Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74654630   427 KRSAHNMIEKRYRSNLNDKIAELRDAVPTLrsgynsttadelkgtyvPLSRKLNKATILSKATEYIKSLQ 496
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELLPTL-----------------PPDKKLSKAEILRLAIEYIKHLQ 53

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in sterol regulatory element-binding protein (SREBP) family and similar proteins; The SREBP family includes SREBP1 and SREBP2, which are bHLHzip transcriptional activator of genes encoding proteins essential for cholesterol biosynthesis/uptake and fatty acid biosynthesis. SREBP1 and SREBP2 are principally found in the liver and in adipocytes and made up of an N-terminal transcription factor portion (composed of an activation domain, a bHLHzip domain, and a nuclear localization signal), a hydrophobic region containing two membrane spanning regions, and a C-terminal regulatory segment. They recognize a symmetric sterol regulatory element (TCACNCCAC) instead of E-box. The family also includes Saccharomyces cerevisiae transcription factor HMS1 (also termed high-copy MEP suppressor protein 1) and serine-rich protein TYE7. HMS1 is a putative bHLHzip transcription factor involved in exit from mitosis and pseudohyphal differentiation. TYE7, also termed basic-helix-loop-helix protein SGC1, is a putative bHLHzip transcription activator required for Ty1-mediated glycolytic gene expression. TYE7 N-terminal is extremely rich in serine residues. It binds DNA on E-box motifs, 5'-CANNTG-3'. TYE7 is not essential for growth.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74654630 426 SKRSAHNMIEKRYRSNLNDKIAELRDAVPTLRSGYNSTTADELKGtyVPLSRKLNKATILSKATEYIKSLQSKNKKLIEE 505
Cdd:cd11395   2 RKRLPHNAIEKRYRSNLNTKIERLRDAIPSLRSPEGKSDDGGLGG--LAPTTKLSKATILTKAIEYIRHLEQENERLEEE 79

                ....*...
gi 74654630 506 NKILQKRL 513
Cdd:cd11395  80 NEELRQQV 87

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in sterol regulatory element-binding protein 1 (SREBP1) and similar proteins; SREBP1, also termed Class D basic helix-loop-helix protein 1 (bHLHd1), or sterol regulatory element-binding transcription factor 1 (SREBF1), is a member of a family of bHLHzip transcription factors that recognize sterol regulatory element 1 (SRE-1). It acts as a transcriptional activator required for lipid homeostasis. It may control transcription of the low-density lipoprotein receptor gene as well as the fatty acid. SREBP1 has dual sequence specificity binding to both an E-box motif (5'-ATCACGTGA-3') and to SRE-1 (5'-ATCACCCCAC-3').

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74654630 427 KRSAHNMIEKRYRSNLNDKIAELRDAVptlrsgynsttadelkgtyVPLSRKLNKATILSKATEYIKSLQSKNKKLIEEN 506
Cdd:cd18921   6 KRTAHNAIEKRYRSSINDKIIELKDLV-------------------VGTEAKLNKSAVLRKAIDYIRFLQQSNQKLKQEN 66

                ....
gi 74654630 507 KILQ 510
Cdd:cd18921  67 MALK 70

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74654630   427 KRSAHNMIEKRYRSNLNDKIAELRDAVPTLrsgynsttadelkgtyvPLSRKLNKATILSKATEYIKSLQ 496
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELLPTL-----------------PPDKKLSKAEILRLAIEYIKHLQ 53

