helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 17647759    134 NARERRRMHDLNDALDELRSVIPYAhsPSVRKLSKIATLLLAKNYILMQQNALEE 188
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTL--PKNKKLSKAEILRLAIEYIKSLQEELQK 53

basic helix-loop-helix (bHLH) domain found in Class E basic helix-loop-helix protein bHLHe22, bHLHe23 and similar proteins; The family 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        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 17647759 130 RLNINARERRRMHDLNDALDELRSVIPYAHSPSVRKLSKIATLLLAKNYILMQQNALEELRR 191
Cdd:cd11468   1 RLSINARERRRMHDLNDALDDLRAVIPYAHSPSVRKLSKIATLLLAKNYILMQARAIEELRR 62

basic helix-loop-helix (bHLH) domain found in Class E basic helix-loop-helix protein 23 (bHLHe23) and similar proteins; bHLHe23, also termed Class B basic helix-loop-helix protein 4 (bHLHb4), is an OLIG-related bHLH transcription factor that 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        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647759 124 RQGKTVRLNINARERRRMHDLNDALDELRSVIPYAHSPSVRKLSKIATLLLAKNYILMQQNALEELRRLLAYIQSTTGAA 203
Cdd:cd18953   2 KEQRSLRLSINARERRRMHDLNDALDGLRSVIPYAHSPSVRKLSKIATLLLAKNYILMQAQALEEMRRLVAYLNQGQTLS 81

basic helix-loop-helix (bHLH) domain found in oligodendrocyte transcription factor 2 (Oligo2) and similar proteins; 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 a bHLH transcription factor that 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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647759 127 KTVRLNINARERRRMHDLNDALDELRSVIPYAHSPSVRKLSKIATLLLAKNYILMQQNALEELRRLLAYI 196
Cdd:cd18940  13 QQLRLKINSRERKRMHDLNIAMDGLREVMPYAHGPSVRKLSKIATLLLARNYILMLTNSLEEMKRLVSEI 82

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 17647759 130 RLNINARERRRMHDLNDALDELRSVIPYAhsPSVRKLSKIATLLLAKNYILMQQNAL 186
Cdd:cd11390   1 RNAANARERRRMHDLNDAFEALRKVLPTV--PPDKKLSKIETLRLAINYIAALSDLL 55

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 17647759 130 RLNINARERRRMHDLNDALDELRSVIP-YAHSpsvRKLSKIATLLLAKNYILMQQNAL 186
Cdd:cd11427   1 RVKANARERNRMHGLNDALDNLRKVVPcYSKT---QKLSKIETLRLARNYIWALSEIL 55

basic helix-loop-helix (bHLH) domain found in 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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 17647759 130 RLNINARERRRMHDLNDALDELRSVIPYAHSPsvRKLSKIATLLLAKNYILMQQNALEELR 190
Cdd:cd19712   2 RLESNERERMRMHSLNDAFQGLREVIPHVNAE--RKLSKIETLTLAKNYIKALTNVICELR 60

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 17647759 130 RLNINARERRRMHDLNDALDELRSVIPYahSPSVRKLSKIATLLLAKNYIlmqqnalEELRRLL 193
Cdd:cd11430   2 RLAANARERRRMNGLNRAFDQLRSVVPS--IGNDKKLSKYETLQMAQIYI-------ETLSELL 56

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 17647759 130 RLNINARERRRMHDLNDALDELRSVIPyaHSPSVRKLSKIATLLLAKNYI 179
Cdd:cd11426   2 RLESNERERLRMHQLNDAFQALREVIP--HVRSERKLSKIETLTLAKNYI 49

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 17647759 120 KQKNRQGKTVRLNINARERRRMHDLNDALDELRSVIP-YAHSpsvRKLSKIATLLLAKNYILmqqnALEELRR 191
Cdd:cd19720  26 KARLERSKLRRQKANARERNRMHDLNSALDNLRKVVPcYSKT---QKLSKIETLRLAKNYIW----ALSEILR 91

