Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 111118999   86 RLKINGRERKRMHDLNLAMDGLREVMPyaHGPSVRKLSKIATLLLARNYILMLT 139
Cdd:pfam00010   2 REAHNERERRRRDRINDAFDELRELLP--TLPPDKKLSKAEILRLAIEYIKHLQ 53

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118999  72 KIKKQLSEQDLQQLRLKINGRERKRMHDLNLAMDGLREVMPYAHGPSVRKLSKIATLLLARNYILMLTSSLEEMKRLVGE 151
Cdd:cd18940    2 KDKKQMSEPELQQLRLKINSRERKRMHDLNIAMDGLREVMPYAHGPSVRKLSKIATLLLARNYILMLTNSLEEMKRLVSE 81

                 ....
gi 111118999 152 IYGG 155
Cdd:cd18940   82 IYGG 85

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 111118999  86 RLKINGRERKRMHDLNLAMDGLREVMPYAHGPSVRKLSKIATLLLARNYILMLTSSLEEMK 146
Cdd:cd11429    1 RLKINSRERKRMHDLNSALDGLRSVMPYAQGPSVRKLSKIATLLLARNYILMLTQALEELR 61

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 111118999  86 RLKINGRERKRMHDLNLAMDGLREVMPYAHGPSVRKLSKIATLLLARNYILMLTSSLEEMKR 147
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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 111118999  80 QDLQQLRLKINGRERKRMHDLNLAMDGLREVMPYAHGPSVRKLSKIATLLLARNYILMLTSSLEEMKRLVGEIYGGH 156
Cdd:cd18953    2 KEQRSLRLSINARERRRMHDLNDALDGLRSVIPYAHSPSVRKLSKIATLLLAKNYILMQAQALEEMRRLVAYLNQGQ 78

basic helix-loop-helix (bHLH) domain found in neurogenic differentiation factor 4 (NeuroD4) and similar proteins; 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118999  54 GESLSRAGAKaagessKYKIKKQLSEQdLQQLRLKINGRERKRMHDLNLAMDGLREVMP-YAhgpSVRKLSKIATLLLAR 132
Cdd:cd19721    6 GEKPKRRGPK------KKKMTKARLER-FRARRVKANARERSRMHGLNDALDNLRRVMPcYS---KTQKLSKIETLRLAR 75

                         90
                 ....*....|..
gi 111118999 133 NYILMLTSSLEE 144
Cdd:cd19721   76 NYIWALSEVLET 87

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 111118999  86 RLKINGRERKRMHDLNLAMDGLREVMPYAHGPsvRKLSKIATLLLARNYILMLTSSLEEMK 146
Cdd:cd19712    2 RLESNERERMRMHSLNDAFQGLREVIPHVNAE--RKLSKIETLTLAKNYIKALTNVICELR 60

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        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 111118999  86 RLKINGRERKRMHDLNLAMDGLREVMPYAhgPSVRKLSKIATLLLARNYILMLTSSL 142
Cdd:cd19717   11 RVKANNRERNRMHNLNAALDSLREVLPTF--PEDAKLTKIETLRFAHNYIWALSETL 65

basic helix-loop-helix (bHLH) domain found in protein atonal homologs ATOH1, ATOH7 and similar proteins; The family includes ATOH1 and ATOH7. ATOH1, also termed Class A basic helix-loop-helix protein 14 (bHLHa14), or helix-loop-helix protein hATH-1 (hATH1), or Math1, or Cath1, is a proneural bHLH transcription factor that is essential for inner ear hair cell differentiation. It dimerizes with E47 and activates E-box (CANNTG) dependent transcription. ATOH1 is a mammalian homolog of the Drosophila melanogaster gene atonal and mouse atonal homolog 1 (Math1). ATOH7, also termed Class A basic helix-loop-helix protein 13 (bHLHa13), or helix-loop-helix protein hATH-5 (hATH5), or Math5, is a bHLH transcription factor involved in the differentiation of retinal ganglion cells. The family also includes protein Amos (also termed absent MD neurons and olfactory sensilla protein, or reduced olfactory organs protein, or rough eye protein). It is a bHLH transcription factor that promotes multiple dendritic neuron formation in the Drosophila peripheral nervous system.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 111118999  86 RLKINGRERKRMHDLNLAMDGLREVMPYAHgpSVRKLSKIATLLLARNYILMLTSSL 142
Cdd:cd11430    2 RLAANARERRRMNGLNRAFDQLRSVVPSIG--NDKKLSKYETLQMAQIYIETLSELL 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 111118999  86 RLKINGRERKRMHDLNLAMDGLREVMPyaHGPSVRKLSKIATLLLARNYILMLTS 140
Cdd:cd11426    2 RLESNERERLRMHQLNDAFQALREVIP--HVRSERKLSKIETLTLAKNYIKSLTN 54

