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        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333656161  82 KKTTKLRLERVKFRRQEANARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEILR 151
Cdd:cd19722     1 KKMTKARMERVKVRRQEANARERNRMHGLNDALDSLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEILR 70

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        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333656161  82 KKTTKLRLERVKFRRQEANARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEILR 151
Cdd:cd19722     1 KKMTKARMERVKVRRQEANARERNRMHGLNDALDSLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEILR 70

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1333656161  100 NARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEILR 151
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPKNKKLSKAEILRLAIEYIKSLQEELQ 52

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        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333656161  82 KKTTKLRLERVKFRRQEANARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEILR 151
Cdd:cd19722     1 KKMTKARMERVKVRRQEANARERNRMHGLNDALDSLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEILR 70

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        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1333656161  74 PRRRGLRKKKTTKLRLERVKFRRQEANARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEILR 151
Cdd:cd19721     9 PKRRGPKKKKMTKARLERFRARRVKANARERSRMHGLNDALDNLRRVMPCYSKTQKLSKIETLRLARNYIWALSEVLE 86

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        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1333656161  96 RQEANARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEIL 150
Cdd:cd11427     1 RVKANARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLARNYIWALSEIL 55

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        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1333656161  95 RRQEANARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEILR 151
Cdd:cd11428     1 RRLKANDRERNRMHNLNDALDALREVLPSFPDETKLTKIETLRFAHNYIWALSETLK 57

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        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1333656161  85 TKLRLERVkfRRQEANARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEILRIG 153
Cdd:cd19717     2 TVLKIKKT--RRVKANNRERNRMHNLNAALDSLREVLPTFPEDAKLTKIETLRFAHNYIWALSETLRLA 68

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 1333656161  95 RRQEANARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEIL 150
Cdd:cd11430     1 RRLAANARERRRMNGLNRAFDQLRSVVPSIGNDKKLSKYETLQMAQIYIETLSELL 56

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        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1333656161  95 RRQEANARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEIL 150
Cdd:cd11421     8 RRIEANARERTRVHTISAAFEALRKAVPSYSYNQKLSKLAILRIACSYILALARLA 63

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        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1333656161  95 RRQEANARERNRMHGLNDALDNLRKVVPCY---SKTQKLSKIETLRLAKNYIWALSEIL 150
Cdd:cd11431     1 RRKTANARERDRMREINDAFEALRRAVPEYpvaGKDGKLTKITTLRLAMNYIKALTDLL 59

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        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1333656161  95 RRQEANARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEIL 150
Cdd:cd19712     1 RRLESNERERMRMHSLNDAFQGLREVIPHVNAERKLSKIETLTLAKNYIKALTNVI 56

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        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1333656161  95 RRQEANARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEIL 150
Cdd:cd19711     1 RRLESNERERQRMHKLNNAFQALREVIPHVRAEKKLSKIETLTLAKNYIKSLTTTI 56

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 1333656161  96 RQEANARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEIL 150
Cdd:cd19686     2 RQAANIRERKRMRSINDAFDGLRRHIPTFPYEKRLSKVDTLRLAIQYINFLTELL 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        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1333656161  95 RRQEANARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEIL 150
Cdd:cd11415     9 QRQAANIRERRRMFNLNEAFDKLRKKVPTFAYEKRLSRIETLRLAIVYISFMTDLL 64

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 1333656161  95 RRQEANARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEIL 150
Cdd:cd11418     1 RVARRNERERRRVQAVNDAFDRLRQHVPYLKRRKKLSKVKTLRRAIEYIRHLQKLL 56

basic helix-loop-helix (bHLH) domain found in Class E basic helix-loop-helix protein 22 (bHLHe22) and similar proteins; bHLHe22, also termed Class B basic helix-loop-helix protein 5 (bHLHb5), or trinucleotide repeat-containing gene 20 protein, is an OLIG-related bHLH 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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1333656161  96 RQEANARERNRMHGLNDALDNLRKVVPcYSKT---QKLSKIETLRLAKNYIW----ALSEILRI 152
Cdd:cd18954     2 RLNINARERRRMHDLNDALDELRAVIP-YAHSpsvRKLSKIATLLLAKNYILmqanALEEMRRL 64

