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 1937924166 105 TTNADRRKAATMRERRRLSKVNEAFETLKRCTSSNPNQRLPKVEILRNAIRYIEGLQALLR 165
Cdd:cd18936     1 TTNADRRKAATMRERRRLSKVNEAFETLKRCTSTNPNQRLPKVEILRNAIRYIESLQALLR 61

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 1937924166 105 TTNADRRKAATMRERRRLSKVNEAFETLKRCTSSNPNQRLPKVEILRNAIRYIEGLQALLR 165
Cdd:cd18936     1 TTNADRRKAATMRERRRLSKVNEAFETLKRCTSTNPNQRLPKVEILRNAIRYIESLQALLR 61

Myogenic determination factor 5; This domain family is found in eukaryotes, and is approximately 70 amino acids in length. The family is found in association with pfam00010, pfam01586. There is a conserved CSD sequence motif. Myf5 is responsible for directing cells to the skeletal myocyte lineage during development. Myf5 is likely to act in a similar way to the other MRF4 proteins such as MyoD which perform the same function. These are histone acetyltransferases and histone deacetylases which activate and repress genes involved in the myocyte lineage.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1937924166 190 EHY---SGDSDASSPRSNCSDGMMDYSGPPSgPRRQNGYDAAYYSEASSEPRPGKSAAVSSLDCLSSIVERI 258
Cdd:pfam12232   1 ENYyglSSDSEASSPRSNCSDGMMDCNSPVW-SSRNSSFSSSYCSDLPNGSSSSKSSVVSSLDCLSSIVDRI 71

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1937924166  115 TMRERRRLSKVNEAFETLKRCTSSNP-NQRLPKVEILRNAIRYIEGLQALLRD 166
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPkNKKLSKAEILRLAIEYIKSLQEELQK 53

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 1937924166 105 TTNADRRKAATMRERRRLSKVNEAFETLKRCTSSNPNQRLPKVEILRNAIRYIEGLQALLR 165
Cdd:cd18936     1 TTNADRRKAATMRERRRLSKVNEAFETLKRCTSTNPNQRLPKVEILRNAIRYIESLQALLR 61

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 1937924166 109 DRRKAATMRERRRLSKVNEAFETLKRCTSSNPNQRLPKVEILRNAIRYIEGLQALLRDQ 167
Cdd:cd18937     1 DRRKAATMRERRRLKKVNQAFETLKRCTTSNPNQRLPKVEILRNAIRYIESLQDLLREQ 59

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 1937924166  27 DDFYDDPCFDSPDLRFFEDLD-PRLVHVG-ALLKPEEHAHFPttvhPGPGAREDEHVRAPSGHHQAGRCLLWACKACKRK 104
Cdd:pfam01586   1 MELYETNCYFFPDQRFYEDGEnPRLQGYDqALYQPRESPSLC----GDGRAAGEEHVRAPPGHHCPGQCLPWACKACKRK 76

                  ....*
gi 1937924166 105 TTNAD 109
Cdd:pfam01586  77 SVTMD 81

Myogenic determination factor 5; This domain family is found in eukaryotes, and is approximately 70 amino acids in length. The family is found in association with pfam00010, pfam01586. There is a conserved CSD sequence motif. Myf5 is responsible for directing cells to the skeletal myocyte lineage during development. Myf5 is likely to act in a similar way to the other MRF4 proteins such as MyoD which perform the same function. These are histone acetyltransferases and histone deacetylases which activate and repress genes involved in the myocyte lineage.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1937924166 190 EHY---SGDSDASSPRSNCSDGMMDYSGPPSgPRRQNGYDAAYYSEASSEPRPGKSAAVSSLDCLSSIVERI 258
Cdd:pfam12232   1 ENYyglSSDSEASSPRSNCSDGMMDCNSPVW-SSRNSSFSSSYCSDLPNGSSSSKSSVVSSLDCLSSIVDRI 71

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 1937924166 111 RKAATMRERRRLSKVNEAFETLKRCTSS-NPNQRLPKVEILRNAIRYIEGLQALL 164
Cdd:cd11390     1 RNAANARERRRMHDLNDAFEALRKVLPTvPPDKKLSKIETLRLAINYIAALSDLL 55