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in the Myc family; The Myc family is a member of the bHLHzip family of transcription factors that play important roles in the control of normal cell proliferation, growth, survival and differentiation. All Myc isoforms contain two independently functioning polypeptide chain regions: N-terminal transactivating residues and a C-terminal bHLHzip segment. The bHLHzip family of bHLH transcription factors are characterized by a highly conserved N-terminal basic region that may bind DNA at a consensus hexanucleotide sequence known as the E-box (CANNTG) followed by HLH and leucine zipper motifs that may interact with other proteins to form homo- and heterodimers. Myc heterodimerizes with Max enabling specific binding to E-box DNA sequences in the promoters of target genes. The Myc proto-oncoprotein family includes at least five different functional members: c-, N-, L-, S- and B-Myc (which is lacking the bHLH domain).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74654630 427 KRSAHNMIEKRYRSNLNDKIAELRDAVPTLRSgyNSTTAdelkgtyvplsrklnKATILSKATEYIKSLQSKNKKLIEEN 506
Cdd:cd11400   1 KRRLHNVLERQRRNDLKNSFEKLRDLVPELAD--NEKAS---------------KVVILKKATEYIKQLQQEEKKLEKEK 63

                ....*.
gi 74654630 507 KILQKR 512
Cdd:cd11400  64 DKLKAR 69

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Saccharomyces cerevisiae centromere-binding protein 1 (CBP-1) and similar proteins; CBP-1, also termed centromere promoter factor 1 (CPF1), or centromere-binding factor 1 (CBF1), is a bHLHzip protein that is required for chromosome stability and methionine prototrophy. It binds as a homodimer to the centromere DNA elements I (CDEI, GTCACATG) region of the centromere that is required for optimal centromere function.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74654630 427 KRSAHNMIEKRYRSNLNDKIAELRDAVPTLrsgynsttadelkgtyvplSRKLNKATILSKATEYIKSLQSKNKKLIEEN 506
Cdd:cd11398   7 RRDNHKEVERRRRENINEGINELAALVPGN-------------------AREKNKGAILARAVEYIQELQETEAKNIEKW 67

                        90       100
                ....*....|....*....|
gi 74654630 507 KiLQKRLSEYTSVIQASLTA 526
Cdd:cd11398  68 T-LEKLLTDQAIAELAALNE 86

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in the microphthalmia-associated transcription factor family (MITF) family; The MITF (also known as microphthalmia-TFE, or MiT) family is a small family that contain a basic helix loop helix domain associated with a leucine zipper (bHLHZip). The MITF family 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 family can form homodimers or heterodimers with each other but not with other bHLH or bHLHzip proteins.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74654630 427 KRSAHNMIEKRYRSNLNDKIAELrdavptlrsgynsttadelkGTYVPLSR----KLNKATILSKATEYIKSLQSKNKKL 502
Cdd:cd11397   5 KKDNHNMIERRRRFNINDRIKEL--------------------GTLLPKSNdpdmRWNKGTILKASVDYIRKLQKEQERL 64

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in c-Myc and similar proteins; c-Myc, also termed Myc proto-oncogene protein, or Class E basic helix-loop-helix protein 39 (bHLHe39), or transcription factor p64, a bHLHZip proto-oncogene protein that functions as a transcription factor, which binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. It activates the transcription of growth-related genes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74654630 427 KRSAHNMIEKRYRSNLNDKIAELRDAVPTLRSgynsttadelkgtyvplSRKLNKATILSKATEYIKSLQSKNKKLIEEN 506
Cdd:cd11458   5 KRRTHNVLERQRRNELKLSFFALRDQIPEVAN-----------------NEKAPKVVILKKATEYILSMQADEQRLISEK 67

                ....*.
gi 74654630 507 KILQKR 512
Cdd:cd11458  68 EQLRRR 73

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74654630 427 KRSAHNMIEKRYRSNLNDKIAELRDAVPTLRSgynsttadelkgtyvplSRKLNKATILSKATEYIKSLQSKNKKLIEEN 506
Cdd:cd11456   5 RRRNHNILERQRRNDLRSSFLTLRDHVPELVK-----------------NEKAAKVVILKKATEYVHSLQAEEQKLLLEK 67

