helix loop helix domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
2203_455C       92 ERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMEVLA 140
Cdd:smart00353   4 ERRRRRKINEAFDELRSLLPTLPKNKKLSKAEILRLAIEYIKSLQEELQ 52

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
                ....*....|....*....|....*....|....*....|....*....|....*.
2203_455C    84 KGVGGPKKERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMEVL 139
Cdd:cd11466   1 RRGSANKKERRRTQSINSAFADLRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 56

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
                ....*....|....*....|....*....|....*....|....*....|
2203_455C    90 KKERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMEVL 139
Cdd:cd11390   6 ARERRRMHDLNDAFEALRKVLPTVPPDKKLSKIETLRLAINYIAALSDLL 55

basic helix-loop-helix (bHLH) domain found in twist-related protein (TWIST) family; The TWIST family includes TWIST1 and TWIST2, which are highly homologous bHLH transcription factors that promote epithelial-mesenchymal transition (EMT) during development and tumor metastasis. They are involved in the negative regulation of cellular determination and in the differentiation of several lineages, including myogenesis, osteogenesis, and neurogenesis. TWIST factors express in broad partially-overlapping patterns during embryo development and dimerize with a broad sets of dimer partners that form numerous unique transcriptional complexes to regulate embryonic development.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
2203_455C    91 KERRRTESINSAFAELRECIPNVPADtKLSKIKTLRLATSYIAYLMEVLARD 142
Cdd:cd11464   8 RERQRTQSLNEAFTSLRKIIPTLPSD-KLSKIQTLKLAARYIDFLYQVLRSD 58

helix loop helix domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
2203_455C       92 ERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMEVLA 140
Cdd:smart00353   4 ERRRRRKINEAFDELRSLLPTLPKNKKLSKAEILRLAIEYIKSLQEELQ 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
                ....*....|....*....|....*....|....*....|....*....|..
2203_455C    91 KERRRTESINSAFAELRECIPNVPADtKLSKIKTLRLATSYIAYLMEVLARD 142
Cdd:cd11412  19 RERQRTQSLNEAFAALRKIIPTLPSD-KLSKIQTLKLAARYIDFLYQVLQSD 69

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
                ....*....|....*....|....*....|....*....|....*....|
2203_455C    90 KKERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMEVL 139
Cdd:cd11418   7 ERERRRVQAVNDAFDRLRQHVPYLKRRKKLSKVKTLRRAIEYIRHLQKLL 56

basic helix-loop-helix (bHLH) domain found in helix-loop-helix protein (HEN) family; The HEN family includes two neuron-specific bHLH transcription factors, HEN-1 (also known as Nhlh1 or bHLHa35 or NSCL-1) and HEN-2 (also known as Nhlh2 or bHLHa34 or NSCL-2). They may serve as DNA-binding protein that is involved in the control of cell-type determination, possibly within the developing nervous system.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
2203_455C    91 KERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMEVL 139
Cdd:cd11414   9 RERIRVEAFNSAFAQLRKLLPTLPPDKKLSKIEILRLAICYISYLNHVL 57

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
                ....*....|....*....|....*....|....*....|....*....
2203_455C    91 KERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMEVL 139
Cdd:cd18951  11 RERDRTNSVNTAFTALRTLIPTEPADRKLSKIETLRLASSYISHLGNVL 59

