Helix-loop-helix DNA-binding domain;

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1AN2_A         3 KRAHHNALERKRRDHIKDSFHSLRDSVPSL-QGEKASRAQILDKATEYIQYMR 54
Cdd:pfam00010  1 RREAHNERERRRRDRINDAFDELRELLPTLpPDKKLSKAEILRLAIEYIKHLQ 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).

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               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1AN2_A       3 KRAHHNALERKRRDHIKDSFHSLRDSVPSL-QGEKASRAQILDKATEYIQYMRRKNHTHQQDIDDLKRQNALLEQQVRAL 81
Cdd:cd11400  1 KRRLHNVLERQRRNDLKNSFEKLRDLVPELaDNEKASKVVILKKATEYIKQLQQEEKKLEKEKDKLKARNEQLRKKLERL 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.

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               ....*....|....*....|....*....|....*....|....*.
1AN2_A      11 ERKRRDHIKDSFHSLRDSVPSL-QGEKASRAQILDKATEYIQYMRR 55
Cdd:cd00083  1 ERRRRDKINDAFEELKRLLPELpDSKKLSKASILQKAVEYIRELQS 46

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-binding protein Mnt and similar proteins; Mnt, also termed Class D basic helix-loop-helix protein 3 (bHLHd3), or Myc antagonist MNT, or protein ROX, is a bHLHZip transcriptional repressor that binds DNA as a heterodimer with MAX. It binds to the canonical E box sequence 5'-CACGTG-3' and, with higher affinity, to 5'-CACGCG-3'. Mnt has an important role as an antagonist and regulator of Myc activities and it is a potential tumor suppressor. Mnt is ubiquitously expressed. Mnt-deficient mice shown to exhibit early postnatal lethality.

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               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
1AN2_A       4 RAHHNALERKRRDHIKDSFHSLRDSVPSLQGEKASRAQILDKATEYIQYMRRKNHTHQQDIDDLKRQNALLEQQ 77
Cdd:cd11402  3 REVHNKLEKNRRAHLKECFETLKRQIPNLDDKKTSNLNILRSALRYIQILKRKEKEYEHEMERLAREKIALQQR 76

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.

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               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
1AN2_A       3 KRAHHNALERKRRDHIKDSFHSLRDSVPSLQGEKASRAQILDKATEYIQYMrrknhthQQDIDDLKRQNALLEQQV 78
Cdd:cd11404  2 RRLNHVRSEKKRRELIKKGYDELCALVPGLDPQKRTKADILQKAADWIQEL-------KEENEKLEEQLDELKEAA 70

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.

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               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1AN2_A       3 KRAHHNALERKRRDHIKDSFHSLRDSVPSLQ----------------GEKASRAQILDKATEYIQYMRRKNHTHQQDIDD 66
Cdd:cd11395  3 KRLPHNAIEKRYRSNLNTKIERLRDAIPSLRspegksddgglgglapTTKLSKATILTKAIEYIRHLEQENERLEEENEE 82

               ....
1AN2_A      67 LKRQ 70
Cdd:cd11395 83 LRQQ 86

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-like protein X (Mlx) and similar proteins; 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.

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               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
1AN2_A       3 KRAHHNALERKRRDHIKDSFHSLRDSVPSLQ------GEKASRAQILDKATEYIQYMRRKNHTHQQDIDDLKRQ 70
Cdd:cd19687  2 RREAHTQAEQKRRDAIKKGYDDLQDIVPTCQqqddigSQKLSKATILQRSIDYIQFLHQQKKKQEEELSALRKE 75

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'.

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               ....*....|....*....|....*....|....*....|....*....|....*
1AN2_A       3 KRAHHNALERKRRDHIKDSFHSLRDSVPSLQGEKASRAQILDKATEYIQYMRRKN 57
Cdd:cd11419  4 RREIANSNERRRMQSINAGFQSLRTLLPHCDGEKLSKAAILQQTAEYIFSLEQEK 58

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.

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1AN2_A       2 DKRAHHNALERKRRDHIKDSFHSLRDSVPSLQG-EKASRAQILDKATEYIQYMRRKNHTHQQDIDDLKRQNALLEQQVRA 80
Cdd:cd11457  6 AKRKNHNFLERKRRNDLRSRFLALRDEVPGLAScSKTPKVVILSKATEYLRGLVSAERRMAAEKRQLKSRQQQLLRRIAQ 85

               ..
1AN2_A      81 LE 82
Cdd:cd11457 86 LK 87

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.

