basic helix-loop-helix (bHLH) domain found in transcription factor 4 (TCF-4) and similar proteins; TCF-4, also termed E2-2, or Class B basic helix-loop-helix protein 19 (bHLHb19), or immunoglobulin transcription factor 2 (ITF-2), or SL3-3 enhancer factor 2 (SEF-2), is a bHLH transcription factor that binds to the immunoglobulin enhancer Mu-E5/KE5-motif. It is involved in the initiation of neuronal differentiation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1015809798 537 KIEREKERRMANNARERLRVRDINEAFKELGRMCQLHLKSEKPQTKLLILHQAVAVILSLEQQVRERNLNPKAACLKRRE 616
Cdd:cd18945     1 KAEREKERRMANNARERLRVRDINEAFKELGRMVQLHLKSDKPQTKLLILHQAVAVILSLEQQVRERNLNPKAACLKRRE 80

                  ....*
gi 1015809798 617 EEKVS 621
Cdd:cd18945    81 EEKVS 85

basic helix-loop-helix (bHLH) domain found in transcription factor 4 (TCF-4) and similar proteins; TCF-4, also termed E2-2, or Class B basic helix-loop-helix protein 19 (bHLHb19), or immunoglobulin transcription factor 2 (ITF-2), or SL3-3 enhancer factor 2 (SEF-2), is a bHLH transcription factor that binds to the immunoglobulin enhancer Mu-E5/KE5-motif. It is involved in the initiation of neuronal differentiation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1015809798 537 KIEREKERRMANNARERLRVRDINEAFKELGRMCQLHLKSEKPQTKLLILHQAVAVILSLEQQVRERNLNPKAACLKRRE 616
Cdd:cd18945     1 KAEREKERRMANNARERLRVRDINEAFKELGRMVQLHLKSDKPQTKLLILHQAVAVILSLEQQVRERNLNPKAACLKRRE 80

                  ....*
gi 1015809798 617 EEKVS 621
Cdd:cd18945    81 EEKVS 85

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1015809798 544 RRMANNARERLRVRDINEAFKELgRMCQLHLKSEKPQTKLLILHQAVAVILSLE 597
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDEL-RELLPTLPPDKKLSKAEILRLAIEYIKHLQ 53

basic helix-loop-helix (bHLH) domain found in transcription factor 4 (TCF-4) and similar proteins; TCF-4, also termed E2-2, or Class B basic helix-loop-helix protein 19 (bHLHb19), or immunoglobulin transcription factor 2 (ITF-2), or SL3-3 enhancer factor 2 (SEF-2), is a bHLH transcription factor that binds to the immunoglobulin enhancer Mu-E5/KE5-motif. It is involved in the initiation of neuronal differentiation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1015809798 537 KIEREKERRMANNARERLRVRDINEAFKELGRMCQLHLKSEKPQTKLLILHQAVAVILSLEQQVRERNLNPKAACLKRRE 616
Cdd:cd18945     1 KAEREKERRMANNARERLRVRDINEAFKELGRMVQLHLKSDKPQTKLLILHQAVAVILSLEQQVRERNLNPKAACLKRRE 80

                  ....*
gi 1015809798 617 EEKVS 621
Cdd:cd18945    81 EEKVS 85

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1015809798 543 ERRMANNARERLRVRDINEAFKELGRMCQLHLKSEKPQTKLLILHQAVAVILSLEQQVRERNLNPKAACLKRRE 616
Cdd:cd18944     1 ERRVANNARERLRVRDINEAFKELGRMCQLHLNSEKPQTKLLILHQAVSVILNLEQQVRERNLNPKAACLKRRE 74

basic helix-loop-helix (bHLH) domain found in Drosophila melanogaster protein daughterless (Da) and similar proteins; Da is a nuclear bHLH transcription factor that is a sole E protein ortholog essential for both neurogenesis and sex determination in Drosophila. Da is expressed in a broad range of tissues and is involved in diverse developmental processes such as oogenesis, sex determination and neurogenesis depending on its bHLH-binding partners. Da and achaete-scute complex (AS-C) form heterodimers that act as transcriptional activators of neural cell fates and are involved in sex determination.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1015809798 543 ERRMANNARERLRVRDINEAFKELGRMCQLHLKSEKPQTKLLILHQAVAVILSLEQQVRERNLNPKAACL 612
Cdd:cd11467     1 ERRQANNARERIRIRDINEALKELGRMCMTHLKSDKPQTKLGILNMAVEVIMTLEQQVRERNLNPKAACL 70

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1015809798  549 NARERLRVRDINEAFKELGRMCQLHLKSEKPqTKLLILHQAVAVILSLEQQVRE 602
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPKNKKL-SKAEILRLAIEYIKSLQEELQK 53

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 1015809798 545 RMANNARERLRVRDINEAFKELgRMCQLHLKSEKPQTKLLILHQAVAVILSLEQ 598
Cdd:cd11390     1 RNAANARERRRMHDLNDAFEAL-RKVLPTVPPDKKLSKIETLRLAINYIAALSD 53

