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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1678752216  96 DRRKAATLRERRRLKKINEAFDVLKRKTVANPNQRLPKVEILRSAISYIERLQDLLQTLDEQEK 159
Cdd:cd18934     1 DRRKAATLRERRRLKKINEAFEALKRRTVPNPNQRLPKVEILRSAINYIEKLQDLLHSLDQQEK 64

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 1678752216  96 DRRKAATLRERRRLKKINEAFDVLKRKTVANPNQRLPKVEILRSAISYIERLQDLLQTLDEQEK 159
Cdd:cd18934     1 DRRKAATLRERRRLKKINEAFEALKRRTVPNPNQRLPKVEILRSAINYIEKLQDLLHSLDQQEK 64

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1678752216  102 TLRERRRLKKINEAFDVLKRKTVANP-NQRLPKVEILRSAISYIERLQDLLQT 153
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPkNKKLSKAEILRLAIEYIKSLQEELQK 53

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 1678752216  96 DRRKAATLRERRRLKKINEAFDVLKRKTVANPNQRLPKVEILRSAISYIERLQDLLQTLDEQEK 159
Cdd:cd18934     1 DRRKAATLRERRRLKKINEAFEALKRRTVPNPNQRLPKVEILRSAINYIEKLQDLLHSLDQQEK 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 1678752216  96 DRRKAATLRERRRLKKINEAFDVLKRKTVANPNQRLPKVEILRSAISYIERLQDLL 151
Cdd:cd19699     1 DRRKAATMRERRRLRKVNEAFEVLKRRTCPNPNQRLPKVEILRNAIEYIESLEDLL 56

Basic domain in HLH proteins of MYOD family;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1678752216    2 MDLFETNPYLFNDLRYLDeGDHGPLQHLDMSGVSPLYngndsPLSPGQDNVPSEtGGESSGEEHVLAPPGlrAHCDGQCL 81
Cdd:smart00520   1 MELFETNCYFFPSQRFYD-GDCFPSPDLGFFEDLGPR-----ELGHCGALLKDE-LRGSEEEEHVRAPSG--HHQPGQCL 71

                           90       100
                   ....*....|....*....|
gi 1678752216   82 MWACKICKRKSAPPDRRKAA 101
Cdd:smart00520  72 PWACKACKRKSVTMDRRKAA 91

basic helix-loop-helix (bHLH) domain found in myogenic factor 5 (Myf-5) and similar proteins; Myf-5, also termed Class C basic helix-loop-helix protein 2 (bHLHc2), is a nuclear bHLH transcriptional activator that promotes transcription of muscle-specific target genes and plays a role in muscle specification and differentiation. It also acts as an RNA-binding protein which enhances Ccnd1/Cyclin D1 mRNA translation during myogenesis.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1678752216  96 DRRKAATLRERRRLKKINEAFDVLKRKTVANPNQRLPKVEILRSAISYIERLQDLLQ 152
Cdd:cd18937     1 DRRKAATMRERRRLKKVNQAFETLKRCTTSNPNQRLPKVEILRNAIRYIESLQDLLR 57

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1678752216  102 TLRERRRLKKINEAFDVLKRKTVANP-NQRLPKVEILRSAISYIERLQDLLQT 153
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPkNKKLSKAEILRLAIEYIKSLQEELQK 53

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 1678752216  97 RRKAatlRERRRLKKINEAFDVLKRKT-VANPNQRLPKVEILRSAISYIERLQDLL 151
Cdd:cd11418     4 RRNE---RERRRVQAVNDAFDRLRQHVpYLKRRKKLSKVKTLRRAIEYIRHLQKLL 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 1678752216  89 KRKSAPPDRRKAATLRERRRLKKINEAFDVLKRK--TVANpNQRLPKVEILRSAISYIERLQDLL 151
Cdd:cd11415     1 RKRVITYAQRQAANIRERRRMFNLNEAFDKLRKKvpTFAY-EKRLSRIETLRLAIVYISFMTDLL 64

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 1678752216  98 RKAATLRERRRLKKINEAFDVLKRKTVANPNQRLP-KVEILRSAISYIERLQDLLQ 152
Cdd:cd11422     1 RRVANARERERVRNLNSGFSKLRRIVPLIPRDRKPsKVDTLKGATEYIRLLQRILE 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
                  ....*....|....*....|....*....|....*....|....*....
gi 1678752216 104 RERRRLKKINEAFDVLKRK-TVANPNQRLPKVEILRSAISYIERLQDLL 151
Cdd:cd19724     8 RERQRVRCVNEGYARLRRHlPLENKDKRLSKVETLRAAIRYIKHLQELL 56

