basic helix-loop-helix (bHLH) domain found in achaete-scute-like protein 1 (ASCL-1) and similar proteins; 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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 15131817 110 QQPAAVARRNERERNRVKLVNLGFATLREHVPNGAANKKMSKVETLRSAVQYIRALQQLLDEHDAVSAAFQ 180
Cdd:cd19742   1 QQPAAVARRNERERNRVKLVNMGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLLDEHDAVSAAFQ 71

basic helix-loop-helix (bHLH) domain found in achaete-scute-like protein 1 (ASCL-1) and similar proteins; 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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 15131817 110 QQPAAVARRNERERNRVKLVNLGFATLREHVPNGAANKKMSKVETLRSAVQYIRALQQLLDEHDAVSAAFQ 180
Cdd:cd19742   1 QQPAAVARRNERERNRVKLVNMGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLLDEHDAVSAAFQ 71

Helix-loop-helix DNA-binding domain;

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 15131817   129 VNLGFATLREHVPNGAANKKMSKVETLRSAVQYIRALQ 166
Cdd:pfam00010  16 INDAFDELRELLPTLPPDKKLSKAEILRLAIEYIKHLQ 53

basic helix-loop-helix (bHLH) domain found in achaete-scute-like protein 1 (ASCL-1) and similar proteins; 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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 15131817 110 QQPAAVARRNERERNRVKLVNLGFATLREHVPNGAANKKMSKVETLRSAVQYIRALQQLLDEHDAVSAAFQ 180
Cdd:cd19742   1 QQPAAVARRNERERNRVKLVNMGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLLDEHDAVSAAFQ 71

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 15131817 114 AVARRNERERNRVKLVNLGFATLREHVPNGAANKKMSKVETLRSAVQYIRALQQLL 169
Cdd:cd19723   1 AVARRNERERNRVKLVNLGFATLREHVPNGRANKKMSKVETLRSAVEYIRQLQQLL 56

tissue specific basic helix-loop-helix (bHLH-TS) domain family; Tissue specific bHLH domain family includes transcription regulators whose expression are restricted to certain tissues. They are involved in cell-fate determination and process in neurogenesis, cardiogenesis, myogenesis, and hematopoiesis and include proteins from myogenic regulatory factor (MRF) family, twist-related protein (TWIST) family, scleraxis-like family, heart- and neural crest derivatives-expressed protein (HAND) family, helix-loop-helix protein (HEN) family, musculin-like family, germline alpha (FIGLA) family, T-cell acute lymphocytic leukemia protein/ lymphoblastic leukemia-derived sequence (TAL/LYL) family, ovary, uterus and testis protein (OUT) family, mesoderm posterior protein (Mesp) family, muscle, intestine and stomach expression 1 (MIST-1) family, protein atonal homologs (ATOH) family, neurogenin (NGN) family, neurogenic differentiation factor (NeuroD) family, achaete-scute complex-like (ASCL) family, Fer3-like protein (FERD3L)-like family, and Oligodendrocyte lineage genes (OLIG) family of transcription factors.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 15131817 126 VKLVNLGFATLREHVPNGAANKKMSKVETLRSAVQYIRALQQLL 169
Cdd:cd11390  12 MHDLNDAFEALRKVLPTVPPDKKLSKIETLRLAINYIAALSDLL 55