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 17647759 130 RLNINARERRRMHDLNDALDELRSVIPyaHSPSVRKLSKIATLLLAKNYI 179
Cdd:cd19711   2 RLESNERERQRMHKLNNAFQALREVIP--HVRAEKKLSKIETLTLAKNYI 49

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 17647759 124 RQGKTVRLNINARERRRMHDLNDALDELRSVIPYAhsPSVRKLSKIATLLLAKNYILmqqnALEELRRL 192
Cdd:cd19718   3 KQKRNRRMKANDRERNRMHNLNSALDALRSVLPTF--PDDAKLTKIETLRFAHNYIW----ALTETLRM 65

basic helix-loop-helix (bHLH) domain found in neurogenin-1 (NGN-1) and similar proteins; NGN-1, also termed Class A basic helix-loop-helix protein 6 (bHLHa6), or neurogenic basic-helix-loop-helix protein, or neurogenic differentiation factor 3 (NeuroD3), is a neural-specific bHLH transcription factor involved in the initiation of neuronal differentiation. It activates transcription by binding to the E box (5'-CANNTG-3').

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 17647759 127 KTVRLNINARERRRMHDLNDALDELRSVIPyaHSPSVRKLSKIATLLLAKNYILmqqnALEELRRL 192
Cdd:cd19716  15 KSRRVKANDRERNRMHNLNAALDELRSVLP--SFPDDTKLTKIETLRFAHNYIW----ALSETLRL 74

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647759 130 RLNINARERRRMHDLNDALDELRSVIPYAHSPsvRKLSKIATLLLAKNYIlmqqNALEEL 189
Cdd:cd19713   7 RLAANARERRRMHGLNHAFDQLRNVIPSFNND--KKLSKYETLQMAQIYI----NALSEL 60

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 17647759 134 NARERRRMHDLNDALDELRSVIPYAhsPSVRKLSKIATLLLAKNYILMQQNAL 186
Cdd:cd19686   6 NIRERKRMRSINDAFDGLRRHIPTF--PYEKRLSKVDTLRLAIQYINFLTELL 56

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 17647759 120 KQKNRQGKTVRLNINARERRRMHDLNDALDELRSVIP-YAHSpsvRKLSKIATLLLAKNYILmqqnALEELRR 191
Cdd:cd19719  19 KARLERFKMRRMKANARERNRMHGLNAALDNLRKVVPcYSKT---QKLSKIETLRLAKNYIW----ALSEILR 84

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
                ....*....|....*....|....*....|....*....|....*....|..
gi 17647759 130 RLNINARERRRMHDLNDALDELRSVIP-YAHSpsvRKLSKIATLLLAKNYIL 180
Cdd:cd11421   9 RIEANARERTRVHTISAAFEALRKAVPsYSYN---QKLSKLAILRIACSYIL 57

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 17647759 130 RLNINARERRRMHDLNDALDELRSVIPYAHSPSVRKLSKIATLLLAKNYIlmqqnalEELRRLL 193
Cdd:cd11425   2 RQLANERERLRMRTLADALGELRQHLPPSVAPKGKRLSKIQTLKYAIRYI-------GYLGNVL 58

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 17647759 130 RLNINARERRRMHDLNDALDELRSVIPyaHSPSVRKLSKIATLLLAKNYI 179
Cdd:cd11466   2 RGSANKKERRRTQSINSAFADLRECIP--NVPADTKLSKIKTLRLATSYI 49

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 17647759 130 RLNINARERRRMHDLNDALDELRSVIPYAhsPSvRKLSKIATLLLAKNYI 179
Cdd:cd11464   2 RVLANVRERQRTQSLNEAFTSLRKIIPTL--PS-DKLSKIQTLKLAARYI 48

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 17647759 130 RLNINARERRRMHDLNDALDELRSVIPYahSPSVRKLSKIATLLLAKNYILMQQNALE 187
Cdd:cd11422   1 RRVANARERERVRNLNSGFSKLRRIVPL--IPRDRKPSKVDTLKGATEYIRLLQRILE 56

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 17647759 121 QKNRQGKTVRLNINARERRRMHDLNDALDELRSVIPYAHSPsvrKLSKIATLLLAKNYI 179
Cdd:cd11412   4 QSFEELQTQRVMANVRERQRTQSLNEAFAALRKIIPTLPSD---KLSKIQTLKLAARYI 59

