helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 209915594   552 NARERVRVRDINEAFRELGRMCQMHLKSDKaQTKLLILQQAVQVILGLEQQVRE 605
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPKNKK-LSKAEILRLAIEYIKSLQEELQK 53

basic helix-loop-helix (bHLH) domain found in transcription factor 4 (TCF-4) and similar proteins; TCF-4, also termed E2-2, or Class B basic helix-loop-helix protein 19 (bHLHb19), or immunoglobulin transcription factor 2 (ITF-2), or SL3-3 enhancer factor 2 (SEF-2), is a bHLH transcription factor that binds to the immunoglobulin enhancer Mu-E5/KE5-motif. It is involved in the initiation of neuronal differentiation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209915594 543 RDRERRMANNARERVRVRDINEAFRELGRMCQMHLKSDKAQTKLLILQQAVQVILGLEQQVRERNLNPKAACLKRREEEK 622
Cdd:cd18945    4 REKERRMANNARERLRVRDINEAFKELGRMVQLHLKSDKPQTKLLILHQAVAVILSLEQQVRERNLNPKAACLKRREEEK 83

                 ..
gi 209915594 623 VS 624
Cdd:cd18945   84 VS 85

basic helix-loop-helix (bHLH) domain found in transcription factor E2-alpha (E2A) and similar proteins; E2A, also termed Class B basic helix-loop-helix protein 21 (bHLHb21), or immunoglobulin enhancer-binding factor E12/E47, or immunoglobulin transcription factor 1, or Kappa-E2-binding factor, or transcription factor 3 (TCF-3), or transcription factor ITF-1, is a bHLH transcriptional regulator involved in the initiation of neuronal differentiation.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 209915594 546 ERRMANNARERVRVRDINEAFRELGRMCQMHLKSDKAQTKLLILQQAVQVILGLEQQVRERNLNPKAACLKRRE 619
Cdd:cd18944    1 ERRVANNARERLRVRDINEAFKELGRMCQLHLNSEKPQTKLLILHQAVSVILNLEQQVRERNLNPKAACLKRRE 74

basic helix-loop-helix (bHLH) domain found in E proteins family; The E proteins family corresponds to class I bHLH proteins, which are widely expressed within the immune system and on which the majority of this chapter will be focused. Members in this family include E2A (also referred to as TCF-3), E47, TCF-12 (also referred to as HEB), and TCF-4 (also referred to as E2-2) in vertebrates, as well as the E protein ortholog, Daughterless (Da), from Drosophila melanogaster. E-proteins are expressed broadly and in certain complexes they are restricted to specific cell types. E-proteins homodimerize and heterodimerize with the tissue specific bHLH factors to bind DNA and regulate transcription and differentiation of cells during development. The activity of the E-proteins is regulated by two main mechanisms: first, the relative concentrations of E-proteins, tissue specific bHLH factors, and the Id proteins, and second, covalent modification.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 209915594 555 ERVRVRDINEAFRELGRMCQMHLKSDKAQTKLLILQQAVQVILGLEQ 601
Cdd:cd11420    1 ERIRVRDINEAFKELGRMCQLHLKSDKPQTKLLILHQAVSVITSLEQ 47

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 209915594  547 RRMANNARERVRVRDINEAFRELGRMCQmHLKSDKAQTKLLILQQAVQVILGLE 600
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELLP-TLPPDKKLSKAEILRLAIEYIKHLQ 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
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 209915594 547 RRMANNARERVRVRDINEAFRELgRMC--QMHLKSDKAQ-TKLLILQQAVQVILGLEQ 601
Cdd:cd11431    1 RRKTANARERDRMREINDAFEAL-RRAvpEYPVAGKDGKlTKITTLRLAMNYIKALTD 57

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 209915594 555 ERVRVRDINEAFRELGRMCQMHLKSDKaQTKLLILQQAVQVILGLEQ 601
Cdd:cd00083    1 ERRRRDKINDAFEELKRLLPELPDSKK-LSKASILQKAVEYIRELQS 46

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 209915594 544 DRERRmanNARERVRVRDINEAFRELgRMCQMHLKSDKAQTKLLILQQAVQVILGLEQQ 602
Cdd:cd11418    1 RVARR---NERERRRVQAVNDAFDRL-RQHVPYLKRRKKLSKVKTLRRAIEYIRHLQKL 55

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
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 209915594 545 RERRMANNARERVRVRDINEAFRELGRMCQmHLKSDKAQTKLLILQQAVQVILGL 599
Cdd:cd19714    6 ARRRLAANARERRRMQGLNTAFDRLRKVVP-QWGQDKKLSKYETLQMALSYIMAL 59

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 209915594 547 RRMANNARERVRVRDINEAFRELGRMCQmHLKSDKAQTKLLILQQAVQVILGL 599
Cdd:cd11426    1 RRLESNERERLRMHQLNDAFQALREVIP-HVRSERKLSKIETLTLAKNYIKSL 52

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 209915594 546 ERRMANNaRERVRVRDINEAFRELgRMCQMHLKSDKAQTKLLILQQAVQVI 596
Cdd:cd19686    1 QRQAANI-RERKRMRSINDAFDGL-RRHIPTFPYEKRLSKVDTLRLAIQYI 49

