basic helix-loop-helix-orange (bHLH-O) domain found in hairy/enhancer-of-split related with YRPW motif-like protein (HEYL) and similar proteins; HEYL, also termed Class B basic helix-loop-helix protein 33 (bHLHb33), or hairy-related transcription factor 3 (HRT-3), is a bHLH-O transcriptional repressor that is strongly expressed in the presomitic mesoderm, the somites, the peripheral nervous system and smooth muscle of all arteries and is a downstream effector of the Notch and transforming growth factor-beta pathways. It promotes neuronal differentiation by activating proneural genes and inhibiting other hairy and enhancer of split (HES) and hairy/enhancer-of-split related with YRPW motif protein (HEY) proteins. HEYL also functions as a tumor suppressor involved in the progression of human cancers.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1519314394  36 PSSSQMQARKKHRGIIEKRRRDRINSSLSELRRLVPTAFEKQGSSKLEKAEVLQMTVDHLKMLHATGGTGFFDA 109
Cdd:cd11447     1 TTSSQIQARKKRRGIIEKRRRDRINSSLSELRRLVPTAFEKQGSSKLEKAEILQMTVDHLKMLHATGGAGKFDA 74

large tegument protein UL36; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1519314394  136 EGPSSRADPVRIRLLSHLNSYAAEMEPSPTPTGPL--AFPAWPWSFFHSC----PGLPALSNQLAILGRVPSPVLPGVSS 209
Cdd:PHA03247  2650 ERPRDDPAPGRVSRPRRARRLGRAAQASSPPQRPRrrAARPTVGSLTSLAdpppPPPTPEPAPHALVSATPLPPGPAAAR 2729

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1519314394  210 PAYPIPALRTAPLRRATGIILPARRNVLPSRGASSTRRArplerPATP-VPVAPSSRAARSSHIAPLLQSSSPTPPGPTG 288
Cdd:PHA03247  2730 QASPALPAAPAPPAVPAGPATPGGPARPARPPTTAGPPA-----PAPPaAPAAGPPRRLTRPAVASLSESRESLPSPWDP 2804

                          170       180
                   ....*....|....*....|...
gi 1519314394  289 SAAYVAVPTPNSSSPgPAGRPAG 311
Cdd:PHA03247  2805 ADPPAAVLAPAAALP-PAASPAG 2826

basic helix-loop-helix-orange (bHLH-O) domain found in hairy/enhancer-of-split related with YRPW motif-like protein (HEYL) and similar proteins; HEYL, also termed Class B basic helix-loop-helix protein 33 (bHLHb33), or hairy-related transcription factor 3 (HRT-3), is a bHLH-O transcriptional repressor that is strongly expressed in the presomitic mesoderm, the somites, the peripheral nervous system and smooth muscle of all arteries and is a downstream effector of the Notch and transforming growth factor-beta pathways. It promotes neuronal differentiation by activating proneural genes and inhibiting other hairy and enhancer of split (HES) and hairy/enhancer-of-split related with YRPW motif protein (HEY) proteins. HEYL also functions as a tumor suppressor involved in the progression of human cancers.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1519314394  36 PSSSQMQARKKHRGIIEKRRRDRINSSLSELRRLVPTAFEKQGSSKLEKAEVLQMTVDHLKMLHATGGTGFFDA 109
Cdd:cd11447     1 TTSSQIQARKKRRGIIEKRRRDRINSSLSELRRLVPTAFEKQGSSKLEKAEILQMTVDHLKMLHATGGAGKFDA 74

helix loop helix domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1519314394   50 IIEKRRRDRINSSLSELRRLVPTAFEkqgSSKLEKAEVLQMTVDHLKML 98
Cdd:smart00353   2 ARERRRRRKINEAFDELRSLLPTLPK---NKKLSKAEILRLAIEYIKSL 47

