basic helix-loop-helix (bHLH) domain found in myogenin (MYOG) and similar proteins; MYOG, also termed Class C basic helix-loop-helix protein 3 (bHLHc3), or myogenic factor 4 (Myf-4), is a bHLH transcriptional activator that promotes transcription of muscle-specific target genes and plays a role in muscle differentiation, cell cycle exit and muscle atrophy.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 13654247  81 DRRRAATLREKRRLKKVNEAFEALKRSTLLNPNQRLPKVEILRSAIQYIERLQALLSSL 139
Cdd:cd18935   1 DRRRAATLREKRRLKKVNEAFEALKRSTLLNPNQRLPKVEILRSAIQYIERLQALLSSL 59

basic helix-loop-helix (bHLH) domain found in myogenin (MYOG) and similar proteins; MYOG, also termed Class C basic helix-loop-helix protein 3 (bHLHc3), or myogenic factor 4 (Myf-4), is a bHLH transcriptional activator that promotes transcription of muscle-specific target genes and plays a role in muscle differentiation, cell cycle exit and muscle atrophy.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 13654247  81 DRRRAATLREKRRLKKVNEAFEALKRSTLLNPNQRLPKVEILRSAIQYIERLQALLSSL 139
Cdd:cd18935   1 DRRRAATLREKRRLKKVNEAFEALKRSTLLNPNQRLPKVEILRSAIQYIERLQALLSSL 59

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 13654247    82 RRRAATLREKRRLKKVNEAFEALKRS-TLLNPNQRLPKVEILRSAIQYIERLQ 133
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELlPTLPPDKKLSKAEILRLAIEYIKHLQ 53

basic helix-loop-helix (bHLH) domain found in myogenin (MYOG) and similar proteins; MYOG, also termed Class C basic helix-loop-helix protein 3 (bHLHc3), or myogenic factor 4 (Myf-4), is a bHLH transcriptional activator that promotes transcription of muscle-specific target genes and plays a role in muscle differentiation, cell cycle exit and muscle atrophy.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 13654247  81 DRRRAATLREKRRLKKVNEAFEALKRSTLLNPNQRLPKVEILRSAIQYIERLQALLSSL 139
Cdd:cd18935   1 DRRRAATLREKRRLKKVNEAFEALKRSTLLNPNQRLPKVEILRSAIQYIERLQALLSSL 59

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 13654247  81 DRRRAATLREKRRLKKVNEAFEALKRSTLLNPNQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd11411   1 DRRKAATMRERRRLKKVNEAFEALKRCTSANPNQRLPKVEILRNAIEYIESLQDLL 56

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 13654247  81 DRRRAATLREKRRLKKVNEAFEALKRSTLLNPNQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd19699   1 DRRKAATMRERRRLRKVNEAFEVLKRRTCPNPNQRLPKVEILRNAIEYIESLEDLL 56

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 13654247  81 DRRRAATLREKRRLKKVNEAFEALKRSTLLNPNQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd18937   1 DRRKAATMRERRRLKKVNQAFETLKRCTTSNPNQRLPKVEILRNAIRYIESLQDLL 56

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 13654247    82 RRRAATLREKRRLKKVNEAFEALKRS-TLLNPNQRLPKVEILRSAIQYIERLQ 133
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELlPTLPPDKKLSKAEILRLAIEYIKHLQ 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 13654247  80 VDRRRAatlREKRRLKKVNEAFEAL-KRSTLLNPNQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd11418   2 VARRNE---RERRRVQAVNDAFDRLrQHVPYLKRRKKLSKVKTLRRAIEYIRHLQKLL 56

