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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186910325 278 RRRTHNVMERQRRNELKNCFLRLRDNVPELSNNDKASKVVILKRAKESIRNLESENQRLTSKRDKLRERQEQLKARLEQL 357
Cdd:cd11400    1 KRRLHNVLERQRRNDLKNSFEKLRDLVPELADNEKASKVVILKKATEYIKQLQQEEKKLEKEKDKLKARNEQLRKKLERL 80

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186910325 278 RRRTHNVMERQRRNELKNCFLRLRDNVPELSNNDKASKVVILKRAKESIRNLESENQRLTSKRDKLRERQEQLKARLEQL 357
Cdd:cd11400    1 KRRLHNVLERQRRNDLKNSFEKLRDLVPELADNEKASKVVILKKATEYIKQLQQEEKKLEKEKDKLKARNEQLRKKLERL 80

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 186910325   283 NVMERQRRNELKNCFLRLRDNVPELSNNDKASKVVILKRAKESIRNLESENQ 334
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPKNKKLSKAEILRLAIEYIKSLQEELQ 52

Myc amino-terminal region; The myc family belongs to the basic helix-loop-helix leucine zipper class of transcription factors, see pfam00010. Myc forms a heterodimer with Max, and this complex regulates cell growth through direct activation of genes involved in cell replication. Mutations in the C-terminal 20 residues of this domain cause unique changes in the induction of apoptosis, transformation, and G2 arrest.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186910325   30 KDLQCIPTPPQSPPMKPGLAK-NMSTVDQLELVSELLMEDTdflqldWNFTGPASSADDP------LSEDCLW-----RP 97
Cdd:pfam01056  45 KKFELLPTPPLSPSRRSSLSSpFPSTADQLEMVTELLGADL------VNQSFICDPDEDDsflksiIIQDCMWsgfsaAA 118

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186910325   98 DGDKQTEDKL---SAVLSTSPLLSDIDTQIFAEIAGST------------LDCHTAALAC-------------------- 142
Cdd:pfam01056 119 KLEKVVSEKLasgQAARKEGAATLAAGAASSAGRAHSGsagggrsssgylQDLSHSASECvdpsvvfpfplnkrekapvp 198

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186910325  143 ------QALESEDSPLDSQEQIESTSDYGSLSTGGESSTSDSEEE----------IDVVTVRRSSTLTRSQHQQQLEDSR 206
Cdd:pfam01056 199 papspaLALDPPATPPRSSGSSSSSGDSKGLSSSGEDTLSDSDDEeeeeeeeeeeIDVVTVEKRQPSSKRKEVSTLTTAL 278

                         250       260
                  ....*....|....*....|....*
gi 186910325  207 ---REQQR--ALKRYHFeIQQQHNY 226
Cdd:pfam01056 279 ghsRPQHSplVLKRCHV-IIHQHNY 302

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186910325 278 RRRTHNVMERQRRNELKNCFLRLRDNVPELSNNDKASKVVILKRAKESIRNLESENQRLTSKRDKLRERQEQLKARLEQL 357
Cdd:cd11400    1 KRRLHNVLERQRRNDLKNSFEKLRDLVPELADNEKASKVVILKKATEYIKQLQQEEKKLEKEKDKLKARNEQLRKKLERL 80

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 186910325 274 DEEERRRTHNVMERQRRNELKNCFLRLRDNVPELSNNDKASKVVILKRAKESIRNLESENQRLTSKRDKLRERQEQLKAR 353
Cdd:cd11456    1 EDSERRRNHNILERQRRNDLRSSFLTLRDHVPELVKNEKAAKVVILKKATEYVHSLQAEEQKLLLEKEKLQARQQQLLKK 80

                 ....*
gi 186910325 354 LEQLK 358
Cdd:cd11456   81 IEQAR 85

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 186910325 279 RRTHNVMERQRRNELKNCFLRLRDNVPELSNNDKASKVVILKRAKESIRNLESENQRLTSKRDKLRERQEQLKARL 354
Cdd:cd11401    1 RSTHNELEKNRRAHLRLCLERLKELVPLGPDATRHTTLSLLTKAKAYIKNLEDKEKRQRQQKEQLRREQRELKRRL 76