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1937924166  115 TMRERRRLSKVNEAFETLKRCTSSNP-NQRLPKVEILRNAIRYIEGLQALLRD 166
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 1937924166 110 RRKAatmRERRRLSKVNEAFETLKRCTSS-NPNQRLPKVEILRNAIRYIEGLQALL 164
Cdd:cd11418     4 RRNE---RERRRVQAVNDAFDRLRQHVPYlKRRKKLSKVKTLRRAIEYIRHLQKLL 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 1937924166 117 RERRRLSKVNEAFETLKRCTS-SNPNQRLPKVEILRNAIRYIEGLQALL 164
Cdd:cd19724     8 RERQRVRCVNEGYARLRRHLPlENKDKRLSKVETLRAAIRYIKHLQELL 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 1937924166 102 KRKTTNAdRRKAATMRERRRLSKVNEAFETLKRCTSSNP-NQRLPKVEILRNAIRYIEGLQALL 164
Cdd:cd11415     2 KRVITYA-QRQAANIRERRRMFNLNEAFDKLRKKVPTFAyEKRLSRIETLRLAIVYISFMTDLL 64

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 1937924166 110 RRKAATMRERRRLSKVNEAFETLKRCTSSNP-NQRLPKVEILRNAIRYIEGLQALLRDQD 168
Cdd:cd11413     1 RRIFTNTRERWRQQNVNGAFAELRKLIPTHPpDKKLSKNEILRLAMKYIKFLEKILEDQE 60

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 1937924166 111 RKAATMRERRRLSKVNEAFETLKRCTSSNPNQRLP-KVEILRNAIRYIEGLQALLR 165
Cdd:cd11422     1 RRVANARERERVRNLNSGFSKLRRIVPLIPRDRKPsKVDTLKGATEYIRLLQRILE 56

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1937924166 117 RERRRLSKVNEAFETLKR-CTSSNPNQRLPKVEILRNAIRYIEGLQALLRDQDAAppgAAAF 177
Cdd:cd19742    12 RERNRVKLVNMGFATLREhVPNGAANKKMSKVETLRSAVEYIRALQQLLDEHDAV---SAAF 70

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 1937924166 110 RRKAATMRERRRLSKVNEAFETLKRCT-SSNPNQRLPKVEILRNAIRYIEGLQALL 164
Cdd:cd11430     1 RRLAANARERRRMNGLNRAFDQLRSVVpSIGNDKKLSKYETLQMAQIYIETLSELL 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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1937924166 110 RRKAATMRERRRLSKVNEAFETLKRCTSS-NPNQRLPKVEILRNAIRYIEGLQALLRD 166
Cdd:cd19714     8 RRLAANARERRRMQGLNTAFDRLRKVVPQwGQDKKLSKYETLQMALSYIMALTRILAE 65

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937924166 110 RRKAATMRERRRLSKVNEAFETLKRCTSSNP-NQRLPKVEILRNAIRYIEGLQALLRDQD 168
Cdd:cd19707     2 RKIFTNTRERWRQQNVNSAFAELRKLIPTHPpDKKLSKNEILRLAMKYINFLVKLLGDQG 61

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 1937924166 110 RRKAATMRERRRLSKVNEAFETLKRCTSSNPNQRLPKVEILRNAIRYIEGLQALLRDQD 168
Cdd:cd11464     1 QRVLANVRERQRTQSLNEAFTSLRKIIPTLPSDKLSKIQTLKLAARYIDFLYQVLRSDE 59

basic helix-loop-helix (bHLH) domain found in achaete-scute-like protein 3 (ASCL-3) and similar proteins; 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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1937924166 117 RERRRLSKVNEAFETLKR-CTSSNPNQRLPKVEILRNAIRYIEGLQALL 164
Cdd:cd19745    11 RERQRVKCVNEGYAKLRRhLPQEYSEKRLSKVETLRAAIKYIKHLQSVL 59

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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1937924166 110 RRKAATMRERRRLSKVNEAFETLKRCTSSNP-NQRLPKVEILRNAIRYIeglqALLRD 166
Cdd:cd11416     5 QRHAANIRERKRMLSINSAFEELRCHVPTFPyEKRLSKIDTLRLAIAYI----ALLRD 58

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 1937924166 110 RRKAATMRERRRLSKVNEAFETLKR---CTSSnpNQRLPKVEILRNAIRYIEGLQALLR 165
Cdd:cd19722    14 RRQEANARERNRMHGLNDALDSLRKvvpCYSK--TQKLSKIETLRLAKNYIWALSEILR 70

basic helix-loop-helix (bHLH) domain found in protein atonal homolog 1 (ATOH1) and similar proteins; ATOH1, also termed Class A basic helix-loop-helix protein 14 (bHLHa14), or helix-loop-helix protein hATH-1 (hATH1), or Math1, or Cath1, is a proneural bHLH transcription factor that is essential for inner ear hair cell differentiation. It dimerizes with E47 and activates E-box (CANNTG) dependent transcription. ATOH1 is a mammalian homolog of the Drosophila melanogaster gene atonal and mouse atonal homolog 1 (Math1).