                ....*.
gi 74654630 507 KILQKR 512
Cdd:cd11456  68 EKLQAR 73

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-like protein X (Mlx) and similar proteins; Mlx, also termed Class D basic helix-loop-helix protein 13 (bHLHd13), or Max-like bHLHZip protein, or protein BigMax, or transcription factor-like protein 4, is a Max-like bHLHZip transcription regulator that interacts with the Max network of transcription factors. It forms a sequence-specific DNA-binding protein complex with some member of Mad family (Mad1 and Mad4) and Mondo family but not the Myc family and bind the E-box DNA to control transcription.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74654630 427 KRSAHNMIEKRYRSNLNDKIAELRDAVPTLRSgyNSTTAdelkgtyvplSRKLNKATILSKATEYIKSLQSKNKKLIEEN 506
Cdd:cd19687   2 RREAHTQAEQKRRDAIKKGYDDLQDIVPTCQQ--QDDIG----------SQKLSKATILQRSIDYIQFLHQQKKKQEEEL 69

                ....*
gi 74654630 507 KILQK 511
Cdd:cd19687  70 SALRK 74

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 74654630 427 KRSAHNMIEKRYRSNLNDKIAELrdavptlrsgynsttadelkGTYVPLSRKL----NKATILSKATEYIKSLQSKNKK 501
Cdd:cd18927  11 KKDNHNLIERRRRFNINDRIKEL--------------------GTLIPKTNDLdvrwNKGTILKASVDYIKRMQKDLQR 69

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in aryl hydrocarbon receptor nuclear translocator (ARNT) family; The ARNT family of bHLH-PAS transcription regulators includes ARNT, ARNT-like proteins (ARNTL and ARNTL2), and Drosophila melanogaster protein cycle. They act as the heterodimeric partner for bHLH-PAS proteins such as aryl hydrocarbon receptor (AhR), hypoxia-inducible factor (HIF), and single-minded (SIM). These bHLH-PAS transcription complexes are involved in transcriptional responses to xenobiotic, hypoxia, and developmental pathways. Heterodimerization of bHLH-PAS proteins with ARNT is mediated by contacts between both the bHLH and the tandem PAS domains. ARNT use bHLH and/or PAS domains to interact with several transcriptional coactivators. It is required for activity of the aryl hydrocarbon (dioxin) receptor. ARNTL, also termed Basic-helix-loop-helix-PAS protein MOP3, or brain and muscle ARNT-like 1 (BMAL1), or Class E basic helix-loop-helix protein 5 (bHLHe5), or member of PAS protein 3, or PAS domain-containing protein 3 (PASD3), or bHLH-PAS protein JAP3, is a member of the bHLH-PAS transcription factor family that forms heterodimers with another bHLH-PAS protein, CLOCK (circadian locomotor output cycle kaput), which regulates circadian rhythm. ARNTL-CLOCK heterodimer complex activates transcription from E-box (CANNTG) elements found in the promoter of circadian responsive genes. ARNTL is highly homologous to ARNT. ARNTL2, also termed Basic-helix-loop-helix-PAS protein MOP9, or brain and muscle ARNT-like 2 (BMAL2), or CYCLE-like factor (CLIF), or Class E basic helix-loop-helix protein 6 (bHLHe6), or member of PAS protein 9, or PAS domain-containing protein 9 (PASD9), is a neuronal bHLH-PAS transcriptional factor, regulating cell cycle progression and preventing cell death, whose sustained expression might ensure brain neuron survival. It also plays important roles in tumor angiogenesis. Protein cycle, also termed brain and muscle ARNT-like 1 (BMAL1), or MOP3, is a putative bHLH-PAS transcription factor involved in the generation of biological rhythms in Drosophila. It activates cycling transcription of Period (PER) and Timeless (TIM) by binding to the E-box (5'-CACGTG-3') present in their promoters.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 74654630 427 KRSAHNMIEKRYRSNLNDKIAELRDAVPTLRsgynsttadelkgtyvPLSRKLNKATILSKATEYIKSLQSKN 499
Cdd:cd11437   1 SRSNHSEIEKRRRDKMNAYIQELSALVPACN----------------AMSRKLDKLTVLRMAVQHLKSLRGTG 57

