helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 565671767   193 NSRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLL 243
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPKNKKLSKAEILRLAIEYIKSLQEEL 51

basic helix-loop-helix (bHLH) domain found in T-cell acute lymphocytic leukemia protein/ lymphoblastic leukemia-derived sequence (TAL/LYL) family; The TAL/LYL family includes a group of bHLH transcription factors (TAL1, TAL2 and LYL1) implicated in T cell acute leukaemia. They act as mediators of T cell leukaemogenesis. TAL-1, also termed Class A basic helix-loop-helix protein 17 (bHLHa17), or stem cell protein (SCL), or T-cell leukemia/lymphoma protein 5, is a hematopoietic-specific bHLH transcription factor that functions in embryonic and adult hematopoiesis in vertebrates. It is also required for embryonic vascular remodeling. It acts as a regulator of erythroid differentiation and binds to regulatory regions of a large cohort of erythroid genes as part of a complex with GATA-1, LMO2 and Ldb1. TAL-2, also termed Class A basic helix-loop-helix protein 19 (bHLHa19), is a bHLH transcription factor essential for the normal brain development. Lyl-1, also termed Class A basic helix-loop-helix protein 18 (bHLHa18), or lymphoblastic leukemia-derived sequence 1, is a proto-oncogenic bHLH transcription factor that plays an important role in hematopoietic stem cell function and is required for the late stages of postnatal angiogenesis to limit the formation of new blood vessels, notably by regulating the activity of the small GTPase Rap1. LYL-1 deficiency induces a stress erythropoiesis.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 565671767 188 RRIFTNSRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLLNDQE 247
Cdd:cd11413    1 RRIFTNTRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYIKFLEKILEDQE 60

basic helix-loop-helix (bHLH) domain found in protein lyl-1 and similar proteins; 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 involved in T-cell acute lymphoblastic leukemia. It plays an important role in hematopoietic stem cell function and is required for the late stages of postnatal angiogenesis to limit the formation of new blood vessels, notably by regulating the activity of the small GTPase Rap1. LYL-1 deficiency induces a stress erythropoiesis.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 565671767 185 KVVRRIFTNSRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLLNDQ 246
Cdd:cd19705    3 KVARRVFTNSRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYIDFLVTLLRDQ 64

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 565671767 189 RIFTNSRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLL 243
Cdd:cd11390    1 RNAANARERRRMHDLNDAFEALRKVLPTVPPDKKLSKIETLRLAINYIAALSDLL 55

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 565671767   193 NSRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLL 243
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPKNKKLSKAEILRLAIEYIKSLQEEL 51

basic helix-loop-helix (bHLH) domain found in achaete-scute complex-like (ASCL) family; The achaete-scute complex-like (ASCL, also known as achaete-scute complex homolog or ASH) family of bHLH transcription factors, ASCL1-5, have been implicated in cell fate specification and differentiation. They are critical for proper development of the nervous system. The deregulation of ASCL plays a key role in psychiatric and neurological disorders. ASCL-1, also termed Class A basic helix-loop-helix protein 46 (bHLHa46), or achaete-scute homolog 1 (ASH-1), or mammalian achaete-scute homolog 1 (Mash1), is a neural-specific bHLH transcription factor that is expressed in subsets of neural progenitors in both the central and peripheral nervous system. It plays a key role in neuronal differentiation and specification in the nervous system. ASCL-2, also termed achaete-scute homolog 2 (ASH-2), or Class A basic helix-loop-helix protein 45 (bHLHa45), or mammalian achaete-scute homolog 2 (Mash2), is a bHLH transcription factor that is involved in Schwann cell differentiation and control of proliferation in adult peripheral nerves. ASCL-3, also termed Class A basic helix-loop-helix protein 42 (bHLHa42), or bHLH transcriptional regulator Sgn-1, or achaete-scute homolog 3 (ASH-3), is a bHLH transcription factor specifically localized in the duct cells of the salivary glands. It may act as transcriptional repressor that inhibits myogenesis. The family also includes Drosophila melanogaster achaete-scute complex (AS-C) proteins, which consists of lethal of scute (also known as achaete-scute complex protein T3 or AST3), scute (also known as achaete-scute complex protein T4 or AST4), achaete (also known as achaete-scute complex protein T5 or AST5), and asense (also known as achaete-scute complex protein T8 or AST8). They are involved in the determination of the neuronal precursors in the peripheral nervous system and the central nervous system, as well as in sex determination and dosage compensation.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 565671767 185 KVVRRiftNSRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLL 243
Cdd:cd11418    1 RVARR---NERERRRVQAVNDAFDRLRQHVPYLKRRKKLSKVKTLRRAIEYIRHLQKLL 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        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 565671767 194 SRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLL 243
Cdd:cd11414    8 TRERIRVEAFNSAFAQLRKLLPTLPPDKKLSKIEILRLAICYISYLNHVL 57

