helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 530380724   103 ERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDVLAK 152
Cdd:smart00353   4 ERRRRRKINEAFDELRSLLPTLPKNKKLSKAEILRLAIEYIKSLQEELQK 53

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 530380724  95 RKGSGPKKERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 150
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
                 ....*....|....*....|....*....|....*....|....*....|...
gi 530380724  98 SGPKKERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 150
Cdd:cd11390    3 AANARERRRMHDLNDAFEALRKVLPTVPPDKKLSKIETLRLAINYIAALSDLL 55

basic helix-loop-helix (bHLH) domain found in Fer3-like protein (FERD3L), pancreas transcription factor 1 subunit alpha (PTF1A) and similar proteins; The family corresponds to a group of bHLH transcription factors, including FERD3L and PTF1A. FERD3L, also termed basic helix-loop-helix protein N-twist, or Class A basic helix-loop-helix protein 31 (bHLHa31), or nephew of atonal 3 (NATO3), or Neuronal twist (NTWIST), is expressed in the developing central nervous system (CNS). It regulates floor plate (FP) cells development. FP is a critical organizing center located at the ventral-most midline of the neural tube. FERD3L binds to the E-box and functions as inhibitor of transcription. PTF1A, also termed Class A basic helix-loop-helix protein 29 (bHLHa29), or pancreas-specific transcription factor 1a, or bHLH transcription factor p48, or p48 DNA-binding subunit of transcription factor PTF1 (PTF1-p48), is implicated in the cell fate determination in various organs. It binds to the E-box consensus sequence 5'-CANNTG-3' and plays a role in early and late pancreas development and differentiation.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 530380724 102 KERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 150
Cdd:cd19686    8 RERKRMRSINDAFDGLRRHIPTFPYEKRLSKVDTLRLAIQYINFLTELL 56

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 530380724   95 RKGSGPKKERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYL 146
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELLPTLPPDKKLSKAEILRLAIEYIKHL 52

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
                 ....*....|....*....|....*....|....*....|....*....|..
gi 530380724 102 KERRRTESINSAFAELRECIPNVPADtKLSKIKTLRLATSYIAYLMDVLAKD 153
Cdd:cd11464    8 RERQRTQSLNEAFTSLRKIIPTLPSD-KLSKIQTLKLAARYIDFLYQVLRSD 58

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 530380724  94 RRKGSGPKKERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDVLAKDAQSGD 158
Cdd:cd18951    3 RQRHTANARERDRTNSVNTAFTALRTLIPTEPADRKLSKIETLRLASSYISHLGNVLLVGEACGD 67

basic helix-loop-helix (bHLH) domain found in Caenorhabditis elegans Helix-loop-helix protein 13 (HLH13) and similar proteins; Caenorhabditis elegans HLH13, also termed Fer3-like protein, or nephew of atonal 3, is a bHLH transcription factor that plays a role in the negative regulation of exit from L1 arrest and dauer diapause dependent on IIS signaling (insulin and insulin-like growth factor (IGF) signaling).

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 530380724 102 KERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 150
Cdd:cd11416   12 RERKRMLSINSAFEELRCHVPTFPYEKRLSKIDTLRLAIAYIALLRDIL 60

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
                 ....*....|....*....|....*....|....*....|....*....
gi 530380724 102 KERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 150
Cdd:cd19707    9 RERWRQQNVNSAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLVKLL 57

basic helix-loop-helix (bHLH) domain found in pancreas transcription factor 1 subunit alpha (PTF1A) and similar proteins; PTF1A, also termed Class A basic helix-loop-helix protein 29 (bHLHa29), or pancreas-specific transcription factor 1a, or bHLH transcription factor p48, or p48 DNA-binding subunit of transcription factor PTF1 (PTF1-p48), is a bHLH transcription factor implicated in the cell fate determination in various organs. It binds to the E-box consensus sequence 5'-CANNTG-3' and plays a role in early and late pancreas development and differentiation.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 530380724 102 KERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 150
Cdd:cd11417    8 RERRRMQSINDAFEGLRSHIPTLPYEKRLSKVDTLRLAIGYINFLSELV 56

