helix loop helix domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 22658430    134 VNLGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLLDE 176
Cdd:smart00353  11 INEAFDELRSLLPTLPKNKKLSKAEILRLAIEYIKSLQEELQK 53

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        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 22658430 119 AVARRNERERNRVKLVNLGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLL 174
Cdd:cd19723   1 AVARRNERERNRVKLVNLGFATLREHVPNGRANKKMSKVETLRSAVEYIRQLQQLL 56

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
                ....*....|....*....|....*....|....*....|....*..
gi 22658430 128 RNRVKLVNLGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLL 174
Cdd:cd11418  10 RRRVQAVNDAFDRLRQHVPYLKRRKKLSKVKTLRRAIEYIRHLQKLL 56

basic helix-loop-helix (bHLH) domain found in achaete-scute-like proteins, ASCL3-5, and similar proteins; This subfamily includes three ASCL family of transcription factors, ASCL-3, ASCL-4 and ASCL-5. 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 specifically localized in the duct cells of the salivary glands. It may act as transcriptional repressor that inhibits myogenesis. ASCL-4, also termed Class A basic helix-loop-helix protein 44 (bHLHa44), or achaete-scute homolog 4 (ASH-4), or Hash4, may be involved in skin development. ASCL-5, also termed Class A basic helix-loop-helix protein 47 (bHLHa47), or achaete-scute homolog 5 (ASH-5), is an uncharacterized bHLH transcription factor that is close related to ASCL-3 and ASCL-4.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 22658430 128 RNRVKLVNLGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLL 174
Cdd:cd19724  10 RQRVRCVNEGYARLRRHLPLENKDKRLSKVETLRAAIRYIKHLQELL 56

basic helix-loop-helix (bHLH) domain found in achaete-scute-like protein 4 (ASCL-4) and similar proteins; ASCL-4, also termed Class A basic helix-loop-helix protein 44 (bHLHa44), or achaete-scute homolog 4 (ASH-4), or Hash4, is a bHLH transcriptional regulator that may be involved in skin development.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 22658430 116 QPAAVARRNERERNRVKLVNLGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLLD 175
Cdd:cd19746   5 EPAFIRKRNERERQRVRCVNEGYARLREHLPQELADKRLSKVETLRAAIDYIKHLQELLE 64

basic helix-loop-helix (bHLH) domain found in achaete-scute-like protein 5 (ASCL-5) and similar proteins; ASCL-5, also termed Class A basic helix-loop-helix protein 47 (bHLHa47), or achaete-scute homolog 5 (ASH-5), is an uncharacterized bHLH transcription factor that belongs to AS-C (achaete, scute, lethal of scute, and asense) family.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 22658430 116 QPAAVARRNERERNRVKLVNLGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLL 174
Cdd:cd19747   3 EPAFIQKRNERERQRVKCVNEGYARLRDHLPGAMAEKRLSKVETLRAAIRYIKYLQDLL 61

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
                ....*....|....*....|....*....|....*....|....
gi 22658430 131 VKLVNLGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLL 174
Cdd:cd11422  12 VRNLNSGFSKLRRIVPLIPRDRKPSKVDTLKGATEYIRLLQRIL 55

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
                ....*....|....*....|....*....|....*....
gi 22658430 134 VNLGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQQ 172
Cdd:cd00083   8 INDAFEELKRLLPELPDSKKLSKASILQKAVEYIRELQS 46

basic helix-loop-helix (bHLH) domain found in T-cell acute lymphocytic leukemia protein/ lymphoblastic leukemia-derived sequence (TAL/LYL) family; The TAL/LYL family includes a group of bHLH transcription factors (TAL1, TAL2 and LYL1) implicated in T cell acute leukaemia. They act as mediators of T cell leukaemogenesis. TAL-1, also termed Class A basic helix-loop-helix protein 17 (bHLHa17), or stem cell protein (SCL), or T-cell leukemia/lymphoma protein 5, is a hematopoietic-specific bHLH transcription factor that functions in embryonic and adult hematopoiesis in vertebrates. It is also required for embryonic vascular remodeling. It acts as a regulator of erythroid differentiation and binds to regulatory regions of a large cohort of erythroid genes as part of a complex with GATA-1, LMO2 and Ldb1. TAL-2, also termed Class A basic helix-loop-helix protein 19 (bHLHa19), is a bHLH transcription factor essential for the normal brain development. Lyl-1, also termed Class A basic helix-loop-helix protein 18 (bHLHa18), or lymphoblastic leukemia-derived sequence 1, is a proto-oncogenic bHLH transcription factor that plays an important role in hematopoietic stem cell function and is required for the late stages of postnatal angiogenesis to limit the formation of new blood vessels, notably by regulating the activity of the small GTPase Rap1. LYL-1 deficiency induces a stress erythropoiesis.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 22658430 134 VNLGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLLDEHD 178
Cdd:cd11413  16 VNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYIKFLEKILEDQE 60

