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        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1721939047 119 EEPFAQREIANVRERQRTQSLNDAFASLRQIIPTLPSDKLSKIQILKLASRYIDFLYQVLQNDDADGKPA 188
Cdd:cd11412     7 EELQTQRVMANVRERQRTQSLNEAFAALRKIIPTLPSDKLSKIQTLKLAARYIDFLYQVLQSDELDSKMA 76

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1721939047 119 EEPFAQREIANVRERQRTQSLNDAFASLRQIIPTLPSDKLSKIQILKLASRYIDFLYQVLQNDDADGKPA 188
Cdd:cd11412     7 EELQTQRVMANVRERQRTQSLNEAFAALRKIIPTLPSDKLSKIQTLKLAARYIDFLYQVLQSDELDSKMA 76

helix loop helix domain;

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                   ....*....|....*....|....*....|....*....|....*....|..
gi 1721939047  129 NVRERQRTQSLNDAFASLRQIIPTLPSD-KLSKIQILKLASRYIDFLYQVLQ 179
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPKNkKLSKAEILRLAIEYIKSLQEELQ 52

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1721939047 119 EEPFAQREIANVRERQRTQSLNDAFASLRQIIPTLPSDKLSKIQILKLASRYIDFLYQVLQNDDADGKPA 188
Cdd:cd11412     7 EELQTQRVMANVRERQRTQSLNEAFAALRKIIPTLPSDKLSKIQTLKLAARYIDFLYQVLQSDELDSKMA 76

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1721939047 119 EEPFAQREIANVRERQRTQSLNDAFASLRQIIPTLPSDKLSKIQILKLASRYIDFLYQVLQNDDADGK 186
Cdd:cd19700    12 EELQSQRILANVRERQRTQSLNEAFAALRKIIPTLPSDKLSKIQTLKLAARYIDFLYQVLQSDEMDNK 79

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1721939047 124 QREIANVRERQRTQSLNDAFASLRQIIPTLPSDK-LSKIQILKLASRYIDFLYQVL 178
Cdd:cd19686     1 QRQAANIRERKRMRSINDAFDGLRRHIPTFPYEKrLSKVDTLRLAIQYINFLTELL 56

basic helix-loop-helix (bHLH) domain found in heart- and neural crest derivatives-expressed protein (HAND) family; The HAND family includes two bHLH transcription factors, HAND1 and HAND2. HAND1, also termed Class A basic helix-loop-helix protein 27 (bHLHa27), or extraembryonic tissues, heart, autonomic nervous system and neural crest derivatives-expressed protein 1 (eHAND), plays an essential role in both trophoblast-giant cells differentiation and in cardiac morphogenesis. HAND2, also termed Class A basic helix-loop-helix protein 26 (bHLHa26), or deciduum, heart, autonomic nervous system and neural crest derivatives-expressed protein 2 (dHAND), is essential for cardiac morphogenesis, particularly for the formation of the right ventricle and of the aortic arch arteries.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1721939047 125 REIANVRERQRTQSLNDAFASLRQIIPTLPSD-KLSKIQILKLASRYIDFLYQVL 178
Cdd:cd11466     2 RGSANKKERRRTQSINSAFADLRECIPNVPADtKLSKIKTLRLATSYIAYLMDVL 56

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1721939047  129 NVRERQRTQSLNDAFASLRQIIPTLPSD-KLSKIQILKLASRYIDFLYQVLQ 179
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPKNkKLSKAEILRLAIEYIKSLQEELQ 52

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1721939047 124 QREIANVRERQRTQSLNDAFASLRQIIPTLPSD-KLSKIQILKLASRYIDFLYQVLQNDDAD 184
Cdd:cd11471     1 RRGTANRKERRRTQSINSAFAELRECIPNVPADtKLSKIKTLRLATSYIAYLMDLLAKDDQN 62

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1721939047 124 QREIANVRERQRTQSLNDAFASLRQIIPTLPSD-KLSKIQILKLASRYIDFLYQVLQNDD 182
Cdd:cd19707     2 RKIFTNTRERWRQQNVNSAFAELRKLIPTHPPDkKLSKNEILRLAMKYINFLVKLLGDQG 61

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1721939047 124 QREIANVRERQRTQSLNDAFASLRQIIPTLPSD-KLSKIQILKLASRYIDFLYQVLQNDD 182
Cdd:cd11413     1 RRIFTNTRERWRQQNVNGAFAELRKLIPTHPPDkKLSKNEILRLAMKYIKFLEKILEDQE 60

basic helix-loop-helix (bHLH) domain found in factor in the germline alpha (FIGLA) and similar proteins; FIGLA, also termed FIGalpha, or Class C basic helix-loop-helix protein 8 (bHLHc8), or folliculogenesis-specific basic helix-loop-helix protein, or transcription factor FIGa, is a germ-cell-specific bHLH transcription factor expressed abundantly in female and less so in male germ cells. It is essential for primordial follicle formation and expression of many genes required for folliculogenesis, fertilization and early embryonic survival. FIGLA knockout mice cannot form primordial follicles and lose oocytes rapidly after birth, whereas male gonads are unaffected.