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
                 ....*....|....*....|....*....|....*....|....*....
gi 530380724 102 KERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 150
Cdd:cd11423    8 RERARMRVLSKAFSRLKTTLPWVPPDTKLSKLDTLRLAASYIAHLRQIL 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 530380724  95 RKGSGPKKERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYL 146
Cdd:cd19711    1 RRLESNERERQRMHKLNNAFQALREVIPHVRAEKKLSKIETLTLAKNYIKSL 52

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
                 ....*....|....*....|....*....|....*....|....*....
gi 530380724 102 KERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 150
Cdd:cd19701   23 RERIRVEAFNVAFAELRKLLPTLPPDKKLSKIEILRLAICYISYLNHVL 71

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 530380724 102 KERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 150
Cdd:cd19709    7 RERSRVRTLRQAFLALQAALPSVPPDTKLSKLDVLVLATSYIAHLTRTL 55

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
                 ....*....|....*....|....*....|....*....|....*....|
gi 530380724 102 KERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDVLA 151
Cdd:cd11428    8 RERNRMHNLNDALDALREVLPSFPDETKLTKIETLRFAHNYIWALSETLK 57

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 530380724 102 KERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDVLAK 152
Cdd:cd11413    8 RERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYIKFLEKILED 58

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 530380724 102 KERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 150
Cdd:cd11422    7 RERERVRNLNSGFSKLRRIVPLIPRDRKPSKVDTLKGATEYIRLLQRIL 55

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
                 ....*....|....*....|....*....|....*....|....*....
gi 530380724 102 KERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 150
Cdd:cd11430    8 RERRRMNGLNRAFDQLRSVVPSIGNDKKLSKYETLQMAQIYIETLSELL 56

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 530380724  95 RKGSGPKKERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 150
Cdd:cd19717   10 RRVKANNRERNRMHNLNAALDSLREVLPTFPEDAKLTKIETLRFAHNYIWALSETL 65

basic Helix Loop Helix (bHLH) domain superfamily; bHLH proteins are transcriptional regulators that are found in organisms from yeast to humans. Members of the bHLH superfamily have two highly conserved and functionally distinct regions. The basic part is at the amino end of the bHLH that may bind DNA to a consensus hexanucleotide sequence known as the E box (CANNTG). Different families of bHLH proteins recognize different E-box consensus sequences. At the carboxyl-terminal end of the region is the HLH region that interacts with other proteins to form homo- and heterodimers. bHLH proteins function as a diverse set of regulatory factors because they recognize different DNA sequences and dimerize with different proteins. The bHLH proteins can be divided to cell-type specific and widely expressed proteins. The cell-type specific members of bHLH superfamily are involved in cell-fate determination and act in neurogenesis, cardiogenesis, myogenesis, and hematopoiesis.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 530380724 103 ERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYL 146
Cdd:cd00083    1 ERRRRDKINDAFEELKRLLPELPDSKKLSKASILQKAVEYIREL 44

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 530380724 102 KERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 150
Cdd:cd11424    7 RERSRVRTLRTAFQSLQRALPAVPPDTKLSKLDVLLLASRYIAHLTRKL 55

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 530380724  93 GRRKGSGPKKERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 150
Cdd:cd19713    4 KQRRLAANARERRRMHGLNHAFDQLRNVIPSFNNDKKLSKYETLQMAQIYINALSELL 61