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana BES1-interacting Myc-like proteins (BIMs) and similar proteins; The family includes Arabidopsis thaliana BIM1 and its homologs (BIM2 and BIM3), which are bHLH transcription factors that interact with BES1 to regulate transcription of Brassinosteroid (BR)-induced gene. BR regulates many growth and developmental processes such as cell elongation, vascular development, senescence stress responses, and photomorphogenesis. BIM1 heterodimerize with BES1 and bind to E-box sequences present in many BR-induced promoters to regulated BR-induced genes.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 74654630 428 RSAHNMIEKRYRSNLNDKIAELRDAVPtlrsgyNSttadelkgtyvplSRKLNKATILSKATEYIKSLQSKNKKL 502
Cdd:cd11453   4 RSKHSATEQRRRSKINERLQALRDLIP------HS-------------DQKRDKASFLLEVIEYIQALQEKVAKL 59

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in microphthalmia-associated transcription factor (MITF) and similar proteins; MITF, also termed Class E basic helix-loop-helix protein 32 (bHLHe32), is a bHLHzip transcription factor that is involved in neural crest melanocytes development as well as the pigmented retinal epithelium. It regulates the expression of genes with essential roles in cell differentiation, proliferation and survival. It binds to M-boxes (5'-TCATGTG-3') and symmetrical DNA sequences (E-boxes) (5'-CACGTG-3') found in the promoters of target genes, such as BCL2 and tyrosinase (TYR).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74654630 427 KRSAHNMIEKRYRSNLNDKIAELrdavptlrsgynsttadelkGTYVPLSR----KLNKATILSKATEYIKSLQ------ 496
Cdd:cd18926  13 KKDNHNLIERRRRFNINDRIKEL--------------------GTLIPKSNdpdmRWNKGTILKASVDYIRKLQreqqra 72

                        90       100
                ....*....|....*....|...
gi 74654630 497 ----SKNKKLIEENKILQKRLSE 515
Cdd:cd18926  73 keleNRQKKLEHANRHLLLRIQE 95

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-binding protein Mnt and similar proteins; Mnt, also termed Class D basic helix-loop-helix protein 3 (bHLHd3), or Myc antagonist MNT, or protein ROX, is a bHLHZip transcriptional repressor that binds DNA as a heterodimer with MAX. It binds to the canonical E box sequence 5'-CACGTG-3' and, with higher affinity, to 5'-CACGCG-3'. Mnt has an important role as an antagonist and regulator of Myc activities and it is a potential tumor suppressor. Mnt is ubiquitously expressed. Mnt-deficient mice shown to exhibit early postnatal lethality.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74654630 428 RSAHNMIEKRYRSNLNDKIAELRDAVPTLRsgynsttadelkgtyvplSRKLNKATILSKATEYIKSLQSKNK------- 500
Cdd:cd11402   3 REVHNKLEKNRRAHLKECFETLKRQIPNLD------------------DKKTSNLNILRSALRYIQILKRKEKeyeheme 64