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        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1333656161  93 KFRRQEANARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEILRIG 153
Cdd:cd11416     3 KVQRHAANIRERKRMLSINSAFEELRCHVPTFPYEKRLSKIDTLRLAIAYIALLRDILRSG 63

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        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1333656161  95 RRQEANARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEIL 150
Cdd:cd11417     1 QRQAANLRERRRMQSINDAFEGLRSHIPTLPYEKRLSKVDTLRLAIGYINFLSELV 56

basic helix-loop-helix (bHLH) domain found in oligodendrocyte transcription factors, Oligo2, Oligo3 and similar proteins; The family includes two bHLH transcription factors, Oligo2 and Oligo3. 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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1333656161  96 RQEANARERNRMHGLNDALDNLRKVVPcYSK---TQKLSKIETLRLAKNYIWALSEILRIGKR 155
Cdd:cd19725     2 RLKINSRERKRMHDLNSALDGLREVMP-YAHgpsVRKLSKIATLLLARNYILMLTNSLEEMKR 63

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        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1333656161  95 RRQEANARERNRMHGLNDALDNLRKVVPCYSkTQKLSKIETLRLAKNYIWALSEILRIG 153
Cdd:cd11464     1 QRVLANVRERQRTQSLNEAFTSLRKIIPTLP-SDKLSKIQTLKLAARYIDFLYQVLRSD 58

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1333656161  90 ERVKFRRQEANARERNRMHGLNDALDNLRKVVPCYSkTQKLSKIETLRLAKNYIWALSEILR 151
Cdd:cd11412     7 EELQTQRVMANVRERQRTQSLNEAFAALRKIIPTLP-SDKLSKIQTLKLAARYIDFLYQVLQ 67

basic helix-loop-helix (bHLH) domain found in Class E basic helix-loop-helix protein 23 (bHLHe23) and similar proteins; bHLHe23, also termed Class B basic helix-loop-helix protein 4 (bHLHb4), is an OLIG-related bHLH transcription factor that 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        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1333656161  96 RQEANARERNRMHGLNDALDNLRKVVPcYSKT---QKLSKIETLRLAKNYIW----ALSEILRI 152
Cdd:cd18953     8 RLSINARERRRMHDLNDALDGLRSVIP-YAHSpsvRKLSKIATLLLAKNYILmqaqALEEMRRL 70

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        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333656161  95 RRQEANARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEILRIGK 154
Cdd:cd19708     1 RRMFTNSRERWRQQNVNGAFAELRKLVPTHPPDKKLSKNEILRLAIKYIRLLSNVLEWQK 60

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        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1333656161  95 RRQEANARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEIL 150
Cdd:cd11466     1 RRGSANKKERRRTQSINSAFADLRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 56

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 1333656161 103 ERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSE 148
Cdd:cd00083     1 ERRRRDKINDAFEELKRLLPELPDSKKLSKASILQKAVEYIRELQS 46

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        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1333656161 100 NARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEIL 150
Cdd:cd19724     6 NERERQRVRCVNEGYARLRRHLPLENKDKRLSKVETLRAAIRYIKHLQELL 56

basic helix-loop-helix (bHLH) domain found in musculin, transcription factor 21 (TCF-21) and similar proteins; The family includes two bHLH transcription factors, musculin and transcription factor 21 (TCF-21). Musculin, also termed activated B-cell factor 1 (ABF-1), or Class A basic helix-loop-helix protein 22 (bHLHa22), is a bHLH transcription factor expressed in activated B lymphocytes. It acts as a transcription repressor capable of inhibiting the transactivation capability of TCF3/E47. Musculin may play a role in regulating antigen-dependent B-cell differentiation. The mouse homolog, musculin, is suggested to be a repressor of myogenesis that is expressed in developing muscle and in the spleen. TCF-21, also termed capsulin, or Class A basic helix-loop-helix protein 23 (bHLHa23), or epicardin, or podocyte-expressed 1 (Pod-1), is a bHLH transcription factor expressed specifically in mesodermally-derived cells that surround the epithelium of the developing gastrointestinal, genitourinary and respiratory systems during mouse embryogenesis. It may play a role in the specification or differentiation of one or more subsets of epicardial cell types.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1333656161  95 RRQEANARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEIL 150
Cdd:cd11423     1 QRNAANARERARMRVLSKAFSRLKTTLPWVPPDTKLSKLDTLRLAASYIAHLRQIL 56