basic helix-loop-helix (bHLH) domain found in musculin, transcription factor 21 (TCF-21) and similar proteins; The family includes two bHLH transcription factors, musculin and transcription factor 21 (TCF-21). Musculin, also termed activated B-cell factor 1 (ABF-1), or Class A basic helix-loop-helix protein 22 (bHLHa22), is a bHLH transcription factor expressed in activated B lymphocytes. It acts as a transcription repressor capable of inhibiting the transactivation capability of TCF3/E47. Musculin may play a role in regulating antigen-dependent B-cell differentiation. The mouse homolog, musculin, is suggested to be a repressor of myogenesis that is expressed in developing muscle and in the spleen. TCF-21, also termed capsulin, or Class A basic helix-loop-helix protein 23 (bHLHa23), or epicardin, or podocyte-expressed 1 (Pod-1), is a bHLH transcription factor expressed specifically in mesodermally-derived cells that surround the epithelium of the developing gastrointestinal, genitourinary and respiratory systems during mouse embryogenesis. It may play a role in the specification or differentiation of one or more subsets of epicardial cell types.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
2203_455C    91 KERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMEVL 139
Cdd:cd11423   8 RERARMRVLSKAFSRLKTTLPWVPPDTKLSKLDTLRLAASYIAHLRQIL 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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
2203_455C    91 KERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMEVLARD 142
Cdd:cd19704  11 RERARMRVLSKAFSRLKTTLPWVPPDTKLSKLDTLRLASSYIAHLRQILAND 62

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
2203_455C    91 KERRRTESINSAFAELRECIPNVPADtKLSKIKTLRLATSYIAYLMEVLARD 142
Cdd:cd19700  24 RERQRTQSLNEAFAALRKIIPTLPSD-KLSKIQTLKLAARYIDFLYQVLQSD 74

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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
2203_455C    91 KERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMEVLA 140
Cdd:cd11428   8 RERNRMHNLNDALDALREVLPSFPDETKLTKIETLRFAHNYIWALSETLK 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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
2203_455C    79 RLGRRKGVGGPKKERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMEVL 139
Cdd:cd19717   5 KIKKTRRVKANNRERNRMHNLNAALDSLREVLPTFPEDAKLTKIETLRFAHNYIWALSETL 65

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
                ....*....|....*....|....*....|....*....|....*....|
2203_455C    90 KKERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMEVL 139
Cdd:cd19711   7 ERERQRMHKLNNAFQALREVIPHVRAEKKLSKIETLTLAKNYIKSLTTTI 56

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        50
                ....*....|....*....|....*....|....*....|....*....|
2203_455C    90 KKERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMEVL 139
Cdd:cd19712   7 ERERMRMHSLNDAFQGLREVIPHVNAERKLSKIETLTLAKNYIKALTNVI 56

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
                ....*....|....*....|....*....|....*....|....*....
2203_455C    91 KERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMEVL 139
Cdd:cd19715  15 RERRRMNSLNVAFDKLRDVVPSLGDDRKLSKYETLQMAQSYITALKELL 63

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
                ....*....|....*....|....*....|....*....|....*....|....
2203_455C    86 VGGPKKERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMEVL 139
Cdd:cd11424   2 AGNAARERSRVRTLRTAFQSLQRALPAVPPDTKLSKLDVLLLASRYIAHLTRKL 55

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
                ....*....|....*....|....*....|....*....|....*....
2203_455C    91 KERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMEVL 139
Cdd:cd19702  23 RERIRVEAFNLAFAELRKLLPTLPPDKKLSKIEILRLAICYISYLNHVL 71

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
                ....*....|....*....|....*....|....*....|....*....
2203_455C    91 KERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMEVL 139
Cdd:cd11427   7 RERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLARNYIWALSEIL 55

basic helix-loop-helix (bHLH) domain found in Fer3-like protein (FERD3L) and similar proteins; FERD3L, also termed basic helix-loop-helix protein N-twist, or Class A basic helix-loop-helix protein 31 (bHLHa31), or nephew of atonal 3 (NATO3), or Neuronal twist (NTWIST), is a bHLH transcription factor expressed in the developing central nervous system (CNS). It regulates floor plate (FP) cells development. FP is a critical organizing center located at the ventral-most midline of the neural tube. FERD3L binds to the E-box and functions as inhibitor of transcription.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
2203_455C    91 KERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMEVL 139
Cdd:cd11415  16 RERRRMFNLNEAFDKLRKKVPTFAYEKRLSRIETLRLAIVYISFMTDLL 64