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        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1015809798 544 RRMANnARERLRVRDINEAFKELGRMCQLHLKSEKPqTKLLILHQAVAVILSLEQ 598
Cdd:cd11422     1 RRVAN-ARERERVRNLNSGFSKLRRIVPLIPRDRKP-SKVDTLKGATEYIRLLQR 53

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        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1015809798 540 REKERRMANNARERLRVRDINEAFKELgRMCQLHLKSEKPQTKLLILHQAVAVILSL 596
Cdd:cd18912     4 RSKARRVAANVRERKRILDYNQAFNAL-RLALKHDLGGKRLSKIATLRRAINRISAL 59

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
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1015809798 542 KERRMANNARERLRVRDINEAFKELGRMCQLHLKSEKpQTKLLILHQAVAVILSLEQ 598
Cdd:cd11421     6 RQRRIEANARERTRVHTISAAFEALRKAVPSYSYNQK-LSKLAILRIACSYILALAR 61

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1015809798 544 RRMANNARERLRVRDINEAFKELGRMCQlHLKSEKPQTKLLILHQAVAVILSL 596
Cdd:cd11426     1 RRLESNERERLRMHQLNDAFQALREVIP-HVRSERKLSKIETLTLAKNYIKSL 52

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 1015809798 537 KIEREKERRMANNARERLRVRDINEAFKELGRMCQlHLKSEKPQTKLLILHQAVAVILSL 596
Cdd:cd19714     1 RLESAARRRLAANARERRRMQGLNTAFDRLRKVVP-QWGQDKKLSKYETLQMALSYIMAL 59

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1015809798 537 KIEREKERRMANNARERLRVRDINEAFKELGRMCQLHLKSEKpQTKLLILHQAVAVILSLEQQVR 601
Cdd:cd19720    28 RLERSKLRRQKANARERNRMHDLNSALDNLRKVVPCYSKTQK-LSKIETLRLAKNYIWALSEILR 91

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        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1015809798 543 ERRMANNaRERLRVRDINEAFKELgRMCQLHLKSEKPQTKLLILHQAVAVI 593
Cdd:cd19686     1 QRQAANI-RERKRMRSINDAFDGL-RRHIPTFPYEKRLSKVDTLRLAIQYI 49

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
                  ....*....|....*....|....*....|....*....|..
gi 1015809798 537 KIEREKERRMANNARERLRVRDINEAFKELGRMCQLHLKSEK 578
Cdd:cd19721    23 RLERFRARRVKANARERSRMHGLNDALDNLRRVMPCYSKTQK 64

basic helix-loop-helix (bHLH) domain found in protein atonal homologs ATOH1, ATOH7 and similar proteins; The family includes ATOH1 and ATOH7. ATOH1, also termed Class A basic helix-loop-helix protein 14 (bHLHa14), or helix-loop-helix protein hATH-1 (hATH1), or Math1, or Cath1, is a proneural bHLH transcription factor that is essential for inner ear hair cell differentiation. It dimerizes with E47 and activates E-box (CANNTG) dependent transcription. ATOH1 is a mammalian homolog of the Drosophila melanogaster gene atonal and mouse atonal homolog 1 (Math1). ATOH7, also termed Class A basic helix-loop-helix protein 13 (bHLHa13), or helix-loop-helix protein hATH-5 (hATH5), or Math5, is a bHLH transcription factor involved in the differentiation of retinal ganglion cells. The family also includes protein Amos (also termed absent MD neurons and olfactory sensilla protein, or reduced olfactory organs protein, or rough eye protein). It is a bHLH transcription factor that promotes multiple dendritic neuron formation in the Drosophila peripheral nervous system.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1015809798 544 RRMANNARERLRVRDINEAFKELgRMCQLHLKSEKPQTKLLILHQAVAVILSLEQ 598
Cdd:cd11430     1 RRLAANARERRRMNGLNRAFDQL-RSVVPSIGNDKKLSKYETLQMAQIYIETLSE 54

basic helix-loop-helix (bHLH) domain found in neurogenic differentiation factor 1 (NeuroD1) and similar proteins; NeuroD1, also termed Class A basic helix-loop-helix protein 3 (bHLHa3), is a neuronal bHLH transcription factor involved in the development and maintenance of the endocrine pancreas and neuronal elements. It acts as an essential regulator of glutamatergic neuronal differentiation. Loss of NeuroD1 causes ataxia, cerebellar hypoplasia, sensorineural deafness, and severe retinal dystrophy in mice.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1015809798 528 EDEDLNPEQK-----------IEREKERRMANNARERLRVRDINEAFKELGRMCQLHLKSEKpQTKLLILHQAVAVILSL 596
Cdd:cd19719     1 EDDDQKPKRRgpkkkkmtkarLERFKMRRMKANARERNRMHGLNAALDNLRKVVPCYSKTQK-LSKIETLRLAKNYIWAL 79

                  ....*
gi 1015809798 597 EQQVR 601
Cdd:cd19719    80 SEILR 84

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 1015809798 543 ERRMANNARERLRVRDINEAFKELGRMCQLHLKSEKPqtKLLILHQAVAVILSLE 597
Cdd:cd11411     1 DRRKAATMRERRRLKKVNEAFEALKRCTSANPNQRLP--KVEILRNAIEYIESLQ 53