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
                 ....*....|....*....|....*....|....*....|....*....
gi 530380724 102 KERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 150
Cdd:cd19708    8 RERWRQQNVNGAFAELRKLVPTHPPDKKLSKNEILRLAIKYIRLLSNVL 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
                 ....*....|....*....|....*....|....*....|....*....
gi 530380724 102 KERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 150
Cdd:cd19706   11 RERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLL 59

basic helix-loop-helix (bHLH) domain found in achaete-scute-like protein 5 (ASCL-5) and similar proteins; ASCL-5, also termed Class A basic helix-loop-helix protein 47 (bHLHa47), or achaete-scute homolog 5 (ASH-5), is an uncharacterized bHLH transcription factor that belongs to AS-C (achaete, scute, lethal of scute, and asense) family.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 530380724 101 KKERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 150
Cdd:cd19747   12 ERERQRVKCVNEGYARLRDHLPGAMAEKRLSKVETLRAAIRYIKYLQDLL 61

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 530380724  95 RKGSGPKKERRRTESINSAFAELRECIPNV--PADTKLSKIKTLRLATSYIAYLMDVL 150
Cdd:cd11425    1 QRQLANERERLRMRTLADALGELRQHLPPSvaPKGKRLSKIQTLKYAIRYIGYLGNVL 58

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 530380724 101 KKERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 150
Cdd:cd19742   11 ERERNRVKLVNMGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLL 60

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 530380724 101 KKERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 150
Cdd:cd19745   10 ERERQRVKCVNEGYAKLRRHLPQEYSEKRLSKVETLRAAIKYIKHLQSVL 59

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
                 ....*....|....*....|....*....|....*....|....*
gi 530380724 103 ERRRTESINSAFAELRECIPNVpADTKLSKIKTLRLATSYIAYLM 147
Cdd:cd11419   12 ERRRMQSINAGFQSLRTLLPHC-DGEKLSKAAILQQTAEYIFSLE 55

basic helix-loop-helix (bHLH) domain found in Oligodendrocyte lineage genes (OLIG) family of transcription factors; The OLIG family includes three bHLH transcription factors, Oligo1-3, which are expressed in both the developing and mature central nervous system. Oligo1 and Oligo2 are expressed in a nervous tissue-specific manner, but Oligo3 is found mainly in non-neural tissues. Oligo (also known as Olig) have key roles in the specification of motor neurons, dorsal interneurons, and oligodendrocytes. Oligo1, also termed Class B basic helix-loop-helix protein 6 (bHLHb6), or Class E basic helix-loop-helix protein 21 (bHLHe21), promotes formation and maturation of oligodendrocytes, especially within the brain. Oligo2, also termed Class B basic helix-loop-helix protein 1 (bHLHb1), or Class E basic helix-loop-helix protein 19 (bHLHe19), or protein kinase C-binding protein 2, or protein kinase C-binding protein RACK17, is required for oligodendrocyte and motor neuron specification in the spinal cord, as well as for the development of somatic motor neurons in the hindbrain. It cooperates with OLIG1 to establish the MN progenitors (pMN) domain of the embryonic neural tube. Oligo3, also termed Class B basic helix-loop-helix protein 7 (bHLHb7), or Class E basic helix-loop-helix protein 20 (bHLHe20), is expressed in the ventricular zone of the dorsal alar plate of the hindbrain and involved in regulating the development of dorsal and ventral spinal cord. It may determine the distinct specification program of class A neurons in the dorsal part of the spinal cord and suppress specification of class B neurons. This family also includes two OLIG-related bHLH transcription factors, bHLHe22 and bHLHe23. bHLHe22, also termed Class B basic helix-loop-helix protein 5 (bHLHb5), or trinucleotide repeat-containing gene 20 protein, is a neural-specific transcriptional repressor that is expressed in both excitatory (unipolar brush cells) and inhibitory neurons (cartwheel cells) of the dorsal cochlear nucleus (DCN) during development. It is important for the proper development and/or survival of a number of neural cell types. bHLHe23, also termed Class B basic helix-loop-helix protein 4 (bHLHb4), is expressed in rod bipolar cells and is required for rod bipolar cell maturation. bHLHe23 have roles in spinal interneuron differentiation by mechanisms linked to the Notch signaling pathway. It modulates the expression of genes required for the differentiation and/or maintenance of pancreatic and neuronal cell types.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 530380724 102 KERRRTESINSAFAELRECIP--NVPADTKLSKIKTLRLATSYIAYLMDVL 150
Cdd:cd11429    7 RERKRMHDLNSALDGLRSVMPyaQGPSVRKLSKIATLLLARNYILMLTQAL 57