basic helix-loop-helix (bHLH) domain found in neurogenin-3 (NGN-3) and similar proteins; NGN-3, also termed Class A basic helix-loop-helix protein 7 (bHLHa7), or protein atonal homolog 5 (ATOH5), is a neural-specific bHLH transcription factor expressed in the developing central nervous system and the embryonic pancreas. It is involved in neurogenesis and plays an important role in spermatogenesis.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
2203_455C    82 RRKGVGGPKKERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMEVL 139
Cdd:cd19718   6 RNRRMKANDRERNRMHNLNSALDALRSVLPTFPDDAKLTKIETLRFAHNYIWALTETL 63

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
                ....*....|....*....|....*....|....*....|....*....
2203_455C    91 KERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMEVL 139
Cdd:cd19706  11 RERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLL 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
                ....*....|....*....|....*....|....*....|....*....
2203_455C    91 KERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMEVL 139
Cdd:cd19708   8 RERWRQQNVNGAFAELRKLVPTHPPDKKLSKNEILRLAIKYIRLLSNVL 56

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
                ....*....|....*....|....*....|....*....|....*....
2203_455C    91 KERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMEVL 139
Cdd:cd19724   8 RERQRVRCVNEGYARLRRHLPLENKDKRLSKVETLRAAIRYIKHLQELL 56

basic helix-loop-helix (bHLH) domain found in achaete-scute-like protein 4 (ASCL-4) and similar proteins; ASCL-4, also termed Class A basic helix-loop-helix protein 44 (bHLHa44), or achaete-scute homolog 4 (ASH-4), or Hash4, is a bHLH transcriptional regulator that may be involved in skin development.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
2203_455C    90 KKERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMEVL 139
Cdd:cd19746  14 ERERQRVRCVNEGYARLREHLPQELADKRLSKVETLRAAIDYIKHLQELL 63

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
                ....*....|....*....|....*....|....*....|....*....|..
2203_455C    90 KKERRRTESINSAFAELRECIPNV--PADTKLSKIKTLRLATSYIAYLMEVL 139
Cdd:cd11425   7 ERERLRMRTLADALGELRQHLPPSvaPKGKRLSKIQTLKYAIRYIGYLGNVL 58

basic helix-loop-helix (bHLH) domain found in protein atonal homolog 8 (ATOH8) and similar proteins; ATOH8, also termed Class A basic helix-loop-helix protein 21 (bHLHa21), or helix-loop-helix protein hATH-6 (hATH6), is a bHLH shear-stress-responsive transcription factor expressed in activated satellite cells and proliferating myoblasts of human skeletal muscle tissue. It regulates endothelial cell proliferation, migration and tube-like structures formation. ATOH8 binds a palindromic (canonical) core consensus DNA sequence 5'-CANNTG- 3' known as an E-box element, possibly as a heterodimer with other bHLH proteins.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
2203_455C    91 KERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMEVLARDSQ 144
Cdd:cd11421  15 RERTRVHTISAAFEALRKAVPSYSYNQKLSKLAILRIACSYILALARLADLDYS 68

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'.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
2203_455C    92 ERRRTESINSAFAELRECIPNVpADTKLSKIKTLRLATSYIAYLMEVLAR 141
Cdd:cd11419  12 ERRRMQSINAGFQSLRTLLPHC-DGEKLSKAAILQQTAEYIFSLEQEKTR 60

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in USF/MITF family; The USF (upstream stimulatory factor)/MITF (microphthalmia-associated transcription factor) family includes two bHLHzip transcription factor subfamilies. USFs are ubiquitously expressed and key regulators of a wide number of gene regulation networks, including the stress and immune responses, cell cycle and proliferation, lipid and glucid metabolism. USFs recruit chromatin remodeling enzymes and interact with co-activators and the members of the transcription pre-initiation complex. USFs interact with high affinity to E-box regulatory elements. The MITF (also known as microphthalmia-TFE, or MiT) subfamily comprises four genes in mammals (MITF, TFE3, TFEB, and TFEC); each gene has different functions. MITF is involved in neural crest melanocytes development as well as the pigmented retinal epithelium. TFEB is required for vascularization of the mouse placenta. TFE3 is involved in B cell function. TFEC regulates gene expression in macrophages. The MITF subfamily proteins can form homodimers or heterodimers with each other but not with other bHLH or bHLHzip proteins.