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1678752216  94 PPDRRKAATLRERRRLKKINEAFDVLKRKTVANP-NQRLPKVEILRSAISYIERLQDLLQT 153
Cdd:cd11416     2 YKVQRHAANIRERKRMLSINSAFEELRCHVPTFPyEKRLSKIDTLRLAIAYIALLRDILRS 62

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 1678752216  97 RRKAATLRERRRLKKINEAFDVLkRKTVANPN--QRLPKVEILRSAISYIERLQDLL 151
Cdd:cd11430     1 RRLAANARERRRMNGLNRAFDQL-RSVVPSIGndKKLSKYETLQMAQIYIETLSELL 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 1678752216  97 RRKAATLRERRRLKKINEAFDVLKR---KTVANPNQRLPKVEILRSAISYIERLQDLLQ 152
Cdd:cd11425     1 QRQLANERERLRMRTLADALGELRQhlpPSVAPKGKRLSKIQTLKYAIRYIGYLGNVLQ 59

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1678752216  93 APPDRRKAATLRERRRLKKINEAFDVLKRKTVA-NPNQRLPKVEILRSAISYIERLQDLLQT 153
Cdd:cd19713     2 VQKQRRLAANARERRRMHGLNHAFDQLRNVIPSfNNDKKLSKYETLQMAQIYINALSELLQG 63

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1678752216 104 RERRRLKKINEAFDVLKRKTV-ANPNQRLPKVEILRSAISYIERLQDLL 151
Cdd:cd19747    13 RERQRVKCVNEGYARLRDHLPgAMAEKRLSKVETLRAAIRYIKYLQDLL 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        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1678752216  97 RRKAATLRERRRLKKINEAFDVLKRKTVANPN-QRLPKVEILRSAISYIERLQDLLQ 152
Cdd:cd19715     8 RRLAANARERRRMNSLNVAFDKLRDVVPSLGDdRKLSKYETLQMAQSYITALKELLS 64

basic helix-loop-helix (bHLH) domain found in scleraxis, transcription factor 15 (TCF-15) and similar proteins; The family includes scleraxis and transcription factor 15 (TCF-15). 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. TCF-15, also termed Class A basic helix-loop-helix protein 40 (bHLHa40), or paraxis, or protein bHLH-EC2, is a bHLH transcription factor expressed in caudal lateral and paraxial mesoderm dermomyotome and sclerotome fore limb buds during embryo development. It may function as an early transcriptional regulator involved in the patterning of the mesoderm and in lineage determination of cell types derived from the mesoderm.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1678752216  98 RKAATLRERRRLKKINEAFDVLKRKTVANP-NQRLPKVEILRSAISYIERLQDLL 151
Cdd:cd11465     1 RQAANARERDRTHSVNSAFTALRTLIPTEPaDRKLSKIETLRLASSYISHLATVL 55

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1678752216  96 DRRKAATLRERRRLKKINEAFDVLKRKTVANPNQRLPKVEILRSAISYIERLQDLLQTlDE 156
Cdd:cd11412    11 TQRVMANVRERQRTQSLNEAFAALRKIIPTLPSDKLSKIQTLKLAARYIDFLYQVLQS-DE 70

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 1678752216  98 RKAATLRERRRLKKINEAFDVLKRKTVANPNQRLPKVEILRSAISYIERLQDLLQTLDEQEK 159
Cdd:cd19682     1 RLRHKKRERERRSELRELFDKLKQLLGLDSDEKASKLAVLTEAIEEIQQLKREEDELQKEKA 62

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 1678752216  97 RRKAATLRERRRLKKINEAFDVLkRKTVAN--PNQRLPKVEILRSAISYIERLQDLLQTLDE 156
Cdd:cd11471     1 RRGTANRKERRRTQSINSAFAEL-RECIPNvpADTKLSKIKTLRLATSYIAYLMDLLAKDDQ 61

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 1678752216  97 RRKAATLRERRRLKKINEAFDVLkRKTVA--NPNQRLPKVEILRSAISYIERLQDLLQ 152
Cdd:cd19722    14 RRQEANARERNRMHGLNDALDSL-RKVVPcySKTQKLSKIETLRLAKNYIWALSEILR 70

