helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 408360247    56 ARERSRVQTLRHAFLELQRTLPSVPPDTKLSKLDVLLLATTYIAHLTRSLQD 107
Cdd:smart00353   2 ARERRRRRKINEAFDELRSLLPTLPKNKKLSKAEILRLAIEYIKSLQEELQK 53

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 408360247  51 AAANAARERSRVQTLRHAFLELQRTLPSVPPDTKLSKLDVLLLATTYIAHLTRSL 105
Cdd:cd11424    1 AAGNAARERSRVRTLRTAFQSLQRALPAVPPDTKLSKLDVLLLASRYIAHLTRKL 55

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 408360247  53 ANAARERSRVQTLRHAFLELQRTLPSVPPDTKLSKLDVLLLATTYIAHLTRSL 105
Cdd:cd11390    3 AANARERRRMHDLNDAFEALRKVLPTVPPDKKLSKIETLRLAINYIAALSDLL 55

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 408360247    56 ARERSRVQTLRHAFLELQRTLPSVPPDTKLSKLDVLLLATTYIAHLTRSLQD 107
Cdd:smart00353   2 ARERRRRRKINEAFDELRSLLPTLPKNKKLSKAEILRLAIEYIKSLQEELQK 53

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 408360247  52 AANAaRERSRVQTLRHAFLELQRTLPSVPPDTKLSKLDVLLLATTYIAHLTRSLQDD 108
Cdd:cd19703    7 AANA-RERARMRVLSKAFSRLKTSLPWVPPDTKLSKLDTLRLASSYIAHLRQLLQED 62

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
                 ....*....|....*....|....*....|....*....|....*.
gi 408360247  57 RERSRVQTLRHAFLELQRTLPSVPPDTKLSKLDVLLLATTYIAHLT 102
Cdd:cd11466    8 KERRRTQSINSAFADLRECIPNVPADTKLSKIKTLRLATSYIAYLM 53

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 408360247  57 RERSRVQTLRHAFLELQRTLPSVPPDTKLSKLDVLLLATTYIAHLTRSLQDD 108
Cdd:cd18952    9 KERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDVLAKD 60

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 408360247  52 AANAaRERSRVQTLRHAFLELQRTLPSVPPDTKLSKLDVLLLATTYIAHLTRSL 105
Cdd:cd11465    3 AANA-RERDRTHSVNSAFTALRTLIPTEPADRKLSKIETLRLASSYISHLATVL 55

basic helix-loop-helix (bHLH) domain found in helix-loop-helix protein 1 (HEN-1) and similar proteins; HEN-1, also termed nescient helix-loop-helix 1 (Nhlh1), or Class A basic helix-loop-helix protein 35 (bHLHa35), or nescient helix loop helix 1 (NSCL-1), is a neuron-specific bHLH transcription factor that may serve as DNA-binding protein and may be involved in the control of cell-type determination, possibly within the developing nervous system.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 408360247  53 ANAARERSRVQTLRHAFLELQRTLPSVPPDTKLSKLDVLLLATTYIAHLTRSLQ 106
Cdd:cd19701   19 AHATRERIRVEAFNVAFAELRKLLPTLPPDKKLSKIEILRLAICYISYLNHVLD 72

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 408360247  52 AANAaRERSRVQTLRHAFLELQRTLPSVPPDTKLSKLDVLLLATTYIAHLTRSL 105
Cdd:cd11430    4 AANA-RERRRMNGLNRAFDQLRSVVPSIGNDKKLSKYETLQMAQIYIETLSELL 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        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 408360247  52 AANAARERSRVQTLRHAFLELQRTLPSVPPDTKLSKLDVLLLATTYIAHLTRSL 105
Cdd:cd19702   18 SAHATRERIRVEAFNLAFAELRKLLPTLPPDKKLSKIEILRLAICYISYLNHVL 71

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 408360247  57 RERSRVQTLRHAFLELQRTLPSVPPDTKLSKLDVLLLATTYIAHLTRSLQD 107
Cdd:cd11413    8 RERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYIKFLEKILED 58

basic helix-loop-helix (bHLH) domain found in T-cell acute lymphocytic leukemia protein 1 (TAL-1) and similar proteins; TAL-1, also termed Class A basic helix-loop-helix protein 17 (bHLHa17), or stem cell protein (SCL), or T-cell leukemia/lymphoma protein 5, is a hematopoietic-specific bHLH transcription factor that functions in embryonic and adult hematopoiesis in vertebrates. It is also required for embryonic vascular remodeling. It acts as a regulator of erythroid differentiation and binds to regulatory regions of a large cohort of erythroid genes as part of a complex with GATA-1, LMO2 and Ldb1. TAL-1 has been implicated in T-cell acute lymphoblastic leukemia. In common with other tissue-specific bHLH proteins, Tal heterodimerizes with ubiquitously-expressed members of the E2A family and form a DNA-binding complex with an E-box (CANNTG) to regulate transcription at its recognition site.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 408360247  56 ARERSRVQTLRHAFLELQRTLPSVPPDTKLSKLDVLLLATTYIAHLTRSLQDDAE 110
Cdd:cd19706   10 SRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLLNDQEE 64