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
                ....*....|....*....|....*....|....*....|...
gi 22658430 132 KLVNLGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLL 174
Cdd:cd19686  14 RSINDAFDGLRRHIPTFPYEKRLSKVDTLRLAIQYINFLTELL 56

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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 22658430 134 VNLGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLL 174
Cdd:cd11466  16 INSAFADLRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 56

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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 22658430 134 VNLGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLL 174
Cdd:cd18952  17 INSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 57

basic helix-loop-helix (bHLH) domain found in Drosophila melanogaster helix loop helix protein 3B (dHLH3B) and similar proteins; Drosophila HLH3B is an uncharacterized bHLH transcription factor that belongs to the T-cell acute lymphocytic leukemia protein/ lymphoblastic leukemia-derived sequence (TAL/LYL) family.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 22658430 134 VNLGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLLD 175
Cdd:cd19708  16 VNGAFAELRKLVPTHPPDKKLSKNEILRLAIKYIRLLSNVLE 57

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
                ....*....|....*....|....*....|....*
gi 22658430 138 FATLREHVPNGAANKKMSKVETLRSAVEYIRALQQ 172
Cdd:cd11400  20 FEKLRDLVPELADNEKASKVVILKKATEYIKQLQQ 54

basic helix-loop-helix (bHLH) domain found in Drosophila melanogaster myogenic-determination protein (dMYOD) and similar proteins; dMYOD, also termed protein nautilus, or Myd, may play an important role in the early development of muscle in Drosophila.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 22658430 131 VKLVNLGFATLREHVPNGAaNKKMSKVETLRSAVEYIRALQQLL 174
Cdd:cd19699  14 LRKVNEAFEVLKRRTCPNP-NQRLPKVEILRNAIEYIESLEDLL 56

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
                ....*....|....*....|....*....|....*....|....*....|..
gi 22658430 138 FATLREHVPNGAANKKMSKVETLRSAVEYIRALQ----QLLDEHDAVSAAFQ 185
Cdd:cd11456  24 FLTLRDHVPELVKNEKAAKVVILKKATEYVHSLQaeeqKLLLEKEKLQARQQ 75

basic helix-loop-helix (bHLH) domain found in helix-loop-helix protein (HEN) family; The HEN family includes two neuron-specific bHLH transcription factors, HEN-1 (also known as Nhlh1 or bHLHa35 or NSCL-1) and HEN-2 (also known as Nhlh2 or bHLHa34 or NSCL-2). They may serve as DNA-binding protein that is involved in the control of cell-type determination, possibly within the developing nervous system.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 22658430 131 VKLVNLGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLL 174
Cdd:cd11414  14 VEAFNSAFAQLRKLLPTLPPDKKLSKIEILRLAICYISYLNHVL 57

basic helix-loop-helix (bHLH) domain found in DNA-binding protein inhibitor ID2 and similar proteins; ID2, also termed Class B basic helix-loop-helix protein 26 (bHLHb26), or inhibitor of DNA binding 2, or inhibitor of differentiation 2, is a dominant negative helix-loop-helix (dnHLH) transcriptional regulator (lacking a basic DNA binding domain) which negatively regulates the bHLH transcription factors by forming heterodimers and inhibiting their DNA binding and transcriptional activity. It has been implicated in the regulation of cell proliferation and differentiation in myogenesis, neurogenesis, and/or hematopoiesis.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 22658430 134 VNLGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLLDEH 177
Cdd:cd19692  22 MNDCYSKLKELVPSIPQNKKVSKMEILQHVIDYILDLQIALDSH 65

basic helix-loop-helix (bHLH) domain found in muscle, intestine and stomach expression 1 (MIST-1) and similar proteins; MIST-1, also termed Class A basic helix-loop-helix protein 15 (bHLHa15), or Class B basic helix-loop-helix protein 8 (bHLHb8), is a bHLH transcription factor expressed in pancreatic acinar cells and other serous exocrine cells. It is essential for cytoskeletal organization and secretory activity. It also functions as a potent endoplasmic reticulum (ER) stress-inducible transcriptional regulator. MIST-1 is capable of binding to E-box (CANNTG) motifs as a homodimer or a heterodimer with E-proteins (E12 and E47) to regulate transcription.

