helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 506326971   122 NARERRRMHDLNDALDGLRAVIPYAhsPSVRKLSKIATLLLAKNYILMQAQALDE 176
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTL--PKNKKLSKAEILRLAIEYIKSLQEELQK 53

basic helix-loop-helix (bHLH) domain found in Class E basic helix-loop-helix protein 22 (bHLHe22) and similar proteins; bHLHe22, also termed Class B basic helix-loop-helix protein 5 (bHLHb5), or trinucleotide repeat-containing gene 20 protein, is an OLIG-related bHLH 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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 506326971 117 LRLSINARERRRMHDLNDALDGLRAVIPYAHSPSVRKLSKIATLLLAKNYILMQAQALDEMRRLVAFLNQ 186
Cdd:cd18954    1 VRLNINARERRRMHDLNDALDELRAVIPYAHSPSVRKLSKIATLLLAKNYILMQANALEEMRRLVAYLNQ 70

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        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 506326971 118 RLSINARERRRMHDLNDALDGLRAVIPYAHSPSVRKLSKIATLLLAKNYILMQAQALDEMR 178
Cdd:cd11429    1 RLKINSRERKRMHDLNSALDGLRSVMPYAQGPSVRKLSKIATLLLARNYILMLTQALEELR 61

basic helix-loop-helix (bHLH) domain found in oligodendrocyte transcription factor 3 (Oligo3) and similar proteins; Oligo3, also termed Class B basic helix-loop-helix protein 7 (bHLHb7), or Class E basic helix-loop-helix protein 20 (bHLHe20), is a bHLH transcription factor that 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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 506326971 112 REQRSLRLSINARERRRMHDLNDALDGLRAVIPYAHSPSVRKLSKIATLLLAKNYILMQAQALDEMRRLVA 182
Cdd:cd18941   11 QDLQQLRLKINGRERKRMHDLNLAMDGLREVMPYAHGPSVRKLSKIATLLLARNYILMLTSSLEEMKRLVG 81

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 506326971 118 RLSINARERRRMHDLNDALDGLRAVIPYAhsPSVRKLSKIATLLLAKNYILMQAQAL 174
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 506326971 118 RLSINARERRRMHDLNDALDGLRAVIP-YAHSpsvRKLSKIATLLLAKNYILMQAQAL 174
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 506326971 118 RLSINARERRRMHDLNDALDGLRAVIPYAHSPsvRKLSKIATLLLAKNYILMQAQALDEMR 178
Cdd:cd19712    2 RLESNERERMRMHSLNDAFQGLREVIPHVNAE--RKLSKIETLTLAKNYIKALTNVICELR 60

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 506326971 118 RLSINARERRRMHDLNDALDGLRAVIP-YAHSpsvRKLSKIATLLLAKNYILmqaqALDEMRR 179
Cdd:cd19722   15 RQEANARERNRMHGLNDALDSLRKVVPcYSKT---QKLSKIETLRLAKNYIW----ALSEILR 70

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 506326971 118 RLSINARERRRMHDLNDALDGLRAVIPyaHSPSVRKLSKIATLLLAKNYILMQAQALD 175
Cdd:cd11428    2 RLKANDRERNRMHNLNDALDALREVLP--SFPDETKLTKIETLRFAHNYIWALSETLK 57

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 506326971   122 NARERRRMHDLNDALDGLRAVIPYAhsPSVRKLSKIATLLLAKNYILMQAQALDE 176
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTL--PKNKKLSKAEILRLAIEYIKSLQEELQK 53

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 506326971  118 RLSINARERRRMHDLNDALDGLRAVIPyaHSPSVRKLSKIATLLLAKNYILM 169
Cdd:pfam00010   2 REAHNERERRRRDRINDAFDELRELLP--TLPPDKKLSKAEILRLAIEYIKH 51

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 506326971  88 EDDafEQRRRRRGPGSAADGRRRPREQRSLRLSINARERRRMHDLNDALDGLRAVIP-YAHSpsvRKLSKIATLLLAKNY 166
Cdd:cd19719    1 EDD--DQKPKRRGPKKKKMTKARLERFKMRRMKANARERNRMHGLNAALDNLRKVVPcYSKT---QKLSKIETLRLAKNY 75

