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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 32564941 110 SRMRRQIANCNERRRMQSINAGFLALRALLPRKEGEKLSKAAILQQTADMVHQLLGHKGE 169
Cdd:cd11419   1 RRIRREIANSNERRRMQSINAGFQSLRTLLPHCDGEKLSKAAILQQTAEYIFSLEQEKTR 60

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 32564941 110 SRMRRQIANCNERRRMQSINAGFLALRALLPRKEGEKLSKAAILQQTADMVHQLLGHKGE 169
Cdd:cd11419   1 RRIRREIANSNERRRMQSINAGFQSLRTLLPHCDGEKLSKAAILQQTAEYIFSLEQEKTR 60

helix loop helix domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 32564941    118 NCNERRRMQSINAGFLALRALLPR-KEGEKLSKAAILQQTADMVHQL 163
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTlPKNKKLSKAEILRLAIEYIKSL 47

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 32564941 110 SRMRRQIANCNERRRMQSINAGFLALRALLPRKEGEKLSKAAILQQTADMVHQLLGHKGE 169
Cdd:cd11419   1 RRIRREIANSNERRRMQSINAGFQSLRTLLPHCDGEKLSKAAILQQTAEYIFSLEQEKTR 60

helix loop helix domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 32564941    118 NCNERRRMQSINAGFLALRALLPR-KEGEKLSKAAILQQTADMVHQL 163
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTlPKNKKLSKAEILRLAIEYIKSL 47

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
                ....*....|....*....|....*....|....*....|.
gi 32564941 114 RQIANCNERRRMQSINAGFLALRALLP-RKEGEKLSKAAIL 153
Cdd:cd11390   1 RNAANARERRRMHDLNDAFEALRKVLPtVPPDKKLSKIETL 41

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
                ....*....|....*....|....*....|....*....|...
gi 32564941 113 RRQIANCNERRRMQSINAGFLALRALLPRKEGE-KLSKAAILQ 154
Cdd:cd11430   1 RRLAANARERRRMNGLNRAFDQLRSVVPSIGNDkKLSKYETLQ 43

basic helix-loop-helix (bHLH) domain found in Fer3-like protein (FERD3L), pancreas transcription factor 1 subunit alpha (PTF1A) and similar proteins; The family corresponds to a group of bHLH transcription factors, including FERD3L and PTF1A. FERD3L, also termed basic helix-loop-helix protein N-twist, or Class A basic helix-loop-helix protein 31 (bHLHa31), or nephew of atonal 3 (NATO3), or Neuronal twist (NTWIST), is expressed in the developing central nervous system (CNS). It regulates floor plate (FP) cells development. FP is a critical organizing center located at the ventral-most midline of the neural tube. FERD3L binds to the E-box and functions as inhibitor of transcription. PTF1A, also termed Class A basic helix-loop-helix protein 29 (bHLHa29), or pancreas-specific transcription factor 1a, or bHLH transcription factor p48, or p48 DNA-binding subunit of transcription factor PTF1 (PTF1-p48), is implicated in the cell fate determination in various organs. It binds to the E-box consensus sequence 5'-CANNTG-3' and plays a role in early and late pancreas development and differentiation.

                        10        20        30
                ....*....|....*....|....*....|....*..
gi 32564941 114 RQIANCNERRRMQSINAGFLALRALLPR-KEGEKLSK 149
Cdd:cd19686   2 RQAANIRERKRMRSINDAFDGLRRHIPTfPYEKRLSK 38

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
                ....*....|....*....|....*....|....*....|....*
gi 32564941 113 RRQIANCNERRRMQSINAGFLALRALLP----RKEGEKLSKAAIL 153
Cdd:cd11431   1 RRKTANARERDRMREINDAFEALRRAVPeypvAGKDGKLTKITTL 45