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 209915594 547 RRMANNARERVRVRDINEAFRELGRMCQMHlKSDKAQTKLLILQQAVQVILGLEQQVR 604
Cdd:cd19708    1 RRMFTNSRERWRQQNVNGAFAELRKLVPTH-PPDKKLSKNEILRLAIKYIRLLSNVLE 57

RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The SMC (structural maintenance of chromosomes) superfamily proteins have ATP-binding domains at the N- and C-termini, and two extended coiled-coil domains separated by a hinge in the middle. The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics. This family also includes the RecF and RecN proteins that are involved in DNA metabolism and recombination.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209915594   495 SEIKREEKEDEENTSAADHSEEEKKELKAPRA-RTSSTDEVLSLEEKDLRDRERRMANNARERVRvrdINEAFRELgrmc 573
Cdd:pfam02463  321 KEKKKAEKELKKEKEEIEELEKELKELEIKREaEEEEEEELEKLQEKLEQLEEELLAKKKLESER---LSSAAKLK---- 393

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 209915594   574 qmhlksDKAQTKLLILQQAVQVILGLEQQVRERNLNPKAACLKRREEEK 622
Cdd:pfam02463  394 ------EEELELKSEEEKEAQLLLELARQLEDLLKEEKKEELEILEEEE 436

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 209915594 535 LSLEEKDLRDR---ERRMANNARERVRVRDINEAFRELGRMCQMhLKSDKAQTKLLILQQAVQVI 596
Cdd:cd19701    1 LSREERRRRRRataKYRTAHATRERIRVEAFNVAFAELRKLLPT-LPPDKKLSKIEILRLAICYI 64

basic helix-loop-helix (bHLH) domain found in myogenic factor 5 (Myf-5) and similar proteins; Myf-5, also termed Class C basic helix-loop-helix protein 2 (bHLHc2), is a nuclear bHLH transcriptional activator that promotes transcription of muscle-specific target genes and plays a role in muscle specification and differentiation. It also acts as an RNA-binding protein which enhances Ccnd1/Cyclin D1 mRNA translation during myogenesis.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 209915594 546 ERRMANNARERVRVRDINEAFRELGRMCQMHlkSDKAQTKLLILQQAVQVILGLEQQVRER 606
Cdd:cd18937    1 DRRKAATMRERRRLKKVNQAFETLKRCTTSN--PNQRLPKVEILRNAIRYIESLQDLLREQ 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
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 209915594 545 RERRMANNARERVRVRDINEAFRELgRMCQMHLKSDKAQTKLLILQQAVQVILGL 599
Cdd:cd19715    6 KKRRLAANARERRRMNSLNVAFDKL-RDVVPSLGDDRKLSKYETLQMAQSYITAL 59

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 209915594 547 RRMANNARERVRVRDINEAFRELGRMCQMHlKSDKAQTKLLILQQAVQVI 596
Cdd:cd19707    2 RKIFTNTRERWRQQNVNSAFAELRKLIPTH-PPDKKLSKNEILRLAMKYI 50

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 209915594 547 RRMANNARERVRVRDINEAFRELGRMCQMHlKSDKAQTKLLILQQAVQVI 596
Cdd:cd19706    4 RRIFTNSRERWRQQNVNGAFAELRKLIPTH-PPDKKLSKNEILRLAMKYI 52

basic helix-loop-helix (bHLH) domain found in Drosophila melanogaster achaete-scute complex (AS-C) proteins, achaete-scute-like proteins, ASCL1-2, and similar proteins; This subfamily includes Drosophila melanogaster AS-C proteins and two ASCL family of transcription factors, ASCL-1 and ASCL-2. Drosophila melanogaster AS-C proteins includes lethal of scute (also known as achaete-scute complex protein T3 or AST3), scute (also known as achaete-scute complex protein T4 or AST4), achaete (also known as achaete-scute complex protein T5 or AST5), and asense (also known as achaete-scute complex protein T8 or AST8). They are involved in the determination of the neuronal precursors in the peripheral nervous system and the central nervous system, as well as in sex determination and dosage compensation. ASCL-1, also termed Class A basic helix-loop-helix protein 46 (bHLHa46), or achaete-scute homolog 1 (ASH-1), or mammalian achaete scute homolog 1 (Mash1), is expressed in subsets of neural progenitors in both the central and peripheral nervous system. It plays a key role in neuronal differentiation and specification in the nervous system. ASCL-2, also termed achaete-scute homolog 2 (ASH-2), or Class A basic helix-loop-helix protein 45 (bHLHa45), or mammalian achaete scute homolog 2 (Mash2), is involved in Schwann cell differentiation and control of proliferation in adult peripheral nerves.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 209915594 552 NARERVRVRDINEAFRELgRMCQMHLKSDKAQTKLLILQQAVQVILGLEQ 601
Cdd:cd19723    6 NERERNRVKLVNLGFATL-REHVPNGRANKKMSKVETLRSAVEYIRQLQQ 54

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 209915594 551 NNARERVRvRD-INEAFRELGRM---CQMHLKsDKAQTKLLILQQAVQVILGLEQQVRE 605
Cdd:cd11387    2 HNAVERRR-RDnINEKIQELGSLvppSRLETK-DLKPNKGSILSKAVEYIRELQNQNQE 58