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 1333656161 100 NARERNRMHGLNDALDNLRKVVPCY-----------SKTQKLSKIETLRLAKNYIWALSEIL 150
Cdd:cd19744     6 NARERNRVKQVNNGFAILRQHIPQSviedltagggrGKSKKLSKVDTLRMAVEYIRRLQKLL 67

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        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1333656161  95 RRQEANARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEILR 151
Cdd:cd11413     1 RRIFTNTRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYIKFLEKILE 57

basic helix-loop-helix (bHLH) domain found in musculin and similar proteins; Musculin, also termed activated B-cell factor 1 (ABF-1), or Class A basic helix-loop-helix protein 22 (bHLHa22), is a bHLH transcription factor expressed in activated B lymphocytes. It acts as a transcription repressor capable of inhibiting the transactivation capability of TCF3/E47. Musculin may play a role in regulating antigen-dependent B-cell differentiation. The mouse homolog, musculin, is suggested to be a repressor of myogenesis that is expressed in developing muscle and in the spleen. Musculin heterodimerizes with products of the E2A gene.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1333656161  93 KFRRQEANARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEILR 151
Cdd:cd19703     2 QSQRNAANARERARMRVLSKAFSRLKTSLPWVPPDTKLSKLDTLRLASSYIAHLRQLLQ 60

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        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1333656161  95 RRQEANARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEILR 151
Cdd:cd19705     6 RRVFTNSRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYIDFLVTLLR 62

basic helix-loop-helix (bHLH) domain found in achaete-scute-like protein 2 (ASCL-2) and similar proteins; 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1333656161 100 NARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEIL 150
Cdd:cd19743     8 NERERNRVKLVNLGFAALRQHVPQGGASKKMSKVETLRSAVEYIRALQRLL 58

basic helix-loop-helix (bHLH) domain found in T-cell acute lymphocytic leukemia protein 1 (TAL-1) and similar proteins; 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-1 has been implicated in T-cell acute lymphoblastic leukemia. In common with other tissue-specific bHLH proteins, Tal heterodimerizes with ubiquitously-expressed members of the E2A family and form a DNA-binding complex with an E-box (CANNTG) to regulate transcription at its recognition site.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1333656161  95 RRQEANARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEIL 150
Cdd:cd19706     4 RRIFTNSRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLL 59

basic helix-loop-helix (bHLH) domain found in helix-loop-helix protein 1 (HEN-1) and similar proteins; HEN-1, also termed nescient helix-loop-helix 1 (Nhlh1), or Class A basic helix-loop-helix protein 35 (bHLHa35), or nescient helix loop helix 1 (NSCL-1), 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        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1333656161  79 LRKKKTTKLRLERVKFRRQEANaRERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEIL 150
Cdd:cd19701     1 LSREERRRRRRATAKYRTAHAT-RERIRVEAFNVAFAELRKLLPTLPPDKKLSKIEILRLAICYISYLNHVL 71

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 1333656161  93 KFRRQEANARERNRMHGLNDALDNLRKVVPCYSKtQKLSKIETLRLAKNYIWAL 146
Cdd:cd11419     2 RIRREIANSNERRRMQSINAGFQSLRTLLPHCDG-EKLSKAAILQQTAEYIFSL 54

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        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1333656161  79 LRKKKTTKLRLERVKFRRQEANaRERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEILRI 152
Cdd:cd19702     1 LSREEKRRRRRATAKYRSAHAT-RERIRVEAFNLAFAELRKLLPTLPPDKKLSKIEILRLAICYISYLNHVLDV 73

