helix loop helix domain;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 585707874   528 NARERIRVNKLNSAFDLLRSVLPkdllmktehTGKRVFKMSKVETLRCAISYMHKLEMILRK 589
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLP---------TLPKNKKLSKAEILRLAIEYIKSLQEELQK 53

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 585707874 524 RRKANARERIRVNKLNSAFDLLRSVLPkdllmkTEHTGKrvfKMSKVETLRCAISY 579
Cdd:cd11390    1 RNAANARERRRMHDLNDAFEALRKVLP------TVPPDK---KLSKIETLRLAINY 47

helix loop helix domain;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 585707874   528 NARERIRVNKLNSAFDLLRSVLPkdllmktehTGKRVFKMSKVETLRCAISYMHKLEMILRK 589
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLP---------TLPKNKKLSKAEILRLAIEYIKSLQEELQK 53

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 585707874 524 RRKANARERIRVNKLNSAFDLLRSVLPKdlLMKTEHTGkrvfKMSKVETLRCAISYMHKLEMIL 587
Cdd:cd11431    2 RKTANARERDRMREINDAFEALRRAVPE--YPVAGKDG----KLTKITTLRLAMNYIKALTDLL 59

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 585707874 524 RRKANARERIRVNKLNSAFDLLRSVLPkdllmktEHTGKRvfKMSKVETLRCAISYMHKLEMIL 587
Cdd:cd11430    2 RLAANARERRRMNGLNRAFDQLRSVVP-------SIGNDK--KLSKYETLQMAQIYIETLSELL 56

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 585707874 522 FVRRKaNARERIRVNKLNSAFDLLRSVLPKDLLMKtehtgkrvfKMSKVETLRCAISYMHKLEMIL 587
Cdd:cd19724    1 FIRKR-NERERQRVRCVNEGYARLRRHLPLENKDK---------RLSKVETLRAAIRYIKHLQELL 56

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 585707874 524 RRKANARERIRVNKLNSAFDLLRSVLPKdllmKTEHTgkrvfKMSKVETLRCAISYMHKLEMILR 588
Cdd:cd11428    2 RLKANDRERNRMHNLNDALDALREVLPS----FPDET-----KLTKIETLRFAHNYIWALSETLK 57

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 585707874 524 RRKANARERIRVNKLNSAFDLLRSVLPkdllmktehTGKRVFKMSKVETLRCAISYMHKLEMIL 587
Cdd:cd19686    2 RQAANIRERKRMRSINDAFDGLRRHIP---------TFPYEKRLSKVDTLRLAIQYINFLTELL 56

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 585707874 524 RRKANARERIRVNKLNSAFDLLRSVLPKdllmktehTGKRVfKMSKVETLRCAISYMHKLEMIL 587
Cdd:cd19714    9 RLAANARERRRMQGLNTAFDRLRKVVPQ--------WGQDK-KLSKYETLQMALSYIMALTRIL 63

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 585707874 525 RKANARERIRVNKLNSAFDLLRSVLPKDLLMKtehtgkrvfKMSKVETLRCAISYMHKLEMIL 587
Cdd:cd19745    6 RKRNERERQRVKCVNEGYAKLRRHLPQEYSEK---------RLSKVETLRAAIKYIKHLQSVL 59

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 585707874 524 RRKANARERIRVNKLNSAFDLLRSVLPkdllmKTEHTGkrvfKMSKVETLRCAISYMHKLEMIL 587
Cdd:cd19715    9 RLAANARERRRMNSLNVAFDKLRDVVP-----SLGDDR----KLSKYETLQMAQSYITALKELL 63

basic helix-loop-helix (bHLH) domain found in achaete-scute-like protein 4 (ASCL-4) and similar proteins; ASCL-4, also termed Class A basic helix-loop-helix protein 44 (bHLHa44), or achaete-scute homolog 4 (ASH-4), or Hash4, is a bHLH transcriptional regulator that may be involved in skin development.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 585707874 525 RKANARERIRVNKLNSAFDLLRSVLPKDLLMKtehtgkrvfKMSKVETLRCAISYMHKLEMIL 587
Cdd:cd19746   10 RKRNERERQRVRCVNEGYARLREHLPQELADK---------RLSKVETLRAAIDYIKHLQELL 63