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 186910325   283 NVMERQRRNELKNCFLRLRDNVPELSNNDKASKVVILKRAKESIRNLESENQ 334
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPKNKKLSKAEILRLAIEYIKSLQEELQ 52

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 186910325 276 EERRRTHNVMERQRRNELKNCFLRLRDNVPELSNND---------------KASKVVILKRAKESIRNLESENQRLTSKR 340
Cdd:cd11395    1 PRKRLPHNAIEKRYRSNLNTKIERLRDAIPSLRSPEgksddgglgglapttKLSKATILTKAIEYIRHLEQENERLEEEN 80

                 ....*.
gi 186910325 341 DKLRER 346
Cdd:cd11395   81 EELRQQ 86

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 186910325 286 ERQRRNELKNCFLRLRDNVPELSNNDKASKVVILKRAKESIRNLES 331
Cdd:cd00083    1 ERRRRDKINDAFEELKRLLPELPDSKKLSKASILQKAVEYIRELQS 46

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-associated protein 3 (Mad3) and similar proteins; Mad3, also termed Max dimerization protein 3, or Max dimerizer 3 (MXD3), or Class C basic helix-loop-helix protein 13 (bHLHc13), or Max-interacting transcriptional repressor MAD3, or Myx, is a bHLHZip Max-interacting transcriptional repressor that plays an important role in cellular proliferation. It suppresses c-myc dependent transformation and is expressed during neural and epidermal differentiation.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 186910325 279 RRTHNVMERQRRNELKNCFLRLRDNVPELSNNDKASKVVILKRAKESIRNLESENQRLTSKRDKLRERQEQLKARLEQL 357
Cdd:cd18932    7 RSVHNELEKHRRAQLRRCLEQLKQQVPLGADCSRYTTLSLLRRARLHIQKLEEQEQRAQQLKERLRWEQQKLRRRLESL 85

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-interacting protein 1 (MXI1) and similar proteins; MXI1, also termed Max interactor 1, or Class C basic helix-loop-helix protein 11 (bHLHc11), is a bHLHZip transcriptional repressor that binds with MAX to form a sequence-specific DNA-binding protein complex which recognizes the core sequence 5'-CAC[GA]TG-3'. It thus antagonizes MYC transcriptional activity by competing for MAX. It plays an important role in the regulation of cell proliferation.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 186910325 279 RRTHNVMERQRRNELKNCFLRLRDNVPELSNNDKASKVVILKRAKESIRNLESENQRLTSKRDKLRERQEQLKARLEQL 357
Cdd:cd18930    2 RSTHNELEKNRRAHLRLCLERLKVLIPLGPDCTRHTTLGLLNKAKAHIKKLEEADRKSQHQLENLEREQRFLKRRLEQL 80

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 186910325 279 RRTHNVMERQRRNELKNCFLRLRDNVPELSNNDKASKVVILKRAKESIRNLESENQRLTSKRDKLRERQEQLKARLEQLK 358
Cdd:cd18929    3 RSSHNELEKHRRAKLRLYLEQLKQLVPLGPDSTRHTTLSLLKRAKMHIKKLEEQDRKALNIKEQLQREHRYLKRRLEQLS 82

                 ..
gi 186910325 359 RH 360
Cdd:cd18929   83 VQ 84

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 186910325 276 EERRRTHNVMERQRRNELKNCFLRLRD--NVPELSNNDKASKVVILKRAKESIRNLESENQRLTS 338
Cdd:cd11388    1 PVKKWKHVEAEKKRRNQIKKGFEDLINliNYPRNNNEKRISKSELLNKAVDDIRGLLKANEQLQE 65

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 186910325 276 EERRRTHNVMERQRRNELKNCFLRLRDNVPELSNND--KASKVVILKRAKESIRNLESENQRLTSKRDKLRER 346
Cdd:cd11405    1 EQRRLSHISAEQKRRFNIKSGFDTLQSLIPSLGQNPnqKVSKAAMLQKAAEYIKSLKRERQQMQEEAEQLRQE 73