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 111118999  86 RLKINGRERKRMHDLNLAMDGLREVMP-YAhgpSVRKLSKIATLLLARNYILMLTSSL 142
Cdd:cd19722   15 RQEANARERNRMHGLNDALDSLRKVVPcYS---KTQKLSKIETLRLAKNYIWALSEIL 69

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 111118999    90 NGRERKRMHDLNLAMDGLREVMPYahGPSVRKLSKIATLLLARNYILMLTSSLEE 144
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPT--LPKNKKLSKAEILRLAIEYIKSLQEELQK 53

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
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 111118999  86 RLKINGRERKRMHDLNLAMDGLREVMPYAhgPSVRKLSKIATLLLARNYILMLTSSL 142
Cdd:cd19716   18 RVKANDRERNRMHNLNAALDELRSVLPSF--PDDTKLTKIETLRFAHNYIWALSETL 72

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 111118999  83 QQLRLKINGRERKRMHDLNLAMDGLREVMP-YAHGpsvRKLSKIATLLLARNYILMLTSSLEE 144
Cdd:cd11421    6 RQRRIEANARERTRVHTISAAFEALRKAVPsYSYN---QKLSKLAILRIACSYILALARLADL 65

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 111118999  82 LQQLRLKINGRERKRMHDLNLAMDGLREVMPyAHGPSvRKLSKIATLLLARNYILMLTSSLE 143
Cdd:cd19715    5 LKKRRLAANARERRRMNSLNVAFDKLRDVVP-SLGDD-RKLSKYETLQMAQSYITALKELLS 64

basic helix-loop-helix (bHLH) domain found in scleraxis, transcription factor 15 (TCF-15) and similar proteins; The family includes scleraxis and transcription factor 15 (TCF-15). Scleraxis, also termed SCX, or Class A basic helix-loop-helix protein 41 (bHLHa41), or Class A basic helix-loop-helix protein 48 (bHLHa48), is a bHLH transcription factor that is expressed in sclerotome limb bud cranial and body wall mesenchyme, pericardium and heart valves, ligaments and tendons. It is required for tendon formation ligaments, connective tissue, the diaphragm, and testis development. Scleraxis plays a central role in promoting fibroblast proliferation and matrix synthesis during the embryonic development of tendons. TCF-15, also termed Class A basic helix-loop-helix protein 40 (bHLHa40), or paraxis, or protein bHLH-EC2, is a bHLH transcription factor expressed in caudal lateral and paraxial mesoderm dermomyotome and sclerotome fore limb buds during embryo development. It may function as an early transcriptional regulator involved in the patterning of the mesoderm and in lineage determination of cell types derived from the mesoderm.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 111118999  86 RLKINGRERKRMHDLNLAMDGLREVMPYAhgPSVRKLSKIATLLLARNYILMLTSSL 142
Cdd:cd11465    1 RQAANARERDRTHSVNSAFTALRTLIPTE--PADRKLSKIETLRLASSYISHLATVL 55