                        10        20        30
                ....*....|....*....|....*....|....*..
gi 22658430 134 VNLGFATLREHVPNGAANKKMSKVETLRSAVEYIRAL 170
Cdd:cd19711  16 LNNAFQALREVIPHVRAEKKLSKIETLTLAKNYIKSL 52

basic helix-loop-helix (bHLH) domain found in DNA-binding protein inhibitor ID4 and similar proteins; ID4, also termed Class B basic helix-loop-helix protein 27 (bHLHb27), or inhibitor of DNA binding 4, or inhibitor of differentiation 4, is a dominant negative helix-loop-helix (dnHLH) transcriptional regulator (lacking a basic DNA binding domain) which negatively regulates the bHLH transcription factors by forming heterodimers and inhibiting their DNA binding and transcriptional activity. It plays a role in adipose cell differentiation.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 22658430 134 VNLGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLLDEHDAV 180
Cdd:cd19694  11 MNDCYSRLKRLVPTIPPNKKVSKVEILQHVIDYILDLQLALETHPAL 57

basic helix-loop-helix (bHLH) domain found in protein atonal homolog 8 (ATOH8) and similar proteins; ATOH8, also termed Class A basic helix-loop-helix protein 21 (bHLHa21), or helix-loop-helix protein hATH-6 (hATH6), is a bHLH shear-stress-responsive transcription factor expressed in activated satellite cells and proliferating myoblasts of human skeletal muscle tissue. It regulates endothelial cell proliferation, migration and tube-like structures formation. ATOH8 binds a palindromic (canonical) core consensus DNA sequence 5'-CANNTG- 3' known as an E-box element, possibly as a heterodimer with other bHLH proteins.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 22658430 130 RVKLVNLGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLLDE 176
Cdd:cd11421  19 RVHTISAAFEALRKAVPSYSYNQKLSKLAILRIACSYILALARLADL 65

basic helix-loop-helix (bHLH) domain found in helix-loop-helix protein 2 (HEN-2) and similar proteins; HEN-2, also termed nescient helix-loop-helix 2 (Nhlh2), or Class A basic helix-loop-helix protein 34 (bHLHa34), or nescient helix loop helix 2 (NSCL-2), is a neuron-specific bHLH transcription factor that may serve as DNA-binding protein and may be involved in the control of cell-type determination, possibly within the developing nervous system.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 22658430 131 VKLVNLGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLLD 175
Cdd:cd19702  28 VEAFNLAFAELRKLLPTLPPDKKLSKIEILRLAICYISYLNHVLD 72

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
                ....*....|....*....|....*....|....*....
gi 22658430 134 VNLGFATLREHVPNgAANKKMSKVETLRSAVEYIRALQQ 172
Cdd:cd11419  19 INAGFQSLRTLLPH-CDGEKLSKAAILQQTAEYIFSLEQ 56

basic helix-loop-helix (bHLH) domain found in transcription factor 15 (TCF-15) and similar proteins; TCF-15, also termed Class A basic helix-loop-helix protein 40 (bHLHa40), or paraxis, or protein bHLH-EC2, is a bHLH transcription factor expressed in caudal lateral and paraxial mesoderm dermomyotome and sclerotome fore limb buds during embryo development. It may function as an early transcriptional regulator involved in the patterning of the mesoderm and in lineage determination of cell types derived from the mesoderm.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 22658430 134 VNLGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLL 174
Cdd:cd11470  23 VNTAFTALRTLIPTEPVDRKLSKIETLRLASSYIAHLANVL 63

