Basic domain in HLH proteins of MYOD family;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 205605        1 MELYETSPYFYQEPHFYDGENYLPVHLQGFEPPGYERTEL---SLSPEARGPLEEKGLGTP--EHCPGQCLPWACKVCKR 75
Cdd:smart00520   1 MELFETNCYFFPSQRFYDGDCFPSPDLGFFEDLGPRELGHcgaLLKDELRGSEEEEHVRAPsgHHQPGQCLPWACKACKR 80

                           90
                   ....*....|.
gi 205605       76 KSVSVDRRRAA 86
Cdd:smart00520  81 KSVTMDRRKAA 91

Basic domain in HLH proteins of MYOD family;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 205605        1 MELYETSPYFYQEPHFYDGENYLPVHLQGFEPPGYERTEL---SLSPEARGPLEEKGLGTP--EHCPGQCLPWACKVCKR 75
Cdd:smart00520   1 MELFETNCYFFPSQRFYDGDCFPSPDLGFFEDLGPRELGHcgaLLKDELRGSEEEEHVRAPsgHHQPGQCLPWACKACKR 80

                           90
                   ....*....|.
gi 205605       76 KSVSVDRRRAA 86
Cdd:smart00520  81 KSVTMDRRKAA 91

Myogenic Basic domain; This basic domain is found in the MyoD family of muscle specific proteins that control muscle development. The bHLH region of the MyoD family includes the basic domain and the Helix-loop-helix (HLH) motif. The bHLH region mediates specific DNA binding. With 12 residues of the basic domain involved in DNA binding. The basic domain forms an extended alpha helix in the structure.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 205605       1 MELYETSPYFYQEPHFY-DGENylpVHLQGFEPPGY-ERTELSLSPEARGPLEEKGLGTP-EHCPGQCLPWACKVCKRKS 77
Cdd:pfam01586   1 MELYETNCYFFPDQRFYeDGEN---PRLQGYDQALYqPRESPSLCGDGRAAGEEHVRAPPgHHCPGQCLPWACKACKRKS 77

                  ....
gi 205605      78 VSVD 81
Cdd:pfam01586  78 VTMD 81

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 205605       87 TLREKRRLKKVNEAFEALKRST-LLNPNQRLPKVEILRSAIQYIERLQALLSS 138
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLpTLPKNKKLSKAEILRLAIEYIKSLQEELQK 53

Basic domain in HLH proteins of MYOD family;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 205605        1 MELYETSPYFYQEPHFYDGENYLPVHLQGFEPPGYERTEL---SLSPEARGPLEEKGLGTP--EHCPGQCLPWACKVCKR 75
Cdd:smart00520   1 MELFETNCYFFPSQRFYDGDCFPSPDLGFFEDLGPRELGHcgaLLKDELRGSEEEEHVRAPsgHHQPGQCLPWACKACKR 80

                           90
                   ....*....|.
gi 205605       76 KSVSVDRRRAA 86
Cdd:smart00520  81 KSVTMDRRKAA 91

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 205605    81 DRRRAATLREKRRLKKVNEAFEALKRSTLLNPNQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd11411   1 DRRKAATMRERRRLKKVNEAFEALKRCTSANPNQRLPKVEILRNAIEYIESLQDLL 56

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 205605    81 DRRRAATLREKRRLKKVNEAFEALKRSTLLNPNQRLPKVEILRSAIQYIERLQALLSSLNQEER 144
Cdd:cd18934   1 DRRKAATLRERRRLKKINEAFEALKRRTVPNPNQRLPKVEILRSAINYIEKLQDLLHSLDQQEK 64

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 205605    77 SVSVDRRRAATLREKRRLKKVNEAFEALKRSTLLNPNQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd18936   1 TTNADRRKAATMRERRRLSKVNEAFETLKRCTSTNPNQRLPKVEILRNAIRYIESLQALL 60

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 205605    83 RRAATLREKRRLKKVNEAFEALKRST-LLNPNQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd11390   1 RNAANARERRRMHDLNDAFEALRKVLpTVPPDKKLSKIETLRLAINYIAALSDLL 55

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 205605       87 TLREKRRLKKVNEAFEALKRST-LLNPNQRLPKVEILRSAIQYIERLQALLSS 138
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLpTLPKNKKLSKAEILRLAIEYIKSLQEELQK 53

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 205605    83 RRAATLREKRRLKKVNEAFEALKRSTLLNP-NQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd19686   2 RQAANIRERKRMRSINDAFDGLRRHIPTFPyEKRLSKVDTLRLAIQYINFLTELL 56