basic helix-loop-helix (bHLH) domain found in Drosophila melanogaster achaete-scute complex (AS-C) proteins, achaete-scute-like proteins, ASCL1-2, and similar proteins; This subfamily includes Drosophila melanogaster AS-C proteins and two ASCL family of transcription factors, ASCL-1 and ASCL-2. Drosophila melanogaster AS-C proteins includes lethal of scute (also known as achaete-scute complex protein T3 or AST3), scute (also known as achaete-scute complex protein T4 or AST4), achaete (also known as achaete-scute complex protein T5 or AST5), and asense (also known as achaete-scute complex protein T8 or AST8). They are involved in the determination of the neuronal precursors in the peripheral nervous system and the central nervous system, as well as in sex determination and dosage compensation. ASCL-1, also termed Class A basic helix-loop-helix protein 46 (bHLHa46), or achaete-scute homolog 1 (ASH-1), or mammalian achaete scute homolog 1 (Mash1), is expressed in subsets of neural progenitors in both the central and peripheral nervous system. It plays a key role in neuronal differentiation and specification in the nervous system. ASCL-2, also termed achaete-scute homolog 2 (ASH-2), or Class A basic helix-loop-helix protein 45 (bHLHa45), or mammalian achaete scute homolog 2 (Mash2), is involved in Schwann cell differentiation and control of proliferation in adult peripheral nerves.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 13654247  79 SVDRRRAatlREKRRLKKVNEAFEALkRSTLLN--PNQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd19723   1 AVARRNE---RERNRVKLVNLGFATL-REHVPNgrANKKMSKVETLRSAVEYIRQLQQLL 56

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 13654247  83 RRAATLREKRRLKKVNEAFEALKRSTLLNPNQRLP-KVEILRSAIQYIERLQALL 136
Cdd:cd11422   1 RRVANARERERVRNLNSGFSKLRRIVPLIPRDRKPsKVDTLKGATEYIRLLQRIL 55

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
                ....*....|....*....|....*....|....*....|....*.
gi 13654247  90 EKRRLKKVNEAFEALKRST-LLNPNQRLPKVEILRSAIQYIERLQA 134
Cdd:cd00083   1 ERRRRDKINDAFEELKRLLpELPDSKKLSKASILQKAVEYIRELQS 46

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 13654247  82 RRRAATLREKRRLKKVNEAFEALKRST----LLNPNQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd11431   1 RRKTANARERDRMREINDAFEALRRAVpeypVAGKDGKLTKITTLRLAMNYIKALTDLL 59

basic helix-loop-helix (bHLH) domain found in protein atonal homolog 8 (ATOH8) and similar proteins; ATOH8, also termed Class A basic helix-loop-helix protein 21 (bHLHa21), or helix-loop-helix protein hATH-6 (hATH6), is a bHLH shear-stress-responsive transcription factor expressed in activated satellite cells and proliferating myoblasts of human skeletal muscle tissue. It regulates endothelial cell proliferation, migration and tube-like structures formation. ATOH8 binds a palindromic (canonical) core consensus DNA sequence 5'-CANNTG- 3' known as an E-box element, possibly as a heterodimer with other bHLH proteins.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 13654247  76 KSVSVDRRRAATLREKRRLKKVNEAFEALKRSTllnP----NQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd11421   2 KNMTRQRRIEANARERTRVHTISAAFEALRKAV---PsysyNQKLSKLAILRIACSYILALARLA 63

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 13654247  83 RRAATLREKRRLKKVNEAFEALKRSTLLNP-NQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd11465   1 RQAANARERDRTHSVNSAFTALRTLIPTEPaDRKLSKIETLRLASSYISHLATVL 55