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 408360247  57 RERSRVQTLRHAFLELQRTLPSVPPDtKLSKLDVLLLATTYIAHLTRSLQDD 108
Cdd:cd11412   19 RERQRTQSLNEAFAALRKIIPTLPSD-KLSKIQTLKLAARYIDFLYQVLQSD 69

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 408360247  52 AANAaRERSRVQTLRHAFLELQRTLPSVPPDTKLSKLDVLLLATTYIAHLTRSLQ 106
Cdd:cd19713    9 AANA-RERRRMHGLNHAFDQLRNVIPSFNNDKKLSKYETLQMAQIYINALSELLQ 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
                 ....*....|....*....|....*....|....*....|....*....|.
gi 408360247  57 RERSRVQTLRHAFLELQRTLPSVPPDTKLSKLDVLLLATTYIAHLTRSLQD 107
Cdd:cd19707    9 RERWRQQNVNSAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLVKLLGD 59

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 408360247  56 ARERSRVQTLRHAFLELQRTLPSVPPDTKLSKLDVLLLATTYIAHLTRSLQ 106
Cdd:cd19708    7 SRERWRQQNVNGAFAELRKLVPTHPPDKKLSKNEILRLAIKYIRLLSNVLE 57

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 408360247  53 ANAaRERSRVQTLRHAFLELQRTLPSVPPDTKLSKLDVLLLATTYIAHLTRSL 105
Cdd:cd11427    4 ANA-RERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLARNYIWALSEIL 55

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 408360247  53 ANAaRERSRVQTLRHAFLELQRTLPSVPP---DTKLSKLDVLLLATTYIAHLTRSL 105
Cdd:cd11431    5 ANA-RERDRMREINDAFEALRRAVPEYPVagkDGKLTKITTLRLAMNYIKALTDLL 59

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 408360247  57 RERSRVQTLRHAFLELQRTLPSVPPDTKLSKLDVLLLATTYIAHLTRSLQ 106
Cdd:cd19717   17 RERNRMHNLNAALDSLREVLPTFPEDAKLTKIETLRFAHNYIWALSETLR 66

basic helix-loop-helix (bHLH) domain found in Drosophila melanogaster protein dimmed and similar proteins; Dimmed, also termed DIMM, is a bHLH transcription factor that regulates neurosecretory (NS) cell function and neuroendocrine cell fate in Drosophila.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 408360247  57 RERSRVQTLRHAFLELQRTLPSVPPDTKLSKLDVLLLATTYIAHLT 102
Cdd:cd19712    8 RERMRMHSLNDAFQGLREVIPHVNAERKLSKIETLTLAKNYIKALT 53

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 408360247  56 ARERSRVQTLRHAFLELQRTLPSV--PPDTKLSKLDVLLLATTYIAHLTRSLQ 106
Cdd:cd11425    7 ERERLRMRTLADALGELRQHLPPSvaPKGKRLSKIQTLKYAIRYIGYLGNVLQ 59

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 408360247  56 ARERSRVQTLRHAFLELQRTLPSVPPDTKLSKLDVLLLATTYIAHLTRSL 105
Cdd:cd18951   10 ARERDRTNSVNTAFTALRTLIPTEPADRKLSKIETLRLASSYISHLGNVL 59

basic helix-loop-helix (bHLH) domain found in Drosophila melanogaster protein Amos and similar proteins; Amos, also termed absent MD neurons and olfactory sensilla protein, or reduced olfactory organs protein, or rough eye protein, is a bHLH transcription factor that promotes multiple dendritic neuron formation in the Drosophila peripheral nervous system.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 408360247  52 AANAaRERSRVQTLRHAFLELQRTLPSVPPDTKLSKLDVLLLATTYIAHLTRSLQ 106
Cdd:cd19715   11 AANA-RERRRMNSLNVAFDKLRDVVPSLGDDRKLSKYETLQMAQSYITALKELLS 64

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
                 ....*....|....*....|....*....|....*....|....*....
gi 408360247  57 RERSRVQTLRHAFLELQRTLPSVPPDTKLSKLDVLLLATTYIAHLTRSL 105
Cdd:cd19724    8 RERQRVRCVNEGYARLRRHLPLENKDKRLSKVETLRAAIRYIKHLQELL 56

