Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 403420620   95 RKRNERERQRVKCVNEGYARLRRHLPEDYLEKRLSKVETLRAAIKYISYLQ 145
Cdd:pfam00010   3 EAHNERERRRRDRINDAFDELRELLPTLPPDKKLSKAEILRLAIEYIKHLQ 53

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 403420620  93 FIRKRNERERQRVKCVNEGYARLRRHLPEDYLEKRLSKVETLRAAIKYISYLQSLL 148
Cdd:cd19724    1 FIRKRNERERQRVRCVNEGYARLRRHLPLENKDKRLSKVETLRAAIRYIKHLQELL 56

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 403420620  89 YGPAFIRKRNERERQRVKCVNEGYARLRRHLPEDYLEKRLSKVETLRAAIKYISYLQSLL 148
Cdd:cd19747    2 FEPAFIQKRNERERQRVKCVNEGYARLRDHLPGAMAEKRLSKVETLRAAIRYIKYLQDLL 61

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 403420620  96 KRNERERQRVKCVNEGYARLRRHLPEDYLEKRLSKVETLRAAIKYISYLQSLL 148
Cdd:cd19723    4 RRNERERNRVKLVNLGFATLREHVPNGRANKKMSKVETLRSAVEYIRQLQQLL 56

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
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 403420620  91 PAFIRKRNERERQRVKCVNEGYARLRRHLPEDYLEKRLSKVETLRAAIKYISYLQSLL 148
Cdd:cd19742    3 PAAVARRNERERNRVKLVNMGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLL 60

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 403420620  94 IRKRNERERQRVKCVNEGYARLRRHLPEDYLE-----------KRLSKVETLRAAIKYISYLQSLL 148
Cdd:cd19744    2 VARRNARERNRVKQVNNGFAILRQHIPQSVIEdltagggrgksKKLSKVDTLRMAVEYIRRLQKLL 67

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 403420620    98 NERERQRVKCVNEGYARLRRHLPEDYLEKRLSKVETLRAAIKYISYLQSLL 148
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPKNKKLSKAEILRLAIEYIKSLQEEL 51

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 403420620  98 NERERQRVKCVNEGYARLRRHLPEDYLEKRLSKVETLRAAIKYISYLQSLL 148
Cdd:cd19686    6 NIRERKRMRSINDAFDGLRRHIPTFPYEKRLSKVDTLRLAIQYINFLTELL 56

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 403420620  98 NERERQRVKCVNEGYARLRRHLPEDYLEKRLSKVETLRAAIKYISYLQSLL 148
Cdd:cd11413    6 NTRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYIKFLEKIL 56

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 403420620  98 NERERQRVKCVNEGYARLRRHLPEDYLEKRLSKVETLRAAIKYISYLQSLL 148
Cdd:cd11430    6 NARERRRMNGLNRAFDQLRSVVPSIGNDKKLSKYETLQMAQIYIETLSELL 56

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 403420620  98 NERERQRVKCVNEGYARLRR---HLPEDylekRLSKVETLRAAIKYISYLQSLLYPDETETK 156
Cdd:cd11412   17 NVRERQRTQSLNEAFAALRKiipTLPSD----KLSKIQTLKLAARYIDFLYQVLQSDELDSK 74

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 403420620  93 FIRKRNERERQRVKCVNEGYARLRRHLPEDYLEKRLSKVETLRAAIKYISYLQSLL 148
Cdd:cd11466    1 RRGSANKKERRRTQSINSAFADLRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 56

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 403420620 100 RERQRVKCVNEGYARLRRHLPEDYLEKRLSKVETLRAAIKYISYLQSLL 148
Cdd:cd11414    9 RERIRVEAFNSAFAQLRKLLPTLPPDKKLSKIEILRLAICYISYLNHVL 57

basic helix-loop-helix (bHLH) domain found in T-cell acute lymphocytic leukemia protein 2 (TAL-2) and similar proteins; TAL-2, also termed Class A basic helix-loop-helix protein 19 (bHLHa19), is a bHLH transcription factor essential for the normal brain development. It has been implicated in T-cell acute lymphoblastic leukemia.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 403420620  98 NERERQRVKCVNEGYARLRRHLPEDYLEKRLSKVETLRAAIKYISYLQSLL 148
Cdd:cd19707    7 NTRERWRQQNVNSAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLVKLL 57