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 205605    82 RRRAAtlREKRRLKKVNEAFEALKRS-TLLNPNQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd19724   3 RKRNE--RERQRVRCVNEGYARLRRHlPLENKDKRLSKVETLRAAIRYIKHLQELL 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 205605    82 RRRAATLREKRRLKKVNEAFEALKRSTLLNP-NQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd11417   1 QRQAANLRERRRMQSINDAFEGLRSHIPTLPyEKRLSKVDTLRLAIGYINFLSELV 56

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 205605    74 KRKSVSVDRRRAATLREKRRLKKVNEAFEAL-KRSTLLNPNQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd11415   1 RKRVITYAQRQAANIRERRRMFNLNEAFDKLrKKVPTFAYEKRLSRIETLRLAIVYISFMTDLL 64

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 205605    82 RRRAATLREKRRLKKVNEAFEALKRST----LLNPNQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd11431   1 RRKTANARERDRMREINDAFEALRRAVpeypVAGKDGKLTKITTLRLAMNYIKALTDLL 59

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 205605    79 SVDRRRAatlREKRRLKKVNEAF------------EALKRSTLLNPNQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd19744   1 SVARRNA---RERNRVKQVNNGFailrqhipqsviEDLTAGGGRGKSKKLSKVDTLRMAVEYIRRLQKLL 67

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 205605    82 RRRAATLREKRRLKKVNEAFEALkRSTL--LNPNQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd11430   1 RRLAANARERRRMNGLNRAFDQL-RSVVpsIGNDKKLSKYETLQMAQIYIETLSELL 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 205605    75 RKSVSVDRRRAATLREKRRLKKVNEAFEALKRST-LLNPNQRLPKVEILRSAIQYIERLQALLSSLNQE 142
Cdd:cd19714   1 RLESAARRRLAANARERRRMQGLNTAFDRLRKVVpQWGQDKKLSKYETLQMALSYIMALTRILAEAERY 69

basic helix-loop-helix (bHLH) domain found in twist-related protein 1 (TWIST1) and similar proteins; TWIST1, also termed Class A basic helix-loop-helix protein 38 (bHLHa38), or H-twist, is a bHLH transcriptional regulator that inhibits myogenesis by sequestrating E proteins, inhibiting trans-activation by MEF2, and inhibiting DNA-binding by MYOD1 through physical interaction. It also represses expression of proinflammatory cytokines such as TNFA and IL1B. In addition, TWIST1 is involved in cancer development and progression.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 205605    81 DRRRAATLREKRRLKKVNEAFEALKRSTLLNPNQRLPKVEILRSAIQYIERLQALLSS 138
Cdd:cd11412  11 TQRVMANVRERQRTQSLNEAFAALRKIIPTLPSDKLSKIQTLKLAARYIDFLYQVLQS 68

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in MAX gene-associated protein (MGA) family; The MGA family includes MGA, Schizosaccharomyces pombe ESC1 (spESC1) and similar proteins. MGA, also termed MAX dimerization protein 5 (MAD5), is a dual specificity T-box/ bHLHzip transcription factor that regulates the expression of both Max-network and T-box family target genes. It contains a Myc-like bHLHZip motif and requires heterodimerization with Max for binding to the preferred Myc-Max-binding site CACGTG. In addition to the bHLHZip domain, MGA harbors a second DNA-binding domain, the T-box or T-domain. It thus binds the preferred Brachyury-binding sequence and represses transcription of reporter genes containing promoter-proximal Brachyury-binding sites. spESC1 is a bHLHzip protein with homology to human MyoD and Myf-5 myogenic differentiation inducers. It is involved in the sexual differentiation process.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 205605    83 RRAATLREKRRLKKVNEAFEALKRSTLLNPNQRLPKVEILRSAIQYIERLQALLSSLNQEERDLR 147
Cdd:cd19682   1 RLRHKKRERERRSELRELFDKLKQLLGLDSDEKASKLAVLTEAIEEIQQLKREEDELQKEKARLT 65

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 205605    75 RKSVSVDRRRAATLREKRRLKKVNEAFEALKRStLLNP--NQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd18912   1 RPVRSKARRVAANVRERKRILDYNQAFNALRLA-LKHDlgGKRLSKIATLRRAINRISALSLFL 63

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 205605    84 RAATLREKRRLKKVNEAFEALKRSTLLN-PNQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd19746  10 RKRNERERQRVRCVNEGYARLREHLPQElADKRLSKVETLRAAIDYIKHLQELL 63

