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 396578161  76 PFEPAFIQKRNERERQRVKCVNEGYARLRGHLPGALTEKRLSKVETLRAAIRYIKYLQELL 136
Cdd:cd19747    1 PFEPAFIQKRNERERQRVKCVNEGYARLRDHLPGAMAEKRLSKVETLRAAIRYIKYLQDLL 61

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 396578161  76 PFEPAFIQKRNERERQRVKCVNEGYARLRGHLPGALTEKRLSKVETLRAAIRYIKYLQELL 136
Cdd:cd19747    1 PFEPAFIQKRNERERQRVKCVNEGYARLRDHLPGAMAEKRLSKVETLRAAIRYIKYLQDLL 61

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 396578161    86 NERERQRVKCVNEGYARLRGHLPGALTEKRLSKVETLRAAIRYIKYLQELL 136
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPKNKKLSKAEILRLAIEYIKSLQEEL 51

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 396578161  76 PFEPAFIQKRNERERQRVKCVNEGYARLRGHLPGALTEKRLSKVETLRAAIRYIKYLQELL 136
Cdd:cd19747    1 PFEPAFIQKRNERERQRVKCVNEGYARLRDHLPGAMAEKRLSKVETLRAAIRYIKYLQDLL 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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 396578161  74 DYPFEPAFIQKRNERERQRVKCVNEGYARLRGHLPGALTEKRLSKVETLRAAIRYIKYLQELL 136
Cdd:cd19746    1 DYSFEPAFIRKRNERERQRVRCVNEGYARLREHLPQELADKRLSKVETLRAAIDYIKHLQELL 63

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 396578161  81 FIQKRNERERQRVKCVNEGYARLRGHLPGALTEKRLSKVETLRAAIRYIKYLQELL 136
Cdd:cd11418    1 RVARRNERERRRVQAVNDAFDRLRQHVPYLKRRKKLSKVKTLRRAIEYIRHLQKLL 56

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 396578161  80 AFIQKRNERERQRVKCVNEGYARLRGHLPGALTEKRLSKVETLRAAIRYIKYLQELL 136
Cdd:cd19743    2 AAVERRNERERNRVKLVNLGFAALRQHVPQGGASKKMSKVETLRSAVEYIRALQRLL 58

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 396578161   83 QKRNERERQRVKCVNEGYARLRGHLPGALTEKRLSKVETLRAAIRYIKYLQ 133
Cdd:pfam00010   3 EAHNERERRRRDRINDAFDELRELLPTLPPDKKLSKAEILRLAIEYIKHLQ 53

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 396578161  82 IQKRNERERQRVKCVNEGYARLRGHLPGALTE-----------KRLSKVETLRAAIRYIKYLQELL 136
Cdd:cd19744    2 VARRNARERNRVKQVNNGFAILRQHIPQSVIEdltagggrgksKKLSKVDTLRMAVEYIRRLQKLL 67

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 396578161  83 QKRNERERQRVKCVNEGYARLRGHLPGALTEKRLSKVETLRAAIRYIKYLQELL 136
Cdd:cd19686    3 QAANIRERKRMRSINDAFDGLRRHIPTFPYEKRLSKVDTLRLAIQYINFLTELL 56

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 396578161  83 QKRNERERQRVKCVNEGYARLRGHLPGALTEKRLSKVETLRAAIRYIKYLQELL 136
Cdd:cd11417    3 QAANLRERRRMQSINDAFEGLRSHIPTLPYEKRLSKVDTLRLAIGYINFLSELV 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 396578161  86 NERERQRVKCVNEGYARLRGHLPGALTEKRLSKVETLRAAIRYIKYLQELL 136
Cdd:cd11413    6 NTRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYIKFLEKIL 56

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 396578161  84 KRNERERQRVKCVNEGYARLRGHLPGALTEKRLSKVETLRAAIRYIKYLQELL 136
Cdd:cd11427    3 KANARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLARNYIWALSEIL 55

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        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 396578161  83 QKRNERERQRVKCVNEGYARLRGHLPGALTEKRLSKVETLRAAIRYIKYLQELL 136
Cdd:cd11465    2 QAANARERDRTHSVNSAFTALRTLIPTEPADRKLSKIETLRLASSYISHLATVL 55