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana OBP3-responsive gene 2 (ORG2), 3 (ORG3) and similar proteins; The family includes ORG2 (also termed AtbHLH38, or EN 8) and ORG3 (also termed AtbHLH39, or EN 9), both of which act as bHLH transcription factors.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 403420620  96 KRNERERQRVKCVNEGYARLRRHLPEDYLEKRLSKVETLRAAIKYISYLQ 145
Cdd:cd18914    4 LHNDVERQRRQEMASLFSSLRSLLPLQYIKGKLSVSDHVDEAVNYIKELQ 53

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        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 403420620  98 NERERQRVKCVNEGYARLRRHLPEDYLEKRLSKVETLRAAIKYISYLQSLLYPDE 152
Cdd:cd11471    6 NRKERRRTQSINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDLLAKDD 60

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
                 ....*....|....*....|....*....|....*....|....*....|.
gi 403420620  98 NERERQRVKCVNEGYARLRRHLPEDYLEKRLSKVETLRAAIKYISYLQSLL 148
Cdd:cd19708    6 NSRERWRQQNVNGAFAELRKLVPTHPPDKKLSKNEILRLAIKYIRLLSNVL 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 403420620 101 ERQRVKCVNEGYARLRRHLPEDYLEKRLSKVETLRAAIKYISYLQS 146
Cdd:cd00083    1 ERRRRDKINDAFEELKRLLPELPDSKKLSKASILQKAVEYIRELQS 46

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 403420620  98 NERERQRVKCVNEGYARLRR---HLPEDylekRLSKVETLRAAIKYISYLQSLLYPDE 152
Cdd:cd11464    6 NVRERQRTQSLNEAFTSLRKiipTLPSD----KLSKIQTLKLAARYIDFLYQVLRSDE 59

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 403420620  95 RKRNERERQRVKCVNEGYARLRRHLPEdYLEK----RLSKVETLRAAIKYISYLQSLL 148
Cdd:cd11431    3 KTANARERDRMREINDAFEALRRAVPE-YPVAgkdgKLTKITTLRLAMNYIKALTDLL 59

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        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 403420620  98 NERERQRVKCVNEGYARLRRHLPEDYLEKRLSKVETLRAAIKYISYLQSLLYPDETE 154
Cdd:cd19714   13 NARERRRMQGLNTAFDRLRKVVPQWGQDKKLSKYETLQMALSYIMALTRILAEAERY 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        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 403420620  98 NERERQRVKCVNEGYARLRRHLPEDYLEKRLSKVETLRAAIKYISYLQSLL 148
Cdd:cd11426    6 NERERLRMHQLNDAFQALREVIPHVRSERKLSKIETLTLAKNYIKSLTNMI 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 403420620 100 RERQRVKCVNEGYARLRRHLPEDyLEKRLSKVETLRAAIKYISYLQSLL 148
Cdd:cd11411    9 RERRRLKKVNEAFEALKRCTSAN-PNQRLPKVEILRNAIEYIESLQDLL 56

basic helix-loop-helix (bHLH) domain found in myogenin (MYOG) and similar proteins; MYOG, also termed Class C basic helix-loop-helix protein 3 (bHLHc3), or myogenic factor 4 (Myf-4), is a bHLH transcriptional activator that promotes transcription of muscle-specific target genes and plays a role in muscle differentiation, cell cycle exit and muscle atrophy.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 403420620 100 RERQRVKCVNEGYARLRRHLPEDyLEKRLSKVETLRAAIKYISYLQSLL 148
Cdd:cd18935    9 REKRRLKKVNEAFEALKRSTLLN-PNQRLPKVEILRSAIQYIERLQALL 56

basic helix-loop-helix (bHLH) domain found in mesogenin-1 (Msgn1) and similar proteins; Msgn1, also termed paraxial mesoderm-specific mesogenin1, or pMesogenin1 (pMsgn1), is a bHLH transcription factor required for maturation and segmentation of paraxial mesoderm. It may regulate the expression of T-box transcription factors essential for mesoderm formation and differentiation.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 403420620  95 RKRNERERQRVKCVNEGYARLRRHLPEDYLEKR--LSKVETLRAAIKYISYLQSLL 148
Cdd:cd18939   10 RKASEREKLRMRTLAEALHTLRNYLPPVYSQRGqpLTKIQTLKCTIQYISELSGLL 65