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 32564941 114 RQIANCNERRRMQSINAGFLALRALLPRK-EGEKLSKAAILQQTADMVHQLL 164
Cdd:cd11422   1 RRVANARERERVRNLNSGFSKLRRIVPLIpRDRKPSKVDTLKGATEYIRLLQ 52

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
                ....*....|....*....|....*....|....*....|....*.
gi 32564941 110 SRMRRQIANCNERRRMQSINAGFLALRALLPR-KEGEKLSKAAILQ 154
Cdd:cd11421   5 TRQRRIEANARERTRVHTISAAFEALRKAVPSySYNQKLSKLAILR 50

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in protein Max and similar proteins; Max, also termed Class D basic helix-loop-helix protein 4 (bHLHd4), or Myc-associated factor X, is a bHLHZip transcription regulator that forms a sequence-specific DNA-binding protein complex with MYC or MAD which recognizes the core sequence 5'-CAC[GA]TG-3'. The MYC:MAX complex is a transcriptional activator, whereas the MAD:MAX complex is a transcriptional repressor. Max homodimer bind DNA but is transcriptionally inactive. Targeted deletion of max results in early embryonic lethality in mice.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 32564941 113 RRQIANCNERRRMQSINAGFLALRALLPRKEGEKLSKAAILQQTADMVHQL 163
Cdd:cd11406   1 KRAHHNALERKRRDHIKDSFHSLRDSVPSLQGEKASRAQILKKATEYIQYM 51

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
                ....*....|....*....|....*....|....*....|....*
gi 32564941 111 RMRRQIANCNERRRMQSINAGFLALRALLPRKEGE-KLSKAAILQ 154
Cdd:cd19713   4 KQRRLAANARERRRMHGLNHAFDQLRNVIPSFNNDkKLSKYETLQ 48

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-like protein X (Mlx) and similar proteins; Mlx, also termed Class D basic helix-loop-helix protein 13 (bHLHd13), or Max-like bHLHZip protein, or protein BigMax, or transcription factor-like protein 4, is a Max-like bHLHZip transcription regulator that interacts with the Max network of transcription factors. It forms a sequence-specific DNA-binding protein complex with some member of Mad family (Mad1 and Mad4) and Mondo family but not the Myc family and bind the E-box DNA to control transcription.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 32564941 113 RRQIANCNERRRMQSINAGFLALRALLPRKE------GEKLSKAAILQQTADMVHQLlgHKgedipdggepKKLKLEED 185
Cdd:cd19687   2 RREAHTQAEQKRRDAIKKGYDDLQDIVPTCQqqddigSQKLSKATILQRSIDYIQFL--HQ----------QKKKQEEE 68

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in USF/MITF family; The USF (upstream stimulatory factor)/MITF (microphthalmia-associated transcription factor) family includes two bHLHzip transcription factor subfamilies. USFs are ubiquitously expressed and key regulators of a wide number of gene regulation networks, including the stress and immune responses, cell cycle and proliferation, lipid and glucid metabolism. USFs recruit chromatin remodeling enzymes and interact with co-activators and the members of the transcription pre-initiation complex. USFs interact with high affinity to E-box regulatory elements. The MITF (also known as microphthalmia-TFE, or MiT) subfamily comprises four genes in mammals (MITF, TFE3, TFEB, and TFEC); each gene has different functions. MITF is involved in neural crest melanocytes development as well as the pigmented retinal epithelium. TFEB is required for vascularization of the mouse placenta. TFE3 is involved in B cell function. TFEC regulates gene expression in macrophages. The MITF subfamily proteins can form homodimers or heterodimers with each other but not with other bHLH or bHLHzip proteins.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 32564941 118 NCNERRRMQSINAGFLALRALLP----RKEGEKLSKAAILQQTADMVHQL 163
Cdd:cd11387   3 NAVERRRRDNINEKIQELGSLVPpsrlETKDLKPNKGSILSKAVEYIREL 52

