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 568961138 434 KIEREKERRMANNARERLRVRDINEAFKELGRMCQLHLKSEKPQTKLLILHQAVAVILSLEQQVRERNLNPKAACLKRRE 513
Cdd:cd18945    1 KAEREKERRMANNARERLRVRDINEAFKELGRMVQLHLKSDKPQTKLLILHQAVAVILSLEQQVRERNLNPKAACLKRRE 80

                 ....*
gi 568961138 514 EEKVS 518
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 568961138 434 KIEREKERRMANNARERLRVRDINEAFKELGRMCQLHLKSEKPQTKLLILHQAVAVILSLEQQVRERNLNPKAACLKRRE 513
Cdd:cd18945    1 KAEREKERRMANNARERLRVRDINEAFKELGRMVQLHLKSDKPQTKLLILHQAVAVILSLEQQVRERNLNPKAACLKRRE 80

                 ....*
gi 568961138 514 EEKVS 518
Cdd:cd18945   81 EEKVS 85

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568961138  441 RRMANNARERLRVRDINEAFKELgRMCQLHLKSEKPQTKLLILHQAVAVILSLE 494
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 568961138 434 KIEREKERRMANNARERLRVRDINEAFKELGRMCQLHLKSEKPQTKLLILHQAVAVILSLEQQVRERNLNPKAACLKRRE 513
Cdd:cd18945    1 KAEREKERRMANNARERLRVRDINEAFKELGRMVQLHLKSDKPQTKLLILHQAVAVILSLEQQVRERNLNPKAACLKRRE 80

                 ....*
gi 568961138 514 EEKVS 518
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 568961138 440 ERRMANNARERLRVRDINEAFKELGRMCQLHLKSEKPQTKLLILHQAVAVILSLEQQVRERNLNPKAACLKRRE 513
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 568961138 440 ERRMANNARERLRVRDINEAFKELGRMCQLHLKSEKPQTKLLILHQAVAVILSLEQQVRERNLNPKAACL 509
Cdd:cd11467    1 ERRQANNARERIRIRDINEALKELGRMCMTHLKSDKPQTKLGILNMAVEVIMTLEQQVRERNLNPKAACL 70

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 568961138   446 NARERLRVRDINEAFKELGRMCQLHLKSEKPqTKLLILHQAVAVILSLEQQVRE 499
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 568961138 442 RMANNARERLRVRDINEAFKELgRMCQLHLKSEKPQTKLLILHQAVAVILSLEQ 495
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 568961138 441 RRMANnARERLRVRDINEAFKELGRMCQLHLKSEKPqTKLLILHQAVAVILSLEQ 495
Cdd:cd11422    1 RRVAN-ARERERVRNLNSGFSKLRRIVPLIPRDRKP-SKVDTLKGATEYIRLLQR 53

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 568961138 441 RRMANNARERLRVRDINEAFKELGRMCQLHLKSEKPQ--TKLLILHQAVAVILSLEQ 495
Cdd:cd11431    1 RRKTANARERDRMREINDAFEALRRAVPEYPVAGKDGklTKITTLRLAMNYIKALTD 57

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 568961138 439 KERRMANNARERLRVRDINEAFKELGRMCQLHLKSEKpQTKLLILHQAVAVILSLEQ 495
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 568961138 441 RRMANNARERLRVRDINEAFKELGRMCQlHLKSEKPQTKLLILHQAVAVILSL 493
Cdd:cd11426    1 RRLESNERERLRMHQLNDAFQALREVIP-HVRSERKLSKIETLTLAKNYIKSL 52

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 568961138 434 KIEREKERRMANNARERLRVRDINEAFKELGRMCQLHLKSEKpQTKLLILHQAVAVILSLEQQVR 498
Cdd:cd19720   28 RLERSKLRRQKANARERNRMHDLNSALDNLRKVVPCYSKTQK-LSKIETLRLAKNYIWALSEILR 91

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568961138 432 EQKIEREKERRMANNARERLRVRDINEAFKELGRMCQLHLKSEKpQTKLLILHQAVAVILSLEQQVR 498
Cdd:cd19722    5 KARMERVKVRRQEANARERNRMHGLNDALDSLRKVVPCYSKTQK-LSKIETLRLAKNYIWALSEILR 70

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 568961138 438 EKERRMANNARERLRVRDINEAFKELgRMCQLHLKSEKPQTKLLILHQAVAVILSLEQ 495
Cdd:cd19713    3 QKQRRLAANARERRRMHGLNHAFDQL-RNVIPSFNNDKKLSKYETLQMAQIYINALSE 59

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 568961138 440 ERRMANNaRERLRVRDINEAFKELgRMCQLHLKSEKPQTKLLILHQAVAVI 490
Cdd:cd19686    1 QRQAANI-RERKRMRSINDAFDGL-RRHIPTFPYEKRLSKVDTLRLAIQYI 49

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 568961138 441 RRMANNARERLRVRDINEAFKELgRMCQLHLKSEKPQTKLLILHQAVAVILSL 493
Cdd:cd19711    1 RRLESNERERQRMHKLNNAFQAL-REVIPHVRAEKKLSKIETLTLAKNYIKSL 52

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 568961138 441 RRMANNARERLRVRDINEAFKELgRMCQLHLKSEKPQTKLLILHQAVAVILSLEQ 495
Cdd:cd11430    1 RRLAANARERRRMNGLNRAFDQL-RSVVPSIGNDKKLSKYETLQMAQIYIETLSE 54

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 568961138 440 ERRMANNARERLRVRDINEAFKELGRMCQLHLKSEKPqtKLLILHQAVAVILSLEQQVR 498
Cdd:cd18936    5 DRRKAATMRERRRLSKVNEAFETLKRCTSTNPNQRLP--KVEILRNAIRYIESLQALLR 61

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

                         10        20
                 ....*....|....*....|....*
gi 568961138 439 KERRMANNARERLRVRDINEAFKEL 463
Cdd:cd19715    6 KKRRLAANARERRRMNSLNVAFDKL 30