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 205605    76 KSVSVDRRRAATLREKRRLKKVNEAFEALKRST-LLNPNQRLPKVEILRSAIQYIERLQALLS 137
Cdd:cd19715   2 KDVLKKRRLAANARERRRMNSLNVAFDKLRDVVpSLGDDRKLSKYETLQMAQSYITALKELLS 64

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 205605    81 DRRRAATLREKRRLKKVNEAFEALKRSTLLNPNQRLP--KVEILRSAIQYIERL--QALLSSLNQEERDLRYR 149
Cdd:cd18944   1 ERRVANNARERLRVRDINEAFKELGRMCQLHLNSEKPqtKLLILHQAVSVILNLeqQVRERNLNPKAACLKRR 73

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 205605    82 RRRAATLREKRRLKKVNEAFEALKRSTLLNP-NQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd11413   1 RRIFTNTRERWRQQNVNGAFAELRKLIPTHPpDKKLSKNEILRLAMKYIKFLEKIL 56

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 205605    82 RRRAATLREKRRLKKVNEAFEALKR---STLLNPNQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd11425   1 QRQLANERERLRMRTLADALGELRQhlpPSVAPKGKRLSKIQTLKYAIRYIGYLGNVL 58

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 205605    82 RRRAATLREKRRLKKVNEAFEALKRSTLLNPNQRLPKVEILRSAIQYIERLQALLSS 138
Cdd:cd11464   1 QRVLANVRERQRTQSLNEAFTSLRKIIPTLPSDKLSKIQTLKLAARYIDFLYQVLRS 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 205605    82 RRRAATLREKRRLKKVNEAFEALKRST-LLNPNQRLPKVEILRSAIQYIERLQALLS 137
Cdd:cd19722  14 RRQEANARERNRMHGLNDALDSLRKVVpCYSKTQKLSKIETLRLAKNYIWALSEILR 70

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 205605    82 RRRAATLREKRRLKKVNEAFEALKRST-LLNPNQRLPKVEILRSAIQYIERLQALLSSLN 140
Cdd:cd19711   1 RRLESNERERQRMHKLNNAFQALREVIpHVRAEKKLSKIETLTLAKNYIKSLTTTILNMS 60

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 205605    82 RRRAATLREKRRLKKVNEAFEALKRSTLLNPNQ-RLPKVEILRSAIQYIERLQALLS 137
Cdd:cd11428   1 RRLKANDRERNRMHNLNDALDALREVLPSFPDEtKLTKIETLRFAHNYIWALSETLK 57

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 205605    83 RRAATLREKRRLKKVNEAFEALKRST-LLNPNQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd11427   1 RVKANARERNRMHGLNDALDNLRKVVpCYSKTQKLSKIETLRLARNYIWALSEIL 55

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 205605    82 RRRAATLREKRRLKKVNEAFEALKR---STLLNPNQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd18938   1 QRQSASEREKLRMRDLAKALHNLRRylpPSVAPAGQSLTKIETLRLTIRYISHLSAQL 58

basic helix-loop-helix-orange (bHLH-O) domain found in HERP/HES-like family; The HERP/HES-like family includes bHLH-O transcriptional regulators that are related to the Drosophila hairy and Enhancer-of-split (HES) proteins. The HERP (HES-related repressor protein) subfamily proteins contain a basic helix-loop-helix (bHLH) domain with an invariant glycine residue in its basic region, an orange domain in the central region and YXXW sequence motif at its C-terminal region. Hairy and enhancer of split (HES)-related repressor protein (HERP) proteins (HEY1, HEY2 and HEYL) act as downstream effectors of Notch signaling. They are involved in cardiovascular development and have roles in somitogenesis, myogenesis and gliogenesis. Hairy and enhancer of split-related protein HELT is a transcriptional repressor expressed in the developing central nervous system. It binds preferentially to the canonical E box sequence 5'-CACGCG-3' and regulates neuronal differentiation and/or identity. Differentially expressed in chondrocytes proteins, DEC1 and DEC2, are widely expressed in both embryonic and adult tissues and have been implicated in apoptosis, cell proliferation, and circadian rhythms, as well as malignancy in various cancers. Drosophila melanogaster protein clockwork orange (Cwo) is also included in this subfamily. It is involved in the regulation of Drosophila circadian rhythms. It functions as both an activator and a repressor of clock gene expression. The HES subfamily proteins contain a basic helix-loop-helix (bHLH) domain with an invariant proline residue in its basic region, an orange domain in the central region and a conserved tetrapeptide motif, WRPW, at its C-terminal region. They form heterodimers or homodimers via their HLH domain and bind DNA to repress gene transcription that play an essential role in development of both compartment and boundary cells of the central nervous system.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 205605    90 EKRRLKKVNEAFEALKRSTLLN----PNQRLPKVEILRSAIQYIERLQA 134
Cdd:cd19685   2 EKRRRQRINDKLNQLKELLPPNlskqSRSKLSKAEILEMAITELRRLQQ 50