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 15131817 123 RNRVKLVNLGFATLREHVPNGAANKKMSKVETLRSAVQYIRALQQLL 169
Cdd:cd19724  10 RQRVRCVNEGYARLRRHLPLENKDKRLSKVETLRAAIRYIKHLQELL 56

basic helix-loop-helix (bHLH) domain found in achaete-scute-like protein 3 (ASCL-3) and similar proteins; 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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 15131817 112 PAAVARRNERERNRVKLVNLGFATLREHVPNGAANKKMSKVETLRSAVQYIRALQQLL 169
Cdd:cd19745   2 PAFIRKRNERERQRVKCVNEGYAKLRRHLPQEYSEKRLSKVETLRAAIKYIKHLQSVL 59

basic helix-loop-helix (bHLH) domain found in Drosophila melanogaster achaete-scute complex (AS-C) proteins and similar proteins; 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.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 15131817 114 AVARRNERERNRVKLVNLGFATLREHVP--------NGA---ANKKMSKVETLRSAVQYIRALQQLL 169
Cdd:cd19744   1 SVARRNARERNRVKQVNNGFAILRQHIPqsviedltAGGgrgKSKKLSKVDTLRMAVEYIRRLQKLL 67

Helix-loop-helix DNA-binding domain;

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 15131817   129 VNLGFATLREHVPNGAANKKMSKVETLRSAVQYIRALQ 166
Cdd:pfam00010  16 INDAFDELRELLPTLPPDKKLSKAEILRLAIEYIKHLQ 53

basic helix-loop-helix (bHLH) domain found in scleraxis, transcription factor 15 (TCF-15) and similar proteins; The family includes scleraxis and transcription factor 15 (TCF-15). Scleraxis, also termed SCX, or Class A basic helix-loop-helix protein 41 (bHLHa41), or Class A basic helix-loop-helix protein 48 (bHLHa48), is a bHLH transcription factor that is expressed in sclerotome limb bud cranial and body wall mesenchyme, pericardium and heart valves, ligaments and tendons. It is required for tendon formation ligaments, connective tissue, the diaphragm, and testis development. Scleraxis plays a central role in promoting fibroblast proliferation and matrix synthesis during the embryonic development of tendons. 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 15131817 129 VNLGFATLREHVPNGAANKKMSKVETLRSAVQYIRALQQLL 169
Cdd:cd11465  15 VNSAFTALRTLIPTEPADRKLSKIETLRLASSYISHLATVL 55

basic helix-loop-helix (bHLH) domain found in heart- and neural crest derivatives-expressed protein 2 (HAND2) and similar proteins; 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 a bHLH transcription factor that is essential for cardiac morphogenesis, particularly for the formation of the right ventricle and of the aortic arch arteries.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 15131817 129 VNLGFATLREHVPNGAANKKMSKVETLRSAVQYIRALQQLLDEHD 173
Cdd:cd11471  16 INSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDLLAKDD 60

basic helix-loop-helix (bHLH) domain found in neurogenic differentiation factor (NeuroD) family; The NeuroD family includes NeuroD1, NeuroD2, NeuroD4 and NeuroD6. NeuroD1, also termed Class A basic helix-loop-helix protein 3 (bHLHa3), is a neuronal bHLH transcription factor involved in the development and maintenance of the endocrine pancreas and neuronal elements. It acts as an essential regulator of glutamatergic neuronal differentiation. Loss of NeuroD1 causes ataxia, cerebellar hypoplasia, sensorineural deafness, and severe retinal dystrophy in mice. NeuroD2, also termed Class A basic helix-loop-helix protein 1 (bHLHa1), or NeuroD-related factor (NDRF), is a neuronal calcium-dependent bHLH transcription factor that induces neuronal differentiation and promotes neuronal survival. It plays a central role in thalamocortical synaptic maturation. NeuroD2 mediates calcium-dependent transcription activation by binding to E box-containing promoter. 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. 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
                ....*....|....*....|....*....|....
gi 15131817 136 LREHVPNGAANKKMSKVETLRSAVQYIRALQQLL 169
Cdd:cd11427  22 LRKVVPCYSKTQKLSKIETLRLARNYIWALSEIL 55

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 15131817 129 VNLGFATLREHVPNGAANKKMSKVETLRSAVQYIRALQQLL 169
Cdd:cd11466  16 INSAFADLRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 56