                        90
                ....*....|...
gi 74654630 501 KLIEENKILQKRL 513
Cdd:cd11402  65 RLAREKIALQQRL 77

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-like protein X (Mlx) family; Mlx, also termed Class D basic helix-loop-helix protein 13 (bHLHd13), or Max-like bHLHZip protein, or protein BigMax, or transcription factor-like protein 4, is a Max-like bHLHZip transcription regulator that interacts with the Max network of transcription factors. It forms a sequence-specific DNA-binding protein complex with some member of Mad family (Mad1 and Mad4) and Mondo family but not the Myc family and bind the E-box DNA to control transcription. The family also includes Saccharomyces cerevisiae INO4, which is a bHLH transcriptional activator of phospholipid synthetic genes (such as INO1, CHO1/PSS, CHO2/PEM1, OPI3/PEM2, etc.). It is required for de-repression of phospholipid biosynthetic gene expression in response to inositol deprivation in yeast.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74654630 427 KRSAHNMIEKRYRSNLNDKIAELRDAVPTLRsgynsttadelkgtyvplSRKLNKATILSKATEYIkslqsknKKLIEEN 506
Cdd:cd11404   2 RRLNHVRSEKKRRELIKKGYDELCALVPGLD------------------PQKRTKADILQKAADWI-------QELKEEN 56

                        90
                ....*....|.
gi 74654630 507 KILQKRLSEYT 517
Cdd:cd11404  57 EKLEEQLDELK 67

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        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 74654630 433 MIEKRYRSNLNDKIAELRDAVPTLRsgynsttadelkgtyvplsrKLNKATILSKATEYIKSLQSKNKKLIEE 505
Cdd:cd11443   5 MAERRRRKKLNDRLYMLRSVVPKIT--------------------KMDRASILGDAIDYVKELLQEINELQDE 57

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 74654630 428 RSAHNMIEKRYRSNLNDKIAELRDAVPtlrsgynsttadelkgtYVPLSRKLNKATILSKATEYIKSLQ 496
Cdd:cd11390   1 RNAANARERRRMHDLNDAFEALRKVLP-----------------TVPPDKKLSKIETLRLAINYIAALS 52

basic helix-loop-helix-orange (bHLH-O) domain found in HERP/HES-like family; The HERP/HES-like family includes bHLH-O transcriptional regulators that are related to the Drosophila hairy and Enhancer-of-split (HES) proteins. The HERP (HES-related repressor protein) subfamily proteins contain a basic helix-loop-helix (bHLH) domain with an invariant glycine residue in its basic region, an orange domain in the central region and YXXW sequence motif at its C-terminal region. Hairy and enhancer of split (HES)-related repressor protein (HERP) proteins (HEY1, HEY2 and HEYL) act as downstream effectors of Notch signaling. They are involved in cardiovascular development and have roles in somitogenesis, myogenesis and gliogenesis. Hairy and enhancer of split-related protein HELT is a transcriptional repressor expressed in the developing central nervous system. It binds preferentially to the canonical E box sequence 5'-CACGCG-3' and regulates neuronal differentiation and/or identity. Differentially expressed in chondrocytes proteins, DEC1 and DEC2, are widely expressed in both embryonic and adult tissues and have been implicated in apoptosis, cell proliferation, and circadian rhythms, as well as malignancy in various cancers. Drosophila melanogaster protein clockwork orange (Cwo) is also included in this subfamily. It is involved in the regulation of Drosophila circadian rhythms. It functions as both an activator and a repressor of clock gene expression. The HES subfamily proteins contain a basic helix-loop-helix (bHLH) domain with an invariant proline residue in its basic region, an orange domain in the central region and a conserved tetrapeptide motif, WRPW, at its C-terminal region. They form heterodimers or homodimers via their HLH domain and bind DNA to repress gene transcription that play an essential role in development of both compartment and boundary cells of the central nervous system.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 74654630 434 IEKRYRSNLNDKIAELRDAVPTLRSgynsttadelkgtyVPLSRKLNKATILSKATEYIKSLQSKN 499
Cdd:cd19685   1 SEKRRRQRINDKLNQLKELLPPNLS--------------KQSRSKLSKAEILEMAITELRRLQQEV 52

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in upstream stimulatory factor 1 (USF1) and similar proteins; USF1, also termed Class B basic helix-loop-helix protein 11 (bHLHb11), or major late transcription factor 1, is a bHLHzip transcription factor that binds to a symmetrical DNA sequence (E-boxes) (5'-CACGTG-3') that is found in a variety of viral and cellular promoters. It is ubiquitously expressed and involved in the transcription activation of various functional genes implicated in lipid and glucose metabolism, stress response, immune response, cell cycle control and tumour suppression. USF-1 recruits chromatin remodeling enzymes and interact with co-activators and the members of the transcription pre-initiation complex. Genetic polymorphisms of USF1 are associated with some metabolic and cardiovascular diseases, like diabetes, atherosclerosis, coronary artery calcifications and familial combined hyperlipidaemia (FCHL).