basic helix-loop-helix (bHLH) domain found in achaete-scute complex-like (ASCL) family; The achaete-scute complex-like (ASCL, also known as achaete-scute complex homolog or ASH) family of bHLH transcription factors, ASCL1-5, have been implicated in cell fate specification and differentiation. They are critical for proper development of the nervous system. The deregulation of ASCL plays a key role in psychiatric and neurological disorders. ASCL-1, also termed Class A basic helix-loop-helix protein 46 (bHLHa46), or achaete-scute homolog 1 (ASH-1), or mammalian achaete-scute homolog 1 (Mash1), is a neural-specific bHLH transcription factor that is expressed in subsets of neural progenitors in both the central and peripheral nervous system. It plays a key role in neuronal differentiation and specification in the nervous system. ASCL-2, also termed achaete-scute homolog 2 (ASH-2), or Class A basic helix-loop-helix protein 45 (bHLHa45), or mammalian achaete-scute homolog 2 (Mash2), is a bHLH transcription factor that is involved in Schwann cell differentiation and control of proliferation in adult peripheral nerves. ASCL-3, also termed Class A basic helix-loop-helix protein 42 (bHLHa42), or bHLH transcriptional regulator Sgn-1, or achaete-scute homolog 3 (ASH-3), is a bHLH transcription factor specifically localized in the duct cells of the salivary glands. It may act as transcriptional repressor that inhibits myogenesis. The family also includes Drosophila melanogaster achaete-scute complex (AS-C) proteins, which consists of lethal of scute (also known as achaete-scute complex protein T3 or AST3), scute (also known as achaete-scute complex protein T4 or AST4), achaete (also known as achaete-scute complex protein T5 or AST5), and asense (also known as achaete-scute complex protein T8 or AST8). They are involved in the determination of the neuronal precursors in the peripheral nervous system and the central nervous system, as well as in sex determination and dosage compensation.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 111118999  85 LRLKINGRERKRMHDLNLAMDGLREVMPYAhgPSVRKLSKIATLLLARNYILMLTSSL 142
Cdd:cd11418    1 RVARRNERERRRVQAVNDAFDRLRQHVPYL--KRRKKLSKVKTLRRAIEYIRHLQKLL 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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 111118999  78 SEQDLQQLRLKINGRERKRMHDLNLAMDGLREVMPYAhgPSvRKLSKIATLLLARNYILMLTSSLE 143
Cdd:cd11412    5 SFEELQTQRVMANVRERQRTQSLNEAFAALRKIIPTL--PS-DKLSKIQTLKLAARYIDFLYQVLQ 67

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 111118999  86 RLKINGRERKRMHDLNLAMDGLREVMP-YAHGpsvRKLSKIATLLLARNYILMLT 139
Cdd:cd11415   10 RQAANIRERRRMFNLNEAFDKLRKKVPtFAYE---KRLSRIETLRLAIVYISFMT 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 111118999  90 NGRERKRMHDLNLAMDGLREVMPyaHGPSVRKLSKIATLLLARNYI 135
Cdd:cd19723    6 NERERNRVKLVNLGFATLREHVP--NGRANKKMSKVETLRSAVEYI 49

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 111118999  86 RLKINGRERKRMHDLNLAMDGLREVMPYAhgPSVRKLSKIATLLLARNYILMLTSSLE 143
Cdd:cd11422    1 RRVANARERERVRNLNSGFSKLRRIVPLI--PRDRKPSKVDTLKGATEYIRLLQRILE 56

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 111118999  86 RLKINGRERKRMHDLNLAMDGLREVMPYAhgPSVRKLSKIATLLLARNYILMLTSSL 142
Cdd:cd11470    9 RQAANARERDRTQSVNTAFTALRTLIPTE--PVDRKLSKIETLRLASSYIAHLANVL 63

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 111118999  86 RLKINGRERKRMHDLNLAMDGLREVMpyAHGPSVRKLSKIATLLLARNYILMLTSSL 142
Cdd:cd18912    9 RVAANVRERKRILDYNQAFNALRLAL--KHDLGGKRLSKIATLRRAINRISALSLFL 63

basic helix-loop-helix (bHLH) domain found in T-cell acute lymphocytic leukemia protein/ lymphoblastic leukemia-derived sequence (TAL/LYL) family; The TAL/LYL family includes a group of bHLH transcription factors (TAL1, TAL2 and LYL1) implicated in T cell acute leukaemia. They act as mediators of T cell leukaemogenesis. TAL-1, also termed Class A basic helix-loop-helix protein 17 (bHLHa17), or stem cell protein (SCL), or T-cell leukemia/lymphoma protein 5, is a hematopoietic-specific bHLH transcription factor that functions in embryonic and adult hematopoiesis in vertebrates. It is also required for embryonic vascular remodeling. It acts as a regulator of erythroid differentiation and binds to regulatory regions of a large cohort of erythroid genes as part of a complex with GATA-1, LMO2 and Ldb1. TAL-2, also termed Class A basic helix-loop-helix protein 19 (bHLHa19), is a bHLH transcription factor essential for the normal brain development. Lyl-1, also termed Class A basic helix-loop-helix protein 18 (bHLHa18), or lymphoblastic leukemia-derived sequence 1, is a proto-oncogenic bHLH transcription factor that plays an important role in hematopoietic stem cell function and is required for the late stages of postnatal angiogenesis to limit the formation of new blood vessels, notably by regulating the activity of the small GTPase Rap1. LYL-1 deficiency induces a stress erythropoiesis.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118999  86 RLKINGRERKRMHDLNLAMDGLREVMPyAHGPSvRKLSKIATLLLARNYILMLTSSLEEM 145
Cdd:cd11413    2 RIFTNTRERWRQQNVNGAFAELRKLIP-THPPD-KKLSKNEILRLAMKYIKFLEKILEDQ 59