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
                ....*....|....*....|....*....|....*....|....
gi 17647759 136 RERRRMHDLNDALDELRSVIPyaHSPSVRKLSKIATLLLAKNYI 179
Cdd:cd18952   9 KERRRTESINSAFAELRECIP--NVPADTKLSKIKTLRLATSYI 50

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 17647759 130 RLNINARERRRMHDLNDALDELRSVIPyAHSPSvRKLSKIATLLLAKNYILMQQNALEE 188
Cdd:cd11413   2 RIFTNTRERWRQQNVNGAFAELRKLIP-THPPD-KKLSKNEILRLAMKYIKFLEKILED 58

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
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 17647759 134 NARERRRMHDLNDALDELRSVIPyaHSPSVRKLSKIATLLLAKNYIlmqqNALEEL 189
Cdd:cd19723   6 NERERNRVKLVNLGFATLREHVP--NGRANKKMSKVETLRSAVEYI----RQLQQL 55

basic helix-loop-helix (bHLH) domain found in Drosophila melanogaster helix loop helix protein 3B (dHLH3B) and similar proteins; Drosophila HLH3B is an uncharacterized bHLH transcription factor that belongs to the T-cell acute lymphocytic leukemia protein/ lymphoblastic leukemia-derived sequence (TAL/LYL) family.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 17647759 130 RLNINARERRRMHDLNDALDELRSVIPyAHSPSvRKLSKIATLLLAKNYILMQQNALE 187
Cdd:cd19708   2 RMFTNSRERWRQQNVNGAFAELRKLVP-THPPD-KKLSKNEILRLAIKYIRLLSNVLE 57

basic helix-loop-helix (bHLH) domain found in musculin and similar proteins; Musculin, also termed activated B-cell factor 1 (ABF-1), or Class A basic helix-loop-helix protein 22 (bHLHa22), is a bHLH transcription factor expressed in activated B lymphocytes. It acts as a transcription repressor capable of inhibiting the transactivation capability of TCF3/E47. Musculin may play a role in regulating antigen-dependent B-cell differentiation. The mouse homolog, musculin, is suggested to be a repressor of myogenesis that is expressed in developing muscle and in the spleen. Musculin heterodimerizes with products of the E2A gene.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 17647759 134 NARERRRMHDLNDALDELRSVIPYAhsPSVRKLSKIATLLLAKNYILMQQNALEELR 190
Cdd:cd19703   9 NARERARMRVLSKAFSRLKTSLPWV--PPDTKLSKLDTLRLASSYIAHLRQLLQEDR 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
                ....*....|....*....|....*....|....*....|....*.
gi 17647759 134 NARERRRMHDLNDALDELRSVIPYAhsPSVRKLSKIATLLLAKNYI 179
Cdd:cd11423   6 NARERARMRVLSKAFSRLKTTLPWV--PPDTKLSKLDTLRLAASYI 49

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 17647759 134 NARERRRMHDLNDALDELRSVIPYAhsPSVRKLSKIATLLLAKNYIlmqqnalEELRRLLA 194
Cdd:cd19704   9 NARERARMRVLSKAFSRLKTTLPWV--PPDTKLSKLDTLRLASSYI-------AHLRQILA 60

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        50
                ....*....|....*....|....*....|....*....|....*....|
gi 17647759 130 RLNINARERRRMHDLNDALDELRSVIPyAHSPSvRKLSKIATLLLAKNYI 179
Cdd:cd19705   7 RVFTNSRERWRQQNVNGAFAELRKLIP-THPPD-KKLSKNEILRLAMKYI 54

basic helix-loop-helix (bHLH) domain found in the mesoderm posterior protein (Mesp) family; Mesp, a bHLH tissue specific transcription factor, acts as a key regulator of the cardiovascular transcriptional network by inducing directly and/or indirectly the expression of the majority of key cardiovascular transcription factors. The Mesp family includes two bHLH transcription factors, Mesp1 and Mesp2. Mesp1, also termed Class C basic helix-loop-helix protein 5 (bHLHc5), promotes cardiovascular differentiation during embryonic development and embryonic stem cell differentiation. Mesp2, also termed Class C basic helix-loop-helix protein 6 (bHLHc6), plays an important role in somitogenesis.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 17647759 130 RLNINARERRRMHDLNDALDELRSVIPYAHSPSVRKLSKIATLLLAKNYI 179
Cdd:cd18938   2 RQSASEREKLRMRDLAKALHNLRRYLPPSVAPAGQSLTKIETLRLTIRYI 51