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 74654630 427 KRSAHNMIEKRYRSNLNDKIAELRDAVPTlrSGYNSTTADELKGtyvplsrklnkaTILSKATEYIKSLQSKNKK 501
Cdd:cd18924   5 RRAQHNEVERRRRDKINNWIVQLSKIIPD--CSMESTKSGQSKG------------GILSKACDYIQELRQSNHR 65

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in aryl hydrocarbon receptor nuclear translocator (ARNT) and similar proteins; ARNT, also termed Class E basic helix-loop-helix protein 2 (bHLHe2), or Dioxin receptor, nuclear translocator, or hypoxia-inducible factor 1-beta (HIF1b), or HIF-1-beta, or HIF1-beta, is a member of bHLH-PAS transcription regulators that acts as the heterodimeric partner for bHLH-PAS proteins such as aryl hydrocarbon receptor (AhR), hypoxia-inducible factor (HIF), and single-minded (SIM). These bHLH-PAS transcription complexes are involved in transcriptional responses to xenobiotic, hypoxia, and developmental pathways. Heterodimerization of bHLH-PAS proteins with ARNT is mediated by contacts between both the bHLH and the tandem PAS domains. ARNT use bHLH and/or PAS domains to interact with several transcriptional coactivators. It is required for activity of the aryl hydrocarbon (dioxin) receptor.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74654630 427 KRSAHNMIEKRYRSNLNDKIAELRDAVPTLRSgynsttadelkgtyvpLSRKLNKATILSKATEYIKSLQ 496
Cdd:cd18947   5 ARENHSEIERRRRNKMTAYITELSDMVPTCSA----------------LARKPDKLTILRMAVSHMKSLR 58

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein ABA-INDUCIBLE bHLH-TYPE (AIB) and similar proteins; The family includes several bHLH transcription factors from Arabidopsis thaliana, such as AIB and MYC proteins (MYC2, MYC3 and MYC4). AIB, also termed AtbHLH17, or EN 35, is a transcription activator that regulates positively abscisic acid (ABA) response. MYC2, also termed protein jasmonate insensitive 1, or R-homologous Arabidopsis protein 1 (RAP-1), or AtbHLH6, or EN 38, or Z-box binding factor 1 protein, is a transcriptional activator involved in abscisic acid (ABA), jasmonic acid (JA), and light signaling pathways. MYC3, also termed protein altered tryptophan regulation 2, or AtbHLH5, or transcription factor ATR2, or EN 36, is a transcription factor involved in tryptophan, jasmonic acid (JA) and other stress-responsive gene regulation. MYC4, also termed AtbHLH4, or EN 37, is a transcription factor involved in jasmonic acid (JA) gene regulation. MYC2, together with MYC3 and MYC4, controls additively subsets of JA-dependent responses.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74654630 435 EKRYRSNLNDKIAELRDAVPTLRsgynsttadelkgtyvplsrKLNKATILSKATEYIKSLQSKNKKLIEENKILQKRLS 514
Cdd:cd11449  13 ERQRREKLNQRFYALRAVVPNVS--------------------KMDKASLLGDAISYINELKSKVQDMETEKKEMKRQES 72