                 ....*...
gi 506326971 167 ILMQAQAL 174
Cdd:cd19719   76 IWALSEIL 83

basic helix-loop-helix (bHLH) domain found in Drosophila melanogaster protein taxi and similar proteins; Protein taxi, also termed protein delilah (Dei), is a bHLH transcription factor that is involved in regulation of cell adhesion and attachment that is expressed in specialized cells that provide anchoring sites to either muscles (tendon cells), or proprioceptors (chordotonal attachment cells) during embryonic development. It probably plays an important role in the differentiation of epidermal cells into the tendon cells that form the attachment sites for all muscles.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 506326971 118 RLSINARERRRMHDLNDALDGLRAVIPYAHSPSVR-KLSKIATLLLAKNYILMQAQAL 174
Cdd:cd11431    2 RKTANARERDRMREINDAFEALRRAVPEYPVAGKDgKLTKITTLRLAMNYIKALTDLL 59

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 506326971 114 QRSLRLSINARERRRMHDLNDALDGLRAVIPYAHSPsvRKLSKIATLLLAKNYI 167
Cdd:cd19713    3 QKQRRLAANARERRRMHGLNHAFDQLRNVIPSFNND--KKLSKYETLQMAQIYI 54

basic helix-loop-helix (bHLH) domain found in Drosophila melanogaster protein Amos and similar proteins; Amos, also termed absent MD neurons and olfactory sensilla protein, or reduced olfactory organs protein, or rough eye protein, is a bHLH transcription factor that promotes multiple dendritic neuron formation in the Drosophila peripheral nervous system.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 506326971 115 RSLRLSINARERRRMHDLNDALDGLRAVIPYAHSPsvRKLSKIATLLLAKNYI 167
Cdd:cd19715    6 KKRRLAANARERRRMNSLNVAFDKLRDVVPSLGDD--RKLSKYETLQMAQSYI 56

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 506326971 114 QRSLRLSINARERRRMHDLNDALDGLRAVIP-YAHSpsvRKLSKIATLLLAKNYILMQAQALDE 176
Cdd:cd11421    5 TRQRRIEANARERTRVHTISAAFEALRKAVPsYSYN---QKLSKLAILRIACSYILALARLADL 65

basic helix-loop-helix (bHLH) domain found in protein atonal homolog 7 (ATOH7) and similar proteins; ATOH7, also termed Class A basic helix-loop-helix protein 13 (bHLHa13), or helix-loop-helix protein hATH-5 (hATH5), or Math5, is a bHLH transcription factor involved in the differentiation of retinal ganglion cells.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 506326971 118 RLSINARERRRMHDLNDALDGLRAVIPYAHSPsvRKLSKIATLLLAKNYILMQAQALDEMRR 179
Cdd:cd19714    9 RLAANARERRRMQGLNTAFDRLRKVVPQWGQD--KKLSKYETLQMALSYIMALTRILAEAER 68

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
                 ....*....|....*....|....*....|....*....|....*...
gi 506326971 122 NARERRRMHDLNDALDGLRAVIPYAhsPSVRKLSKIATLLLAKNYILM 169
Cdd:cd11418    6 NERERRRVQAVNDAFDRLRQHVPYL--KRRKKLSKVKTLRRAIEYIRH 51

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
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 506326971 118 RLSINARERRRMHDLNDALDGLRAVIP-YAHSpsvRKLSKIATLLLAKNYILMQAQAL 174
Cdd:cd11415   10 RQAANIRERRRMFNLNEAFDKLRKKVPtFAYE---KRLSRIETLRLAIVYISFMTDLL 64

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 506326971 118 RLSINARERRRMHDLNDALDGLRAVIPYAHSPsvrKLSKIATLLLAKNYI--LMQAQALDE 176
Cdd:cd11464    2 RVLANVRERQRTQSLNEAFTSLRKIIPTLPSD---KLSKIQTLKLAARYIdfLYQVLRSDE 59

basic helix-loop-helix (bHLH) domain found in heart- and neural crest derivatives-expressed protein 2 (HAND2) and similar proteins; HAND2, also termed Class A basic helix-loop-helix protein 26 (bHLHa26), or deciduum, heart, autonomic nervous system and neural crest derivatives-expressed protein 2 (dHAND), is a bHLH transcription factor that is essential for cardiac morphogenesis, particularly for the formation of the right ventricle and of the aortic arch arteries.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 506326971 118 RLSINARERRRMHDLNDALDGLRAVIPyaHSPSVRKLSKIATLLLAKNYI--LMQAQALDE 176
Cdd:cd11471    2 RGTANRKERRRTQSINSAFAELRECIP--NVPADTKLSKIKTLRLATSYIayLMDLLAKDD 60