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 585707874 502 KETHRMPSNKGSSPETDSKEFVRR-KANARERIRVNKLNSAFDLLRSVLPkdLLMKTEhtgkrvfKMSKVETLRCAISYM 580
Cdd:cd19719    6 KPKRRGPKKKKMTKARLERFKMRRmKANARERNRMHGLNAALDNLRKVVP--CYSKTQ-------KLSKIETLRLAKNYI 76

                 ....*...
gi 585707874 581 HKLEMILR 588
Cdd:cd19719   77 WALSEILR 84

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        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 585707874 531 ERIRVNKLNSAFDLLRSVLPkdllmktEHTGKRvfKMSKVETLRCAISYMHKLE 584
Cdd:cd00083    1 ERRRRDKINDAFEELKRLLP-------ELPDSK--KLSKASILQKAVEYIRELQ 45

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 585707874 524 RRKANARERIRVNKLNSAFDLLRSVLPKdllMKTEHtgkrvfKMSKVETLRCAISYMHKLEMIL 587
Cdd:cd19711    2 RLESNERERQRMHKLNNAFQALREVIPH---VRAEK------KLSKIETLTLAKNYIKSLTTTI 56

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 585707874 524 RRKANARERIRVNKLNSAFDLLRSVLPKDLLMKTEhtgkrvfKMSKVETLRCAISYMHKLEMIL 587
Cdd:cd11425    2 RQLANERERLRMRTLADALGELRQHLPPSVAPKGK-------RLSKIQTLKYAIRYIGYLGNVL 58

basic helix-loop-helix (bHLH) domain found in helix-loop-helix protein (HEN) family; The HEN family includes two neuron-specific bHLH transcription factors, HEN-1 (also known as Nhlh1 or bHLHa35 or NSCL-1) and HEN-2 (also known as Nhlh2 or bHLHa34 or NSCL-2). They may serve as DNA-binding protein that is involved in the control of cell-type determination, possibly within the developing nervous system.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 585707874 525 RKANA-RERIRVNKLNSAFDLLRSVLPKDLLMKtehtgkrvfKMSKVETLRCAISYMHKLEMIL 587
Cdd:cd11414    3 RNAHAtRERIRVEAFNSAFAQLRKLLPTLPPDK---------KLSKIEILRLAICYISYLNHVL 57

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 585707874 524 RRKANARERIRVNKLNSAFDLLRSVLPKdllmkteHTGKRVFKMSKVETLRCAISYMHKLEMILR 588
Cdd:cd11429    1 RLKINSRERKRMHDLNSALDGLRSVMPY-------AQGPSVRKLSKIATLLLARNYILMLTQALE 58

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 585707874 524 RRKANARERIRVNKLNSAFDLLRSVLPKDLlmktehTGKRvfkMSKVETLRCAISYMHKLEMIL 587
Cdd:cd18912    9 RVAANVRERKRILDYNQAFNALRLALKHDL------GGKR---LSKIATLRRAINRISALSLFL 63

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 585707874 524 RRkaNARERIRVNKLNSAFDLLRSVLPKDllmkteHTGKrvfKMSKVETLRCAISYMHKLEMIL 587
Cdd:cd19743    6 RR--NERERNRVKLVNLGFAALRQHVPQG------GASK---KMSKVETLRSAVEYIRALQRLL 58