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 396578161  83 QKR--NERERQRVKCVNEGYARLRGHLPGALTEKRLSKVETLRAAIRYIKYLQELL 136
Cdd:cd11415    9 QRQaaNIRERRRMFNLNEAFDKLRKKVPTFAYEKRLSRIETLRLAIVYISFMTDLL 64

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 396578161  86 NERERQRVKCVNEGYARLRGHLPGALTEKRLSKVETLRAAIRYIKYLQELLS 137
Cdd:cd11471    6 NRKERRRTQSINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDLLA 57

basic helix-loop-helix (bHLH) domain found in twist-related protein 1 (TWIST1) and similar proteins; TWIST1, also termed Class A basic helix-loop-helix protein 38 (bHLHa38), or H-twist, is a bHLH transcriptional regulator that inhibits myogenesis by sequestrating E proteins, inhibiting trans-activation by MEF2, and inhibiting DNA-binding by MYOD1 through physical interaction. It also represses expression of proinflammatory cytokines such as TNFA and IL1B. In addition, TWIST1 is involved in cancer development and progression.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 396578161  86 NERERQRVKCVNEGYARLRGHLPgALTEKRLSKVETLRAAIRYIKYLQELLSA 138
Cdd:cd11412   17 NVRERQRTQSLNEAFAALRKIIP-TLPSDKLSKIQTLKLAARYIDFLYQVLQS 68

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 396578161  86 NERERQRVKCVNEGYARLRGHLPGALTEKRLSKVETLRAAIRYIKYLQELL 136
Cdd:cd19707    7 NTRERWRQQNVNSAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLVKLL 57

basic helix-loop-helix (bHLH) domain found in heart- and neural crest derivatives-expressed protein 1 (HAND1) and similar proteins; HAND1, also termed Class A basic helix-loop-helix protein 27 (bHLHa27), or extraembryonic tissues, heart, autonomic nervous system and neural crest derivatives-expressed protein 1 (eHAND), is a bHLH transcription factor that plays an essential role in both trophoblast-giant cells differentiation and in cardiac morphogenesis.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 396578161  87 ERERQRVKCVNEGYARLRGHLPGALTEKRLSKVETLRAAIRYIKYLQELLS 137
Cdd:cd18952    8 KKERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDVLA 58

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 396578161  86 NERERQRVKCVNEGYARLRGHLPGALTEKRLSKVETLRAAIRYIKYLQELL 136
Cdd:cd11423    6 NARERARMRVLSKAFSRLKTTLPWVPPDTKLSKLDTLRLAASYIAHLRQIL 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        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 396578161  86 NERERQRVKCVNEGYARLRGHLPGALTEKRLSKVETLRAAIRYIKYLQELL 136
Cdd:cd19708    6 NSRERWRQQNVNGAFAELRKLVPTHPPDKKLSKNEILRLAIKYIRLLSNVL 56

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 396578161  83 QKRNERERQRVKCVNEGYARLRGHLPGALTEKRLSKVETLRAAIRYIKYLQELLSATP 140
Cdd:cd19714   10 LAANARERRRMQGLNTAFDRLRKVVPQWGQDKKLSKYETLQMALSYIMALTRILAEAE 67

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 396578161  86 NERERQRVKCVNEGYARLRGHLPGALTEKRLSKVETLRAAIRYIKYL 132
Cdd:cd11426    6 NERERLRMHQLNDAFQALREVIPHVRSERKLSKIETLTLAKNYIKSL 52

basic helix-loop-helix (bHLH) domain found in twist-related protein 2 (TWIST2) and similar proteins; TWIST2, also termed Class A basic helix-loop-helix protein 39 (bHLHa39), or Dermis-expressed protein 1, or Dermo-1, is a bHLH transcription factor that regulates the development of mesenchymal tissues and plays a critical role in embryogenesis. It binds to the E-box consensus sequence 5'-CANNTG-3' as a heterodimer and inhibits transcriptional activation by MYOD1, MYOG, MEF2A and MEF2C.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 396578161  86 NERERQRVKCVNEGYARLRGHLPgALTEKRLSKVETLRAAIRYIKYLQELLSA 138
Cdd:cd19700   22 NVRERQRTQSLNEAFAALRKIIP-TLPSDKLSKIQTLKLAARYIDFLYQVLQS 73