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 15131817 129 VNLGFATLREHVPNGAANKKMSKVETLRSAVQYIRALQQLLD 170
Cdd:cd19708  16 VNGAFAELRKLVPTHPPDKKLSKNEILRLAIKYIRLLSNVLE 57

basic helix-loop-helix (bHLH) domain found in Drosophila melanogaster protein taxi and similar proteins; Protein taxi, also termed protein delilah (Dei), is a bHLH transcription factor that is involved in regulation of cell adhesion and attachment that is expressed in specialized cells that provide anchoring sites to either muscles (tendon cells), or proprioceptors (chordotonal attachment cells) during embryonic development. It probably plays an important role in the differentiation of epidermal cells into the tendon cells that form the attachment sites for all muscles.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 15131817 129 VNLGFATLREHVP---NGAANKKMSKVETLRSAVQYIRALQQLL 169
Cdd:cd11431  16 INDAFEALRRAVPeypVAGKDGKLTKITTLRLAMNYIKALTDLL 59

basic helix-loop-helix (bHLH) domain found in pancreas transcription factor 1 subunit alpha (PTF1A) and similar proteins; 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 a bHLH transcription factor 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 15131817 129 VNLGFATLREHVPNGAANKKMSKVETLRSAVQYIRALQQLL 169
Cdd:cd11417  16 INDAFEGLRSHIPTLPYEKRLSKVDTLRLAIGYINFLSELV 56

basic helix-loop-helix (bHLH) domain found in Fer3-like protein (FERD3L) and similar proteins; 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 a bHLH transcription factor 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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 15131817 129 VNLGFATLREHVPNGAANKKMSKVETLRSAVQYIRALQQLL 169
Cdd:cd11415  24 LNEAFDKLRKKVPTFAYEKRLSRIETLRLAIVYISFMTDLL 64

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 15131817 129 VNLGFATLREHVPNGAANKKMSKVETLRSAVQYIRAL 165
Cdd:cd19711  16 LNNAFQALREVIPHVRAEKKLSKIETLTLAKNYIKSL 52

basic helix-loop-helix (bHLH) domain found in protein atonal homolog 7 (ATOH7) and similar proteins; 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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 15131817 129 VNLGFATLREHVPNGAANKKMSKVETLRSAVQYIRALQQLLDE 171
Cdd:cd19714  23 LNTAFDRLRKVVPQWGQDKKLSKYETLQMALSYIMALTRILAE 65

basic helix-loop-helix (bHLH) domain found in Caenorhabditis elegans Helix-loop-helix protein 13 (HLH13) and similar proteins; Caenorhabditis elegans HLH13, also termed Fer3-like protein, or nephew of atonal 3, is a bHLH transcription factor that plays a role in the negative regulation of exit from L1 arrest and dauer diapause dependent on IIS signaling (insulin and insulin-like growth factor (IGF) signaling).

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 15131817 129 VNLGFATLREHVPNGAANKKMSKVETLRSAVQYIRALQQLL 169
Cdd:cd11416  20 INSAFEELRCHVPTFPYEKRLSKIDTLRLAIAYIALLRDIL 60

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 15131817 126 VKLVNLGFATLREHVPNGAANKKMSKVETLRSAVQYIRALQQLLD 170
Cdd:cd19702  28 VEAFNLAFAELRKLLPTLPPDKKLSKIEILRLAICYISYLNHVLD 72

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 15131817 133 FATLREHVPNGAANKKMSKVETLRSAVQYIRALQ----QLLDEHDAVSAAFQ 180
Cdd:cd11456  24 FLTLRDHVPELVKNEKAAKVVILKKATEYVHSLQaeeqKLLLEKEKLQARQQ 75

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 15131817 129 VNLGFATLREHVPNGAANKKMSKVETLRSAVQYIRALQQLLDEHDAV 175
Cdd:cd19694  11 MNDCYSRLKRLVPTIPPNKKVSKVEILQHVIDYILDLQLALETHPAL 57