                .
gi 74654630 515 E 515
Cdd:cd11449  73 E 73

basic Helix-Loop-Helix (bHLH) domain found in Arabidopsis thaliana MYC1 and similar proteins; MYC1, also termed AtbHLH12, or EN 58, acts as a transcription activator, when associated with MYB75/PAP1 or MYB90/PAP2.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74654630 431 HNMIEKRYRSNLNDKIAELRDAVPtlrsgyNSTTADelkgtyvplsrklnKATILSKATEYIKSLQSKnkklIEENKIL- 509
Cdd:cd18918   1 LFATERERREKLNEKFSDLRNLIP------NPTKND--------------RASILSDAIKYINELQRT----VEELKSLv 56

                ....
gi 74654630 510 -QKR 512
Cdd:cd18918  57 eKKR 60

basic helix-loop-helix-orange (bHLH-O) domain found in hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1) and similar proteins; HEY1, also termed cardiovascular helix-loop-helix factor 2 (CHF-2), or Class B basic helix-loop-helix protein 31 (bHLHb31), or HES-related repressor protein 1, or hairy and enhancer of split-related protein 1 (HESR-1), or hairy-related transcription factor 1 (HRT-1), is a bHLH-O transcriptional repressor that acts as an essential downstream effector of the Notch signaling pathway and may play a fundamental role in vascular development. HEY1 also participates several cancer-related pathways. It acts as a positive regulator of the tumor suppressor p53.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 74654630 425 LSKRSAHNMIEKRYRSNLNDKIAELRDAVPtlrsgynstTADELKGtyvplSRKLNKATILSKATEYIKSLQSK 498
Cdd:cd19748   7 LARKRRRGIIEKRRRDRINNSLSELRRLVP---------SAFEKQG-----SAKLEKAEILQMTVDHLKMLHAA 66

basic helix-loop-helix-orange (bHLH-O) domain found in hairy/enhancer-of-split related with YRPW motif protein 2 (HEY2) and similar proteins; HEY2, also termed cardiovascular helix-loop-helix factor 1 (CHF-1), or Class B basic helix-loop-helix protein 32 (bHLHb32), or HES-related repressor protein 2, or hairy and enhancer of split-related protein 2 (HESR-2), or hairy-related transcription factor 2 (HRT-2), or protein gridlock homolog, is a bHLH-O transcriptional repressor expressed preferentially in the developing and adult cardiovascular system. As a downstream effector of Notch signaling, HEY2 may be required for cardiovascular development. It also plays an important role in neurologic development, as well as in the progression of human cancers.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 74654630 425 LSKRSAHNMIEKRYRSNLNDKIAELRDAVPtlrsgynstTADELKGtyvplSRKLNKATILSKATEYIKSLQSKNKK 501
Cdd:cd18920   8 MARKKRRGIIEKRRRDRINNSLSELRRLVP---------TAFEKQG-----SAKLEKAEILQMTVDHLKMLQATGGK 70

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana Fe-deficiency induced transcription factor 1 (FIT) and similar proteins; The family includes bHLH transcription factors from Arabidopsis thaliana, such as FIT and DYT1. FIT, also termed FER-like iron deficiency-induced transcription factor, or FER-like regulator of iron uptake, or AtbHLH29, or EN 43, is a bHLH transcription factor that is required for the iron deficiency response in plant. It regulates FRO2 at the level of mRNA accumulation and IRT1 at the level of protein accumulation. DYT1, also termed AtbHLH22, or protein dysfunctional tapetum 1, or EN 49, is a bHLH transcription factor involved in the control of tapetum development. It is required for male fertility and pollen differentiation, especially during callose deposition.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74654630 426 SKRSAHNMIEKRYRSNLNDKIAELRDAVPtlrsgyNSTtadelkgtyvplsrKLNKATILSKATEYIKSLQSKNKKLIEE 505
Cdd:cd11450   2 SPASKNLVSERNRRQKLNQRLFALRSVVP------NIT--------------KMDKASIIKDAISYIQELQYQEKKLEAE 61