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gi 1721939047 125 REIANVRERQRTQSLNDAFASLRQIIPTLPSD-KLSKIQILKLASRYIDFLYQVLQ 179
Cdd:cd11422     1 RRVANARERERVRNLNSGFSKLRRIVPLIPRDrKPSKVDTLKGATEYIRLLQRILE 56

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'.

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                  ....*....|....*....|....*....|....*....|....*..
gi 1721939047 125 REIANVRERQRTQSLNDAFASLRQIIPTLPSDKLSKIQILKLASRYI 171
Cdd:cd11419     5 REIANSNERRRMQSINAGFQSLRTLLPHCDGEKLSKAAILQQTAEYI 51

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1721939047 123 AQREIANVRERQRTQSLNDAFASLRQIIPTLPSD-KLSKIQILKLASRYIDFLYQVLQNDD 182
Cdd:cd19706     3 VRRIFTNSRERWRQQNVNGAFAELRKLIPTHPPDkKLSKNEILRLAMKYINFLAKLLNDQE 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.

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                  ....*....|....*....|....*....|....*....|....*....|.
gi 1721939047 129 NVRERQRTQSLNDAFASLRQIIPTLPSDK-LSKIQILKLASRYIDFLYQVL 178
Cdd:cd11418     6 NERERRRVQAVNDAFDRLRQHVPYLKRRKkLSKVKTLRRAIEYIRHLQKLL 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1721939047 124 QREIANVRERQRTQSLNDAFASLRQIIPTLPSD-KLSKIQILKLASRYIDFLYQVLQ 179
Cdd:cd19708     1 RRMFTNSRERWRQQNVNGAFAELRKLVPTHPPDkKLSKNEILRLAIKYIRLLSNVLE 57

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).

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                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1721939047 124 QREIANVRERQRTQSLNDAFASLRQIIPTLPSDK-LSKIQILKLASRYIDFLYQVLQND 181
Cdd:cd11416     5 QRHAANIRERKRMLSINSAFEELRCHVPTFPYEKrLSKIDTLRLAIAYIALLRDILRSG 63

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1721939047 124 QREIANVRERQRTQSLNDAFASLRQIIPTLPSD-KLSKIQILKLASRYIDFLYQVLQ 179
Cdd:cd11428     1 RRLKANDRERNRMHNLNDALDALREVLPSFPDEtKLTKIETLRFAHNYIWALSETLK 57

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1721939047 124 QREIANVRERQRTQSLNDAFASLRQIIPTLPSD-KLSKIQILKLASRYIDFLYQVLQN 180
Cdd:cd19711     1 RRLESNERERQRMHKLNNAFQALREVIPHVRAEkKLSKIETLTLAKNYIKSLTTTILN 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1721939047 124 QREIANVRERQRTQSLNDAFASLRQIIPTLPSD-KLSKIQILKLASRYIDFLYQVL 178
Cdd:cd11423     1 QRNAANARERARMRVLSKAFSRLKTTLPWVPPDtKLSKLDTLRLAASYIAHLRQIL 56

basic helix-loop-helix (bHLH) domain found in transcription factor 21 (TCF-21) and similar proteins; 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1721939047 124 QREIANVRERQRTQSLNDAFASLRQIIPTLPSD-KLSKIQILKLASRYIDFLYQVLQND 181
Cdd:cd19704     4 QRNAANARERARMRVLSKAFSRLKTTLPWVPPDtKLSKLDTLRLASSYIAHLRQILAND 62

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1721939047 124 QREIANVRERQRTQSLNDAFASLRQIIPTLPSD-KLSKIQILKLASRYIDFLYQVL 178
Cdd:cd11426     1 RRLESNERERLRMHQLNDAFQALREVIPHVRSErKLSKIETLTLAKNYIKSLTNMI 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').