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in MLX-interacting protein (MLXIP), MLX-interacting protein-like (MLXIPL) and similar proteins; The family includes MLXIP and MLXIPL. MLXIP, also termed Class E basic helix-loop-helix protein 36 (bHLHe36), or transcriptional activator MondoA, is a bHLHZip transcriptional activator that binds DNA as a heterodimer with Mlx. It binds to the canonical E box sequence 5'-CACGTG-3' and plays a role in transcriptional activation of glycolytic target genes. MLXIP is most highly expressed in skeletal muscle and functions as an indirect glucose sensor, by sensing glucose 6-phosphate and shuttling between the nucleus and the cytoplasm. MLXIPL, also termed carbohydrate-responsive element-binding protein (ChREBP), or Class D basic helix-loop-helix protein 14 (bHLHd14), or MLX interactor, or WS basic-helix-loop-helix leucine zipper protein (WS-bHLH), or Williams-Beuren syndrome chromosomal region 14 protein (WBSCR14), is a bHLHZip transcriptional factor integral to the regulation of glycolysis and lipogenesis in the liver. It forms heterodimers with the bHLHZip protein Mlx to bind the DNA sequence 5'-CACGTG-3'.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 17647759 130 RLN-INARERRRMhDLNDALDELRSVIPYAHSPSVRKLSKIATLLLAKNYI--LMQQNA--LEELRRL 192
Cdd:cd11405   4 RLShISAEQKRRF-NIKSGFDTLQSLIPSLGQNPNQKVSKAAMLQKAAEYIksLKRERQqmQEEAEQL 70

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 17647759 134 NARERRRMHDLNDALDELRSVIPYAhsPSVRKLSKIATLLLAKNYIlmqqNALEEL 189
Cdd:cd19724   6 NERERQRVRCVNEGYARLRRHLPLE--NKDKRLSKVETLRAAIRYI----KHLQEL 55

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
                ....*....|....*....|....*....|....*....|....*....|
gi 17647759 130 RLNINARERRRMHDLNDALDELRSVIPYAHSPSVRKLSKIATLLLAKNYI 179
Cdd:cd18939   9 RRKASEREKLRMRTLAEALHTLRNYLPPVYSQRGQPLTKIQTLKCTIQYI 58

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 17647759 130 RLNINARERRRMHDLNDALDELRSVIPYAHSPsvrKLSKIATLLLAKNYI--LMQQNA-LEELRRLL 193
Cdd:cd19682   1 RLRHKKRERERRSELRELFDKLKQLLGLDSDE---KASKLAVLTEAIEEIqqLKREEDeLQKEKARL 64

basic helix-loop-helix (bHLH) domain found in transcription factor 24 (TCF-24) and similar proteins; TCF-24 is an uncharacterized bHLH transcription factor that shows high sequence similarity with TCF-23.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 17647759 135 ARERRRMHDLNDALDELRSVIPYAhsPSVRKLSKIATLLLAKNYI--LMQ 182
Cdd:cd19710   7 ARERSRVQTLRSAFLELQRTLPSV--PPDTKLSKLDVLVLATTYIahLMR 54

