Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 429325228   67 QRILANVRERQRTQSLNEAFAALRKIIPTLPSD-KLSKIQTLKLAARYIDFL 117
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELLPTLPPDkKLSKAEILRLAIEYIKHL 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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 429325228  57 SAQSFEELQSQRILANVRERQRTQSLNEAFAALRKIIPTLPSDKLSKIQTLKLAARYIDFLYQVLQSDEMDNKMTS 132
Cdd:cd11412    2 SPQSFEELQTQRVMANVRERQRTQSLNEAFAALRKIIPTLPSDKLSKIQTLKLAARYIDFLYQVLQSDELDSKMAS 77

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 429325228  68 RILANVRERQRTQSLNEAFAALRKIIPTLPSD-KLSKIQTLKLAARYIDFLYQVL 121
Cdd:cd11390    1 RNAANARERRRMHDLNDAFEALRKVLPTVPPDkKLSKIETLRLAINYIAALSDLL 55

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 429325228  68 RILANVRERQRTQSLNEAFAALRKIIPTLPSD-KLSKIQTLKLAARYIDFLYQVL 121
Cdd:cd11466    2 RGSANKKERRRTQSINSAFADLRECIPNVPADtKLSKIKTLRLATSYIAYLMDVL 56

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 429325228  67 QRILANVRERQRTQSLNEAFAALRKIIPTLPSD-KLSKIQTLKLAARYIDFLYQVLQSDEMD 127
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 429325228  66 SQRILANVRERQRTQSLNEAFAALRKIIPTLPSD-KLSKIQTLKLAARYIDFLYQVLQSDE 125
Cdd:cd19707    1 TRKIFTNTRERWRQQNVNSAFAELRKLIPTHPPDkKLSKNEILRLAMKYINFLVKLLGDQG 61

basic helix-loop-helix (bHLH) domain found in transcription factor 15 (TCF-15) and similar proteins; TCF-15, also termed Class A basic helix-loop-helix protein 40 (bHLHa40), or paraxis, or protein bHLH-EC2, is a bHLH transcription factor expressed in caudal lateral and paraxial mesoderm dermomyotome and sclerotome fore limb buds during embryo development. It may function as an early transcriptional regulator involved in the patterning of the mesoderm and in lineage determination of cell types derived from the mesoderm.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 429325228  67 QRILANVRERQRTQSLNEAFAALRKIIPTLPSD-KLSKIQTLKLAARYIDFLYQVL 121
Cdd:cd11470    8 QRQAANARERDRTQSVNTAFTALRTLIPTEPVDrKLSKIETLRLASSYIAHLANVL 63

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 429325228  67 QRILANVRERQRTQSLNEAFAALRKIIPTLPSD-KLSKIQTLKLAARYIDFLYQVLQSDE 125
Cdd:cd11413    1 RRIFTNTRERWRQQNVNGAFAELRKLIPTHPPDkKLSKNEILRLAMKYIKFLEKILEDQE 60

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 429325228  74 RERQRTQSLNEAFAALRKIIPTLPSD-KLSKIQTLKLAARYIDFLYQVLQSD 124
Cdd:cd18952    9 KERRRTESINSAFAELRECIPNVPADtKLSKIKTLRLATSYIAYLMDVLAKD 60

basic helix-loop-helix (bHLH) domain found in scleraxis and similar proteins; 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 429325228  67 QRILANVRERQRTQSLNEAFAALRKIIPTLPSD-KLSKIQTLKLAARYIDFLYQVL 121
Cdd:cd18951    4 QRHTANARERDRTNSVNTAFTALRTLIPTEPADrKLSKIETLRLASSYISHLGNVL 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 429325228  68 RILANVRERQRTQSLNEAFAALRKIIPTLP----SDKLSKIQTLKLAARYIDFLYQVL 121
Cdd:cd11431    2 RKTANARERDRMREINDAFEALRRAVPEYPvagkDGKLTKITTLRLAMNYIKALTDLL 59