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1678752216  97 RRKAATLRERRRLKKINEAFDVLKR-KTVANPNQRLPKVEILRSAISYIERLQDLLQT 153
Cdd:cd19721    30 RRVKANARERSRMHGLNDALDNLRRvMPCYSKTQKLSKIETLRLARNYIWALSEVLET 87

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 1678752216  97 RRKAATLRERRRLKKINEAFDVLKRKTVANPN-QRLPKVEILRSAISYIERLQDLL 151
Cdd:cd18912     8 RRVAANVRERKRILDYNQAFNALRLALKHDLGgKRLSKIATLRRAINRISALSLFL 63

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 1678752216  97 RRKAATLRERRRLKKINEAFDVLKRKTVANP-NQRLPKVEILRSAISYIERLQDLLQTLD 155
Cdd:cd11413     1 RRIFTNTRERWRQQNVNGAFAELRKLIPTHPpDKKLSKNEILRLAMKYIKFLEKILEDQE 60

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1678752216  89 KRKSAPPDRRKAATLRERRRLKKINEAFDVLkRKTVAN--PNQRLPKVEILRSAISYIERLQDLLQ 152
Cdd:cd19701     8 RRRRATAKYRTAHATRERIRVEAFNVAFAEL-RKLLPTlpPDKKLSKIEILRLAICYISYLNHVLD 72

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 1678752216  96 DRRKAATLRERRRLKKINEAFDVLKRKTVANPNQRLPKVEILRSAISYIERLQDLLQTlDEQE 158
Cdd:cd19700    16 SQRILANVRERQRTQSLNEAFAALRKIIPTLPSDKLSKIQTLKLAARYIDFLYQVLQS-DEMD 77

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in transcription factor AP-4 (TFAP4) and similar proteins; TFAP4, also termed activating enhancer-binding protein 4, or Class C basic helix-loop-helix protein 41 (bHLHc41), is a bHLHzip transcription factor that activates both viral and cellular genes involved in the regulation of cellular proliferation, stemness, and epithelial-mesenchymal transition by binding to the symmetrical DNA sequence 5'-CAGCTG-3'.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1678752216  97 RRKAATLRERRRLKKINEAFDVLKRKTVANPNQRLPKVEILRSAISYIERLQ 148
Cdd:cd11419     4 RREIANSNERRRMQSINAGFQSLRTLLPHCDGEKLSKAAILQQTAEYIFSLE 55

basic helix-loop-helix (bHLH) domain found in neurogenin (NGN) family; The NGN family includes three neural-specific bHLH transcription factors, NGN1-3, which may function at neuroblast selection genes during the development of several neuronal lineages. NGN-1, also termed Class A basic helix-loop-helix protein 6 (bHLHa6), or neurogenic basic-helix-loop-helix protein, or neurogenic differentiation factor 3 (NeuroD3), is a neural-specific bHLH transcription factor involved in the initiation of neuronal differentiation. NGN-2, also termed Class A basic helix-loop-helix protein 8 (bHLHa8), or protein atonal homolog 4 (ATOH4), is a neural-specific bHLH transcription factor required for sensory neurogenesis. NGN-3, also termed Class A basic helix-loop-helix protein 7 (bHLHa7), or protein atonal homolog 5 (ATOH5), is a neural-specific bHLH transcription factor expressed in the developing central nervous system and the embryonic pancreas. It is involved in neurogenesis and plays an important role in spermatogenesis.

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                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1678752216  97 RRKAATLRERRRLKKINEAFDVLKRKTVANPNQ-RLPKVEILRSAISYIERLQDLLQ 152
Cdd:cd11428     1 RRLKANDRERNRMHNLNDALDALREVLPSFPDEtKLTKIETLRFAHNYIWALSETLK 57

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1678752216  97 RRKAATLRERRRLKKINEAFDVLkRKTVA--NPNQRLPKVEILRSAISYIERLQDLLQT 153
Cdd:cd19720    35 RRQKANARERNRMHDLNSALDNL-RKVVPcySKTQKLSKIETLRLAKNYIWALSEILRS 92

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1678752216  95 PDRRKAATLRERRRLKKINEAFDVLKRKTVANPNQR-LPKVEILRSAISYIERLQDLL 151
Cdd:cd18951     2 PRQRHTANARERDRTNSVNTAFTALRTLIPTEPADRkLSKIETLRLASSYISHLGNVL 59

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1678752216  97 RRKAATLRERRRLKKINEAFDVLKRKTV-ANPNQRLPKVEILRSAISYIERLQDLL 151
Cdd:cd19704     4 QRNAANARERARMRVLSKAFSRLKTTLPwVPPDTKLSKLDTLRLASSYIAHLRQIL 59