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 32564941 109 RSRMRRQIANCNERRRMQSINAGFLALRALLPRK-EGEKLSKAAILQQTADMVHQL 163
Cdd:cd18912   4 RSKARRVAANVRERKRILDYNQAFNALRLALKHDlGGKRLSKIATLRRAINRISAL 59

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
                ....*....|....*....|....*....|....*....|....*...
gi 32564941 113 RRQIANCNERRRMQSINAGFLALRALLPRKEGEKLSKAAILQQTADMV 160
Cdd:cd11464   1 QRVLANVRERQRTQSLNEAFTSLRKIIPTLPSDKLSKIQTLKLAARYI 48

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 32564941 109 RSRMRRQIANCNERRRMQSINAGFLALRALLP-RKEGEKLSKAAILQQTADMVHQL 163
Cdd:cd19722  10 RVKVRRQEANARERNRMHGLNDALDSLRKVVPcYSKTQKLSKIETLRLAKNYIWAL 65

basic helix-loop-helix (bHLH) domain found in transcription factor 15 (TCF-15) and similar proteins; 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 32564941 113 RRQIANCNERRRMQSINAGFLALRALLPRKE-GEKLSKAAILQQTADMVHQL 163
Cdd:cd11470   8 QRQAANARERDRTQSVNTAFTALRTLIPTEPvDRKLSKIETLRLASSYIAHL 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
                ....*....|....*....|....*....|....*....|
gi 32564941 111 RMRRQIANCNERRRMQSINAGFLALRALLPRKEGEK-LSK 149
Cdd:cd11416   3 KVQRHAANIRERKRMLSINSAFEELRCHVPTFPYEKrLSK 42

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').

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 32564941 108 RRSRMRRQIANCNERRRMQSINAGFLALRALLPR-KEGEKLSKAAILQ 154
Cdd:cd19717   5 KIKKTRRVKANNRERNRMHNLNAALDSLREVLPTfPEDAKLTKIETLR 52

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 32564941 113 RRQIANCNERRRMQSINAGFLALRALLPRKEGE-KLSKAAILQQTADMVHQL 163
Cdd:cd19711   1 RRLESNERERQRMHKLNNAFQALREVIPHVRAEkKLSKIETLTLAKNYIKSL 52

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
                ....*....|....*....|....*....|....*....|....*..
gi 32564941 121 ERRRMQSINAGFLALRALLP----RKEGEKLSKAAILQQTADMVHQL 163
Cdd:cd11389   5 EKRRRDRINESLAELRRLVPearkSKGSGKLEKAEILEMTLQHLKAL 51

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
                ....*....|....*....|....*....|....*....|....*....|.
gi 32564941 113 RRQIANCNERRRMQSINAGFLALRALLPRKEGeKLSKAAILQQTADMVHQL 163
Cdd:cd11394   6 KRSAHNAIEKRYRSSINDRIIELKDLVVGPDA-KMNKSAVLRKAIDYIRYL 55

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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 32564941 113 RRQIANCNERRRMQSINAGFLALRALLP-RKEGEKLSKAAILQ 154
Cdd:cd19705   6 RRVFTNSRERWRQQNVNGAFAELRKLIPtHPPDKKLSKNEILR 48

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
                ....*....|....*....|....*....|....*...
gi 32564941 113 RRQIANCNERRRMQSINAGFLALRALLPRKEGE-KLSK 149
Cdd:cd11466   1 RRGSANKKERRRTQSINSAFADLRECIPNVPADtKLSK 38

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 32564941 113 RRQIANCNERRRMQSINAGFLALRALLPRKEGE-KLSKAAILQ---QTADMVHQLLGHKG 168
Cdd:cd19707   2 RKIFTNTRERWRQQNVNSAFAELRKLIPTHPPDkKLSKNEILRlamKYINFLVKLLGDQG 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
                ....*....|....*....|....*....|....*....|....*..
gi 32564941 113 RRQIANCNERRRMQSINAGFLALRALLPR---KEGEKLSKAAILQQT 156
Cdd:cd11425   1 QRQLANERERLRMRTLADALGELRQHLPPsvaPKGKRLSKIQTLKYA 47