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 429325228  72 NVRERQRTQSLNEAFAALRKIIPTLPSDK-LSKIQTLKLAARYIDFLYQVL 121
Cdd:cd11418    6 NERERRRVQAVNDAFDRLRQHVPYLKRRKkLSKVKTLRRAIEYIRHLQKLL 56

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 429325228  67 QRILANVRERQRTQSLNEAFAALRKIIPTLPSD-KLSKIQTLKLAARYIDFLYQVLQSDEMD 127
Cdd:cd19706    4 RRIFTNSRERWRQQNVNGAFAELRKLIPTHPPDkKLSKNEILRLAMKYINFLAKLLNDQEEE 65

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 429325228  67 QRILANVRERQRTQSLNEAFAALRKIIPTLPSD-KLSKIQTLKLAARYIDFLYQVLQ 122
Cdd:cd19708    1 RRMFTNSRERWRQQNVNGAFAELRKLVPTHPPDkKLSKNEILRLAIKYIRLLSNVLE 57

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        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 429325228  68 RILANVRERQRTQSLNEAFAALRKIIPTLPSD-KLSKIQTLKLAARYIDFLYQVL 121
Cdd:cd11414    3 RNAHATRERIRVEAFNSAFAQLRKLLPTLPPDkKLSKIEILRLAICYISYLNHVL 57

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 429325228  65 QSQRILANVRERQRTQSLNEAFAALRKIIPTLPSD-KLSKIQTLKLAARYIDFLYQVLQ 122
Cdd:cd19717    8 KTRRVKANNRERNRMHNLNAALDSLREVLPTFPEDaKLTKIETLRFAHNYIWALSETLR 66

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 429325228  67 QRILANVRERQRTQSLNEAFAALRKIIPTLPSD-KLSKIQTLKLAARYIDFLYQVLQS 123
Cdd:cd19713    6 RRLAANARERRRMHGLNHAFDQLRNVIPSFNNDkKLSKYETLQMAQIYINALSELLQG 63

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 429325228  68 RILANVRERQRTQSLNEAFAALRKIIPTLPSD-KLSKIQTLKLAARYIDFLYQVL 121
Cdd:cd11430    2 RLAANARERRRMNGLNRAFDQLRSVVPSIGNDkKLSKYETLQMAQIYIETLSELL 56

basic helix-loop-helix (bHLH) domain found in muscle, intestine and stomach expression 1 (MIST-1) and similar proteins; MIST-1, also termed Class A basic helix-loop-helix protein 15 (bHLHa15), or Class B basic helix-loop-helix protein 8 (bHLHb8), is a bHLH transcription factor expressed in pancreatic acinar cells and other serous exocrine cells. It is essential for cytoskeletal organization and secretory activity. It also functions as a potent endoplasmic reticulum (ER) stress-inducible transcriptional regulator. MIST-1 is capable of binding to E-box (CANNTG) motifs as a homodimer or a heterodimer with E-proteins (E12 and E47) to regulate transcription.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 429325228  67 QRILANVRERQRTQSLNEAFAALRKIIPTLPSD-KLSKIQTLKLAARYIDFL 117
Cdd:cd19711    1 RRLESNERERQRMHKLNNAFQALREVIPHVRAEkKLSKIETLTLAKNYIKSL 52

basic helix-loop-helix (bHLH) domain found in neurogenin-1 (NGN-1) and similar proteins; 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. It activates transcription by binding to the E box (5'-CANNTG-3').

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 429325228  65 QSQRILANVRERQRTQSLNEAFAALRKIIPTLPSD-KLSKIQTLKLAARYIDFLYQVLQ 122
Cdd:cd19716   15 KSRRVKANDRERNRMHNLNAALDELRSVLPSFPDDtKLTKIETLRFAHNYIWALSETLR 73

basic helix-loop-helix (bHLH) domain found in 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. The family also includes 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 429325228  67 QRILANVRERQRTQSLNEAFAALRKIIPT--LPSDK-LSKIQTLKLAARYIDFLYQVLQ 122
Cdd:cd11425    1 QRQLANERERLRMRTLADALGELRQHLPPsvAPKGKrLSKIQTLKYAIRYIGYLGNVLQ 59

