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 2217367294 534 KTENRRITHISAEQKRRFNIKLGFDTLHGLVSTLSAQPSLKVSKATTLQKTAEYILMLQQERAGLQEEAQQLRDEI 609
Cdd:cd19689     1 KTETRRITHISAEQKRRFNIKLGFDTLHSLVTTLSSQPSIKISKATTLQKTAEYISKLQQERAQLQEEAQRLRDQI 76

nuclear export signal 2 (NES2) and nuclear import signal (NLS) domains found in carbohydrate-responsive element-binding protein (ChREBP), MLX-interacting protein (MLXIP), and similar proteins; This family includes two transcription factors: ChREBP and MLXIP. ChREBP, also called class D basic helix-loop-helix protein 14 (bHLHd14), Max-like protein (MLX) interactor or MIO, MLX-interacting protein-like (MLXIPL), WS basic-helix-loop-helix leucine zipper protein (WS-bHLH), or Williams-Beuren syndrome chromosomal region 14 protein (WBSCR14), functions at two levels; nuclear localization and DNA binding. ChREBP binds to the canonical and non-canonical E box sequences 5'-CACGTG-3'. It also binds DNA as a heterodimer with TCFL4/MLX. MLXIP, also called class E basic helix-loop-helix protein 36 (bHLHe36), transcriptional activator MondoA, or MIR, is a novel basic helix-loop-helix-leucine zipper transcriptional activator that constitutes a positive branch of a max-like network. MLXIP binds DNA by forming a heterodimer with Max-like protein (MLX), and activates transcription. It binds to the canonical E box sequence 5'-CACGTG-3'. MLXIP plays a role in transcriptional activation of glycolytic target genes and is involved in glucose-responsive gene regulation. Members in this family may contain functional domains, including two nuclear export signals, NES1 and NES2, and a nuclear import signal (NLS) in the N-terminal region. This model corresponds to NES2 and NLS domains.

                          10
                  ....*....|....*
gi 2217367294   1 MREYHKWRIYYKKRV 15
Cdd:cd21771    98 MKEYHKWRIYYKKRL 112

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 2217367294 534 KTENRRITHISAEQKRRFNIKLGFDTLHGLVSTLSAQPSLKVSKATTLQKTAEYILMLQQERAGLQEEAQQLRDEI 609
Cdd:cd19689     1 KTETRRITHISAEQKRRFNIKLGFDTLHSLVTTLSSQPSIKISKATTLQKTAEYISKLQQERAQLQEEAQRLRDQI 76

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2217367294  545 AEQKRRFNIKLGFDTLHGLVSTLsaQPSLKVSKATTLQKTAEYILMLQQE 594
Cdd:smart00353   3 RERRRRRKINEAFDELRSLLPTL--PKNKKLSKAEILRLAIEYIKSLQEE 50

nuclear export signal 2 (NES2) and nuclear import signal (NLS) domains found in carbohydrate-responsive element-binding protein (ChREBP), and similar proteins; ChREBP, also called class D basic helix-loop-helix protein 14 (bHLHd14), Max-like protein (MLX) interactor or MIO, MLX-interacting protein-like (MLXIPL), WS basic-helix-loop-helix leucine zipper protein (WS-bHLH), or Williams-Beuren syndrome chromosomal region 14 protein (WBSCR14), is a large transcription factor that functions at two levels, nuclear localization and DNA binding. It binds to the canonical and non-canonical E box sequences 5'-CACGTG-3'. It also binds DNA as a heterodimer with TCFL4/MLX. ChREBP contains functional domains, including two nuclear export signals, NES1 and NES2, and a nuclear import signal (NLS) in the N-terminal region. This model corresponds to NES2 and NLS domains.