Possible nuclease of RNase H fold, RuvC/YqgF family [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186910325 262 RSLVVRQPVDTEDEEERRRTHNVME--------RQRRNELKncflRLRDNVPELSNNDKASKVVI------LKRAKES-- 325
Cdd:COG2433  383 EELIEKELPEEEPEAEREKEHEERElteeeeeiRRLEEQVE----RLEAEVEELEAELEEKDERIerlereLSEARSEer 458

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 186910325 326 --------IRNLESENQRLTSKRDKLRERQEQLKARLEQLKRH 360
Cdd:COG2433  459 reirkdreISRLDREIERLERELEEERERIEELKRKLERLKEL 501

Myc amino-terminal region; The myc family belongs to the basic helix-loop-helix leucine zipper class of transcription factors, see pfam00010. Myc forms a heterodimer with Max, and this complex regulates cell growth through direct activation of genes involved in cell replication. Mutations in the C-terminal 20 residues of this domain cause unique changes in the induction of apoptosis, transformation, and G2 arrest.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186910325   30 KDLQCIPTPPQSPPMKPGLAK-NMSTVDQLELVSELLMEDTdflqldWNFTGPASSADDP------LSEDCLW-----RP 97
Cdd:pfam01056  45 KKFELLPTPPLSPSRRSSLSSpFPSTADQLEMVTELLGADL------VNQSFICDPDEDDsflksiIIQDCMWsgfsaAA 118

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186910325   98 DGDKQTEDKL---SAVLSTSPLLSDIDTQIFAEIAGST------------LDCHTAALAC-------------------- 142
Cdd:pfam01056 119 KLEKVVSEKLasgQAARKEGAATLAAGAASSAGRAHSGsagggrsssgylQDLSHSASECvdpsvvfpfplnkrekapvp 198

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186910325  143 ------QALESEDSPLDSQEQIESTSDYGSLSTGGESSTSDSEEE----------IDVVTVRRSSTLTRSQHQQQLEDSR 206
Cdd:pfam01056 199 papspaLALDPPATPPRSSGSSSSSGDSKGLSSSGEDTLSDSDDEeeeeeeeeeeIDVVTVEKRQPSSKRKEVSTLTTAL 278

                         250       260
                  ....*....|....*....|....*
gi 186910325  207 ---REQQR--ALKRYHFeIQQQHNY 226
Cdd:pfam01056 279 ghsRPQHSplVLKRCHV-IIHQHNY 302

basic helix-loop-helix (bHLH) domain found in Drosophila melanogaster achaete-scute complex (AS-C) proteins, achaete-scute-like proteins, ASCL1-2, and similar proteins; This subfamily includes Drosophila melanogaster AS-C proteins and two ASCL family of transcription factors, ASCL-1 and ASCL-2. Drosophila melanogaster AS-C proteins includes lethal of scute (also known as achaete-scute complex protein T3 or AST3), scute (also known as achaete-scute complex protein T4 or AST4), achaete (also known as achaete-scute complex protein T5 or AST5), and asense (also known as achaete-scute complex protein T8 or AST8). They are involved in the determination of the neuronal precursors in the peripheral nervous system and the central nervous system, as well as in sex determination and dosage compensation. ASCL-1, also termed Class A basic helix-loop-helix protein 46 (bHLHa46), or achaete-scute homolog 1 (ASH-1), or mammalian achaete scute homolog 1 (Mash1), is expressed in subsets of neural progenitors in both the central and peripheral nervous system. It plays a key role in neuronal differentiation and specification in the nervous system. ASCL-2, also termed achaete-scute homolog 2 (ASH-2), or Class A basic helix-loop-helix protein 45 (bHLHa45), or mammalian achaete scute homolog 2 (Mash2), is involved in Schwann cell differentiation and control of proliferation in adult peripheral nerves.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 186910325 283 NVMERQRRNELKNCFLRLRDNVPELSNNDKASKVVILKRAKESIRNLE 330
Cdd:cd19723    6 NERERNRVKLVNLGFATLREHVPNGRANKKMSKVETLRSAVEYIRQLQ 53