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 403420620  98 NERERQRVKCVNEGYARLRRHLPEDYLEKRLSKVETLRAAIKYISYLQSLLYPDET 153
Cdd:cd11421   13 NARERTRVHTISAAFEALRKAVPSYSYNQKLSKLAILRIACSYILALARLADLDYS 68

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        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 403420620  90 GPAFIRKR----NERERQRVKCVNEGYARLRRHLPEDYLEKRLSKVETLRAAIKYISYLQSLL 148
Cdd:cd19715    1 GKDVLKKRrlaaNARERRRMNSLNVAFDKLRDVVPSLGDDRKLSKYETLQMAQSYITALKELL 63

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 403420620  98 NERERQRVKCVNEGYARLRRHLPEDYLEKRLSKVETLRAAIKYISYLQSLL 148
Cdd:cd11423    6 NARERARMRVLSKAFSRLKTTLPWVPPDTKLSKLDTLRLAASYIAHLRQIL 56

basic helix-loop-helix (bHLH) domain found in muscle-specific regulatory factor 4 (MRF4) and similar proteins; MRF4, also termed Class C basic helix-loop-helix protein 4 (bHLHc4), or myogenic factor 6 (Myf-6), is a bHLH transcription factor associated with myogenesis. It plays a role in skeletal muscle differentiation.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 403420620 100 RERQRVKCVNEGYARL-RRHLPEDylEKRLSKVETLRAAIKYISYLQSLLYPDETETK 156
Cdd:cd18934    9 RERRRLKKINEAFEALkRRTVPNP--NQRLPKVEILRSAINYIEKLQDLLHSLDQQEK 64

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 403420620 100 RERQRVKCVNEGYARLRRHLPEDyLEKRLSKVETLRAAIKYISYLQSLL 148
Cdd:cd18936   13 RERRRLSKVNEAFETLKRCTSTN-PNQRLPKVEILRNAIRYIESLQALL 60

basic helix-loop-helix (bHLH) domain found in the mesoderm posterior protein (Mesp) family; Mesp, a bHLH tissue specific transcription factor, acts as a key regulator of the cardiovascular transcriptional network by inducing directly and/or indirectly the expression of the majority of key cardiovascular transcription factors. The Mesp family includes two bHLH transcription factors, Mesp1 and Mesp2. Mesp1, also termed Class C basic helix-loop-helix protein 5 (bHLHc5), promotes cardiovascular differentiation during embryonic development and embryonic stem cell differentiation. Mesp2, also termed Class C basic helix-loop-helix protein 6 (bHLHc6), plays an important role in somitogenesis.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 403420620  98 NERERQRVKCVNEGYARLRRHLPEDY--LEKRLSKVETLRAAIKYISYLQSLL 148
Cdd:cd18938    6 SEREKLRMRDLAKALHNLRRYLPPSVapAGQSLTKIETLRLTIRYISHLSAQL 58

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
                 ....*....|....*....|....*....|....*....|....*....
gi 403420620 100 RERQRVKCVNEGYARLRRHLPEDyLEKRLSKVETLRAAIKYISYLQSLL 148
Cdd:cd18937    9 RERRRLKKVNQAFETLKRCTTSN-PNQRLPKVEILRNAIRYIESLQDLL 56

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
                 ....*....|....*....|....*....|....*....|....*....|...
gi 403420620  96 KRNERERQRVKCVNEGYARLRRHLPEDYLEKRLSKVETLRAAIKYISYLQSLL 148
Cdd:cd19717   13 KANNRERNRMHNLNAALDSLREVLPTFPEDAKLTKIETLRFAHNYIWALSETL 65