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 565671767 188 RRIFTNSRERWRQQNVNGAFAELRKLIPTHPPDkKLSKNEILRLAMKYINFLAKLLNDQE 247
Cdd:cd11464    1 QRVLANVRERQRTQSLNEAFTSLRKIIPTLPSD-KLSKIQTLKLAARYIDFLYQVLRSDE 59

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 565671767 188 RRIFTNSRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLL 243
Cdd:cd11466    1 RRGSANKKERRRTQSINSAFADLRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 56

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        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 565671767 188 RRIFTNSRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLL 243
Cdd:cd11417    1 QRQAANLRERRRMQSINDAFEGLRSHIPTLPYEKRLSKVDTLRLAIGYINFLSELV 56

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 565671767 194 SRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLLN 244
Cdd:cd19701   22 TRERIRVEAFNVAFAELRKLLPTLPPDKKLSKIEILRLAICYISYLNHVLD 72

basic helix-loop-helix (bHLH) domain found in achaete-scute-like proteins, ASCL3-5, and similar proteins; This subfamily includes three ASCL family of transcription factors, ASCL-3, ASCL-4 and ASCL-5. ASCL-3, also termed Class A basic helix-loop-helix protein 42 (bHLHa42), or bHLH transcriptional regulator Sgn-1, or achaete-scute homolog 3 (ASH-3), is specifically localized in the duct cells of the salivary glands. It may act as transcriptional repressor that inhibits myogenesis. ASCL-4, also termed Class A basic helix-loop-helix protein 44 (bHLHa44), or achaete-scute homolog 4 (ASH-4), or Hash4, may be involved in skin development. ASCL-5, also termed Class A basic helix-loop-helix protein 47 (bHLHa47), or achaete-scute homolog 5 (ASH-5), is an uncharacterized bHLH transcription factor that is close related to ASCL-3 and ASCL-4.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 565671767 193 NSRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLL 243
Cdd:cd19724    6 NERERQRVRCVNEGYARLRRHLPLENKDKRLSKVETLRAAIRYIKHLQELL 56

basic helix-loop-helix (bHLH) domain found in protein atonal homolog 7 (ATOH7) and similar proteins; 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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 565671767 188 RRIFTNSRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLLNDQEEE 249
Cdd:cd19714    8 RRLAANARERRRMQGLNTAFDRLRKVVPQWGQDKKLSKYETLQMALSYIMALTRILAEAERY 69

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 565671767 189 RIFTNSRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLL 243
Cdd:cd11427    1 RVKANARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLARNYIWALSEIL 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 565671767 188 RRIFTNSRERWRQQNVNGAFAELRKLIPTHPP---DKKLSKNEILRLAMKYINFLAKLL 243
Cdd:cd11431    1 RRKTANARERDRMREINDAFEALRRAVPEYPVagkDGKLTKITTLRLAMNYIKALTDLL 59

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 565671767 188 RRIFTNSRERWRQQNVNGAFAELRKLIPTHPPDkKLSKNEILRLAMKYINFLAKLLNDQE 247
Cdd:cd19700   17 QRILANVRERQRTQSLNEAFAALRKIIPTLPSD-KLSKIQTLKLAARYIDFLYQVLQSDE 75

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 565671767 186 VVRRIFTNSRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLL 243
Cdd:cd11415    7 YAQRQAANIRERRRMFNLNEAFDKLRKKVPTFAYEKRLSRIETLRLAIVYISFMTDLL 64

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 565671767 188 RRIFTNSRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLL 243
Cdd:cd18952    2 RKGAGPKKERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 57

basic helix-loop-helix (bHLH) domain found in neurogenic differentiation factor 6 (NeuroD6) and similar proteins; NeuroD6, also termed Class A basic helix-loop-helix protein 2 (bHLHa2), or protein atonal homolog 2 (ATH-2), or Atoh2, or Math2, or Nex1, is a neurogenic bHLH transcription factor involved in neuronal development, differentiation, and survival in Alzheimer's disease (AD) brains of both cohorts. It plays an integrative role in coordinating increase in mitochondrial mass with cytoskeletal remodeling, suggesting that it may act as a co-regulator of neuronal differentiation and energy metabolism.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 565671767 187 VRRIFTNSRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLL 243
Cdd:cd19722   13 VRRQEANARERNRMHGLNDALDSLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEIL 69

basic helix-loop-helix (bHLH) domain found in neurogenin-1 (NGN-1) and similar proteins; NGN-1, also termed Class A basic helix-loop-helix protein 6 (bHLHa6), or neurogenic basic-helix-loop-helix protein, or neurogenic differentiation factor 3 (NeuroD3), is a neural-specific bHLH transcription factor involved in the initiation of neuronal differentiation. It activates transcription by binding to the E box (5'-CANNTG-3').

