 KERQKKDNHNLIERRRR-------FNINDRIKELgmlipkANdlDVRWNKGTILKASVDYIRRMQKDLQK-SRELENHSR 303
Cdd:cd11458   1 EENDKRRTHNVLERQRRnelklsfFALRDQIPEV------AN--NEKAPKVVILKKATEYILSMQADEQRlISEKEQLRR 72

                        90
                ....*....|....*.
gi 24307933 304 RLEmtnkQLWLRIQEL 319
Cdd:cd11458  73 RRE----QLKHRLEQL 84