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 111118999  93 ERKRMHDLNLAMDGLREVMPYAHGPsvRKLSKIATLLLARNYILMLTS 140
Cdd:cd00083    1 ERRRRDKINDAFEELKRLLPELPDS--KKLSKASILQKAVEYIRELQS 46

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 111118999  86 RLKINGRERKRMHDLNLAMDGLREVMPYAhgPSVRKLSKIATLLLARNYILMLTSSL 142
Cdd:cd18951    5 RHTANARERDRTNSVNTAFTALRTLIPTE--PADRKLSKIETLRLASSYISHLGNVL 59

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 111118999  86 RLKINGRERKRMHDLNLAMDGLREVMPyAHGPSvRKLSKIATLLLARNYILMLTSSLEEMK 146
Cdd:cd19708    2 RMFTNSRERWRQQNVNGAFAELRKLVP-THPPD-KKLSKNEILRLAIKYIRLLSNVLEWQK 60

basic helix-loop-helix (bHLH) domain found in achaete-scute-like protein 2 (ASCL-2) and similar proteins; 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 111118999  90 NGRERKRMHDLNLAMDGLREVMPyaHGPSVRKLSKIATLLLARNYILMLTSSLEE 144
Cdd:cd19743    8 NERERNRVKLVNLGFAALRQHVP--QGGASKKMSKVETLRSAVEYIRALQRLLGE 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 111118999  86 RLKINGRERKRMHDLNLAMDGLREVMPyAHGPSvRKLSKIATLLLARNYILMLTSSLEE 144
Cdd:cd19705    7 RVFTNSRERWRQQNVNGAFAELRKLIP-THPPD-KKLSKNEILRLAMKYIDFLVTLLRD 63

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 111118999  83 QQLRLKINGRERKRMHDLNLAMDGLREVMPYAhgPSVRKLSKIATLLLARNYILMLTSSLEEMK 146
Cdd:cd19704    2 QVQRNAANARERARMRVLSKAFSRLKTTLPWV--PPDTKLSKLDTLRLASSYIAHLRQILANDK 63

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 111118999  92 RERKRMHDLNLAMDGLREVMPYAhgPSVRKLSKIATLLLARNYILMLTSSLE 143
Cdd:cd19709    7 RERSRVRTLRQAFLALQAALPSV--PPDTKLSKLDVLVLATSYIAHLTRTLD 56

basic helix-loop-helix (bHLH) domain found in Drosophila melanogaster achaete-scute complex (AS-C) proteins and similar proteins; Drosophila melanogaster AS-C proteins includes lethal of scute (also known as achaete-scute complex protein T3 or AST3), scute (also known as achaete-scute complex protein T4 or AST4), achaete (also known as achaete-scute complex protein T5 or AST5), and asense (also known as achaete-scute complex protein T8 or AST8). They are involved in the determination of the neuronal precursors in the peripheral nervous system and the central nervous system, as well as in sex determination and dosage compensation.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 111118999  90 NGRERKRMHDLNLAMDGLREVMPYA----------HGPSvRKLSKIATLLLARNYIlmltSSLEEM 145
Cdd:cd19744    6 NARERNRVKQVNNGFAILRQHIPQSviedltagggRGKS-KKLSKVDTLRMAVEYI----RRLQKL 66

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
                 ....*....|....*....|....*....|....*....|....*....|..
gi 111118999  92 RERKRMHDLNLAMDGLREVMPYAhgPSVRKLSKIATLLLARNYILMLTSSLE 143
Cdd:cd19701   23 RERIRVEAFNVAFAELRKLLPTL--PPDKKLSKIEILRLAICYISYLNHVLD 72

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 111118999  88 KINGRERKRMHDLNLAMDGLREVMPYAhgPSVRKLSKIATLLLARNYILMLTSSL 142
Cdd:cd19724    4 KRNERERQRVRCVNEGYARLRRHLPLE--NKDKRLSKVETLRAAIRYIKHLQELL 56

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 111118999  92 RERKRMHDLNLAMDGLREVMPYAhgPSVRKLSKIATLLLARNYILMLTSSL 142
Cdd:cd19710    8 RERSRVQTLRSAFLELQRTLPSV--PPDTKLSKLDVLVLATTYIAHLMRTL 56