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 565671767 183 HT-KVVRRIFTNSRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLL 243
Cdd:cd19716   11 HTiKKSRRVKANDRERNRMHNLNAALDELRSVLPSFPDDTKLTKIETLRFAHNYIWALSETL 72

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 565671767 188 RRIFTNSRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLL 243
Cdd:cd11428    1 RRLKANDRERNRMHNLNDALDALREVLPSFPDETKLTKIETLRFAHNYIWALSETL 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 565671767 186 VVRRiftNSRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLL 243
Cdd:cd19723    2 VARR---NERERNRVKLVNLGFATLREHVPNGRANKKMSKVETLRSAVEYIRQLQQLL 56

basic helix-loop-helix (bHLH) domain found in neurogenic differentiation factor 2 (NeuroD2) and similar proteins; NeuroD2, also termed Class A basic helix-loop-helix protein 1 (bHLHa1), or NeuroD-related factor (NDRF), is a neuronal calcium-dependent bHLH transcription factor that induces neuronal differentiation and promotes neuronal survival. It plays a central role in thalamocortical synaptic maturation. NeuroD2 mediates calcium-dependent transcription activation by binding to E box-containing promoter.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 565671767 168 KRRPSPYEMEISDgphtkvVRRIFTNSRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLL 243
Cdd:cd19720   21 KRKMTKARLERSK------LRRQKANARERNRMHDLNSALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEIL 90

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 565671767 193 NSRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLL 243
Cdd:cd19745    9 NERERQRVKCVNEGYAKLRRHLPQEYSEKRLSKVETLRAAIKYIKHLQSVL 59

basic helix-loop-helix (bHLH) domain found in transcription factor 24 (TCF-24) and similar proteins; TCF-24 is an uncharacterized bHLH transcription factor that shows high sequence similarity with TCF-23.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 565671767 194 SRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLL 243
Cdd:cd19710    7 ARERSRVQTLRSAFLELQRTLPSVPPDTKLSKLDVLVLATTYIAHLMRTL 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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 565671767 185 KVVRRIFTNSRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLL-NDQ 246
Cdd:cd19704    1 KQVQRNAANARERARMRVLSKAFSRLKTTLPWVPPDTKLSKLDTLRLASSYIAHLRQILaNDK 63

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 565671767 186 VVRRiftNSRERWRQQNVNGAFAELRKLIPTH-----------PPDKKLSKNEILRLAMKYINFLAKLL 243
Cdd:cd19744    2 VARR---NARERNRVKQVNNGFAILRQHIPQSviedltagggrGKSKKLSKVDTLRMAVEYIRRLQKLL 67

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 565671767 186 VVRRiftNSRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLLNDQE 247
Cdd:cd19742    6 VARR---NERERNRVKLVNMGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLLDEHD 64

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 565671767 185 KVVRRIFTNSRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLLNDQEEE 249
Cdd:cd19703    1 KQSQRNAANARERARMRVLSKAFSRLKTSLPWVPPDTKLSKLDTLRLASSYIAHLRQLLQEDRYE 65

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
                 ....*....|....*....|....*....|....*....|....*....|.
gi 565671767 193 NSRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLL 243
Cdd:cd19746   13 NERERQRVRCVNEGYARLREHLPQELADKRLSKVETLRAAIDYIKHLQELL 63

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        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 565671767 194 SRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLLN 244
Cdd:cd19709    6 ARERSRVRTLRQAFLALQAALPSVPPDTKLSKLDVLVLATSYIAHLTRTLD 56

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 565671767 189 RIFTNSRERWRQQNVNGAFAELRKLIP--THPPDKKLSKNEILRLAMKYINFLAKLLND 245
Cdd:cd11429    1 RLKINSRERKRMHDLNSALDGLRSVMPyaQGPSVRKLSKIATLLLARNYILMLTQALEE 59

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.