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 408360247  56 ARERSRVQTLRHAFLELQRTLPSVPPDTKLSKLDVLLLATTYIahltRSLQD 107
Cdd:cd19723    7 ERERNRVKLVNLGFATLREHVPNGRANKKMSKVETLRSAVEYI----RQLQQ 54

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 408360247  52 AANAaRERSRVQTLRHAFLELQRTLPSVPPDTKLSKLDVLLLATTYIAHLT 102
Cdd:cd11415   12 AANI-RERRRMFNLNEAFDKLRKKVPTFAYEKRLSRIETLRLAIVYISFMT 61

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
                 ....*....|....*....|....*....|....*....|....*..
gi 408360247  57 RERSRVQTLRHAFLELQRTLPSvPPDTKLSKLDVLLLATTYIAHLTR 103
Cdd:cd19682    7 RERERRSELRELFDKLKQLLGL-DSDEKASKLAVLTEAIEEIQQLKR 52

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 408360247  57 RERSRVQTLRHAFLELQRTLPS--VPPDTKLSKLDVLLLATTYIAHLTRSL 105
Cdd:cd18938    8 REKLRMRDLAKALHNLRRYLPPsvAPAGQSLTKIETLRLTIRYISHLSAQL 58

basic helix-loop-helix (bHLH) domain found in transcription factor E2-alpha (E2A) and similar proteins; E2A, also termed Class B basic helix-loop-helix protein 21 (bHLHb21), or immunoglobulin enhancer-binding factor E12/E47, or immunoglobulin transcription factor 1, or Kappa-E2-binding factor, or transcription factor 3 (TCF-3), or transcription factor ITF-1, is a bHLH transcriptional regulator involved in the initiation of neuronal differentiation.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 408360247  53 ANAARERSRVQTLRHAFLELQRT----LPSVPPDTKLSkldVLLLATTYIAHLTRSLQDDAEAPADAGL 117
Cdd:cd18944    5 ANNARERLRVRDINEAFKELGRMcqlhLNSEKPQTKLL---ILHQAVSVILNLEQQVRERNLNPKAACL 70

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
                 ....*....|....*....|....*....|....*....|....*....|.
gi 408360247  56 ARERSRVQTLRHAFLELQRTLPSVPPDTKLSKLDVLLLATTYIAHLTRSLQ 106
Cdd:cd19720   41 ARERNRMHDLNSALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEILR 91

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 408360247  56 ARERSRVQTLRHAFLELQRTLPSV-----------PPDTKLSKLDVLLLATTYIahltRSLQD 107
Cdd:cd19744    7 ARERNRVKQVNNGFAILRQHIPQSviedltagggrGKSKKLSKVDTLRMAVEYI----RRLQK 65

basic helix-loop-helix (bHLH) domain found in Drosophila melanogaster protein extra-macrochaetae and similar proteins; Extra-macrochaetae is a negative regulator of sensory organ development in Drosophila. It belongs to dominant negative group of helix-loop-helix (dnHLH) proteins, which lack a basic DNA-binding domain but can form heterodimers with other HLH proteins, thereby inhibiting DNA binding.

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 408360247  69 FLELQRTLPSVPPDTKLSKLDVLLLATTYIAHLTRSLQD 107
Cdd:cd19695   12 LAKLRNLVPTLPKNRKVSKLELLQHVIDYIADLEEQLED 50

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
                 ....*....|....*....|....*....|....*....|....*....|....
gi 408360247  56 ARERSRVQTLRHAFLELQRTLPSVPPDT--KLSKLDVLLLATTYIAHLTRSLQD 107
Cdd:cd11468    6 ARERRRMHDLNDALDDLRAVIPYAHSPSvrKLSKIATLLLAKNYILMQARAIEE 59

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 408360247  56 ARERSRVQTLRHAFLELQRTLPSVPPDTKLSKLDVLLLATTYIAHLTRSLQ 106
Cdd:cd19719   34 ARERNRMHGLNAALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEILR 84

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 408360247  51 AAANAARERSRVQTLRHAFLELQRTLPSVPPDTKLSKLDVLLLATTYIAHLTRSLQD 107
Cdd:cd19742    6 VARRNERERNRVKLVNMGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLLDE 62

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 408360247  53 ANAARERSRVQTLRHAFLELQRTlPSVPPDTKLSKLDVLLLATTYIAHLTRSLQDDAE 110
Cdd:cd18937    5 AATMRERRRLKKVNQAFETLKRC-TTSNPNQRLPKVEILRNAIRYIESLQDLLREQVE 61