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2203_455C    92 ERRRTESINSAFAELRECIPNVP---ADTKLSKIKTLRLATSYIAYLMEVLAR 141
Cdd:cd11387   6 ERRRRDNINEKIQELGSLVPPSRletKDLKPNKGSILSKAVEYIRELQNQNQE 58

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.

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2203_455C    91 KERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMEVL 139
Cdd:cd19720  42 RERNRMHDLNSALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEIL 90

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.

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2203_455C    91 KERRRTESINSAFAELRECIP--NVPADTKLSKIKTLRLATSYIayLMEVLARD 142
Cdd:cd11468   7 RERRRMHDLNDALDDLRAVIPyaHSPSVRKLSKIATLLLAKNYI--LMQARAIE 58

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.

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2203_455C    91 KERRRTESINSAFAELRECIPNV-----------PADTKLSKIKTLRLATSYIAYLMEVL 139
Cdd:cd19744   8 RERNRVKQVNNGFAILRQHIPQSviedltagggrGKSKKLSKVDTLRMAVEYIRRLQKLL 67

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.

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                ....*....|....*....|....*....|....*....|....*....|..
2203_455C    90 KKERRRTESINSAFAELRECIPN--VPADTKLSKIKTLRLATSYIAYLMEVL 139
Cdd:cd18938   7 EREKLRMRDLAKALHNLRRYLPPsvAPAGQSLTKIETLRLTIRYISHLSAQL 58

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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2203_455C    92 ERRRTESINSAFAELRECIPNVPADtKLSKIKTLRLATSYIAYL 135
Cdd:cd11406   9 ERKRRDHIKDSFHSLRDSVPSLQGE-KASRAQILKKATEYIQYM 51

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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2203_455C    92 ERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYL 135
Cdd:cd11400   9 ERQRRNDLKNSFEKLRDLVPELADNEKASKVVILKKATEYIKQL 52

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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2203_455C    91 KERRRTESINSAFAEL-RECIPNvpADTKLSKIKTLRLATSYIAYLMEVLARDSQ 144
Cdd:cd18934   9 RERRRLKKINEAFEALkRRTVPN--PNQRLPKVEILRSAINYIEKLQDLLHSLDQ 61

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in sterol regulatory element-binding protein (SREBP) family and similar proteins; The SREBP family includes SREBP1 and SREBP2, which are bHLHzip transcriptional activator of genes encoding proteins essential for cholesterol biosynthesis/uptake and fatty acid biosynthesis. SREBP1 and SREBP2 are principally found in the liver and in adipocytes and made up of an N-terminal transcription factor portion (composed of an activation domain, a bHLHzip domain, and a nuclear localization signal), a hydrophobic region containing two membrane spanning regions, and a C-terminal regulatory segment. They recognize a symmetric sterol regulatory element (TCACNCCAC) instead of E-box. The family also includes Saccharomyces cerevisiae transcription factor HMS1 (also termed high-copy MEP suppressor protein 1) and serine-rich protein TYE7. HMS1 is a putative bHLHzip transcription factor involved in exit from mitosis and pseudohyphal differentiation. TYE7, also termed basic-helix-loop-helix protein SGC1, is a putative bHLHzip transcription activator required for Ty1-mediated glycolytic gene expression. TYE7 N-terminal is extremely rich in serine residues. It binds DNA on E-box motifs, 5'-CANNTG-3'. TYE7 is not essential for growth.