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 1333656161  97 QEANARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEIL 150
Cdd:cd19747     8 QKRNERERQRVKCVNEGYARLRDHLPGAMAEKRLSKVETLRAAIRYIKYLQDLL 61

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
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1333656161 100 NARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEIL 150
Cdd:cd19746    13 NERERQRVRCVNEGYARLREHLPQELADKRLSKVETLRAAIDYIKHLQELL 63

basic helix-loop-helix (bHLH) domain found in myogenic factor 5 (Myf-5) and similar proteins; Myf-5, also termed Class C basic helix-loop-helix protein 2 (bHLHc2), is a nuclear bHLH transcriptional activator that promotes transcription of muscle-specific target genes and plays a role in muscle specification and differentiation. It also acts as an RNA-binding protein which enhances Ccnd1/Cyclin D1 mRNA translation during myogenesis.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1333656161  95 RRQEANARERNRMHGLNDALDNLRKVVPCySKTQKLSKIETLRLAKNYIWALSEILR 151
Cdd:cd18937     2 RRKAATMRERRRLKKVNQAFETLKRCTTS-NPNQRLPKVEILRNAIRYIESLQDLLR 57

basic helix-loop-helix (bHLH) domain found in ovary, uterus and testis protein (OUT) family; The OUT family includes transcription factor 23 (TCF-23), transcription factor 24 (TCF-24) and similar proteins. TCF-23, also termed Class A basic helix-loop-helix protein 24 (bHLHa24), is a bHLH transcription factor that is essential for progesterone-dependent decidualization. The mouse homolog is also called ovary, uterus and testis protein (OUT), which is expressed predominantly in the reproductive organs such as the uterus, ovary and testis. It shows an Id-like inhibitory activity and functions as a negative regulator of bHLH factors through the formation of a functionally inactive heterodimeric complex. OUT inhibits the formation of TCF3 and MYOD1 homodimers and heterodimers, but lacks DNA binding activity. OUT is involved in the regulation or modulation of smooth muscle contraction of the uterus during pregnancy and particularly around the time of delivery. It also plays a role in the inhibition of myogenesis. Unlike typical bHLH factors, OUT proteins do not bind E-box (CANNTG) or N-box DNA sequences and inhibit DNA binding of homo- and heterodimers consisting of E12 and MyoD in gel mobility shift assays. TCF-24 is an uncharacterized bHLH transcription factor that shows high sequence similarity with TCF-23.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1333656161 101 ARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEIL 150
Cdd:cd11424     6 ARERSRVRTLRTAFQSLQRALPAVPPDTKLSKLDVLLLASRYIAHLTRKL 55

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 1333656161 100 NARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEIL 150
Cdd:cd19745     9 NERERQRVKCVNEGYAKLRRHLPQEYSEKRLSKVETLRAAIKYIKHLQSVL 59

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
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1333656161  95 RRQEANARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWAL 146
Cdd:cd11400     1 KRRLHNVLERQRRNDLKNSFEKLRDLVPELADNEKASKVVILKKATEYIKQL 52

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein aborted microspores (AMS) and similar proteins; The family includes several bHLH transcription factors from Arabidopsis thaliana, such as AMS, ICE1 and SCREAM2. AMS, also termed AtbHLH21, or EN 48, plays a crucial role in tapetum development and it is required for male fertility and pollen differentiation. ICE1, also termed inducer of CBF expression 1, or AtbHLH116, or EN 45, or SCREAM, acts as a transcriptional activator that regulates the cold-induced transcription of CBF/DREB1 genes. It binds specifically to the MYC recognition sites (5'-CANNTG-3') found in the CBF3/DREB1A promoter. SCREAM2, also termed AtbHLH33, or EN 44, mediates stomatal differentiation in the epidermis probably by controlling successive roles of SPCH, MUTE, and FAMA.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1333656161 103 ERNRMHGLNDALDNLRKVVPcysKTQKLSKIETLRLAKNYI 143
Cdd:cd11443     7 ERRRRKKLNDRLYMLRSVVP---KITKMDRASILGDAIDYV 44