basic helix-loop-helix (bHLH) domain found in neurogenic differentiation factor 4 (NeuroD4) and similar proteins; NeuroD4, also termed Class A basic helix-loop-helix protein 4 (bHLHa4), or protein atonal homolog 3 (ATH-3), or Atoh3, or Math-3, is a bHLH transcriptional activator that mediates neuronal differentiation.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 530380724  91 RLGRRKGSGPKKERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 150
Cdd:cd19721   26 RFRARRVKANARERSRMHGLNDALDNLRRVMPCYSKTQKLSKIETLRLARNYIWALSEVL 85

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 530380724 101 KKERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDVLA 151
Cdd:cd19743    9 ERERNRVKLVNLGFAALRQHVPQGGASKKMSKVETLRSAVEYIRALQRLLG 59

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 530380724  95 RKGSGPKKERRRTESINSAFAELRECIPNVPaDTKLSKIKTLRLATSYIAYLMDVLAKDAQS 156
Cdd:cd18937    2 RRKAATMRERRRLKKVNQAFETLKRCTTSNP-NQRLPKVEILRNAIRYIESLQDLLREQVEN 62

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 530380724 102 KERRRTESINSAFAELRECIP--NVPADTKLSKIKTLRLATSYIayLMDVLAKD 153
Cdd:cd11468    7 RERRRMHDLNDALDDLRAVIPyaHSPSVRKLSKIATLLLAKNYI--LMQARAIE 58

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 530380724  91 RLGRRKGSGPKKERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 150
Cdd:cd19719   24 RFKMRRMKANARERNRMHGLNAALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEIL 83

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 530380724  95 RKGSGPKKERRRTESINSAFAELRECIPNVPaDTKLSKIKTLRLATSYIAYLMDVL 150
Cdd:cd18936    6 RRKAATMRERRRLSKVNEAFETLKRCTSTNP-NQRLPKVEILRNAIRYIESLQALL 60

basic helix-loop-helix (bHLH) domain found in muscle-specific regulatory factor 4 (MRF4) and similar proteins; MRF4, also termed Class C basic helix-loop-helix protein 4 (bHLHc4), or myogenic factor 6 (Myf-6), is a bHLH transcription factor associated with myogenesis. It plays a role in skeletal muscle differentiation.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 530380724  95 RKGSGPKKERRRTESINSAFAEL-RECIPNvpADTKLSKIKTLRLATSYIAYLMDVL 150
Cdd:cd18934    2 RRKAATLRERRRLKKINEAFEALkRRTVPN--PNQRLPKVEILRSAINYIEKLQDLL 56

basic helix-loop-helix (bHLH) domain found in DNA-binding protein inhibitor ID3 and similar proteins; ID3, also termed Class B basic helix-loop-helix protein 25 (bHLHb25), or helix-loop-helix protein HEIR-1, or ID-like protein inhibitor HLH 1R21, or inhibitor of DNA binding 3, or inhibitor of differentiation 3, 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 negatively regulates muscle differentiation by inhibiting the DNA-binding activities of the myogenic regulatory factors.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 530380724  91 RLGRRKGSGPKKERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYI 143
Cdd:cd19693    3 RNGSNKGPALEEPVSLLYDMNDCYSRLRELVPGVPQGTKLSQVEILQHVIDYI 55