                        90
                ....*....|
gi 74654630 506 NKILQKRLSE 515
Cdd:cd11450  62 IRELESRPPS 71

basic helix-loop-helix (bHLH) domain found in Saccharomyces cerevisiae phosphate system positive regulatory protein PHO4 and similar proteins; PHO4 is a transcriptional activator that regulates the expression of repressible phosphatase under phosphate starvation conditions in Saccharomyces cerevisiae. The PHO4 protein has four functional domains with the bHLH domain at its carboxyl-terminal region. It regulates transcription by binding to promoter of the genes as a homodimer.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 74654630 426 SKRSAHNMIEKRYRSNLNDKIAELRDAVPTL----RSGYNSTTADELKGTYVPLSRKLNKATILSKATEYIKSLQ 496
Cdd:cd11392   1 SKRTAHKVAERGRRDRLNAALKELASLMPAEfvegKMGADGSASDSNDKEKAAASAAGSKAATVEMAIDYIKHLQ 75

basic helix-loop-helix (bHLH) domain found in the spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein (SOHLH) family and similar proteins; The SOHLH family includes two bHLH transcription factors, SOHLH1 and SOHLH2. They are specifically in spermatogonia and oocytes and essential for early spermatogonial and oocyte differentiation. The family also includes transcription factor-like 5 protein (TCFL5) and similar proteins. TCFL5, also termed Cha transcription factor, or HPV-16 E2-binding protein 1 (E2BP-1), is a bHLH transcription factor that plays a crucial role in spermatogenesis. It regulates cell proliferation or differentiation of cells through binding to a specific DNA sequence like other bHLH molecules.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 74654630 427 KRSAHNMIEKRYRSNLNDKIAELRDAVPTLrsgynsttadelkgtyvplSRKLNKATILSKATEYIKSLQSK 498
Cdd:cd19683   2 SRERHNAKERQRRERIKIACDQLRKLVPGC-------------------SRKTDKATVFEFTVAYIKFLREK 54

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein NAI1 and similar proteins; NAI1, also termed AtbHLH20, or EN 27, is a bHLH transcription activator that regulates the expression of at least NAI2, PYK10 and PBP1. It is required for and mediates the formation of endoplasmic reticulum bodies (ER bodies). It plays a role in the symbiotic interactions with the endophytes of the Sebacinaceae fungus family, such as Piriformospora indica and Sebacina.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 74654630 431 HNMIEKRYRSNLNDKIAELRDAVPTLRsgynsttadelkgtyvplsrKLNKATILSKATEYIKSLQSKNKKLIEENK 507
Cdd:cd11452   6 HILAERKRREKLSQRFIALSALVPGLK--------------------KMDKASVLGDAIKHIKQLQERVKELEEEKK 62

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain family; bHLH-PAS domain has been found in a large group of bHLH transcription regulators that are involved in gene expression responding to environmental change and controlling aspects of neural development, including proteins from aryl hydrocarbon receptor nuclear translocator (ARNT) family, hypoxia-inducible factor (HIF) family, aryl hydrocarbon receptor (AhR) family, neuronal PAS domain-containing protein (NPAS) family, Circadian locomotor output cycles protein kaput (CLOCK)-like family, and single-minded (SIM) family. bHLH-PAS transcriptional regulatory factors have a bHLH DNA-binding domain followed by two PAS domains and a C-terminal activation or repression domain. bHLH-PAS family members can be divided into class I and class II based on their dimerization partner. bHLH-PAS class I factors include AhR, HIF and SIM. The best characterized bHLH-PAS Class II protein is the ubiquitous ARNT. Some members of bHLH-PAS family act as transcriptional coactivators (such as NCoA) that lack the ability to dimerize and bind DNA.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 74654630 428 RSAHNMIEKRYRSNLNDKIAELRDAVPTLRSgynsttadelkgtyvpLSRKLNKATILSKATEYIKSLQ 496
Cdd:cd11391   1 REKSREAAKKRRDKENAEISELASLLPLPPA----------------VGSKLDKLSVLRLAVAYLRLKK 53