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana genes coding transcription factors and similar proteins; bHLH proteins are the second largest class of plant transcription factors that regulate transcription of genes that are involve in many essential physiological and developmental process. bHLH proteins are transcriptional regulators that are found in organisms from yeast to humans. The Arabidopsis bHLH proteins that have been characterized so far have roles in regulation of fruit dehiscence, cell development (carpel, anther and epidermal), phytochrome signaling, flavonoid biosynthesis, hormone signaling and stress responses.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 205605    87 TLREKRRLKKVNEAFEALKrsTLLNPNQRLPKVEILRSAIQYIERLQALLSSL 139
Cdd:cd11393   2 SIAERKRREKINERIRALR--SLVPNGGKTDKASILDEAIEYIKFLQEQVKVL 52

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in c-Myc and similar proteins; c-Myc, also termed Myc proto-oncogene protein, or Class E basic helix-loop-helix protein 39 (bHLHe39), or transcription factor p64, a bHLHZip proto-oncogene protein that functions as a transcription factor, which binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. It activates the transcription of growth-related genes.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 205605    81 DRRRAATLREKRRLKKVNEAFEALKRST-LLNPNQRLPKVEILRSAIQYIERLQALLSSLNQEERDLRYR 149
Cdd:cd11458   4 DKRRTHNVLERQRRNELKLSFFALRDQIpEVANNEKAPKVVILKKATEYILSMQADEQRLISEKEQLRRR 73

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 205605    82 RRRAATLREKRRLKKVNEAFEALKRS-TLLNPNQRLPKVEILRSAIQYIERLQALLsslnQEER 144
Cdd:cd19703   4 QRNAANARERARMRVLSKAFSRLKTSlPWVPPDTKLSKLDTLRLASSYIAHLRQLL----QEDR 63

basic helix-loop-helix (bHLH) domain found in heart- and neural crest derivatives-expressed protein 2 (HAND2) and similar proteins; 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 a bHLH transcription factor that is essential for cardiac morphogenesis, particularly for the formation of the right ventricle and of the aortic arch arteries.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 205605    82 RRRAATLREKRRLKKVNEAFEALKRSTLLNP-NQRLPKVEILRSAIQYIERLQALLSSLNQ 141
Cdd:cd11471   1 RRGTANRKERRRTQSINSAFAELRECIPNVPaDTKLSKIKTLRLATSYIAYLMDLLAKDDQ 61

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        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 205605    82 RRRAATLREKRRLKKVNEAFEALKRSTLLNP-NQRLPKVEILRSAIQYIERLQALLSSLNQE 142
Cdd:cd19706   4 RRIFTNSRERWRQQNVNGAFAELRKLIPTHPpDKKLSKNEILRLAMKYINFLAKLLNDQEEE 65

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Schizosaccharomyces pombe ESC1 (spESC1) and similar proteins; spESC1 is a bHLHzip protein with homology to human MyoD and Myf-5 myogenic differentiation inducers. It is involved in the sexual differentiation process.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 205605    83 RRAATLREKRRLKKVNEAFEALKRSTLLNPNQRLPKVEILRSAIQYIERLQALLSSLNQEERDLR 147
Cdd:cd19690   1 RVSHKLAERKRRKEMKELFEDLRDALPQERGTKASKWEILTKAISYIQQLKRHIRELRSEVNDLR 65

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 205605    80 VDRRRAATLREKRRLKKVNEAFEALKRsTLLNPNQRLPKVEILRSAIQYIERLQALLSSLNQEERDLR 147
Cdd:cd11394   4 VEKRSAHNAIEKRYRSSINDRIIELKD-LVVGPDAKMNKSAVLRKAIDYIRYLQKVNQKLKQENMALK 70

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
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 205605    82 RRRAATLREKRRLKKVNEAFEALKRSTLLNPNQR-LPKVEILRSAIQYIERLQALL 136
Cdd:cd18951   4 QRHTANARERDRTNSVNTAFTALRTLIPTEPADRkLSKIETLRLASSYISHLGNVL 59

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 205605    81 DRRRAATLREKRRLKKVNEAFEALkRSTL--LNPNQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd19718   7 NRRMKANDRERNRMHNLNSALDAL-RSVLptFPDDAKLTKIETLRFAHNYIWALTETL 63