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2203_455C    92 ERRRTESINSAFAELRECIP---------------NVPADTKLSKIKTLRLATSYIAYL 135
Cdd:cd11395  11 EKRYRSNLNTKIERLRDAIPslrspegksddgglgGLAPTTKLSKATILTKAIEYIRHL 69

basic helix-loop-helix (bHLH) domain found in DNA-binding protein inhibitor ID2 and similar proteins; ID2, also termed Class B basic helix-loop-helix protein 26 (bHLHb26), or inhibitor of DNA binding 2, or inhibitor of differentiation 2, is a dominant negative helix-loop-helix (dnHLH) transcriptional regulator (lacking a basic DNA binding domain) which negatively regulates the bHLH transcription factors by forming heterodimers and inhibiting their DNA binding and transcriptional activity. It has been implicated in the regulation of cell proliferation and differentiation in myogenesis, neurogenesis, and/or hematopoiesis.

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2203_455C    98 SINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMevLARDSQP 145
Cdd:cd19692  21 NMNDCYSKLKELVPSIPQNKKVSKMEILQHVIDYILDLQ--IALDSHP 66

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in basic helix-loop-helix domain-containing protein USF3 and similar proteins; USF3, also termed upstream transcription factor 3, is a bHLHzip protein that is involved in the negative regulation of epithelial-mesenchymal transition, the process by which epithelial cells lose their polarity and adhesion properties to become mesenchymal cells with enhanced migration and invasive properties.

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2203_455C    92 ERRRTESINSAFAELRECIPNVPAdTKLSKIKTLRLATSYIAYLME 137
Cdd:cd18910  13 ERRRKDKINAGINKIGELLPDRDA-KKQSKNMILEQAYKYIVELKK 57

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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2203_455C    91 KERRRTESINSAFAELRECIPNVPaDTKLSKIKTLRLATSYIAYLMEVL 139
Cdd:cd11411   9 RERRRLKKVNEAFEALKRCTSANP-NQRLPKVEILRNAIEYIESLQDLL 56

basic helix-loop-helix (bHLH) domain found in oligodendrocyte transcription factor 3 (Oligo3) and similar proteins; Oligo3, also termed Class B basic helix-loop-helix protein 7 (bHLHb7), or Class E basic helix-loop-helix protein 20 (bHLHe20), is a bHLH transcription factor that 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.

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                ....*....|....*....|....*....|....*....|....*....|.
2203_455C    91 KERRRTESINSAFAELRECIPNV--PADTKLSKIKTLRLATSYIAYLMEVL 139
Cdd:cd18941  23 RERKRMHDLNLAMDGLREVMPYAhgPSVRKLSKIATLLLARNYILMLTSSL 73

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

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2203_455C    99 INSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMevLARDSQP 145
Cdd:cd19694  11 MNDCYSRLKRLVPTIPPNKKVSKVEILQHVIDYILDLQ--LALETHP 55

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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2203_455C    92 ERRRTESINSAFAELRECIPNVpADTKLSKIKTLRLATSYIAYLME 137
Cdd:cd11404  10 EKKRRELIKKGYDELCALVPGL-DPQKRTKADILQKAADWIQELKE 54

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.

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2203_455C    91 KERRRTESINSAFAELRECI-PNVPADT------KLSKIKTLRLATSYIAYL 135
Cdd:cd18942  13 RERKRMQDLNLAMDALREVIlPYSAAHCqsspgrKLSKIATLLLARNYILLL 64

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.

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2203_455C    82 RRKGvgGPKKERRRTESINSAFAELRECIPNVPADtKLSKIKTLRLATSYIAYLMEVL 139
Cdd:cd19699   2 RRKA--ATMRERRRLRKVNEAFEVLKRRTCPNPNQ-RLPKVEILRNAIEYIESLEDLL 56