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 585707874 525 RKANARERIRVNKLNSAFDLLRSVLPKDLLMKtehtgkrvfKMSKVETLRCAISYMHKLEMIL 587
Cdd:cd19747    8 QKRNERERQRVKCVNEGYARLRDHLPGAMAEK---------RLSKVETLRAAIRYIKYLQDLL 61

basic helix-loop-helix (bHLH) domain found in oligodendrocyte transcription factors, Oligo2, Oligo3 and similar proteins; The family includes two bHLH transcription factors, Oligo2 and Oligo3. 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 585707874 523 VRRKANARERIRVNKLNSAFDLLRSVLPKDllmktehTGKRVFKMSKVETLRCAISYM 580
Cdd:cd19725    1 LRLKINSRERKRMHDLNSALDGLREVMPYA-------HGPSVRKLSKIATLLLARNYI 51

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 585707874 528 NARERIRVNKLNSAFDLLRSVLPKdllmkteHTGKRvfKMSKVETLRCAISYMHKLEMILRK 589
Cdd:cd11413    6 NTRERWRQQNVNGAFAELRKLIPT-------HPPDK--KLSKNEILRLAMKYIKFLEKILED 58

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 585707874 524 RRKANARERIRVNKLNSAFDLLRSVLPKdllMKTEhtgkrvfKMSKVETLRCAISYMHKLEMILR 588
Cdd:cd11464    2 RVLANVRERQRTQSLNEAFTSLRKIIPT---LPSD-------KLSKIQTLKLAARYIDFLYQVLR 56

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
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 585707874 523 VRRKANARERIRVNKLNSAFDLLRSVLPkdllmkTEHTgKRVFKMSKVETLRCAISYM 580
Cdd:cd18954    1 VRLNINARERRRMHDLNDALDELRAVIP------YAHS-PSVRKLSKIATLLLAKNYI 51

basic helix-loop-helix (bHLH) domain found in myogenic regulatory factor (MRF) family; MRFs are a family of muscle-specific bHLH transcription proteins (MyoD, Myf5, Mrf4 and MyoG) that plays an essential role in regulating skeletal muscle development and growth. MRFs are capable of binding to E-box motifs as a heterodimer with E-proteins to regulate transcription expression.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 585707874 524 RRKANARERIRVNKLNSAFDLLRSVlpkdllmKTEHTGKRvfkMSKVETLRCAISYMHKLEMIL 587
Cdd:cd11411    3 RKAATMRERRRLKKVNEAFEALKRC-------TSANPNQR---LPKVEILRNAIEYIESLQDLL 56

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        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 585707874 524 RRKANARERIRVNKLNSAFDLLRSVL---PKDLlmktehtgkrvfKMSKVETLRCAISYMHKLEMIL 587
Cdd:cd11423    2 RNAANARERARMRVLSKAFSRLKTTLpwvPPDT------------KLSKLDTLRLAASYIAHLRQIL 56

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 585707874 528 NARERIRVNKLNSAFDLLRSVLPkdllmkTEHTGKrvfKMSKVETLRCAISYMHKLEMILR 588
Cdd:cd19708    6 NSRERWRQQNVNGAFAELRKLVP------THPPDK---KLSKNEILRLAIKYIRLLSNVLE 57

basic helix-loop-helix (bHLH) domain found in muscle-specific regulatory factor 4 (MRF4) and similar proteins; MRF4, also termed Class C basic helix-loop-helix protein 4 (bHLHc4), or myogenic factor 6 (Myf-6), is a bHLH transcription factor associated with myogenesis. It plays a role in skeletal muscle differentiation.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 585707874 524 RRKANARERIRVNKLNSAFDLLRSvlpkdllmKTEHTGKRvfKMSKVETLRCAISYMHKLEMILRK 589
Cdd:cd18934    3 RKAATLRERRRLKKINEAFEALKR--------RTVPNPNQ--RLPKVEILRSAINYIEKLQDLLHS 58

basic helix-loop-helix (bHLH) domain found in myoblast determination protein 1 (MYOD1) and similar proteins; MYOD1, also termed Class C basic helix-loop-helix protein 1 (bHLHc1), or myogenic factor 3 (Myf-3), is a bHLH transcriptional activator that promotes transcription of muscle-specific target genes and plays a role in muscle differentiation. Together with Myf-5 and MYOG, MYOD1 co-occupies muscle-specific gene promoter core region during myogenesis.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 585707874 524 RRKANARERIRVNKLNSAFDLLR---SVLPKDllmktehtgkrvfKMSKVETLRCAISYMHKLEMILR 588
Cdd:cd18936    7 RKAATMRERRRLSKVNEAFETLKrctSTNPNQ-------------RLPKVEILRNAIRYIESLQALLR 61