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 15131817 129 VNLGFATLREHVPNGAANKKMSKVETLRSAVQYIRALQQLL 169
Cdd:cd11470  23 VNTAFTALRTLIPTEPVDRKLSKIETLRLASSYIAHLANVL 63

basic helix-loop-helix (bHLH) domain found in protein lyl-1 and similar proteins; 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 involved in T-cell acute lymphoblastic leukemia. It 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 15131817 129 VNLGFATLREHVPNGAANKKMSKVETLRSAVQYIRALQQLLDEH 172
Cdd:cd19705  21 VNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYIDFLVTLLRDQ 64

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 15131817 129 VNLGFATLREHVPNGAANKKMSKVETLRSAVQYIRALQQLL 169
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 15131817 128 LVNLGFATLREHVPNGAANKKMSKVETLRSAVQYIRALQQLL 169
Cdd:cd11426  15 QLNDAFQALREVIPHVRSERKLSKIETLTLAKNYIKSLTNMI 56

basic helix-loop-helix (bHLH) domain found in 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
                ....*....|....*....|....*....|....*..
gi 15131817 129 VNLGFATLREHVPNGAANKKMSKVETLRSAVQYIRAL 165
Cdd:cd19712  16 LNDAFQGLREVIPHVNAERKLSKIETLTLAKNYIKAL 52

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 15131817 129 VNLGFATLREHVPNgAANKKMSKVETLRSAVQYIRALQQ 167
Cdd:cd11419  19 INAGFQSLRTLLPH-CDGEKLSKAAILQQTAEYIFSLEQ 56

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 15131817 133 FATLREHVPNGAaNKKMSKVETLRSAVQYIRALQQLLDEHDA 174
Cdd:cd11402  21 FETLKRQIPNLD-DKKTSNLNILRSALRYIQILKRKEKEYEH 61

basic helix-loop-helix (bHLH) domain found in neurogenin (NGN) family; The NGN family includes three neural-specific bHLH transcription factors, NGN1-3, which may function at neuroblast selection genes during the development of several neuronal lineages. NGN-1, also termed Class A basic helix-loop-helix protein 6 (bHLHa6), or neurogenic basic-helix-loop-helix protein, or neurogenic differentiation factor 3 (NeuroD3), is a neural-specific bHLH transcription factor involved in the initiation of neuronal differentiation. NGN-2, also termed Class A basic helix-loop-helix protein 8 (bHLHa8), or protein atonal homolog 4 (ATOH4), is a neural-specific bHLH transcription factor required for sensory neurogenesis. NGN-3, also termed Class A basic helix-loop-helix protein 7 (bHLHa7), or protein atonal homolog 5 (ATOH5), is a neural-specific bHLH transcription factor expressed in the developing central nervous system and the embryonic pancreas. It is involved in neurogenesis and plays an important role in spermatogenesis.

                        10        20        30
                ....*....|....*....|....*....|....*
gi 15131817 136 LREHVPNGAANKKMSKVETLRSAVQYIRALQQLLD 170
Cdd:cd11428  23 LREVLPSFPDETKLTKIETLRFAHNYIWALSETLK 57

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 15131817 129 VNLGFATLREHVPNGAANKKMSKVETLRSAVQYIRALQQLL 169
Cdd:cd19713  21 LNHAFDQLRNVIPSFNNDKKLSKYETLQMAQIYINALSELL 61

basic helix-loop-helix (bHLH) domain found in neurogenin-2 (NGN-2) and similar proteins; NGN-2, also termed Class A basic helix-loop-helix protein 8 (bHLHa8), or protein atonal homolog 4 (ATOH4), is a neural-specific bHLH transcription factor required for sensory neurogenesis. It activates transcription by binding to the E box (5'-CANNTG-3').