                          10
                  ....*....|....*
gi 2217367294   1 MREYHKWRIYYKKRV 15
Cdd:cd21771    98 MKEYHKWRIYYKKRL 112

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 2217367294 534 KTENRRITHISAEQKRRFNIKLGFDTLHGLVSTLSAQPSLKVSKATTLQKTAEYILMLQQERAGLQEEAQQLRDEI 609
Cdd:cd19689     1 KTETRRITHISAEQKRRFNIKLGFDTLHSLVTTLSSQPSIKISKATTLQKTAEYISKLQQERAQLQEEAQRLRDQI 76

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2217367294 536 ENRRITHISAEQKRRFNIKLGFDTLHGLVSTLSAQPSlkVSKATTLQKTAEYILMLQQERAGLQEEAQQLRDEI 609
Cdd:cd19688     1 KNRRMKHISAEQKRRFNIKICFDTLNSLVSTLKNSKP--ISNAITLQKTVEYIAKLQQERTQMQEETKRLREEI 72

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2217367294 538 RRITHISAEQKRRFNIKLGFDTLHGLVSTLsaQPSLKVSKATTLQKTAEYILMLQ 592
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELLPTL--PPDKKLSKAEILRLAIEYIKHLQ 53

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in the Myc family; The Myc family is a member of the bHLHzip family of transcription factors that play important roles in the control of normal cell proliferation, growth, survival and differentiation. All Myc isoforms contain two independently functioning polypeptide chain regions: N-terminal transactivating residues and a C-terminal bHLHzip segment. The bHLHzip family of bHLH transcription factors are characterized by a highly conserved N-terminal basic region that may bind DNA at a consensus hexanucleotide sequence known as the E-box (CANNTG) followed by HLH and leucine zipper motifs that may interact with other proteins to form homo- and heterodimers. Myc heterodimerizes with Max enabling specific binding to E-box DNA sequences in the promoters of target genes. The Myc proto-oncoprotein family includes at least five different functional members: c-, N-, L-, S- and B-Myc (which is lacking the bHLH domain).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2217367294 538 RRITHISAEQKRRFNIKLGFDTLHGLVSTLSAQPslKVSKATTLQKTAEYILMLQQERAGLQEEAQQLRDEIEELNA 614
Cdd:cd11400     1 KRRLHNVLERQRRNDLKNSFEKLRDLVPELADNE--KASKVVILKKATEYIKQLQQEEKKLEKEKDKLKARNEQLRK 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 2217367294 546 EQKRRFNIKLGFDTLHGLVSTLSAQPslKVSKATTLQKTAEYILMLQQ 593
Cdd:cd00083     1 ERRRRDKINDAFEELKRLLPELPDSK--KLSKASILQKAVEYIRELQS 46

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2217367294  545 AEQKRRFNIKLGFDTLHGLVSTLsaQPSLKVSKATTLQKTAEYILMLQQE 594
Cdd:smart00353   3 RERRRRRKINEAFDELRSLLPTL--PKNKKLSKAEILRLAIEYIKSLQEE 50

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2217367294 538 RRITHISAEQKRRFNIKLGFDTLHGLVSTLSAQpslKVSKATTLQKTAEYILMLQQERAGL 598
Cdd:cd11419     4 RREIANSNERRRMQSINAGFQSLRTLLPHCDGE---KLSKAAILQQTAEYIFSLEQEKTRL 61

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2217367294 539 RITHISAEQKRRFNIKLGFDTLHGLVsTLSAQPslKVSKATTLQKTAEYILMLQQERAGLQEEAQQLR 606
Cdd:cd19682     1 RLRHKKRERERRSELRELFDKLKQLL-GLDSDE--KASKLAVLTEAIEEIQQLKREEDELQKEKARLT 65

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 2217367294 538 RRITHISAEQKRRFNIKLGFDTLHGLVSTLSAqpslKVSKATTLQKTAEYILMLQQERAGLQEEAQ-------QLRDEIE 610
Cdd:cd11398     7 RRDNHKEVERRRRENINEGINELAALVPGNAR----EKNKGAILARAVEYIQELQETEAKNIEKWTleklltdQAIAELA 82

                  ....
gi 2217367294 611 ELNA 614
Cdd:cd11398    83 ALNE 86

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 2217367294 538 RRITHISAEQKRRFNIKLGFDTLHGLVSTLSAQPslKVSKATTLQKTAEYILMLQ-------QERAGLQEEAQQLRDEIE 610
Cdd:cd11456     5 RRRNHNILERQRRNDLRSSFLTLRDHVPELVKNE--KAAKVVILKKATEYVHSLQaeeqkllLEKEKLQARQQQLLKKIE 82

                  ..
gi 2217367294 611 EL 612
Cdd:cd11456    83 QA 84

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 2217367294 542 HISAEQKRRFNIKLGFDTLHGLVStlsaqPSLKVSKATTLQKTAEYILMLQQ 593
Cdd:cd11393     1 HSIAERKRREKINERIRALRSLVP-----NGGKTDKASILDEAIEYIKFLQE 47