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 506326971 125 ERRRMHDLNDALDGLRAVIPYAHSPsvRKLSKIATLLLAKNYILM 169
Cdd:cd00083    1 ERRRRDKINDAFEELKRLLPELPDS--KKLSKASILQKAVEYIRE 43

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 506326971 118 RLSINARERRRMHDLNDALDGLRAVIPYAhsPSVRKLSKIATLLLAKNYILM 169
Cdd:cd11416    6 RHAANIRERKRMLSINSAFEELRCHVPTF--PYEKRLSKIDTLRLAIAYIAL 55

basic helix-loop-helix (bHLH) domain found in scleraxis and similar proteins; Scleraxis, also termed SCX, or Class A basic helix-loop-helix protein 41 (bHLHa41), or Class A basic helix-loop-helix protein 48 (bHLHa48), is a bHLH transcription factor that is expressed in sclerotome limb bud cranial and body wall mesenchyme, pericardium and heart valves, ligaments and tendons. It is required for tendon formation ligaments, connective tissue, the diaphragm, and testis development. Scleraxis plays a central role in promoting fibroblast proliferation and matrix synthesis during the embryonic development of tendons.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 506326971 118 RLSINARERRRMHDLNDALDGLRAVIPYahSPSVRKLSKIATLLLAKNYI 167
Cdd:cd18951    5 RHTANARERDRTNSVNTAFTALRTLIPT--EPADRKLSKIETLRLASSYI 52

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 506326971 118 RLSINARERRRMHDLNDALDGLRAVIPyAHSPSvRKLSKIATLLLAKNYILMQAQALDE 176
Cdd:cd19707    3 KIFTNTRERWRQQNVNSAFAELRKLIP-THPPD-KKLSKNEILRLAMKYINFLVKLLGD 59

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 506326971 118 RLSINARERRRMHDLNDALDGLRAVIPyAHSPSvRKLSKIATLLLAKNYILMQAQALDE 176
Cdd:cd19706    5 RIFTNSRERWRQQNVNGAFAELRKLIP-THPPD-KKLSKNEILRLAMKYINFLAKLLND 61

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
                 ....*....|....*....|....*....|....*....|....*.
gi 506326971 122 NARERRRMHDLNDALDGLRAVIPyaHSPSVRKLSKIATLLLAKNYI 167
Cdd:cd19723    6 NERERNRVKLVNLGFATLREHVP--NGRANKKMSKVETLRSAVEYI 49

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 506326971 118 RLSINARERRRMHDLNDALDGLRAVIPyAHSPSvRKLSKIATLLLAKNYILMQAQALDEM 177
Cdd:cd11413    2 RIFTNTRERWRQQNVNGAFAELRKLIP-THPPD-KKLSKNEILRLAMKYIKFLEKILEDQ 59

basic helix-loop-helix (bHLH) domain found in transcription factor 23 (TCF-23) and similar proteins; TCF-23, also termed Class A basic helix-loop-helix protein 24 (bHLHa24), is a bHLH transcription factor that is essential for progesterone-dependent decidualization. The mouse homolog is also called ovary, uterus and testis protein (OUT), which is expressed predominantly in the reproductive organs such as the uterus, ovary and testis. It shows an Id-like inhibitory activity and functions as a negative regulator of bHLH factors through the formation of a functionally inactive heterodimeric complex. OUT inhibits the formation of TCF3 and MYOD1 homodimers and heterodimers, but lacks DNA binding activity. OUT is involved in the regulation or modulation of smooth muscle contraction of the uterus during pregnancy and particularly around the time of delivery. It also plays a role in the inhibition of myogenesis. Unlike typical bHLH factors, OUT proteins do not bind E-box (CANNTG) or N-box DNA sequences and inhibit DNA binding of homo- and heterodimers consisting of E12 and MyoD in gel mobility shift assays.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 506326971 123 ARERRRMHDLNDALDGLRAVIPYAhsPSVRKLSKIATLLLAKNYILMQAQALD 175
Cdd:cd19709    6 ARERSRVRTLRQAFLALQAALPSV--PPDTKLSKLDVLVLATSYIAHLTRTLD 56