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 585707874 524 RRKANARERIRVNKLNSAFDLLRSVLPkDLLMKTehtgkrvfKMSKVETLRCAISYMHKLEMIL 587
Cdd:cd11466    2 RGSANKKERRRTQSINSAFADLRECIP-NVPADT--------KLSKIKTLRLATSYIAYLMDVL 56

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        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 585707874 520 KEFVRRKANARERIRVNKLNSAFDLLRSVL---PKDLlmktehtgkrvfKMSKVETLRCAISYMHKLEMILRK 589
Cdd:cd19703    1 KQSQRNAANARERARMRVLSKAFSRLKTSLpwvPPDT------------KLSKLDTLRLASSYIAHLRQLLQE 61

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in transcription factor AP-4 (TFAP4) and similar proteins; TFAP4, also termed activating enhancer-binding protein 4, or Class C basic helix-loop-helix protein 41 (bHLHc41), is a bHLHzip transcription factor that activates both viral and cellular genes involved in the regulation of cellular proliferation, stemness, and epithelial-mesenchymal transition by binding to the symmetrical DNA sequence 5'-CAGCTG-3'.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 585707874 523 VRRK-ANARERIRVNKLNSAFDLLRSVLPKdllmkteHTGKrvfKMSKVETLRCAISYMHKLEM 585
Cdd:cd11419    3 IRREiANSNERRRMQSINAGFQSLRTLLPH-------CDGE---KLSKAAILQQTAEYIFSLEQ 56

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        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 585707874 531 ERIRVNKLNSAFDLLRSVLPKdllmktehtgkrVFKMSKVETLRCAISYMHKL 583
Cdd:cd11443    7 ERRRRKKLNDRLYMLRSVVPK------------ITKMDRASILGDAIDYVKEL 47

basic helix-loop-helix (bHLH) domain found in helix-loop-helix protein 2 (HEN-2) and similar proteins; HEN-2, also termed nescient helix-loop-helix 2 (Nhlh2), or Class A basic helix-loop-helix protein 34 (bHLHa34), or nescient helix loop helix 2 (NSCL-2), 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 585707874 524 RRKANA--------RERIRVNKLNSAFDLLRSVLPkdllmktehTGKRVFKMSKVETLRCAISYMHKLEMIL 587
Cdd:cd19702    9 RRRATAkyrsahatRERIRVEAFNLAFAELRKLLP---------TLPPDKKLSKIEILRLAICYISYLNHVL 71

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 585707874 513 SSPETDSkefVRRKANARERIRVNKLNSAFDLLRSVLPKdllmkteHTGKRVFKMSKVETLRCAISYM 580
Cdd:cd18940    8 SEPELQQ---LRLKINSRERKRMHDLNIAMDGLREVMPY-------AHGPSVRKLSKIATLLLARNYI 65

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 585707874 524 RRKANARERIRVNKLNSAFDLLRSVLPKDLLMKTEhtgkrvfKMSKVETLRCAISYMHKLEMILR 588
Cdd:cd18938    2 RQSASEREKLRMRDLAKALHNLRRYLPPSVAPAGQ-------SLTKIETLRLTIRYISHLSAQLG 59

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 585707874 524 RRKANARERIRVNKLNSAFDLLRSVLPKdlLMKTEhtgkrvfKMSKVETLRCAISYMHKLE 584
Cdd:cd11456    6 RRNHNILERQRRNDLRSSFLTLRDHVPE--LVKNE-------KAAKVVILKKATEYVHSLQ 57