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 13654247  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 13654247  81 DRRRAATLREKRRLKKVNEAFEALKRSTLLNPNQRLPKVEILRSAIQYIERLQALLSS 138
Cdd:cd11412  11 TQRVMANVRERQRTQSLNEAFAALRKIIPTLPSDKLSKIQTLKLAARYIDFLYQVLQS 68

basic helix-loop-helix (bHLH) domain found in achaete-scute-like protein 1 (ASCL-1) and similar proteins; ASCL-1, also termed Class A basic helix-loop-helix protein 46 (bHLHa46), or achaete-scute homolog 1 (ASH-1), or mammalian achaete scute homolog 1 (Mash1), is a neural-specific bHLH transcription factor that is expressed in subsets of neural progenitors in both the central and peripheral nervous system. It plays a key role in neuronal differentiation and specification in the nervous system.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 13654247  89 REKRRLKKVNEAFEALkRSTLLN--PNQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd19742  12 RERNRVKLVNMGFATL-REHVPNgaANKKMSKVETLRSAVEYIRALQQLL 60

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 13654247  75 RKSVSVDRRRAATLREKRRLKKVNEAFEALKRStLLNP--NQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd18912   1 RPVRSKARRVAANVRERKRILDYNQAFNALRLA-LKHDlgGKRLSKIATLRRAINRISALSLFL 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
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 13654247  82 RRRAATLREKRRLKKVNEAFEALKRSTLLNP-NQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd11413   1 RRIFTNTRERWRQQNVNGAFAELRKLIPTHPpDKKLSKNEILRLAMKYIKFLEKIL 56

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
                ....*....|....*....|....*....|....*....|....*....
gi 13654247  89 REKRRLKKVNEAFEALKRSTLLN-PNQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd19746  15 RERQRVRCVNEGYARLREHLPQElADKRLSKVETLRAAIDYIKHLQELL 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        50
                ....*....|....*....|....*....|....*....|....*....|
gi 13654247  89 REKRRLKKVNEAFEALkRSTLLN--PNQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd19747  13 RERQRVKCVNEGYARL-RDHLPGamAEKRLSKVETLRAAIRYIKYLQDLL 61

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 13654247  82 RRRAATLREKRRLKKVNEAFEALKR---STLLNPNQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd11425   1 QRQLANERERLRMRTLADALGELRQhlpPSVAPKGKRLSKIQTLKYAIRYIGYLGNVL 58

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
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 13654247  81 DRRRAATLREKRRLKKVNEAFEALKRSTLLNPNQRLPKVEILRSAIQYIERLQALLSS 138
Cdd:cd19700  16 SQRILANVRERQRTQSLNEAFAALRKIIPTLPSDKLSKIQTLKLAARYIDFLYQVLQS 73

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in the Myc family; The Myc family is a member of the bHLHzip family of transcription factors that play important roles in the control of normal cell proliferation, growth, survival and differentiation. All Myc isoforms contain two independently functioning polypeptide chain regions: N-terminal transactivating residues and a C-terminal bHLHzip segment. The bHLHzip family of bHLH transcription factors are characterized by a highly conserved N-terminal basic region that may bind DNA at a consensus hexanucleotide sequence known as the E-box (CANNTG) followed by HLH and leucine zipper motifs that may interact with other proteins to form homo- and heterodimers. Myc heterodimerizes with Max enabling specific binding to E-box DNA sequences in the promoters of target genes. The Myc proto-oncoprotein family includes at least five different functional members: c-, N-, L-, S- and B-Myc (which is lacking the bHLH domain).

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 13654247  91 KRR--LKKvneAFEALKRS--TLLNpNQRLPKVEILRSAIQYIERLQALLSSLNQEERDLRYR 149
Cdd:cd11400  11 QRRndLKN---SFEKLRDLvpELAD-NEKASKVVILKKATEYIKQLQQEEKKLEKEKDKLKAR 69