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1937924166 110 RRKAATMRERRRLSKVNEAFETLKRCTSS-NPNQRLPKVEILRNAIRYIEGLQALL 164
Cdd:cd19713     6 RRLAANARERRRMHGLNHAFDQLRNVIPSfNNDKKLSKYETLQMAQIYINALSELL 61

basic helix-loop-helix (bHLH) domain found in neurogenic differentiation factor 2 (NeuroD2) and similar proteins; NeuroD2, also termed Class A basic helix-loop-helix protein 1 (bHLHa1), or NeuroD-related factor (NDRF), is a neuronal calcium-dependent bHLH transcription factor that induces neuronal differentiation and promotes neuronal survival. It plays a central role in thalamocortical synaptic maturation. NeuroD2 mediates calcium-dependent transcription activation by binding to E box-containing promoter.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1937924166 102 KRKTTNAD------RRKAATMRERRRLSKVNEAFETLKR---CTSSnpNQRLPKVEILRNAIRYIEGLQALLR 165
Cdd:cd19720    21 KRKMTKARlersklRRQKANARERNRMHDLNSALDNLRKvvpCYSK--TQKLSKIETLRLAKNYIWALSEILR 91

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 1937924166 111 RKAATMRERRRLSKVNEAFETLKR---CTSsnPNQRLPKVEILRNAIRYIEGLQALL 164
Cdd:cd11427     1 RVKANARERNRMHGLNDALDNLRKvvpCYS--KTQKLSKIETLRLARNYIWALSEIL 55

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1937924166 110 RRKAatmRERRRLSKVNEAFETLKR------CTS------SNPNQRLPKVEILRNAIRYIEGLQALL 164
Cdd:cd19744     4 RRNA---RERNRVKQVNNGFAILRQhipqsvIEDltagggRGKSKKLSKVDTLRMAVEYIRRLQKLL 67

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 1937924166 109 DRRKAATMRERRRLSKVNEAFETLKRCTSSNPNQRLPKVEILRNAIRYIEGLQALLRDQD 168
Cdd:cd19700    16 SQRILANVRERQRTQSLNEAFAALRKIIPTLPSDKLSKIQTLKLAARYIDFLYQVLQSDE 75

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 1937924166 117 RERRRLSKVNEAFETLKRCTSSN-PNQRLPKVEILRNAIRYIEGLQALL 164
Cdd:cd19746    15 RERQRVRCVNEGYARLREHLPQElADKRLSKVETLRAAIDYIKHLQELL 63

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1937924166 109 DRRKAATMRERRRLSKVNEAFETLKRCTSSNPNQRLP--KVEILRNAIRYIEGLQALLRDQDAAPPGA 174
Cdd:cd18944     1 ERRVANNARERLRVRDINEAFKELGRMCQLHLNSEKPqtKLLILHQAVSVILNLEQQVRERNLNPKAA 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
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1937924166 111 RKAATMRERRRLSKVNEAFETLKRCTSSNPNQRLPKVEILRNAIRYIEGLQ 161
Cdd:cd19682     1 RLRHKKRERERRSELRELFDKLKQLLGLDSDEKASKLAVLTEAIEEIQQLK 51

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1937924166 109 DRRKAATMRERRRLSKVNEAFETLKRCTSSNPNQ-RLPKVEILRNAIRYIEGLQALLRDQD 168
Cdd:cd19718     7 NRRMKANDRERNRMHNLNSALDALRSVLPTFPDDaKLTKIETLRFAHNYIWALTETLRMAD 67

basic helix-loop-helix (bHLH) domain found in heart- and neural crest derivatives-expressed protein 1 (HAND1) and similar proteins; 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), is a bHLH transcription factor that plays an essential role in both trophoblast-giant cells differentiation and in cardiac morphogenesis.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1937924166 110 RRKAATMRERRRLSKVNEAFETLKRCTSSNP-NQRLPKVEILRNAIRYIEGLQALL 164
Cdd:cd18952     2 RKGAGPKKERRRTESINSAFAELRECIPNVPaDTKLSKIKTLRLATSYIAYLMDVL 57