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 2217367294 537 NRRITHIS-------AEQKRRFNIKLGFDTLHGLvstlsaQPSLKVSKATTLQKTAEYILMLQQERAGLQEEAQQLRDEI 609
Cdd:cd11399    19 NDRIAELRdsvpalrEAYKSARGEDEDEEDLGGL------TPATKLNKATILSKATEYIRHLEKKNKRLSRENASLRERL 92

                  ...
gi 2217367294 610 EEL 612
Cdd:cd11399    93 AAH 95

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Schizosaccharomyces pombe ESC1 (spESC1) and similar proteins; spESC1 is a bHLHzip protein with homology to human MyoD and Myf-5 myogenic differentiation inducers. It is involved in the sexual differentiation process.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2217367294 539 RITHISAEQKRRFNIKLGFDTLHGLvstLSAQPSLKVSKATTLQKTAEYIlmlQQeragLQEEAQQLRDEIEEL 612
Cdd:cd19690     1 RVSHKLAERKRRKEMKELFEDLRDA---LPQERGTKASKWEILTKAISYI---QQ----LKRHIRELRSEVNDL 64

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 2217367294 534 KTENRRITHISAEQKRRFNIKLGFDTLHGLVSTlSAQPSLKVSKATTLQKTAEYILMLQQEraglQEEAQQLRDEIEELN 613
Cdd:cd18925     1 KERQKKDNHNLIERRRRYNINYRIKELGTLIPK-SNDPDMRWNKGTILKASVEYIKWLQKE----QQRARELEHRQKKLE 75

                  ..
gi 2217367294 614 AA 615
Cdd:cd18925    76 QA 77

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 2217367294 534 KTENRRITHISAEQKRRFNIKLGFDTLHGLVSTlSAQPSLKVSKATTLQKTAEYILMLQQEraglQEEAQQLRDEIEELN 613
Cdd:cd18926     9 KERQKKDNHNLIERRRRFNINDRIKELGTLIPK-SNDPDMRWNKGTILKASVDYIRKLQRE----QQRAKELENRQKKLE 83

                  ..
gi 2217367294 614 AA 615
Cdd:cd18926    84 HA 85

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana paclobutrazol resistance (PRE) family; The PRE family includes several bHLH transcription factors from Arabidopsis thaliana, such as PRE1-6. PRE1 (also termed AtbHLH136, or protein banquo 1), PRE2 (also termed AtbHLH134, or protein banquo 2, or EN 52), PRE4 (also termed AtbHLH161, or protein banquo 3), and PRE5 (also termed AtbHLH164) are atypical and probable non DNA-binding bHLH transcription factors that integrate multiple signaling pathways to regulate cell elongation and plant development. PRE3 (also termed AtbHLH135, or protein activation-tagged BRI1 suppressor 1, or ATBS1, or protein target of MOOPTEROS 7, or EN 67) is an atypical and probable non DNA-binding bHLH transcription factor required for MONOPTEROS-dependent root initiation in embryo. It promotes the correct definition of the hypophysis cell division plane. PRE5 (also termed AtbHLH163, or protein KIDARI) is an atypical and probable non DNA-binding bHLH transcription factor that regulates light-mediated responses in day light conditions by binding and inhibiting the activity of the bHLH transcription factor HFR1, a critical regulator of light signaling and shade avoidance.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2217367294 543 ISAEQKRRFNIKLgfdtlHGLVSTLSAQPslKVSKATTLQKTAEYILMLQQERAGLQEEAQQLRDE 608
Cdd:cd11442     7 ISDDQKNDLYSRL-----RALLPSIATSD--KVSKATVLEEACNYIRNLHREVDDLSERLSRLLTS 65

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2217367294 539 RITHISAEQKRRFNIKLGFDTLHGLVSTLsaQPSLKVSKATTLQKTAEYILMLQQ 593
Cdd:cd11390     1 RNAANARERRRMHDLNDAFEALRKVLPTV--PPDKKLSKIETLRLAINYIAALSD 53

basic region leucin zipper;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 2217367294  582 QKTAEYILMLQQERAGLQEEAQQLRDEIEELNAAINLCQQQL 623
Cdd:smart00338  22 ERKKAEIEELERKVEQLEAENERLKKEIERLRRELEKLKSEL 63