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 396578161  86 NERERQRVKCVNEGYARLRGHLPGALTEKRLSKVETLRAAIRYIKYLQELLS 137
Cdd:cd19706    9 NSRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLLN 60

basic helix-loop-helix (bHLH) domain found in protein atonal homolog 1 (ATOH1) and similar proteins; ATOH1, also termed Class A basic helix-loop-helix protein 14 (bHLHa14), or helix-loop-helix protein hATH-1 (hATH1), or Math1, or Cath1, is a proneural bHLH transcription factor that is essential for inner ear hair cell differentiation. It dimerizes with E47 and activates E-box (CANNTG) dependent transcription. ATOH1 is a mammalian homolog of the Drosophila melanogaster gene atonal and mouse atonal homolog 1 (Math1).

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 396578161  86 NERERQRVKCVNEGYARLRGHLPGALTEKRLSKVETLRAAIRYIKYLQELL 136
Cdd:cd19713   11 NARERRRMHGLNHAFDQLRNVIPSFNNDKKLSKYETLQMAQIYINALSELL 61

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 396578161  86 NERERQRVKCVNEGYARLRGHLPGALTEKRLSKVETLRAAIRYIKYLQELL 136
Cdd:cd19705   11 NSRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYIDFLVTLL 61

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 396578161  88 RERQRVKCVNEGYARLRGHlPGALTEKRLSKVETLRAAIRYIKYLQELL 136
Cdd:cd19699    9 RERRRLRKVNEAFEVLKRR-TCPNPNQRLPKVEILRNAIEYIESLEDLL 56

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
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 396578161  83 QKRNERERQRVKCVNEGYARLRGHLPGALTEKRLSKVETLRAAIRYIKYLQELLS 137
Cdd:cd19722   16 QEANARERNRMHGLNDALDSLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEILR 70

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        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 396578161  88 RERQRVKCVNEGYARL-RGHLPGAltEKRLSKVETLRAAIRYIKYLQELLSA 138
Cdd:cd18935    9 REKRRLKKVNEAFEALkRSTLLNP--NQRLPKVEILRSAIQYIERLQALLSS 58

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 396578161  83 QKRNERERQRVKCVNEGYARLRGHLPGALT--EKRLSKVETLRAAIRYIKYLQELL 136
Cdd:cd18938    3 QSASEREKLRMRDLAKALHNLRRYLPPSVApaGQSLTKIETLRLTIRYISHLSAQL 58

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 396578161  88 RERQRVKCVNEGYARL-RGHLPGAltEKRLSKVETLRAAIRYIKYLQELL 136
Cdd:cd18934    9 RERRRLKKINEAFEALkRRTVPNP--NQRLPKVEILRSAINYIEKLQDLL 56

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 396578161  88 RERQRVKCVNEGYARLRGHLPGALTEKRLSKVETLRAAIRYIKYLQELL 136
Cdd:cd19702   23 RERIRVEAFNLAFAELRKLLPTLPPDKKLSKIEILRLAICYISYLNHVL 71

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
                 ....*....|....*....|....*....|....*....|....*....|...
gi 396578161  84 KRNERERQRVKCVNEGYARLRGHLPGALTEKRLSKVETLRAAIRYIKYLQELL 136
Cdd:cd19721   33 KANARERSRMHGLNDALDNLRRVMPCYSKTQKLSKIETLRLARNYIWALSEVL 85

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 396578161  88 RERQRVKCVNEGYARLRgHLPGALTEKRLSKVETLRAAIRYIKYLQELL 136
Cdd:cd18936   13 RERRRLSKVNEAFETLK-RCTSTNPNQRLPKVEILRNAIRYIESLQALL 60

basic helix-loop-helix (bHLH) domain found in Class A basic helix-loop-helix protein 9 (bHLHa9) and similar proteins; bHLHa9, also termed Class F basic helix-loop-helix factor 42 (bHLHf42), is a bHLH transcription factor that plays an essential role in limb development.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 396578161  86 NERERQRVKCVNEGYARLRGHLPGALTEKRLSKVETLRAAIRYIKYLQELL 136
Cdd:cd18912   13 NVRERKRILDYNQAFNALRLALKHDLGGKRLSKIATLRRAINRISALSLFL 63

basic helix-loop-helix (bHLH) domain found in neurogenic differentiation factor 1 (NeuroD1) and similar proteins; 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 396578161  84 KRNERERQRVKCVNEGYARLRGHLPGALTEKRLSKVETLRAAIRYIKYLQELLSA 138
Cdd:cd19719   31 KANARERNRMHGLNAALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEILRS 85