basic helix-loop-helix (bHLH) domain found in factor in the germline alpha (FIGLA) and similar proteins; FIGLA, also termed FIGalpha, or Class C basic helix-loop-helix protein 8 (bHLHc8), or folliculogenesis-specific basic helix-loop-helix protein, or transcription factor FIGa, is a germ-cell-specific bHLH transcription factor expressed abundantly in female and less so in male germ cells. It is essential for primordial follicle formation and expression of many genes required for folliculogenesis, fertilization and early embryonic survival. FIGLA knockout mice cannot form primordial follicles and lose oocytes rapidly after birth, whereas male gonads are unaffected.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 186910325 279 RRTHNVMERQRRNELKNCFLRLRDNVPELSNNDKASKVVILKRAKESIRNLE 330
Cdd:cd11422    1 RRVANARERERVRNLNSGFSKLRRIVPLIPRDRKPSKVDTLKGATEYIRLLQ 52

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in upstream stimulatory factor 2 (USF2) and similar proteins; USF2, also termed Class B basic helix-loop-helix protein 12 (bHLHb12), or major late transcription factor 2, or FOS-interacting protein (FIP), or upstream transcription factor 2, 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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 186910325 272 TEDEEERRRTHNVMERQRRNELKNCFLRLRDNVPELSNNDK---ASKVVILKRAKESIRNLESENQRL 336
Cdd:cd18923    2 TPRDERRRAQHNEVERRRRDKINNWIVQLSKIIPDCNTDNSktgASKGGILSKACDYIRELRQTNQRM 69

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 186910325 278 RRRTHNVMERQRRNELKNCFLRLRDNVPELSNND-----KASKVVILKRAKESIRNLESENQRLTSKRDKLR 344
Cdd:cd19687    2 RREAHTQAEQKRRDAIKKGYDDLQDIVPTCQQQDdigsqKLSKATILQRSIDYIQFLHQQKKKQEEELSALR 73

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 186910325 278 RRRTHNVMERQRRNELKNCFLRLRDNVPELsNNDKASKVVILKRAKESIRNLESENQRL 336
Cdd:cd11419    4 RREIANSNERRRMQSINAGFQSLRTLLPHC-DGEKLSKAAILQQTAEYIFSLEQEKTRL 61

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 186910325 275 EEERRRTHNVMERQRRNELKNCFLRLRDNVPElSNNDKASKVVILKRAKESIRNLESENQRL 336
Cdd:cd18910    2 REKKRESHNEVERRRKDKINAGINKIGELLPD-RDAKKQSKNMILEQAYKYIVELKKKNDKL 62

basic helix-loop-helix (bHLH) domain found in achaete-scute complex-like (ASCL) family; The achaete-scute complex-like (ASCL, also known as achaete-scute complex homolog or ASH) family of bHLH transcription factors, ASCL1-5, have been implicated in cell fate specification and differentiation. They are critical for proper development of the nervous system. The deregulation of ASCL plays a key role in psychiatric and neurological disorders. ASCL-1, also termed Class A basic helix-loop-helix protein 46 (bHLHa46), or achaete-scute homolog 1 (ASH-1), or mammalian achaete-scute homolog 1 (Mash1), is a neural-specific bHLH transcription factor that is expressed in subsets of neural progenitors in both the central and peripheral nervous system. It plays a key role in neuronal differentiation and specification in the nervous system. ASCL-2, also termed achaete-scute homolog 2 (ASH-2), or Class A basic helix-loop-helix protein 45 (bHLHa45), or mammalian achaete-scute homolog 2 (Mash2), is a bHLH transcription factor that is involved in Schwann cell differentiation and control of proliferation in adult peripheral nerves. ASCL-3, also termed Class A basic helix-loop-helix protein 42 (bHLHa42), or bHLH transcriptional regulator Sgn-1, or achaete-scute homolog 3 (ASH-3), is a bHLH transcription factor specifically localized in the duct cells of the salivary glands. It may act as transcriptional repressor that inhibits myogenesis. The family also includes Drosophila melanogaster achaete-scute complex (AS-C) proteins, which consists of lethal of scute (also known as achaete-scute complex protein T3 or AST3), scute (also known as achaete-scute complex protein T4 or AST4), achaete (also known as achaete-scute complex protein T5 or AST5), and asense (also known as achaete-scute complex protein T8 or AST8). They are involved in the determination of the neuronal precursors in the peripheral nervous system and the central nervous system, as well as in sex determination and dosage compensation.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 186910325 277 ERRrthNVMERQRRNELKNCFLRLRDNVPELSNNDKASKVVILKRAKESIRNLE 330
Cdd:cd11418    3 ARR---NERERRRVQAVNDAFDRLRQHVPYLKRRKKLSKVKTLRRAIEYIRHLQ 53

