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        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 755515345 148 KELGTLIPKSNDPDMRWNKGTILKASVDYIKWLQKEQQRARELEHRQKKLEHANRQLRLRIQELEIQARAHG 219
Cdd:cd18926   33 KELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQREQQRAKELENRQKKLEHANRHLLLRIQELEMQARAHG 104

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 755515345 148 KELGTLIPKSNDPDMRWNKGTILKASVDYIKWLQKEQQRARELEHRQKKLEHANRQLRLRIQELEIQARAHG 219
Cdd:cd18926   33 KELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQREQQRAKELENRQKKLEHANRHLLLRIQELEMQARAHG 104

SH3 domain-containing protein; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 755515345 148 KELGTLIPKSNDPDMRWNKGTI-----LKASVDYIKWLQKEQQRAR-ELEHRQKKLEHANRQL 204
Cdd:PRK10884 100 NQVKTLTDKLNNIDNTWNQRTAemqqkVAQSDSVINGLKEENQKLKnQLIVAQKKVDAANLQL 162

helix loop helix domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 755515345   140 RYNINYRIKELGTLIPkSNDPDMRWNKGTILKASVDYIKWLQKEQQ 185
Cdd:smart00353   8 RRKINEAFDELRSLLP-TLPKNKKLSKAEILRLAIEYIKSLQEELQ 52

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in microphthalmia-associated transcription factor (MITF) and similar proteins; MITF, also termed Class E basic helix-loop-helix protein 32 (bHLHe32), is a bHLHzip transcription factor that is involved in neural crest melanocytes development as well as the pigmented retinal epithelium. It regulates the expression of genes with essential roles in cell differentiation, proliferation and survival. It binds to M-boxes (5'-TCATGTG-3') and symmetrical DNA sequences (E-boxes) (5'-CACGTG-3') found in the promoters of target genes, such as BCL2 and tyrosinase (TYR).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 755515345 148 KELGTLIPKSNDPDMRWNKGTILKASVDYIKWLQKEQQRARELEHRQKKLEHANRQLRLRIQELEIQARAHG 219
Cdd:cd18926   33 KELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQREQQRAKELENRQKKLEHANRHLLLRIQELEMQARAHG 104

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 755515345 148 KELGTLIPKSNDPDMRWNKGTILKASVDYIKWLQKEQQRARELEHRQKKLEHANRQLRLRI 208
Cdd:cd18928   31 KELGTLIPKSTDPEMRWNKGTILKASVDYIRKLQKEQQRSKEIEMRQRKLEQANRSLQLRI 91

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 755515345 148 KELGTLIPKSNDPDMRWNKGTILKASVDYIKWLQKEQQRARELEH 192
Cdd:cd11397   25 KELGTLLPKSNDPDMRWNKGTILKASVDYIRKLQKEQERLRQLEE 69

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 755515345 134 AVERRRRYNINYRIKELGTLIPKSND--PDMRWNKGTILKASVDYIKWLQKEQQR 186
Cdd:cd11387    4 AVERRRRDNINEKIQELGSLVPPSRLetKDLKPNKGSILSKAVEYIRELQNQNQE 58

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 755515345 149 ELGTLIPKSndpdmRWNKGTILKASVDYIKWLQKeqqrarelehRQKKLEHANRQLRLRIQELE 212
Cdd:cd11399   48 DLGGLTPAT-----KLNKATILSKATEYIRHLEK----------KNKRLSRENASLRERLAAHE 96

Basic region leucine zipper;

                          10        20        30
                  ....*....|....*....|....*....|..
gi 755515345  181 QKEQQRARELEHRQKKLEHANRQLRLRIQELE 212
Cdd:pfam07716  18 EKKKQKEEELEERVKELERENAQLRQKVEQLE 49

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 755515345 135 VERRRRYNINYRIKELGTLIPkSNDPDMrwNKGTILKASVDYIKWLQKEQQRARE--------LEHRQKKLEHANRQLR 205
Cdd:cd11398   14 VERRRRENINEGINELAALVP-GNAREK--NKGAILARAVEYIQELQETEAKNIEkwtlekllTDQAIAELAALNEKLR 89

Basic leucine zipper (bZIP) domain of Fungal Zip1-like transcription factors: a DNA-binding and dimerization domain; This subfamily is composed of fungal bZIP transcription factors including Schizosaccharomyces pombe Zip1, Saccharomyces cerevisiae Methionine-requiring protein 28 (Met28p), and Neurospora crassa cys-3, among others. Zip1 is required for the production of key proteins involved in sulfur metabolism and also plays a role in cadmium response. Met28p acts as a cofactor of Met4p, a transcriptional activator of the sulfur metabolic network; it stabilizes DNA:Met4 complexes. bZIP factors act in networks of homo and heterodimers in the regulation of a diverse set of cellular processes. The bZIP structural motif contains a basic region and a leucine zipper, composed of alpha helices with leucine residues 7 amino acids apart, which stabilize dimerization with a parallel leucine zipper domain. Dimerization of leucine zippers creates a pair of the adjacent basic regions that bind DNA and undergo conformational change. Dimerization occurs in a specific and predictable manner resulting in hundreds of dimers having unique effects on transcription.

                         10        20        30
                 ....*....|....*....|....*....|..
gi 755515345 181 QKEQQRARELEHRQKKLEHANRQLRLRIQELE 212
Cdd:cd14705   17 AKKKQREQELEEKLKELEERIKELERRLDELE 48