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 506326971 118 RLSINARERRRMHDLNDALDGLRAVIPyAHSPSvRKLSKIATLLLAKNYI 167
Cdd:cd19705    7 RVFTNSRERWRQQNVNGAFAELRKLIP-THPPD-KKLSKNEILRLAMKYI 54

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein aborted microspores (AMS) and similar proteins; The family includes several bHLH transcription factors from Arabidopsis thaliana, such as AMS, ICE1 and SCREAM2. AMS, also termed AtbHLH21, or EN 48, plays a crucial role in tapetum development and it is required for male fertility and pollen differentiation. ICE1, also termed inducer of CBF expression 1, or AtbHLH116, or EN 45, or SCREAM, acts as a transcriptional activator that regulates the cold-induced transcription of CBF/DREB1 genes. It binds specifically to the MYC recognition sites (5'-CANNTG-3') found in the CBF3/DREB1A promoter. SCREAM2, also termed AtbHLH33, or EN 44, mediates stomatal differentiation in the epidermis probably by controlling successive roles of SPCH, MUTE, and FAMA.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 506326971 125 ERRRMHDLNDALDGLRAVIpyahsPSVRKLSKIATLLLAKNYI 167
Cdd:cd11443    7 ERRRRKKLNDRLYMLRSVV-----PKITKMDRASILGDAIDYV 44

basic helix-loop-helix (bHLH) domain found in ovary, uterus and testis protein (OUT) family; The OUT family includes transcription factor 23 (TCF-23), transcription factor 24 (TCF-24) and similar proteins. TCF-23, also termed Class A basic helix-loop-helix protein 24 (bHLHa24), is a bHLH transcription factor that is essential for progesterone-dependent decidualization. The mouse homolog is also called ovary, uterus and testis protein (OUT), which is expressed predominantly in the reproductive organs such as the uterus, ovary and testis. It shows an Id-like inhibitory activity and functions as a negative regulator of bHLH factors through the formation of a functionally inactive heterodimeric complex. OUT inhibits the formation of TCF3 and MYOD1 homodimers and heterodimers, but lacks DNA binding activity. OUT is involved in the regulation or modulation of smooth muscle contraction of the uterus during pregnancy and particularly around the time of delivery. It also plays a role in the inhibition of myogenesis. Unlike typical bHLH factors, OUT proteins do not bind E-box (CANNTG) or N-box DNA sequences and inhibit DNA binding of homo- and heterodimers consisting of E12 and MyoD in gel mobility shift assays. TCF-24 is an uncharacterized bHLH transcription factor that shows high sequence similarity with TCF-23.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 506326971 123 ARERRRMHDLNDALDGLRAVIPYAhsPSVRKLSKIATLLLAKNYI 167
Cdd:cd11424    6 ARERSRVRTLRTAFQSLQRALPAV--PPDTKLSKLDVLLLASRYI 48

basic helix-loop-helix (bHLH) domain found in helix-loop-helix protein 1 (HEN-1) and similar proteins; HEN-1, also termed nescient helix-loop-helix 1 (Nhlh1), or Class A basic helix-loop-helix protein 35 (bHLHa35), or nescient helix loop helix 1 (NSCL-1), is a neuron-specific bHLH transcription factor that may serve as DNA-binding protein and may be involved in the control of cell-type determination, possibly within the developing nervous system.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 506326971 103 SAADGRRRPREQRSLRLSINARERRRMHDLNDALDGLRAVIPYAhsPSVRKLSKIATLLLAKNYILMQAQALD 175
Cdd:cd19701    2 SREERRRRRRATAKYRTAHATRERIRVEAFNVAFAELRKLLPTL--PPDKKLSKIEILRLAICYISYLNHVLD 72

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 506326971 113 EQRSLRlSINARERRRMhDLNDALDGLRAVIPYAHSPSVRKLSKIATLLLAKNYILM----QAQALDEMRRL 180
Cdd:cd11405    1 EQRRLS-HISAEQKRRF-NIKSGFDTLQSLIPSLGQNPNQKVSKAAMLQKAAEYIKSlkreRQQMQEEAEQL 70