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 530380724  93 GRRKGSGPKKERRRTESINSAFAELRECIPNVPAdTKLSKIKTLRLATSYIAYL 146
Cdd:cd18910    3 EKKRESHNEVERRRKDKINAGINKIGELLPDRDA-KKQSKNMILEQAYKYIVEL 55

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 530380724  95 RKGSGPKKERRRTESINSAFAELRECIPNVPaDTKLSKIKTLRLATSYIAYLMDVL 150
Cdd:cd11411    2 RRKAATMRERRRLKKVNEAFEALKRCTSANP-NQRLPKVEILRNAIEYIESLQDLL 56

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 530380724 102 KERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 150
Cdd:cd18912   15 RERKRILDYNQAFNALRLALKHDLGGKRLSKIATLRRAINRISALSLFL 63

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain family; bHLH-PAS domain has been found in a large group of bHLH transcription regulators that are involved in gene expression responding to environmental change and controlling aspects of neural development, including proteins from aryl hydrocarbon receptor nuclear translocator (ARNT) family, hypoxia-inducible factor (HIF) family, aryl hydrocarbon receptor (AhR) family, neuronal PAS domain-containing protein (NPAS) family, Circadian locomotor output cycles protein kaput (CLOCK)-like family, and single-minded (SIM) family. bHLH-PAS transcriptional regulatory factors have a bHLH DNA-binding domain followed by two PAS domains and a C-terminal activation or repression domain. bHLH-PAS family members can be divided into class I and class II based on their dimerization partner. bHLH-PAS class I factors include AhR, HIF and SIM. The best characterized bHLH-PAS Class II protein is the ubiquitous ARNT. Some members of bHLH-PAS family act as transcriptional coactivators (such as NCoA) that lack the ability to dimerize and bind DNA.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 530380724  94 RRKGSGPKKERRRTEsiNSAFAELRECIPNVPADT-KLSKIKTLRLATSYI 143
Cdd:cd11391    1 REKSREAAKKRRDKE--NAEISELASLLPLPPAVGsKLDKLSVLRLAVAYL 49

basic helix-loop-helix (bHLH) domain found in oligodendrocyte transcription factor 2 (Oligo2) and similar proteins; Oligo2, also termed Class B basic helix-loop-helix protein 1 (bHLHb1), or Class E basic helix-loop-helix protein 19 (bHLHe19), or protein kinase C-binding protein 2, or protein kinase C-binding protein RACK17, is a bHLH transcription factor that is required for oligodendrocyte and motor neuron specification in the spinal cord, as well as for the development of somatic motor neurons in the hindbrain. It cooperates with OLIG1 to establish the MN progenitors (pMN) domain of the embryonic neural tube.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 530380724 102 KERRRTESINSAFAELRECIPNV--PADTKLSKIKTLRLATSYIAYLMDVL 150
Cdd:cd18940   22 RERKRMHDLNIAMDGLREVMPYAhgPSVRKLSKIATLLLARNYILMLTNSL 72

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 530380724  95 RKGSGPKKERRRTESINSAFAELRECIPNVPADtKLSKIKTLRLATSYIAYLMDVL 150
Cdd:cd19699    2 RRKAATMRERRRLRKVNEAFEVLKRRTCPNPNQ-RLPKVEILRNAIEYIESLEDLL 56

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Saccharomyces cerevisiae centromere-binding protein 1 (CBP-1) and similar proteins; CBP-1, also termed centromere promoter factor 1 (CPF1), or centromere-binding factor 1 (CBF1), is a bHLHzip protein that is required for chromosome stability and methionine prototrophy. It binds as a homodimer to the centromere DNA elements I (CDEI, GTCACATG) region of the centromere that is required for optimal centromere function.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 530380724  94 RRKGSGPKKERRRTESINSAFAELRECIPNvpADTKLSKIKTLRLATSYIAYL 146
Cdd:cd11398    6 QRRDNHKEVERRRRENINEGINELAALVPG--NAREKNKGAILARAVEYIQEL 56