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 13654247  81 DRRRAATLREKRRLKKVNEAFEALKRSTLLNPNQRLP--KVEILRSAIQYIERL--QALLSSLNQEERDLRYR 149
Cdd:cd18944   1 ERRVANNARERLRVRDINEAFKELGRMCQLHLNSEKPqtKLLILHQAVSVILNLeqQVRERNLNPKAACLKRR 73

basic helix-loop-helix (bHLH) domain found in helix-loop-helix protein (HEN) family; The HEN family includes two neuron-specific bHLH transcription factors, HEN-1 (also known as Nhlh1 or bHLHa35 or NSCL-1) and HEN-2 (also known as Nhlh2 or bHLHa34 or NSCL-2). They may serve as DNA-binding protein that is involved in the control of cell-type determination, possibly within the developing nervous system.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 13654247  83 RRAATLREKRRLKKVNEAFEALkRSTL--LNPNQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd11414   3 RNAHATRERIRVEAFNSAFAQL-RKLLptLPPDKKLSKIEILRLAICYISYLNHVL 57

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 13654247  74 KRKSVSVDRRRAATLREKRRLKKVNEAFEALKRS-TLLNPNQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd19701   8 RRRRATAKYRTAHATRERIRVEAFNVAFAELRKLlPTLPPDKKLSKIEILRLAICYISYLNHVL 71

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana BES1-interacting Myc-like proteins (BIMs) and similar proteins; The family includes Arabidopsis thaliana BIM1 and its homologs (BIM2 and BIM3), which are bHLH transcription factors that interact with BES1 to regulate transcription of Brassinosteroid (BR)-induced gene. BR regulates many growth and developmental processes such as cell elongation, vascular development, senescence stress responses, and photomorphogenesis. BIM1 heterodimerize with BES1 and bind to E-box sequences present in many BR-induced promoters to regulated BR-induced genes.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 13654247  90 EKRRLKKVNEAFEALkRSTLLNPNQRLPKVEILRSAIQYIERLQA 134
Cdd:cd11453  11 EQRRRSKINERLQAL-RDLIPHSDQKRDKASFLLEVIEYIQALQE 54

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 13654247  83 RRAATLREKRRLKKVNEAFEALKRST-LLNPNQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd11427   1 RVKANARERNRMHGLNDALDNLRKVVpCYSKTQKLSKIETLRLARNYIWALSEIL 55

basic helix-loop-helix (bHLH) domain found in transcription factor 21 (TCF-21) and similar proteins; TCF-21, also termed capsulin, or Class A basic helix-loop-helix protein 23 (bHLHa23), or epicardin, or podocyte-expressed 1 (Pod-1), is a bHLH transcription factor expressed specifically in mesodermally-derived cells that surround the epithelium of the developing gastrointestinal, genitourinary and respiratory systems during mouse embryogenesis. It may play a role in the specification or differentiation of one or more subsets of epicardial cell types.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 13654247  82 RRRAATLREKRRLKKVNEAFEALKrSTL--LNPNQRLPKVEILRSAIQYIERLQALLSS 138
Cdd:cd19704   4 QRNAANARERARMRVLSKAFSRLK-TTLpwVPPDTKLSKLDTLRLASSYIAHLRQILAN 61

basic helix-loop-helix (bHLH) domain found in T-cell acute lymphocytic leukemia protein 2 (TAL-2) and similar proteins; TAL-2, also termed Class A basic helix-loop-helix protein 19 (bHLHa19), is a bHLH transcription factor essential for the normal brain development. It has been implicated in T-cell acute lymphoblastic leukemia.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 13654247  82 RRRAATLREKRRLKKVNEAFEALKRSTLLNP-NQRLPKVEILRSAIQYIERLQALLSS 138
Cdd:cd19707   2 RKIFTNTRERWRQQNVNSAFAELRKLIPTHPpDKKLSKNEILRLAMKYINFLVKLLGD 59

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 13654247  87 TLREKRRLKKVNEAFEALKrsTLLNPNQRLPKVEILRSAIQYIERLQALLSSL 139
Cdd:cd11393   2 SIAERKRREKINERIRALR--SLVPNGGKTDKASILDEAIEYIKFLQEQVKVL 52

