basic Helix-Loop-Helix-zipper (bHLHzip) domain found in MAX gene-associated protein (MGA) 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.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2217300583 1809 RRTHTANERRRRGEMRDLFEKLKITLGLLHSSKVSKSLILTRAFSEIQGLTDQADKLIGQKNLLT 1873
Cdd:cd18911      1 RRTHTANERRRRNEMRDLFEKLKRTLGLHNLPKVSKYYILKQAFEEIQGLTDQADRLIGQKTLLT 65

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in MAX gene-associated protein (MGA) 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.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2217300583 1809 RRTHTANERRRRGEMRDLFEKLKITLGLLHSSKVSKSLILTRAFSEIQGLTDQADKLIGQKNLLT 1873
Cdd:cd18911      1 RRTHTANERRRRNEMRDLFEKLKRTLGLHNLPKVSKYYILKQAFEEIQGLTDQADRLIGQKTLLT 65

Helix-loop-helix DNA-binding domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2217300583 1808 YRRTHTANERRRRGEMRDLFEKLKITL-GLLHSSKVSKSLILTRAFSEIQGLT 1859
Cdd:pfam00010    1 RREAHNERERRRRDRINDAFDELRELLpTLPPDKKLSKAEILRLAIEYIKHLQ 53

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in MAX gene-associated protein (MGA) 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.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2217300583 1809 RRTHTANERRRRGEMRDLFEKLKITLGLLHSSKVSKSLILTRAFSEIQGLTDQADKLIGQKNLLT 1873
Cdd:cd18911      1 RRTHTANERRRRNEMRDLFEKLKRTLGLHNLPKVSKYYILKQAFEEIQGLTDQADRLIGQKTLLT 65

MGA, conserved domain; This domain can be found in the MAX gene-associated protein (Mga), which is a dual-specificity transcription factor that contains both a bHLHZip domain and a T-box domain and is able to bind to and regulate transcriptional targets through both E-box sites as well as T-box-binding elements (TBEs).

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 2217300583  584 RKRAPPCNNDFCRLGCVCSSLA-LEKRQPAHCRRPDCMFGCTC 625
Cdd:pfam16059    2 KDAKKPCDKDYCQLGCVCDSLAgTRPPKREHCGRADCVLGCVC 44

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 2217300583 1809 RRTHTANERRRRGEMRDLFEKLKITL-GLLHSSKVSKSLILTRAFSEIQGLTDQADKLIGQKNLLTRKRNILIRKVSSL 1886
Cdd:cd11400      2 RRLHNVLERQRRNDLKNSFEKLRDLVpELADNEKASKVVILKKATEYIKQLQQEEKKLEKEKDKLKARNEQLRKKLERL 80

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 2217300583 1816 ERRRRGEMRDLFEKLKITLGLLH-SSKVSKSLILTRAFSEIQGL 1858
Cdd:cd00083      1 ERRRRDKINDAFEELKRLLPELPdSKKLSKASILQKAVEYIREL 44

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2217300583 1809 RRTHTANERRRRGEMRDLFEKLKITLGLLHSSKVSKSLILTRAFSEIQGLTDQADKLIGQKNLLTRKR 1876
Cdd:cd11404      3 RLNHVRSEKKRRELIKKGYDELCALVPGLDPQKRTKADILQKAADWIQELKEENEKLEEQLDELKEAA 70

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2217300583 1809 RRTHTANERRRRGEMRDLFEKLKITL-GLLHSSKVSKSLILTRAFSEIQGLTDQADKLIGQKNLLTRKRNILIRKV 1883
Cdd:cd11456      6 RRNHNILERQRRNDLRSSFLTLRDHVpELVKNEKAAKVVILKKATEYVHSLQAEEQKLLLEKEKLQARQQQLLKKI 81

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 2217300583 1808 YRRTHTANERRRRGEMRDLFEKLK--ITLGLLHSSKVSKSLiLTRAFSEIQGLTDQADKLIGQKNLLTRKRNILIRKVSS 1885
Cdd:cd18929      2 NRSSHNELEKHRRAKLRLYLEQLKqlVPLGPDSTRHTTLSL-LKRAKMHIKKLEEQDRKALNIKEQLQREHRYLKRRLEQ 80

                   ..
gi 2217300583 1886 LS 1887
Cdd:cd18929     81 LS 82

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2217300583 1809 RRTHTANERRRRGEMRDLFEKLKITL-GLLHSSKVSKSLILTRAFSEIQGLTDQADKLIGQKNLLTRKRNILIRKVSSL 1886
Cdd:cd11458      6 RRTHNVLERQRRNELKLSFFALRDQIpEVANNEKAPKVVILKKATEYILSMQADEQRLISEKEQLRRRREQLKHRLEQL 84

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in the Mad family; Members of the Mad family (Mad1, Mxi, Mad3, and Mad4) bear the bHLHzip domain (also known as basic-helix-loop-helix-leucine-zipper or bHLH-LZ domain), which mediates heterodimerization to Max and the sequence-specific DNA binding ability to E-box DNA. Mad family proteins can repress transcription at the E-box through their interaction with co-repressors. Mad family proteins antagonize Myc function in transactivation and transformation and they are growth/tumor suppressors. The developmental phenotypes of the individual Mad family member knockout mice are relatively mild- all these mice have been shown to be viable and normal.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217300583 1809 RRTHTANERRRRGEMRDLFEKLK------------ITLGLlhsskvsksliLTRAFSEIQGLTDQADKLIGQKNLLTRKR 1876
Cdd:cd11401      1 RSTHNELEKNRRAHLRLCLERLKelvplgpdatrhTTLSL-----------LTKAKAYIKNLEDKEKRQRQQKEQLRREQ 69

                   ....*..
gi 2217300583 1877 NILIRKV 1883
Cdd:cd11401     70 RELKRRL 76