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 429325228  67 QRILANVRERQRTQSLNEAFAALRKIIPTLPSD-KLSKIQTLKLAARYIDFLYQVL 121
Cdd:cd11426    1 RRLESNERERLRMHQLNDAFQALREVIPHVRSErKLSKIETLTLAKNYIKSLTNMI 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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 429325228  61 FEELQSQRILANVRERQRTQSLNEAFAALRKIIPTLP-SDKLSKIQTLKLAARYIDFLYQVLQ 122
Cdd:cd19722    8 MERVKVRRQEANARERNRMHGLNDALDSLRKVVPCYSkTQKLSKIETLRLAKNYIWALSEILR 70

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 429325228  72 NVRERQRTQSLNEAFAALRKIIPTLPSDK-LSKIQTLKLAARYIDFLYQVL 121
Cdd:cd19724    6 NERERQRVRCVNEGYARLRRHLPLENKDKrLSKVETLRAAIRYIKHLQELL 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 429325228  41 EDGSPTPGKRG-KKGSPSAQSFEELQSQRILANVRERQRTQSLNEAFAALRKIIPTLP-SDKLSKIQTLKLAARYIDFLY 118
Cdd:cd19719    1 EDDDQKPKRRGpKKKKMTKARLERFKMRRMKANARERNRMHGLNAALDNLRKVVPCYSkTQKLSKIETLRLAKNYIWALS 80

                 ....*
gi 429325228 119 QVLQS 123
Cdd:cd19719   81 EILRS 85

basic helix-loop-helix (bHLH) domain found in transcription factor 23 (TCF-23) 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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 429325228  74 RERQRTQSLNEAFAALRKIIPTLPSD-KLSKIQTLKLAARYIDFLYQVL 121
Cdd:cd19709    7 RERSRVRTLRQAFLALQAALPSVPPDtKLSKLDVLVLATSYIAHLTRTL 55

basic helix-loop-helix (bHLH) domain found in Class E basic helix-loop-helix protein bHLHe22, bHLHe23 and similar proteins; The family 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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 429325228  68 RILANVRERQRTQSLNEAFAALRKIIPTLPSD---KLSKIQTLKLAARYIdfLYQVLQSDEM 126
Cdd:cd11468    1 RLSINARERRRMHDLNDALDDLRAVIPYAHSPsvrKLSKIATLLLAKNYI--LMQARAIEEL 60

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
                 ....*....|....*....|....*....|....*....|....*....
gi 429325228  74 RERQRTQSLNEAFAALRKIIPTLPSD-KLSKIQTLKLAARYIDFLYQVL 121
Cdd:cd11424    7 RERSRVRTLRTAFQSLQRALPAVPPDtKLSKLDVLLLASRYIAHLTRKL 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 429325228  74 RERQRTQSLNEAFAALRKIIPTLPSD-KLSKIQTLKLAARYIDFLYQVL 121
Cdd:cd19710    8 RERSRVQTLRSAFLELQRTLPSVPPDtKLSKLDVLVLATTYIAHLMRTL 56

basic helix-loop-helix (bHLH) domain found in achaete-scute-like protein 3 (ASCL-3) and similar proteins; ASCL-3, also termed Class A basic helix-loop-helix protein 42 (bHLHa42), or bHLH transcriptional regulator Sgn-1, or achaete-scute homolog 3 (ASH-3), is a bHLH transcription factor specifically localized in the duct cells of the salivary glands. It may act as transcriptional repressor that inhibits myogenesis.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 429325228  72 NVRERQRTQSLNEAFAALRKIIPTLPSDK-LSKIQTLKLAARYIDFLYQVL 121
Cdd:cd19745    9 NERERQRVKCVNEGYAKLRRHLPQEYSEKrLSKVETLRAAIKYIKHLQSVL 59