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 396578161  84 KRNERERQRVKCVNEGYARLRGHLPGA--LTEKRLSKVETLRAAIRYIKYLQELL 136
Cdd:cd11429    3 KINSRERKRMHDLNSALDGLRSVMPYAqgPSVRKLSKIATLLLARNYILMLTQAL 57

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 396578161  82 IQKRnERERqrvkcVNEGYARLRGHLPGAL---TEKRLSKVETLRAAIRYIKYLQ 133
Cdd:cd11389    4 IEKR-RRDR-----INESLAELRRLVPEARkskGSGKLEKAEILEMTLQHLKALQ 52

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 396578161  96 VNEGYARLRGHLPGALTEKRLSKVETLRAAIRYIKYLQELLSATP 140
Cdd:cd19694   11 MNDCYSRLKRLVPTIPPNKKVSKVEILQHVIDYILDLQLALETHP 55

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 396578161  87 ERERQRVKCVNEGYARLRGHLPGALTEKRLSKVETLRAAIRYIKYLQELL 136
Cdd:cd11424    6 ARERSRVRTLRTAFQSLQRALPAVPPDTKLSKLDVLLLASRYIAHLTRKL 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 396578161  88 RERQRVKCVNEGYARLRGHLPGALTEKRLSKVETLRAAIRYIKYLQELL 136
Cdd:cd19710    8 RERSRVQTLRSAFLELQRTLPSVPPDTKLSKLDVLVLATTYIAHLMRTL 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 396578161  86 NERERQRVKCVNEGYARLRGHLPGaLTEKRLSKVETLRAAIRYIKYLQ 133
Cdd:cd11402    7 NKLEKNRRAHLKECFETLKRQIPN-LDDKKTSNLNILRSALRYIQILK 53

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein NAI1 and similar proteins; NAI1, also termed AtbHLH20, or EN 27, is a bHLH transcription activator that regulates the expression of at least NAI2, PYK10 and PBP1. It is required for and mediates the formation of endoplasmic reticulum bodies (ER bodies). It plays a role in the symbiotic interactions with the endophytes of the Sebacinaceae fungus family, such as Piriformospora indica and Sebacina.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 396578161  89 ERQRVKCVNEGYARLRGHLPGAlteKRLSKVETLRAAIRYIKYLQELL 136
Cdd:cd11452   10 ERKRREKLSQRFIALSALVPGL---KKMDKASVLGDAIKHIKQLQERV 54

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
                 ....*....|....*....|....*....|....*....|....*....
gi 396578161  85 RNERERQRVKCVNEGYARLRGHLPGALTEKRLSKVETLRAAIRYIKYLQ 133
Cdd:cd11442    1 RSSSSRISDDQKNDLYSRLRALLPSIATSDKVSKATVLEEACNYIRNLH 49

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in MAX gene-associated protein (MGA) family; The MGA family includes MGA, Schizosaccharomyces pombe ESC1 (spESC1) and similar proteins. MGA, also termed MAX dimerization protein 5 (MAD5), is a dual specificity T-box/ bHLHzip transcription factor that regulates the expression of both Max-network and T-box family target genes. It contains a Myc-like bHLHZip motif and requires heterodimerization with Max for binding to the preferred Myc-Max-binding site CACGTG. In addition to the bHLHZip domain, MGA harbors a second DNA-binding domain, the T-box or T-domain. It thus binds the preferred Brachyury-binding sequence and represses transcription of reporter genes containing promoter-proximal Brachyury-binding sites. spESC1 is a bHLHzip protein with homology to human MyoD and Myf-5 myogenic differentiation inducers. It is involved in the sexual differentiation process.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 396578161  84 KRNERERQRVKCVNEGYARLRGHLPGALTEKrLSKVETLRAAIRYIKYLQE 134
Cdd:cd19682    3 RHKKRERERRSELRELFDKLKQLLGLDSDEK-ASKLAVLTEAIEEIQQLKR 52