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                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1721939047 123 AQREIANVRERQRTQSLNDAFASLRQIIPTLPSD-KLSKIQILKLASRYIDFLYQVLQ 179
Cdd:cd19717     9 TRRVKANNRERNRMHNLNAALDSLREVLPTFPEDaKLTKIETLRFAHNYIWALSETLR 66

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1721939047 124 QREIANVRERQRTQSLNDAFASLRQIIPTLPSD-KLSKIQILKLASRYIDFLYQVLQNDD 182
Cdd:cd19718     8 RRMKANDRERNRMHNLNSALDALRSVLPTFPDDaKLTKIETLRFAHNYIWALTETLRMAD 67

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).

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                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1721939047 124 QREIANVRERQRTQSLNDAFASLRQIIPTLPSD-KLSKIQILKLASRYIDFLYQVLQ 179
Cdd:cd19713     6 RRLAANARERRRMHGLNHAFDQLRNVIPSFNNDkKLSKYETLQMAQIYINALSELLQ 62

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.

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                  ....*....|....*....|....*....|....*....|....
gi 1721939047 132 ERQRTQSLNDAFASLRQIIPTLP-SDKLSKIQILKLASRYIDFL 174
Cdd:cd00083     1 ERRRRDKINDAFEELKRLLPELPdSKKLSKASILQKAVEYIREL 44

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1721939047 123 AQREIANVRERQRTQSLNDAFASLRQIIPTLP-SDKLSKIQILKLASRYIDFLYQVLQ 179
Cdd:cd19721    29 ARRVKANARERSRMHGLNDALDNLRRVMPCYSkTQKLSKIETLRLARNYIWALSEVLE 86

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.

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                  ....*....|....*....|....*....|....*....|....*....|.
gi 1721939047 129 NVRERQRTQSLNDAFASLRQIIPTLPSDK-LSKIQILKLASRYIDFLYQVL 178
Cdd:cd19724     6 NERERQRVRCVNEGYARLRRHLPLENKDKrLSKVETLRAAIRYIKHLQELL 56

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in protein Max and similar proteins; Max, also termed Class D basic helix-loop-helix protein 4 (bHLHd4), or Myc-associated factor X, is a bHLHZip transcription regulator that forms a sequence-specific DNA-binding protein complex with MYC or MAD which recognizes the core sequence 5'-CAC[GA]TG-3'. The MYC:MAX complex is a transcriptional activator, whereas the MAD:MAX complex is a transcriptional repressor. Max homodimer bind DNA but is transcriptionally inactive. Targeted deletion of max results in early embryonic lethality in mice.

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                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1721939047 129 NVRERQRTQSLNDAFASLRQIIPTLPSDKLSKIQILKLASRYIDFLYQVLQNDDAD 184
Cdd:cd11406     6 NALERKRRDHIKDSFHSLRDSVPSLQGEKASRAQILKKATEYIQYMRRKNHTHQQD 61

basic helix-loop-helix (bHLH) domain found in neurogenic differentiation factor 2 (NeuroD2) and similar proteins; 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1721939047  92 RPKrpKRSPLQRSPSSGSSlspgpgggEEPFAQREIANVRERQRTQSLNDAFASLRQIIPTLP-SDKLSKIQILKLASRY 170
Cdd:cd19720    13 RPK--KRGPKKRKMTKARL--------ERSKLRRQKANARERNRMHDLNSALDNLRKVVPCYSkTQKLSKIETLRLAKNY 82

                          90
                  ....*....|
gi 1721939047 171 IDFLYQVLQN 180
Cdd:cd19720    83 IWALSEILRS 92

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.

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                  ....*....|....*....|....*....|....*....|....*....|....
gi 1721939047 129 NVRERQRTQSLNDAFASLRQIIPTLPSD---KLSKIQILKLASRYIDFLYQVLQ 179
Cdd:cd11429     5 NSRERKRMHDLNSALDGLRSVMPYAQGPsvrKLSKIATLLLARNYILMLTQALE 58

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).

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                  ....*....|....*....|....*....|....*....|....*..
gi 1721939047 129 NVRERQRTQSLNDAFASLRQIIPTLPS-DKLSKIQILKLASRYIDFL 174
Cdd:cd11400     6 NVLERQRRNDLKNSFEKLRDLVPELADnEKASKVVILKKATEYIKQL 52

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.