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
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 32564941 109 RSRMRRQIANCNERRRMQSINAGFLALRALLP-RKEGEKLSKAAILQQTADMVHQL 163
Cdd:cd19719  24 RFKMRRMKANARERNRMHGLNAALDNLRKVVPcYSKTQKLSKIETLRLAKNYIWAL 79

basic helix-loop-helix (bHLH) domain found in Oligodendrocyte lineage genes (OLIG) family of transcription factors; The OLIG family includes three bHLH transcription factors, Oligo1-3, which are expressed in both the developing and mature central nervous system. Oligo1 and Oligo2 are expressed in a nervous tissue-specific manner, but Oligo3 is found mainly in non-neural tissues. Oligo (also known as Olig) have key roles in the specification of motor neurons, dorsal interneurons, and oligodendrocytes. Oligo1, also termed Class B basic helix-loop-helix protein 6 (bHLHb6), or Class E basic helix-loop-helix protein 21 (bHLHe21), promotes formation and maturation of oligodendrocytes, especially within the brain. Oligo2, also termed Class B basic helix-loop-helix protein 1 (bHLHb1), or Class E basic helix-loop-helix protein 19 (bHLHe19), or protein kinase C-binding protein 2, or protein kinase C-binding protein RACK17, is required for oligodendrocyte and motor neuron specification in the spinal cord, as well as for the development of somatic motor neurons in the hindbrain. It cooperates with OLIG1 to establish the MN progenitors (pMN) domain of the embryonic neural tube. Oligo3, also termed Class B basic helix-loop-helix protein 7 (bHLHb7), or Class E basic helix-loop-helix protein 20 (bHLHe20), is expressed in the ventricular zone of the dorsal alar plate of the hindbrain and involved in regulating the development of dorsal and ventral spinal cord. It may determine the distinct specification program of class A neurons in the dorsal part of the spinal cord and suppress specification of class B neurons. This family also includes two OLIG-related bHLH transcription factors, bHLHe22 and bHLHe23. bHLHe22, also termed Class B basic helix-loop-helix protein 5 (bHLHb5), or trinucleotide repeat-containing gene 20 protein, is a neural-specific transcriptional repressor that is expressed in both excitatory (unipolar brush cells) and inhibitory neurons (cartwheel cells) of the dorsal cochlear nucleus (DCN) during development. It is important for the proper development and/or survival of a number of neural cell types. bHLHe23, also termed Class B basic helix-loop-helix protein 4 (bHLHb4), is expressed in rod bipolar cells and is required for rod bipolar cell maturation. bHLHe23 have roles in spinal interneuron differentiation by mechanisms linked to the Notch signaling pathway. It modulates the expression of genes required for the differentiation and/or maintenance of pancreatic and neuronal cell types.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 32564941 113 RRQIaNCNERRRMQSINAGFLALRALLPRKEG---EKLSKAAIL 153
Cdd:cd11429   1 RLKI-NSRERKRMHDLNSALDGLRSVMPYAQGpsvRKLSKIATL 43

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in N-Myc and similar proteins; N-Myc, also termed Class E basic helix-loop-helix protein 37 (bHLHe37), is a bHLHZip proto-oncogene protein that positively regulates the transcription of MYCNOS in neuroblastoma cells. It is also essential during embryonic development. N-Myc has a critical role in regulating the switch between proliferation and differentiation of progenitor cells. It binds DNA as a heterodimer with MAX. The family also includes S-Myc, encoded by rat or mouse intronless myc gene, which has apoptosis-inducing activity.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 32564941 113 RRQIANCNERRRMQSINAGFLALRALLPR-KEGEKLSKAAILQQTADMVHQL 163
Cdd:cd11456   5 RRRNHNILERQRRNDLRSSFLTLRDHVPElVKNEKAAKVVILKKATEYVHSL 56