                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 565671767 200 QQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYI 236
Cdd:cd19694    8 QYDMNDCYSRLKRLVPTIPPNKKVSKVEILQHVIDYI 44

basic helix-loop-helix (bHLH) domain found in the DNA-binding protein inhibitor (ID) family; The ID family includes a dominant negative group of helix-loop-helix (dnHLH) proteins, ID1-4, that are negative regulators of bHLH transcription factors. They contain the HLH-dimerization domain but lack the basic domain necessary for DNA-binding. ID proteins inhibit binding to DNA and transcriptional transactivation by heterodimerization with bHLH proteins. They also interact with many non-bHLH proteins in complex networks. ID proteins have been implicated in regulating gene expression as well as cell-cycle progression. Whereas ID-1, ID-2 and ID-3, are generally considered as tumor promoters, ID4 on the contrary has emerged as a tumor suppressor.

                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 565671767 200 QQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYI 236
Cdd:cd19684    5 NAEMQDCYSKLKELVPTIPQNKKVSKVEILQHVIDYI 41

basic helix-loop-helix (bHLH) domain found in Saccharomyces cerevisiae protein INO2 and similar proteins; INO2 is a positive regulatory factor required for depression of the co-regulated phospholipid biosynthetic enzymes in Saccharomyces cerevisiae. It is also involved in the expression of ITR1.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 565671767 186 VVRRIFTNSRERWRQQNVNGAFAELRKLIPTHP--PDKKLSKNEILRLAMKYINFLAKlLNDQEEE 249
Cdd:cd11388    1 PVKKWKHVEAEKKRRNQIKKGFEDLINLINYPRnnNEKRISKSELLNKAVDDIRGLLK-ANEQLQE 65

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 565671767 195 RERWRQQNVNGAFAELRKLIP--THPPDKKLSKNEILRLAMKYINFLAKLLNDQEE 248
Cdd:cd18938    8 REKLRMRDLAKALHNLRRYLPpsVAPAGQSLTKIETLRLTIRYISHLSAQLGLSEE 63

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in sterol regulatory element-binding protein (SREBP) family; 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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 565671767 185 KVVRRIFTNSRERWRQQNVNGAFAELRKLIPthPPDKKLSKNEILRLAMKYINFLAKLLNDQEEEGTQ 252
Cdd:cd11394    3 KVEKRSAHNAIEKRYRSSINDRIIELKDLVV--GPDAKMNKSAVLRKAIDYIRYLQKVNQKLKQENMA 68

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 565671767 188 RRIFTNSRERWRQQNVNGAFAEL-RKLIPThpPDKKLSKNEILRLAMKYINFLAKLLN--DQEEE 249
Cdd:cd18934    2 RRKAATLRERRRLKKINEAFEALkRRTVPN--PNQRLPKVEILRSAINYIEKLQDLLHslDQQEK 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 565671767 188 RRIFTNSRERWRQQNVNGAFAELRKLIPTHPpDKKLSKNEILRLAMKYINFLAKLL 243
Cdd:cd19699    2 RRKAATMRERRRLRKVNEAFEVLKRRTCPNP-NQRLPKVEILRNAIEYIESLEDLL 56

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 565671767 189 RIFTNSRERWRQQNVNGAFAELRKLIP--THPPDKKLSKNEILRLAMKYINFLAKLL 243
Cdd:cd11468    1 RLSINARERRRMHDLNDALDDLRAVIPyaHSPSVRKLSKIATLLLAKNYILMQARAI 57

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 565671767 188 RRIFTNSRERWRQQNVNGAFAELRKLIPTHPPdKKLSKNEILRLAMKYINFLaKLLNDQ 246
Cdd:cd18910    5 KRESHNEVERRRKDKINAGINKIGELLPDRDA-KKQSKNMILEQAYKYIVEL-KKKNDK 61

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-like protein X (Mlx) and similar proteins; 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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 565671767 188 RRIFTNSrERWRQQNVNGAFAELRKLIPT-HPPD----KKLSKNEILRLAMKYINFLAKLLNDQEEEGTQRAK 255
Cdd:cd19687    3 REAHTQA-EQKRRDAIKKGYDDLQDIVPTcQQQDdigsQKLSKATILQRSIDYIQFLHQQKKKQEEELSALRK 74

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).

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 565671767 188 RRIFTNSRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLLNDQEEE 249
Cdd:cd11400    1 KRRLHNVLERQRRNDLKNSFEKLRDLVPELADNEKASKVVILKKATEYIKQLQQEEKKLEKE 62