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein ABA-INDUCIBLE bHLH-TYPE (AIB) and similar proteins; The family includes several bHLH transcription factors from Arabidopsis thaliana, such as AIB and MYC proteins (MYC2, MYC3 and MYC4). AIB, also termed AtbHLH17, or EN 35, is a transcription activator that regulates positively abscisic acid (ABA) response. MYC2, also termed protein jasmonate insensitive 1, or R-homologous Arabidopsis protein 1 (RAP-1), or AtbHLH6, or EN 38, or Z-box binding factor 1 protein, is a transcriptional activator involved in abscisic acid (ABA), jasmonic acid (JA), and light signaling pathways. MYC3, also termed protein altered tryptophan regulation 2, or AtbHLH5, or transcription factor ATR2, or EN 36, is a transcription factor involved in tryptophan, jasmonic acid (JA) and other stress-responsive gene regulation. MYC4, also termed AtbHLH4, or EN 37, is a transcription factor involved in jasmonic acid (JA) gene regulation. MYC2, together with MYC3 and MYC4, controls additively subsets of JA-dependent responses.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 186910325 286 ERQRRNELKNCFLRLRDNVPELSNNDKAS----KVVILKRAKESIRNLESENQRL 336
Cdd:cd11449   13 ERQRREKLNQRFYALRAVVPNVSKMDKASllgdAISYINELKSKVQDMETEKKEM 67

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 186910325 273 EDEEERRRTHNVMERQRRNELKNCFLRLRDNVPelSNNDKASKVVILKRAKESIRNLESENQRLTSKRDKLRERQEQLKA 352
Cdd:cd11398    2 EWHRQRRDNHKEVERRRRENINEGINELAALVP--GNAREKNKGAILARAVEYIQELQETEAKNIEKWTLEKLLTDQAIA 79

                 ....*
gi 186910325 353 RLEQL 357
Cdd:cd11398   80 ELAAL 84

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 186910325 278 RRRTHNVMERQRRNELKNCFLRLRDNVPELSNNDKASKVVILKRAKESIRNL 329
Cdd:cd11430    1 RRLAANARERRRMNGLNRAFDQLRSVVPSIGNDKKLSKYETLQMAQIYIETL 52

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 186910325 286 ERQRRNELKNCFLRLRDNVPELSNNDKASKVVILKRAKESIRNLESEnqrltskRDKLRERQEQL 350
Cdd:cd11442    5 SRISDDQKNDLYSRLRALLPSIATSDKVSKATVLEEACNYIRNLHRE-------VDDLSERLSRL 62

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 186910325 281 THNVMERQRRNELKNCFLRLRDNVPEL---SNNDKASKVVILKRAKESIRNLESENQR 335
Cdd:cd11387    1 SHNAVERRRRDNINEKIQELGSLVPPSrleTKDLKPNKGSILSKAVEYIRELQNQNQE 58

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein IAA-leucine resistant 3 (ILR3) and similar proteins; ILR3, also termed AtbHLH105, or EN 133, is a bHLH transcription factor that plays a role in resistance to amide-linked indole-3-acetic acid (IAA) conjugates such as IAA-Leu and IAA-Phe. It may regulate gene expression in response to metal homeostasis changes.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 186910325 286 ERQRRNELKNCFLRLrDNVPELSNNDKASKVVILKRAKESIRNLESENQRLTSKRDKLRERQEQLKARLEQLK 358
Cdd:cd11446    5 EKLRRDKLNERFMEL-SNVLEPGRPPKTDKATILGDAIRMLKQLRGEVQKLKEENSSLQEESKELKAEKNELR 76