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

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                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1678752216  97 RRKAATLRERRRLKKINEAFDVLKRKTVANP-NQRLPKVEILRSAISYIERLQDLLQTLD 155
Cdd:cd19717    10 RRVKANNRERNRMHNLNAALDSLREVLPTFPeDAKLTKIETLRFAHNYIWALSETLRLAD 69

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1678752216  97 RRKAATLRERRRLKKINEAFDVLKRKTVANP-NQRLPKVEILRSAISYIERLQDLLQ 152
Cdd:cd19705     6 RRVFTNSRERWRQQNVNGAFAELRKLIPTHPpDKKLSKNEILRLAMKYIDFLVTLLR 62

basic helix-loop-helix (bHLH) domain found in musculin, transcription factor 21 (TCF-21) and similar proteins; The family includes two bHLH transcription factors, musculin and transcription factor 21 (TCF-21). Musculin, also termed activated B-cell factor 1 (ABF-1), or Class A basic helix-loop-helix protein 22 (bHLHa22), is a bHLH transcription factor expressed in activated B lymphocytes. It acts as a transcription repressor capable of inhibiting the transactivation capability of TCF3/E47. Musculin may play a role in regulating antigen-dependent B-cell differentiation. The mouse homolog, musculin, is suggested to be a repressor of myogenesis that is expressed in developing muscle and in the spleen. TCF-21, also termed capsulin, or Class A basic helix-loop-helix protein 23 (bHLHa23), or epicardin, or podocyte-expressed 1 (Pod-1), is a bHLH transcription factor expressed specifically in mesodermally-derived cells that surround the epithelium of the developing gastrointestinal, genitourinary and respiratory systems during mouse embryogenesis. It may play a role in the specification or differentiation of one or more subsets of epicardial cell types.

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                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1678752216  97 RRKAATLRERRRLKKINEAFDVLKRKTV-ANPNQRLPKVEILRSAISYIERLQDLL 151
Cdd:cd11423     1 QRNAANARERARMRVLSKAFSRLKTTLPwVPPDTKLSKLDTLRLAASYIAHLRQIL 56

basic helix-loop-helix (bHLH) domain found in T-cell acute lymphocytic leukemia protein 1 (TAL-1) and similar proteins; TAL-1, also termed Class A basic helix-loop-helix protein 17 (bHLHa17), or stem cell protein (SCL), or T-cell leukemia/lymphoma protein 5, is a hematopoietic-specific bHLH transcription factor that functions in embryonic and adult hematopoiesis in vertebrates. It is also required for embryonic vascular remodeling. It acts as a regulator of erythroid differentiation and binds to regulatory regions of a large cohort of erythroid genes as part of a complex with GATA-1, LMO2 and Ldb1. TAL-1 has been implicated in T-cell acute lymphoblastic leukemia. In common with other tissue-specific bHLH proteins, Tal heterodimerizes with ubiquitously-expressed members of the E2A family and form a DNA-binding complex with an E-box (CANNTG) to regulate transcription at its recognition site.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1678752216  97 RRKAATLRERRRLKKINEAFDVLKRKTVANP-NQRLPKVEILRSAISYIERLQDLLQTLDEQ 157
Cdd:cd19706     4 RRIFTNSRERWRQQNVNGAFAELRKLIPTHPpDKKLSKNEILRLAMKYINFLAKLLNDQEEE 65

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1678752216  97 RRKAATLRERRRLKKINEAFDVLkRKTVAN--PNQRLPKVEILRSAISYIERLQDLLQTL 154
Cdd:cd19711     1 RRLESNERERQRMHKLNNAFQAL-REVIPHvrAEKKLSKIETLTLAKNYIKSLTTTILNM 59

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1678752216  97 RRKAATLRERRRLKKINEAFDVLkRKTVA--NPNQRLPKVEILRSAISYIERLQDLLQT 153
Cdd:cd19719    28 RRMKANARERNRMHGLNAALDNL-RKVVPcySKTQKLSKIETLRLAKNYIWALSEILRS 85

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1678752216  94 PPDRRKAATLRERRRLKKINEAFDVLKRkTVANPNQRLPKVEILRSAISYIERLQDLLQTLdEQE 158
Cdd:cd11394     3 KVEKRSAHNAIEKRYRSSINDRIIELKD-LVVGPDAKMNKSAVLRKAIDYIRYLQKVNQKL-KQE 65