basic helix-loop-helix (bHLH) domain found in Drosophila melanogaster protein Amos and similar proteins; Amos, also termed absent MD neurons and olfactory sensilla protein, or reduced olfactory organs protein, or rough eye protein, is a bHLH transcription factor that promotes multiple dendritic neuron formation in the Drosophila peripheral nervous system.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 22658430 134 VNLGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLL 174
Cdd:cd19715  23 LNVAFDKLRDVVPSLGDDRKLSKYETLQMAQSYITALKELL 63

basic helix-loop-helix (bHLH) domain found in neurogenic differentiation factor 6 (NeuroD6) and similar proteins; NeuroD6, also termed Class A basic helix-loop-helix protein 2 (bHLHa2), or protein atonal homolog 2 (ATH-2), or Atoh2, or Math2, or Nex1, is a neurogenic bHLH transcription factor involved in neuronal development, differentiation, and survival in Alzheimer's disease (AD) brains of both cohorts. It plays an integrative role in coordinating increase in mitochondrial mass with cytoskeletal remodeling, suggesting that it may act as a co-regulator of neuronal differentiation and energy metabolism.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 22658430 134 VNLGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLL 174
Cdd:cd19722  29 LNDALDSLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEIL 69

basic helix-loop-helix (bHLH) domain found in muscle, intestine and stomach expression 1 (MIST-1) family; MIST-1, also termed Class A basic helix-loop-helix protein 15 (bHLHa15), or Class B basic helix-loop-helix protein 8 (bHLHb8), is a bHLH transcription factor expressed in pancreatic acinar cells and other serous exocrine cells. It is essential for cytoskeletal organization and secretory activity. It also functions as a potent endoplasmic reticulum (ER) stress-inducible transcriptional regulator. MIST-1 is capable of binding to E-box (CANNTG) motifs as a homodimer or a heterodimer with E-proteins (E12 and E47) to regulate transcription. The family also includes Drosophila melanogaster protein dimmed and similar proteins. Dimmed, also termed DIMM, is a bHLH transcription factor that regulates neurosecretory (NS) cell function and neuroendocrine cell fate in Drosophila.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 22658430 133 LVNLGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLL 174
Cdd:cd11426  15 QLNDAFQALREVIPHVRSERKLSKIETLTLAKNYIKSLTNMI 56

basic helix-loop-helix (bHLH) domain found in myogenic regulatory factor (MRF) family; MRFs are a family of muscle-specific bHLH transcription proteins (MyoD, Myf5, Mrf4 and MyoG) that plays an essential role in regulating skeletal muscle development and growth. MRFs are capable of binding to E-box motifs as a heterodimer with E-proteins to regulate transcription expression.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 22658430 131 VKLVNLGFATL-REHVPNgaANKKMSKVETLRSAVEYIRALQQLL 174
Cdd:cd11411  14 LKKVNEAFEALkRCTSAN--PNQRLPKVEILRNAIEYIESLQDLL 56

basic helix-loop-helix (bHLH) domain found in myoblast determination protein 1 (MYOD1) and similar proteins; MYOD1, also termed Class C basic helix-loop-helix protein 1 (bHLHc1), or myogenic factor 3 (Myf-3), is a bHLH transcriptional activator that promotes transcription of muscle-specific target genes and plays a role in muscle differentiation. Together with Myf-5 and MYOG, MYOD1 co-occupies muscle-specific gene promoter core region during myogenesis.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 22658430 134 VNLGFATLREHVPNGAaNKKMSKVETLRSAVEYIRALQQLL 174
Cdd:cd18936  21 VNEAFETLKRCTSTNP-NQRLPKVEILRNAIRYIESLQALL 60

basic helix-loop-helix (bHLH) domain found in protein atonal homolog 1 (ATOH1) and similar proteins; 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).

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 22658430 134 VNLGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLL 174
Cdd:cd19713  21 LNHAFDQLRNVIPSFNNDKKLSKYETLQMAQIYINALSELL 61

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
                ....*....|....*....|....*....|....*...
gi 22658430 139 ATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLLDE 176
Cdd:cd11442  17 SRLRALLPSIATSDKVSKATVLEEACNYIRNLHREVDD 54

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
                ....*....|....*....|....*....|....*....
gi 22658430 138 FATLREHVPNGaanKKMSKVETLRSAVEYIRALQQLLDE 176
Cdd:cd11393  16 IRALRSLVPNG---GKTDKASILDEAIEYIKFLQEQVKV 51