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                  ....*....|....*....|....*....|....*....|....*....|.
gi 1721939047 129 NVRERQRTQSLNDAFASLRQIIPTLP-SDKLSKIQILKLASRYIDFLYQVL 178
Cdd:cd19723     6 NERERNRVKLVNLGFATLREHVPNGRaNKKMSKVETLRSAVEYIRQLQQLL 56

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1721939047 124 QREIANVRERQRTQSLNDAFASLRQIIPTLPSDKLSKIQILKLASRYIDFLYQVLQ 179
Cdd:cd18937     2 RRKAATMRERRRLKKVNQAFETLKRCTTSNPNQRLPKVEILRNAIRYIESLQDLLR 57

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.

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gi 1721939047 129 NVRERQRTQSLNDAFASLRQIIPTLPSDK-LSKIQILKLASRYIDFLYQVL 178
Cdd:cd19745     9 NERERQRVKCVNEGYAKLRRHLPQEYSEKrLSKVETLRAAIKYIKHLQSVL 59

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.

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gi 1721939047 129 NVRERQRTQSLNDAFASLRQIIPTLPSD---KLSKIQILKLASRYI 171
Cdd:cd18954     6 NARERRRMHDLNDALDELRAVIPYAHSPsvrKLSKIATLLLAKNYI 51

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1721939047 124 QREIANVRERQRTQSLNDAFASLRQIIPTLPSDKLSKIQILKLASRYIDFLYQVL 178
Cdd:cd11411     2 RRKAATMRERRRLKKVNEAFEALKRCTSANPNQRLPKVEILRNAIEYIESLQDLL 56

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1721939047 124 QREIANVRERQRTQSLNDAFASLRQIIPTLP-SDKLSKIQILKLASRYIDFLYQVLQN 180
Cdd:cd19719    28 RRMKANARERNRMHGLNAALDNLRKVVPCYSkTQKLSKIETLRLAKNYIWALSEILRS 85

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-like protein X (Mlx) family; Mlx, also termed Class D basic helix-loop-helix protein 13 (bHLHd13), or Max-like bHLHZip protein, or protein BigMax, or transcription factor-like protein 4, is a Max-like bHLHZip transcription regulator that interacts with the Max network of transcription factors. It forms a sequence-specific DNA-binding protein complex with some member of Mad family (Mad1 and Mad4) and Mondo family but not the Myc family and bind the E-box DNA to control transcription. The family also includes Saccharomyces cerevisiae INO4, which is a bHLH transcriptional activator of phospholipid synthetic genes (such as INO1, CHO1/PSS, CHO2/PEM1, OPI3/PEM2, etc.). It is required for de-repression of phospholipid biosynthetic gene expression in response to inositol deprivation in yeast.

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gi 1721939047 124 QREIANVR-ERQRTQSLNDAFASLRQIIPTLPSDKLSKIQILKLASRYIDFLYQ 176
Cdd:cd11404     1 QRRLNHVRsEKKRRELIKKGYDELCALVPGLDPQKRTKADILQKAADWIQELKE 54

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1721939047 124 QREIANVRERQRTQSLNDAFASLRQIIPTLPSDKLSKIQILKLASRYIDFLYQVLQNDDADGK 186
Cdd:cd18934     2 RRKAATLRERRRLKKINEAFEALKRRTVPNPNQRLPKVEILRSAINYIEKLQDLLHSLDQQEK 64

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1721939047 124 QREIANVRERQRTQSLNDAFASLRQIIPTLPSDKLSKIQILKLASRYIDFLYQVL 178
Cdd:cd18935     2 RRRAATLREKRRLKKVNEAFEALKRSTLLNPNQRLPKVEILRSAIQYIERLQALL 56

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana genes coding transcription factors and similar proteins; bHLH proteins are the second largest class of plant transcription factors that regulate transcription of genes that are involve in many essential physiological and developmental process. bHLH proteins are transcriptional regulators that are found in organisms from yeast to humans. The Arabidopsis bHLH proteins that have been characterized so far have roles in regulation of fruit dehiscence, cell development (carpel, anther and epidermal), phytochrome signaling, flavonoid biosynthesis, hormone signaling and stress responses.

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                  ....*....|....*....|....*....|....*....|....*....|.
gi 1721939047 129 NVRERQRTQSLNDAFASLRQIIPtlPSDKLSKIQILKLASRYIDFLYQVLQ 179
Cdd:cd11393     2 SIAERKRREKINERIRALRSLVP--NGGKTDKASILDEAIEYIKFLQEQVK 50

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1721939047 123 AQREIANVRERQRTQSLNDAFASLRQIIP-TLPSDKLSKIQILKLASRYIDFLYQVL 178
Cdd:cd18912     7 ARRVAANVRERKRILDYNQAFNALRLALKhDLGGKRLSKIATLRRAINRISALSLFL 63

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.