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 13654247  90 EKRRLKKVNEAFEALKRSTLLN----PNQRLPKVEILRSAIQYIERLQA 134
Cdd:cd19685   2 EKRRRQRINDKLNQLKELLPPNlskqSRSKLSKAEILEMAITELRRLQQ 50

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 13654247  82 RRRAATLREKRRLKKVNEAFEALKRSTLLNP-NQRLPKVEILRSAIQYIERLQALLSSLNQ 141
Cdd:cd11471   1 RRGTANRKERRRTQSINSAFAELRECIPNVPaDTKLSKIKTLRLATSYIAYLMDLLAKDDQ 61

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein IAA-leucine resistant 3 (ILR3) and similar proteins; ILR3, also termed AtbHLH105, or EN 133, is a bHLH transcription factor that plays a role in resistance to amide-linked indole-3-acetic acid (IAA) conjugates such as IAA-Leu and IAA-Phe. It may regulate gene expression in response to metal homeostasis changes.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 13654247  89 REKRRLKKVNEAFEALkrSTLLNPN--QRLPKVEILRSAIQYI-------ERLQALLSSLNQEERDL 146
Cdd:cd11446   4 REKLRRDKLNERFMEL--SNVLEPGrpPKTDKATILGDAIRMLkqlrgevQKLKEENSSLQEESKEL 68

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 13654247  81 DRRRAATLREKRRLKKVNEAFEALKRST-LLNPNQRLPKVEILRSAIQYIERLQALLSSLNQEERDLRYR 149
Cdd:cd11458   4 DKRRTHNVLERQRRNELKLSFFALRDQIpEVANNEKAPKVVILKKATEYILSMQADEQRLISEKEQLRRR 73

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 13654247  80 VDRRRAATLREKRRLKKVNEAFEALKRsTLLNPNQRLPKVEILRSAIQYIERLQALLSSLNQEERDLR 147
Cdd:cd11394   4 VEKRSAHNAIEKRYRSSINDRIIELKD-LVVGPDAKMNKSAVLRKAIDYIRYLQKVNQKLKQENMALK 70

basic helix-loop-helix (bHLH) domain found in transcription factor E47 and similar proteins; E47 is a class I bHLH transcriptional regulator that forms heterodimers with class II bHLH proteins to regulate distinct differentiation pathways. Its homodimers regulate B lymphocytes development.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 13654247  81 DRRRAATLREKRRLKKVNEAFEALKR--STLLNPNQRLPKVEILRSAIQYIERLQ 133
Cdd:cd18943   9 ERRMANNARERVRVRDINEAFKELGRmcQMHLKSDKAQTKLIILQQAVQVILGLE 63

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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 13654247  82 RRRAATLREKRRLKKVNEAFEALKRS-TLLNPNQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd11423   1 QRNAANARERARMRVLSKAFSRLKTTlPWVPPDTKLSKLDTLRLAASYIAHLRQIL 56

basic helix-loop-helix (bHLH) domain found in heart- and neural crest derivatives-expressed protein (HAND) family; The HAND family includes two bHLH transcription factors, HAND1 and HAND2. HAND1, also termed Class A basic helix-loop-helix protein 27 (bHLHa27), or extraembryonic tissues, heart, autonomic nervous system and neural crest derivatives-expressed protein 1 (eHAND), plays an essential role in both trophoblast-giant cells differentiation and in cardiac morphogenesis. HAND2, also termed Class A basic helix-loop-helix protein 26 (bHLHa26), or deciduum, heart, autonomic nervous system and neural crest derivatives-expressed protein 2 (dHAND), is essential for cardiac morphogenesis, particularly for the formation of the right ventricle and of the aortic arch arteries.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 13654247  82 RRRAATLREKRRLKKVNEAFEALkRSTLLN--PNQRLPKVEILRSAIQYIERLQALL 136
Cdd:cd11466   1 RRGSANKKERRRTQSINSAFADL-RECIPNvpADTKLSKIKTLRLATSYIAYLMDVL 56