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186910325   257 IPGRSRSLVVRQPVDTEDEEERRRThnvmeRQRRNELKNCFLRLRDNVPELSNNDKASKVViLKRAKESIRNLESENQRL 336
Cdd:TIGR02169  655 MTGGSRAPRGGILFSRSEPAELQRL-----RERLEGLKRELSSLQSELRRIENRLDELSQE-LSDASRKIGEIEKEIEQL 728

                           90       100
                   ....*....|....*....|...
gi 186910325   337 TSKRDKLRERQEQLKARLEQLKR 359
Cdd:TIGR02169  729 EQEEEKLKERLEELEEDLSSLEQ 751

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
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 186910325 282 HNVMERQRRNELKNCFLRLRDNVPELSNNDKASkvvILKRAKESIRNLESENQRLTSKR 340
Cdd:cd11451    6 HAMAERRRREKLNERFITLRSMVPFVTKMDKVS---ILGDAIEYLKQLQRRVEELESRR 61

basic helix-loop-helix (bHLH) domain found in Fer3-like protein (FERD3L), pancreas transcription factor 1 subunit alpha (PTF1A) and similar proteins; The family corresponds to a group of bHLH transcription factors, including FERD3L and PTF1A. FERD3L, also termed basic helix-loop-helix protein N-twist, or Class A basic helix-loop-helix protein 31 (bHLHa31), or nephew of atonal 3 (NATO3), or Neuronal twist (NTWIST), is expressed in the developing central nervous system (CNS). It regulates floor plate (FP) cells development. FP is a critical organizing center located at the ventral-most midline of the neural tube. FERD3L binds to the E-box and functions as inhibitor of transcription. PTF1A, also termed Class A basic helix-loop-helix protein 29 (bHLHa29), or pancreas-specific transcription factor 1a, or bHLH transcription factor p48, or p48 DNA-binding subunit of transcription factor PTF1 (PTF1-p48), is implicated in the cell fate determination in various organs. It binds to the E-box consensus sequence 5'-CANNTG-3' and plays a role in early and late pancreas development and differentiation.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 186910325 279 RRTHNVMERQRRNELKNCFLRLRDNVPELSNNDKASKVVILKRAKESIRNL 329
Cdd:cd19686    2 RQAANIRERKRMRSINDAFDGLRRHIPTFPYEKRLSKVDTLRLAIQYINFL 52

basic helix-loop-helix (bHLH) domain found in the DNA-binding protein inhibitor (ID) family; The ID family includes a dominant negative group of helix-loop-helix (dnHLH) proteins, ID1-4, that are negative regulators of bHLH transcription factors. They contain the HLH-dimerization domain but lack the basic domain necessary for DNA-binding. ID proteins inhibit binding to DNA and transcriptional transactivation by heterodimerization with bHLH proteins. They also interact with many non-bHLH proteins in complex networks. ID proteins have been implicated in regulating gene expression as well as cell-cycle progression. Whereas ID-1, ID-2 and ID-3, are generally considered as tumor promoters, ID4 on the contrary has emerged as a tumor suppressor.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 186910325 292 ELKNCFLRLRDNVPELSNNDKASKVVILKRAKESIRNLESE 332
Cdd:cd19684    7 EMQDCYSKLKELVPTIPQNKKVSKVEILQHVIDYILDLQLA 47

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 186910325 275 EEERRRTHNVMERQRRNELKNCFLRLRDNVPELSNND-KASKVVILKRAKESIRNLESENQRltSKRDKLRERQEQLKAR 353
Cdd:cd18928    8 ERQKKDNHNLIERRRRFNINDRIKELGTLIPKSTDPEmRWNKGTILKASVDYIRKLQKEQQR--SKEIEMRQRKLEQANR 85

                 ....*
gi 186910325 354 LEQLK 358
Cdd:cd18928   86 SLQLR 90