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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 22658430 138 FATLREHVPNGAaNKKMSKVETLRSAVEYIRALQQLLDEHDA 179
Cdd:cd11402  21 FETLKRQIPNLD-DKKTSNLNILRSALRYIQILKRKEKEYEH 61

basic helix-loop-helix (bHLH) domain found in Drosophila melanogaster protein extra-macrochaetae and similar proteins; Extra-macrochaetae is a negative regulator of sensory organ development in Drosophila. It belongs to dominant negative group of helix-loop-helix (dnHLH) proteins, which lack a basic DNA-binding domain but can form heterodimers with other HLH proteins, thereby inhibiting DNA binding.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 22658430 138 FATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLLDEH 177
Cdd:cd19695  12 LAKLRNLVPTLPKNRKVSKLELLQHVIDYIADLEEQLEDH 51

basic helix-loop-helix (bHLH) domain found in neurogenic differentiation factor 4 (NeuroD4) and similar proteins; NeuroD4, also termed Class A basic helix-loop-helix protein 4 (bHLHa4), or protein atonal homolog 3 (ATH-3), or Atoh3, or Math-3, is a bHLH transcriptional activator that mediates neuronal differentiation.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 22658430 134 VNLGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLLDE 176
Cdd:cd19721  45 LNDALDNLRRVMPCYSKTQKLSKIETLRLARNYIWALSEVLET 87

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split (HES)-related repressor protein (HERP)-like family; The HERP-like family includes bHLH-O transcriptional regulators that are related to the Drosophila hairy and Enhancer-of-split proteins. They contain a basic helix-loop-helix (bHLH) domain with an invariant glycine residue in its basic region, an orange domain in the central region and YXXW sequence motif at its C-terminal region. HERP proteins (HEY1, HEY2 and HEYL) act as downstream effectors of Notch signaling. They are involved in cardiovascular development and have roles in somitogenesis, myogenesis and gliogenesis. Hairy and enhancer of split-related protein HELT is a transcriptional repressor expressed in the developing central nervous system. It binds preferentially to the canonical E box sequence 5'-CACGCG-3' and regulates neuronal differentiation and/or identity. Differentially expressed in chondrocytes proteins, DEC1 and DEC2, are widely expressed in both embryonic and adult tissues and have been implicated in apoptosis, cell proliferation, and circadian rhythms, as well as malignancy in various cancers. Drosophila melanogaster protein clockwork orange (Cwo) is also included in this family. It is involved in the regulation of Drosophila circadian rhythms. It functions as both an activator and a repressor of clock gene expression.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 22658430 134 VNLGFATLREHVPNGAA---NKKMSKVETLRSAVEYIRALQQLL 174
Cdd:cd11389  12 INESLAELRRLVPEARKskgSGKLEKAEILEMTLQHLKALQSST 55

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
                ....*....|....*....|....*....|....*....|....*....|....
gi 22658430 134 VNLGFATLREHVP---------------NGAANKKMSKVETLRSAVEYIRALQQ 172
Cdd:cd11395  18 LNTKIERLRDAIPslrspegksddgglgGLAPTTKLSKATILTKAIEYIRHLEQ 71

basic helix-loop-helix (bHLH) domain found in twist-related protein (TWIST) family; The TWIST family includes TWIST1 and TWIST2, which are highly homologous bHLH transcription factors that promote epithelial-mesenchymal transition (EMT) during development and tumor metastasis. They are involved in the negative regulation of cellular determination and in the differentiation of several lineages, including myogenesis, osteogenesis, and neurogenesis. TWIST factors express in broad partially-overlapping patterns during embryo development and dimerize with a broad sets of dimer partners that form numerous unique transcriptional complexes to regulate embryonic development.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 22658430 134 VNLGFATLREHVPNGAANKkMSKVETLRSAVEYIRALQQLL 174
Cdd:cd11464  16 LNEAFTSLRKIIPTLPSDK-LSKIQTLKLAARYIDFLYQVL 55

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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 22658430 134 VNLGFATLREHVPNGAANkKMSKVETLRSAVEYIRALQQLL--DEHDAVSAA 183
Cdd:cd11412  27 LNEAFAALRKIIPTLPSD-KLSKIQTLKLAARYIDFLYQVLqsDELDSKMAS 77