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 429325228  72 NVRERQRTQSLNEAFAALRKIIPTLP-SDKLSKIQTLKLAARYIDFLYQVL 121
Cdd:cd19723    6 NERERNRVKLVNLGFATLREHVPNGRaNKKMSKVETLRSAVEYIRQLQQLL 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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 429325228  67 QRILANVRERQRTQSLNEAFAALRKIIPTLPSDKLSKIQTLKLAARYIDFLYQVLQSDEMDN 128
Cdd:cd11406    1 KRAHHNALERKRRDHIKDSFHSLRDSVPSLQGEKASRAQILKKATEYIQYMRRKNHTHQQDI 62

basic helix-loop-helix (bHLH) domain found in oligodendrocyte transcription factor 1 (Oligo1) and similar proteins; Oligo1, also termed Class B basic helix-loop-helix protein 6 (bHLHb6), or Class E basic helix-loop-helix protein 21 (bHLHe21), is a bHLH transcription factor that promotes formation and maturation of oligodendrocytes, especially within the brain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 429325228  62 EELQSQRILANVRERQRTQSLNEAFAALRKII--------PTLPSDKLSKIQTLKLAARYIDFLYQVLQ 122
Cdd:cd18942    1 EEQQQLRRKINSRERKRMQDLNLAMDALREVIlpysaahcQSSPGRKLSKIATLLLARNYILLLGSSLQ 69

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        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 429325228  67 QRILANVRERQRTQSLNEAFAALRKIIPTLPSDKLSKIQTLKLAARYIDFLYQVLQ 122
Cdd:cd18936    6 RRKAATMRERRRLSKVNEAFETLKRCTSTNPNQRLPKVEILRNAIRYIESLQALLR 61

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 429325228  72 NVRERQRTQSLNEAFAALRKIIPTL-PSDKLSKIQTLKLAARYIDFLYQVL 121
Cdd:cd19743    8 NERERNRVKLVNLGFAALRQHVPQGgASKKMSKVETLRSAVEYIRALQRLL 58

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        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 429325228  67 QRILANVRERQRTQSLNEAFAALRKIIPTLPSDKLSKIQTLKLAARYIDFLYQVL 121
Cdd:cd11411    2 RRKAATMRERRRLKKVNEAFEALKRCTSANPNQRLPKVEILRNAIEYIESLQDLL 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 429325228  72 NVRERQRTQSLNEAFAALRKIIPTLPSDK-LSKIQTLKLAARYIDFLYQVLqsDEMD 127
Cdd:cd19742   10 NERERNRVKLVNMGFATLREHVPNGAANKkMSKVETLRSAVEYIRALQQLL--DEHD 64

basic helix-loop-helix (bHLH) domain found in Class E basic helix-loop-helix protein 23 (bHLHe23) and similar proteins; bHLHe23, also termed Class B basic helix-loop-helix protein 4 (bHLHb4), is an OLIG-related bHLH transcription factor that is expressed in rod bipolar cells and is required for rod bipolar cell maturation. bHLHe23 have roles in spinal interneuron differentiation by mechanisms linked to the Notch signaling pathway. It modulates the expression of genes required for the differentiation and/or maintenance of pancreatic and neuronal cell types.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 429325228  62 EELQSQRILANVRERQRTQSLNEAFAALRKIIPTLPSD---KLSKIQTLKLAARYIdfLYQVLQSDEM 126
Cdd:cd18953    2 KEQRSLRLSINARERRRMHDLNDALDGLRSVIPYAHSPsvrKLSKIATLLLAKNYI--LMQAQALEEM 67

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        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 429325228  67 QRILANVRERQRTQSLNEAFAALRKIIPTLPSDKLSKIQTLKLAARYIDFLYQVL 121
Cdd:cd19699    2 RRKAATMRERRRLRKVNEAFEVLKRRTCPNPNQRLPKVEILRNAIEYIESLEDLL 56

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 429325228  67 QRILANVR-ERQRTQSLNEAFAALRKIIPTLPSDKLSKIQTLKLAARYIDFLYQVL-----QSDEMDNKM 130
Cdd:cd11404    1 QRRLNHVRsEKKRRELIKKGYDELCALVPGLDPQKRTKADILQKAADWIQELKEENekleeQLDELKEAA 70