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1AN2_A       2 DKRAHHNALERKRRDHIKDSFHSLRDSVPSL-QGEKASRAQILDKATEYIQYMRRKNHTHQQDIDDLKRQNallEQQVRA 80
Cdd:cd11456  4 ERRRNHNILERQRRNDLRSSFLTLRDHVPELvKNEKAAKVVILKKATEYVHSLQAEEQKLLLEKEKLQARQ---QQLLKK 80

               ....*.
1AN2_A      81 LEKARS 86
Cdd:cd11456 81 IEQART 86

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.

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               ....*....|....*....|....*....|....*....|....*....|....*
1AN2_A       2 DKRAHHNALERKRRDHIKDSFHSLRDSVPsLQGEKASRAQILDKATEYIQYMRRK 56
Cdd:cd19683  1 KSRERHNAKERQRRERIKIACDQLRKLVP-GCSRKTDKATVFEFTVAYIKFLREK 54

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.

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               ....*....|....*....|....*....|....*....|....*....|....*....|....*....
1AN2_A       3 KRAHHNALERKRRDHIKDSFHSLRDSVPSLQGeKASRAQILDKATEYIQYMRRKNHTHQQDIDDLKRQN 71
Cdd:cd11394  6 KRSAHNAIEKRYRSSINDRIIELKDLVVGPDA-KMNKSAVLRKAIDYIRYLQKVNQKLKQENMALKKAL 73

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.

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1AN2_A       4 RAHHNALERKRRDHIKDSFHSLRDSVPSlqGEKASRAQ---ILDKATEYIQYMRRKNHTHQQDIDDLKRQNALL 74
Cdd:cd11401  1 RSTHNELEKNRRAHLRLCLERLKELVPL--GPDATRHTtlsLLTKAKAYIKNLEDKEKRQRQQKEQLRREQREL 72

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.

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1AN2_A       7 HNALERKRRDHIKDSFHSLRDSVPSLQ----GEKASRAQILDKATEYIQYMRRKNH 58
Cdd:cd11396  2 HNEVERRRRDKINNWIVKLAKIVPDCEkdnsKQGQSKGGILSKACDYIQELRSQNE 57

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).

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1AN2_A       3 KRAHHNALERKRRDHIKDSFHSLRDSVPSLQGEKA----SRAQILDKATEYIQYMRRKNH 58
Cdd:cd18924  5 RRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTksgqSKGGILSKACDYIQELRQSNH 64

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.

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1AN2_A       7 HNALERKRRDHIKDSFHSLRDSVPSLQgeKASRAQILDKATEYIQYMRRK 56
Cdd:cd11393  1 HSIAERKRREKINERIRALRSLVPNGG--KTDKASILDEAIEYIKFLQEQ 48

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in sterol regulatory element-binding protein 1 (SREBP1) and similar proteins; SREBP1, also termed Class D basic helix-loop-helix protein 1 (bHLHd1), or sterol regulatory element-binding transcription factor 1 (SREBF1), is a member of a family of bHLHzip transcription factors that recognize sterol regulatory element 1 (SRE-1). It acts as a transcriptional activator required for lipid homeostasis. It may control transcription of the low-density lipoprotein receptor gene as well as the fatty acid. SREBP1 has dual sequence specificity binding to both an E-box motif (5'-ATCACGTGA-3') and to SRE-1 (5'-ATCACCCCAC-3').

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               ....*....|....*....|....*....|....*....|....*....|....*....|....*..
1AN2_A       2 DKRAHHNALERKRRDHIKDSFHSLRDSVPSLQGeKASRAQILDKATEYIQYMRRKNHTHQQDIDDLK 68
Cdd:cd18921  5 EKRTAHNAIEKRYRSSINDKIIELKDLVVGTEA-KLNKSAVLRKAIDYIRFLQQSNQKLKQENMALK 70

basic helix-loop-helix (bHLH) domain found in twist-related protein 1 (TWIST1) and similar proteins; TWIST1, also termed Class A basic helix-loop-helix protein 38 (bHLHa38), or H-twist, is a bHLH transcriptional regulator that inhibits myogenesis by sequestrating E proteins, inhibiting trans-activation by MEF2, and inhibiting DNA-binding by MYOD1 through physical interaction. It also represses expression of proinflammatory cytokines such as TNFA and IL1B. In addition, TWIST1 is involved in cancer development and progression.

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               ....*....|....*....|....*....|....*....|....*....|..
1AN2_A       2 DKRAHHNALERKRRDHIKDSFHSLRDSVPSLQGEKASRAQILDKATEYIQYM 53
Cdd:cd11412 11 TQRVMANVRERQRTQSLNEAFAALRKIIPTLPSDKLSKIQTLKLAARYIDFL 62

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein maternal effect embryo arrest 8 (AtMEE8) and similar proteins; AtMEE8, also termed AtbHLH108, or EN 132, is a bHLH transcription factor required during early embryo development, for the endosperm formation.