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1937924166 102 KRKTTNADRRKAATMRERRRLSKVNEAFETLKRCTSSN--PNQRLPKVEILRNAIRYIEGLQALLRDQDAAP 171
Cdd:cd18943     2 EKDLRDRERRMANNARERVRVRDINEAFKELGRMCQMHlkSDKAQTKLIILQQAVQVILGLEQQVRERNLNP 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
                  ....*....|....*....|....*....|....*....|....*...
gi 1937924166 118 ERRRLSKVNEAFETLKRC---TSSNPnqRLPKVEILRNAIRYIEGLQA 162
Cdd:cd11400     9 ERQRRNDLKNSFEKLRDLvpeLADNE--KASKVVILKKATEYIKQLQQ 54

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1937924166 110 RRKAATMRERRRLSKVNEAFETLKRCTSS-NPNQRLPKVEILRNAIRYIEGLQALL 164
Cdd:cd19711     1 RRLESNERERQRMHKLNNAFQALREVIPHvRAEKKLSKIETLTLAKNYIKSLTTTI 56

basic helix-loop-helix (bHLH) domain found in 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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1937924166 107 NADRRKAATMRERRRLSKVNEAFETLKRCTSSNPNQR---LPKVEILRNAIRYIEGLQALL 164
Cdd:cd18939     5 SAQRRRKASEREKLRMRTLAEALHTLRNYLPPVYSQRgqpLTKIQTLKCTIQYISELSGLL 65

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1937924166 102 KRKTTNAD------RRKAATMRERRRLSKVNEAFETLKRCTSS-NPNQRLPKVEILRNAIRYIEGLQALLR 165
Cdd:cd19719    14 KKKMTKARlerfkmRRMKANARERNRMHGLNAALDNLRKVVPCySKTQKLSKIETLRLAKNYIWALSEILR 84

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1937924166 110 RRKAATMRERRRLSKVNEAFETLKR-CTSSNPNQRLPKVEILRNAIRYIEGLQALL 164
Cdd:cd11426     1 RRLESNERERLRMHQLNDAFQALREvIPHVRSERKLSKIETLTLAKNYIKSLTNMI 56

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split (HES)-related repressor protein (HERP)-like family; The HERP-like family includes bHLH-O transcriptional regulators that are related to the Drosophila hairy and Enhancer-of-split proteins. They 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. 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 family. It is involved in the regulation of Drosophila circadian rhythms. It functions as both an activator and a repressor of clock gene expression.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1937924166 118 ERRRLSKVNEAFETLKR----CTSSNPNQRLPKVEILRNAIRYIEGLQALL 164
Cdd:cd11389     5 EKRRRDRINESLAELRRlvpeARKSKGSGKLEKAEILEMTLQHLKALQSST 55

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in MAX gene-associated protein (MGA) 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1937924166 111 RKAATMRERRRLSKVNEAFETLKRCTSSNPNQRLPKVEILRNAIRYIEGLQ 161
Cdd:cd18911     1 RRTHTANERRRRNEMRDLFEKLKRTLGLHNLPKVSKYYILKQAFEEIQGLT 51

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein transparent testa 8 (TT8) and similar proteins; The family includes several bHLH transcription factors from Arabidopsis thaliana, such as TT8, EGL1, and GL3. TT8, also termed AtbHLH42, or EN 32, is involved in the control of flavonoid pigmentation and plays a key role in regulating leucoanthocyanidin reductase (BANYULS) and dihydroflavonol-4-reductase (DFR). EGL1, also termed AtbHLH2, or EN 30, or AtMYC146, or protein enhancer of GLABRA 3, is involved in epidermal cell fate specification and regulates negatively stomata formation but promotes trichome formation. GL3, also termed AtbHLH1, or AtMYC6, or protein shapeshifter, or EN 31, is involved in epidermal cell fate specification. It regulates negatively stomata formation, but, in association with TTG1 and MYB0/GL1, promotes trichome formation, branching and endoreplication.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1937924166 116 MRERRRLSKVNEAFETLKRCTSSnpNQRLPKVEILRNAIRYIEGLQ 161
Cdd:cd11451     8 MAERRRREKLNERFITLRSMVPF--VTKMDKVSILGDAIEYLKQLQ 51