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 403420620  97 RNERERQRVKCVNEGYARLRRHLPEDYLEKRLSKVETLRAAIKYISYLQS 146
Cdd:cd11400    5 HNVLERQRRNDLKNSFEKLRDLVPELADNEKASKVVILKKATEYIKQLQQ 54

basic helix-loop-helix (bHLH) domain found in neurogenin-3 (NGN-3) and similar proteins; 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 403420620  96 KRNERERQRVKCVNEGYARLRRHLPEDYLEKRLSKVETLRAAIKYISYLQSLL 148
Cdd:cd19718   11 KANDRERNRMHNLNSALDALRSVLPTFPDDAKLTKIETLRFAHNYIWALTETL 63

basic helix-loop-helix (bHLH) domain found in Saccharomyces cerevisiae protein INO2 and similar proteins; INO2 is a positive regulatory factor required for depression of the co-regulated phospholipid biosynthetic enzymes in Saccharomyces cerevisiae. It is also involved in the expression of ITR1.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 403420620  95 RKRNERERQRVKCVNEGYARLRR--HLPEDYLEKRLSKVETLRAAIKYISYLQS 146
Cdd:cd11388    5 WKHVEAEKKRRNQIKKGFEDLINliNYPRNNNEKRISKSELLNKAVDDIRGLLK 58

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        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 403420620  94 IRKRnERERqrvkcVNEGYARLRRHLPEDYL---EKRLSKVETLRAAIKYISYLQSLL 148
Cdd:cd11389    4 IEKR-RRDR-----INESLAELRRLVPEARKskgSGKLEKAEILEMTLQHLKALQSST 55

basic helix-loop-helix (bHLH) domain found in transcription factor 24 (TCF-24) and similar proteins; TCF-24 is an uncharacterized bHLH transcription factor that shows high sequence similarity with TCF-23.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 403420620 100 RERQRVKCVNEGYARLRRHLPEDYLEKRLSKVETLRAAIKYISYLQSLL 148
Cdd:cd19710    8 RERSRVQTLRSAFLELQRTLPSVPPDTKLSKLDVLVLATTYIAHLMRTL 56

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 403420620  95 RKRNERERQRVKCVNEGYARLRRHLPEDYLEKRLSKVETLRAAIKYISYLQSLL 148
Cdd:cd11424    2 AGNAARERSRVRTLRTAFQSLQRALPAVPPDTKLSKLDVLLLASRYIAHLTRKL 55

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        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 403420620  95 RKRNERERQRVKCVNEGYARLRRHLP--EDYLEKRLSKVETLRAAIKYISYLQSLL 148
Cdd:cd11429    2 LKINSRERKRMHDLNSALDGLRSVMPyaQGPSVRKLSKIATLLLARNYILMLTQAL 57

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana paclobutrazol resistance (PRE) family; The PRE family includes several bHLH transcription factors from Arabidopsis thaliana, such as PRE1-6. PRE1 (also termed AtbHLH136, or protein banquo 1), PRE2 (also termed AtbHLH134, or protein banquo 2, or EN 52), PRE4 (also termed AtbHLH161, or protein banquo 3), and PRE5 (also termed AtbHLH164) are atypical and probable non DNA-binding bHLH transcription factors that integrate multiple signaling pathways to regulate cell elongation and plant development. PRE3 (also termed AtbHLH135, or protein activation-tagged BRI1 suppressor 1, or ATBS1, or protein target of MOOPTEROS 7, or EN 67) is an atypical and probable non DNA-binding bHLH transcription factor required for MONOPTEROS-dependent root initiation in embryo. It promotes the correct definition of the hypophysis cell division plane. PRE5 (also termed AtbHLH163, or protein KIDARI) is an atypical and probable non DNA-binding bHLH transcription factor that regulates light-mediated responses in day light conditions by binding and inhibiting the activity of the bHLH transcription factor HFR1, a critical regulator of light signaling and shade avoidance.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 403420620  97 RNERERQRVKCVNEGYARLRRHLPEDYLEKRLSKVETLRAAIKYISYLQS 146
Cdd:cd11442    1 RSSSSRISDDQKNDLYSRLRALLPSIATSDKVSKATVLEEACNYIRNLHR 50