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               ....*....|....*....|....*....|....*....|....*....|....*....|...
1AN2_A       7 HNALERKRRDHIKDSFHSLRDSVPSLQgEKASRAQILDKATEYIQYMRRKNHTHQQDIDDLKR 69
Cdd:cd19698  1 HNLLEKKRRERIKDKIEILKGLTPNCT-PKSDIASILSCVIDYIKSLLLQVEKLSMGICDDWR 62

basic Helix-Loop-Helix (bHLH) domain found in Saccharomyces cerevisiae INO4 and similar proteins; INO4 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. INO4 dimerizes with INO2 and binds to an UAS DNA element to control expression of the genes whose expression is inositol-responsive.

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               ....*....|....*....|....*....|....*....|....*....|....*.
1AN2_A       3 KRAHHNALERKRRDHIKDSFHSLRDSVPSLQG-EKASRAQILDKATEYIQYMRRKN 57
Cdd:cd11403  2 KKENHISSEHKRREAIREGFDRLCAIVPALSSsQSRSEAVVYVKTVEYLKELYERR 57

basic helix-loop-helix (bHLH) domain found in heart- and neural crest derivatives-expressed protein 1 (HAND1) and similar proteins; HAND1, also termed Class A basic helix-loop-helix protein 27 (bHLHa27), or extraembryonic tissues, heart, autonomic nervous system and neural crest derivatives-expressed protein 1 (eHAND), is a bHLH transcription factor that plays an essential role in both trophoblast-giant cells differentiation and in cardiac morphogenesis.

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               ....*....|....*....|....*....|....*....|....
1AN2_A      11 ERKRRDHIKDSFHSLRDSVPSLQGE-KASRAQILDKATEYIQYM 53
Cdd:cd18952 10 ERRRTESINSAFAELRECIPNVPADtKLSKIKTLRLATSYIAYL 53

basic helix-loop-helix (bHLH) domain found in protein atonal homologs ATOH1, ATOH7 and similar proteins; The family includes ATOH1 and ATOH7. ATOH1, also termed Class A basic helix-loop-helix protein 14 (bHLHa14), or helix-loop-helix protein hATH-1 (hATH1), or Math1, or Cath1, is a proneural bHLH transcription factor that is essential for inner ear hair cell differentiation. It dimerizes with E47 and activates E-box (CANNTG) dependent transcription. ATOH1 is a mammalian homolog of the Drosophila melanogaster gene atonal and mouse atonal homolog 1 (Math1). ATOH7, also termed Class A basic helix-loop-helix protein 13 (bHLHa13), or helix-loop-helix protein hATH-5 (hATH5), or Math5, is a bHLH transcription factor involved in the differentiation of retinal ganglion cells. The family also includes protein Amos (also termed absent MD neurons and olfactory sensilla protein, or reduced olfactory organs protein, or rough eye protein). It is a bHLH transcription factor that promotes multiple dendritic neuron formation in the Drosophila peripheral nervous system.

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               ....*....|....*....|....*....|....*....|....*....|
1AN2_A       3 KRAHHNALERKRRDHIKDSFHSLRDSVPSLQGEKA-SRAQILDKATEYIQ 51
Cdd:cd11430  1 RRLAANARERRRMNGLNRAFDQLRSVVPSIGNDKKlSKYETLQMAQIYIE 50

basic helix-loop-helix (bHLH) domain found in heart- and neural crest derivatives-expressed protein (HAND) family; The HAND family includes two bHLH transcription factors, HAND1 and HAND2. HAND1, also termed Class A basic helix-loop-helix protein 27 (bHLHa27), or extraembryonic tissues, heart, autonomic nervous system and neural crest derivatives-expressed protein 1 (eHAND), plays an essential role in both trophoblast-giant cells differentiation and in cardiac morphogenesis. HAND2, also termed Class A basic helix-loop-helix protein 26 (bHLHa26), or deciduum, heart, autonomic nervous system and neural crest derivatives-expressed protein 2 (dHAND), is essential for cardiac morphogenesis, particularly for the formation of the right ventricle and of the aortic arch arteries.

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               ....*....|....*....|....*....|....*....|....*....|..
1AN2_A       3 KRAHHNALERKRRDHIKDSFHSLRDSVPSLQGE-KASRAQILDKATEYIQYM 53
Cdd:cd11466  1 RRGSANKKERRRTQSINSAFADLRECIPNVPADtKLSKIKTLRLATSYIAYL 52