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in sterol regulatory element-binding protein (SREBP) family and similar proteins; 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. The family also includes Saccharomyces cerevisiae transcription factor HMS1 (also termed high-copy MEP suppressor protein 1) and serine-rich protein TYE7. HMS1 is a putative bHLHzip transcription factor involved in exit from mitosis and pseudohyphal differentiation. TYE7, also termed basic-helix-loop-helix protein SGC1, is a putative bHLHzip transcription activator required for Ty1-mediated glycolytic gene expression. TYE7 N-terminal is extremely rich in serine residues. It binds DNA on E-box motifs, 5'-CANNTG-3'. TYE7 is not essential for growth.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 17647759 127 KTVRLNINARERRRMHDLNDALDELRSVIP-------------YAHSPSVRKLSKIATLLLAKNYILMQQNALEELRR 191
Cdd:cd11395   1 PRKRLPHNAIEKRYRSNLNTKIERLRDAIPslrspegksddggLGGLAPTTKLSKATILTKAIEYIRHLEQENERLEE 78

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in transcription factor E3 (TFE3) and similar proteins; TFE3, also termed Class E basic helix-loop-helix protein 33 (bHLHe33), is a bHLHzip transcription factor that is involved in B cell function. It specifically recognizes and binds E-box sequences (5'-CANNTG-3'). Its efficient DNA-binding requires dimerization with itself or with another MiT/TFE family member such as TFEB or MITF.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647759 122 KNRQGKTvrlNINARERRRMHDLNDALDELRSVIPYAHSPSVRkLSKIATLLLAKNYIL-------------MQQNALEE 188
Cdd:cd18928   7 KERQKKD---NHNLIERRRRFNINDRIKELGTLIPKSTDPEMR-WNKGTILKASVDYIRklqkeqqrskeieMRQRKLEQ 82

                ....*
gi 17647759 189 LRRLL 193
Cdd:cd18928  83 ANRSL 87

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 17647759 130 RLNINARERRRMHDLNDALDELRSVIP-YAHSPsvrKLSKIATLLLAKNYILM---QQNALEELRRLL 193
Cdd:cd11400   2 RRLHNVLERQRRNDLKNSFEKLRDLVPeLADNE---KASKVVILKKATEYIKQlqqEEKKLEKEKDKL 66

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 17647759 134 NARERRRMHDLNDALDELRSVIPYAHSPsvRKLSKIATLLLAKNYILMQQNAL 186
Cdd:cd19747  11 NERERQRVKCVNEGYARLRDHLPGAMAE--KRLSKVETLRAAIRYIKYLQDLL 61

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        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 17647759 137 ERRRMHDLNDALDELRSVIPYAHS-PSVRKLSKIATLllaknyilmqQNALEELRRL 192
Cdd:cd19685   2 EKRRRQRINDKLNQLKELLPPNLSkQSRSKLSKAEIL----------EMAITELRRL 48

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in transcription factor EB (TFEB) and similar proteins; TFEB, also termed Class E basic helix-loop-helix protein 35 (bHLHe35), is a bHLHzip transcription factor that is required for vascularization of the mouse placenta. It specifically recognizes and binds E-box sequences (5'-CANNTG-3'). Its efficient DNA-binding requires dimerization with itself or with another MiT/TFE family member such as TFE3 or MITF.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 17647759 122 KNRQGKTvrlNINARERRRMHDLNDALDELRSVIPYAHSPSVRkLSKIATLLLAKNYILMQQNALEELRRL 192
Cdd:cd18927   7 KERQKKD---NHNLIERRRRFNINDRIKELGTLIPKTNDLDVR-WNKGTILKASVDYIKRMQKDLQRSREL 73

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        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 17647759 134 NARERRRMHDLNDALDELRSVIP--YAHspsvRKLSKIATLLLAKNYILMQQNAL 186
Cdd:cd19745   9 NERERQRVKCVNEGYAKLRRHLPqeYSE----KRLSKVETLRAAIKYIKHLQSVL 59

basic helix-loop-helix (bHLH) domain found in Drosophila melanogaster protein daughterless (Da) and similar proteins; Da is a nuclear bHLH transcription factor that is a sole E protein ortholog essential for both neurogenesis and sex determination in Drosophila. Da is expressed in a broad range of tissues and is involved in diverse developmental processes such as oogenesis, sex determination and neurogenesis depending on its bHLH-binding partners. Da and achaete-scute complex (AS-C) form heterodimers that act as transcriptional activators of neural cell fates and are involved in sex determination.