Hairy Orange; The Orange domain is found in the Drosophila proteins Hesr-1, Hairy, and Enhancer of Split. The Orange domain is proposed to mediate specific protein-protein interaction between Hairy and Scute.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1519314394 116 FRSiGFRECLTEVIRYLGVLEGPSSradPVRIRLLSHLNSYAA 158
Cdd:pfam07527   2 FRA-GFNECANEVSRFLSTLEGVDP---DLRQRLLNHLQRCLA 40

basic helix-loop-helix-orange (bHLH-O) domain found in hairy/enhancer-of-split related with YRPW motif-like protein (HEYL) and similar proteins; HEYL, also termed Class B basic helix-loop-helix protein 33 (bHLHb33), or hairy-related transcription factor 3 (HRT-3), is a bHLH-O transcriptional repressor that is strongly expressed in the presomitic mesoderm, the somites, the peripheral nervous system and smooth muscle of all arteries and is a downstream effector of the Notch and transforming growth factor-beta pathways. It promotes neuronal differentiation by activating proneural genes and inhibiting other hairy and enhancer of split (HES) and hairy/enhancer-of-split related with YRPW motif protein (HEY) proteins. HEYL also functions as a tumor suppressor involved in the progression of human cancers.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1519314394  36 PSSSQMQARKKHRGIIEKRRRDRINSSLSELRRLVPTAFEKQGSSKLEKAEVLQMTVDHLKMLHATGGTGFFDA 109
Cdd:cd11447     1 TTSSQIQARKKRRGIIEKRRRDRINSSLSELRRLVPTAFEKQGSSKLEKAEILQMTVDHLKMLHATGGAGKFDA 74

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 1519314394  37 SSSQMQARKKHRGIIEKRRRDRINSSLSELRRLVPTAFEKQGSSKLEKAEVLQMTVDHLKMLHATGGTGF 106
Cdd:cd19748     2 TSSQVLARKRRRGIIEKRRRDRINNSLSELRRLVPSAFEKQGSAKLEKAEILQMTVDHLKMLHAAGGKGY 71

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split (HES)-related repressor protein (HERP)-like family; The HERP-like family includes bHLH-O transcriptional regulators that are related to the Drosophila hairy and Enhancer-of-split proteins. They 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. 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 family. It is involved in the regulation of Drosophila circadian rhythms. It functions as both an activator and a repressor of clock gene expression.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1519314394  47 HRgIIEKRRRDRINSSLSELRRLVPTAFEKQGSSKLEKAEVLQMTVDHLKMLHATG 102
Cdd:cd11389     1 HK-VIEKRRRDRINESLAELRRLVPEARKSKGSGKLEKAEILEMTLQHLKALQSST 55

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split (HES) family; The HES family includes bHLH-O transcriptional regulators that are related to the Drosophila hairy and Enhancer-of-split (HES) proteins. They 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. HES family proteins 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
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1519314394  51 IEKRRRDRINSSLSELRRLVPTAFEKQGS--SKLEKAEVLQMTVDHLKMLHA 100
Cdd:cd11410     1 MEKKRRARINKSLEQLKTLVLEALNKDNTrySKLEKADILEMTVKYLKQLQR 52

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1519314394  44 RKKHRGIIEKRRRDRINSSLSELRRLVPTAFEKQgssKLEKAEVLQMTVDHLKMLH 99
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELLPTLPPDK---KLSKAEILRLAIEYIKHLQ 53

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split HES-1, HES-4 and similar proteins; The family includes two bHLH-O transcriptional repressors, HES-1 and HES-4. HES-1, also termed Class B basic helix-loop-helix protein 39 (bHLHb39), or hairy homolog, or hairy-like protein (HL), plays an essential role in development of both compartment and boundary cells of the central nervous system. It regulates the maintenance of neural stem/progenitor cells by inhibiting proneural gene expression via Notch signaling. HES-4, also termed Class B basic helix-loop-helix protein 42 (bHLHb42), or bHLH factor Hes4, antagonizes the function of Twist-1 to regulate lineage commitment of bone marrow stromal/stem cells (BMSC). Epigenetic dysregulation of HES-4 is associated with striatal degeneration in postmortem Huntington brains. Both HES-1 and HES-4 are mammalian counterparts of the Hairy and Enhancer of split proteins that play a critical role in many physiological processes including cellular differentiation, cell cycle arrest, apoptosis and self-renewal ability.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1519314394  42 QARKKHRGIIEKRRRDRINSSLSELRRLVPTAFEKQGS--SKLEKAEVLQMTVDHLKML 98
Cdd:cd11459     1 EHRKSSKPIMEKRRRARINESLSQLKTLILDALKKDSSrhSKLEKADILEMTVKHLRNL 59