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 15131817 129 VNLGFATLREHVPNGAANKKMSKVETLRSAVQYIRALQQLL 169
Cdd:cd19717  25 LNAALDSLREVLPTFPEDAKLTKIETLRFAHNYIWALSETL 65

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 15131817 129 VNLGFATLREHVPNGAANKKMSKVETLRSAVQYIRALQQLLDE 171
Cdd:cd19721  45 LNDALDNLRRVMPCYSKTQKLSKIETLRLARNYIWALSEVLET 87

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 15131817 133 FATLREHVPNGaanKKMSKVETLRSAVQYIRALQQLLDE 171
Cdd:cd11393  16 IRALRSLVPNG---GKTDKASILDEAIEYIKFLQEQVKV 51

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in MLX-interacting protein (MLXIP) and similar proteins; 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.

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 15131817 129 VNLGFATLREHVPNGAANKKMSKVETLRSAVQYIRALQQ 167
Cdd:cd19688  18 IKICFDTLNSLVSTLKNSKPISNAITLQKTVEYIAKLQQ 56

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 15131817 133 FATLREHVPNGAANKKMSKVETLRSAVQYIRALQQLLDEH 172
Cdd:cd19695  12 LAKLRNLVPTLPKNRKVSKLELLQHVIDYIADLEEQLEDH 51

basic helix-loop-helix (bHLH) domain found in Oligodendrocyte lineage genes (OLIG) family of transcription factors; The OLIG family includes three bHLH transcription factors, Oligo1-3, which are expressed in both the developing and mature central nervous system. Oligo1 and Oligo2 are expressed in a nervous tissue-specific manner, but Oligo3 is found mainly in non-neural tissues. Oligo (also known as Olig) have key roles in the specification of motor neurons, dorsal interneurons, and oligodendrocytes. Oligo1, also termed Class B basic helix-loop-helix protein 6 (bHLHb6), or Class E basic helix-loop-helix protein 21 (bHLHe21), promotes formation and maturation of oligodendrocytes, especially within the brain. Oligo2, also termed Class B basic helix-loop-helix protein 1 (bHLHb1), or Class E basic helix-loop-helix protein 19 (bHLHe19), or protein kinase C-binding protein 2, or protein kinase C-binding protein RACK17, is required for oligodendrocyte and motor neuron specification in the spinal cord, as well as for the development of somatic motor neurons in the hindbrain. It cooperates with OLIG1 to establish the MN progenitors (pMN) domain of the embryonic neural tube. Oligo3, also termed Class B basic helix-loop-helix protein 7 (bHLHb7), or Class E basic helix-loop-helix protein 20 (bHLHe20), is expressed in the ventricular zone of the dorsal alar plate of the hindbrain and involved in regulating the development of dorsal and ventral spinal cord. It may determine the distinct specification program of class A neurons in the dorsal part of the spinal cord and suppress specification of class B neurons. This family also includes two OLIG-related bHLH transcription factors, bHLHe22 and bHLHe23. bHLHe22, also termed Class B basic helix-loop-helix protein 5 (bHLHb5), or trinucleotide repeat-containing gene 20 protein, is a neural-specific transcriptional repressor that is expressed in both excitatory (unipolar brush cells) and inhibitory neurons (cartwheel cells) of the dorsal cochlear nucleus (DCN) during development. It is important for the proper development and/or survival of a number of neural cell types. bHLHe23, also termed Class B basic helix-loop-helix protein 4 (bHLHb4), is expressed in rod bipolar cells and is required for rod bipolar cell maturation. bHLHe23 have roles in spinal interneuron differentiation by mechanisms linked to the Notch signaling pathway. It modulates the expression of genes required for the differentiation and/or maintenance of pancreatic and neuronal cell types.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 15131817 130 NLGFATLREHVP--NGAANKKMSKVETLRSAVQYIRALQQLLDE 171
Cdd:cd11429  16 NSALDGLRSVMPyaQGPSVRKLSKIATLLLARNYILMLTQALEE 59