basic helix-loop-helix-orange (bHLH-O) domain found in transcription factor HES-5 and similar proteins; HES-5, also termed Class B basic helix-loop-helix protein 38 (bHLHb38), or hairy and enhancer of split 5, is a bHLH-O transcription factor that is involved in cell differentiation and proliferation in a variety of tissues. HES-5 is an essential effector for Notch signaling. It acts as a transducer of Notch signals in brain vascular development. It also acts as a key mediator of Wnt-3a-induced neuronal differentiation and plays a crucial role in normal inner ear hair cell development. HES-5 is one mammalian counterpart of the Hairy and Enhancer of split proteins that play a critical role in many physiological processes including cellular differentiation, cell cycle arrest, apoptosis and self-renewal ability.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1519314394  50 IIEKRRRDRINSSLSELRRLVPTAFEK-QGSSKLEKAEVLQMTVDHLK 96
Cdd:cd11461     6 VVEKTRRDRINSSIEQLKTLLEKEFQRhQPNSKLEKADILEMTVSFLK 53

basic helix-loop-helix-orange (bHLH-O) domain found in Drosophila melanogaster enhancer of split mbeta protein (ESMB) and similar proteins; ESMB, also termed E(spl)mbeta, or HLH-mbeta, or split locus enhancer protein mA, is a bHLH-O transcriptional repressor of genes that require a bHLH protein for their transcription. It is involved in the neural-epidermal lineage decision during early neurogenesis. The family also includes Enhancer of split m7 protein (also known as E(spl)m7), which acts as a transcriptional repressor that participates in the control of cell fate choice by uncommitted neuroectodermal cells in the embryo.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1519314394  38 SSQMQARKKHRGIIEKRRRDRINSSLSELRRLVPTAFEKQGS--SKLEKAEVLQMTVDHLKMLHA 100
Cdd:cd19741     2 SKTYQYRKVTKPLLERKRRARINKCLDELKDLMVEALATEAEnvSKLEKADILELTVRHLKKLRR 66

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 1519314394  52 EKRRRDRINSSLSELRRLVPtafEKQGSSKLEKAEVLQMTVDHLKMLHA 100
Cdd:cd00083     1 ERRRRDKINDAFEELKRLLP---ELPDSKKLSKASILQKAVEYIRELQS 46

Orange domain; This domain confers specificity among members of the Hairy/E(SPL) family.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1519314394  115 DFRSiGFRECLTEVIRYLGVLEGPSsraDPVRIRLLSHLNSYAAEMEP 162
Cdd:smart00511   2 SFRS-GYRECANEVSRFLSQLPGTD---PDVRARLLSHLQTHLNQLLQ 45

Hairy Orange; The Orange domain is found in the Drosophila proteins Hesr-1, Hairy, and Enhancer of Split. The Orange domain is proposed to mediate specific protein-protein interaction between Hairy and Scute.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1519314394 116 FRSiGFRECLTEVIRYLGVLEGPSSradPVRIRLLSHLNSYAA 158
Cdd:pfam07527   2 FRA-GFNECANEVSRFLSTLEGVDP---DLRQRLLNHLQRCLA 40

basic helix-loop-helix-orange (bHLH-O) domain found in differentially expressed in chondrocytes protein 2 (DEC2) and similar proteins; DEC2, also termed Class E basic helix-loop-helix protein 41 (bHLHe41), or Class B basic helix-loop-helix protein 3 (bHLHb3), or enhancer-of-split and hairy-related protein 1 (SHARP-1), is a bHLH-O transcriptional repressor involved in the regulation of the circadian rhythm by negatively regulating the activity of the clock genes and clock-controlled genes.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1519314394  47 HRgIIEKRRRDRINSSLSELRRLVPTAFEKQGSSKLEKAEVLQMTVDHLKMLHA 100
Cdd:cd19750    19 HR-LIEKKRRDRINECIAQLKDLLPEHLKLTTLGHLEKAVVLELTLKHLKALTA 71

basic helix-loop-helix-orange (bHLH-O) domain found in differentially expressed in chondrocytes protein (DEC) family; The DEC family includes two bHLH-O transcriptional repressors, DEC1 and DEC2, which 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. They mediate the circadian rhythm by negatively regulating the activity of the clock genes and clock-controlled genes. They are induced by CLOCK:BMAL1 heterodimer via the CACGTG E-box in the promoter.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1519314394  47 HRgIIEKRRRDRINSSLSELRRLVPTAFEKQGSSKLEKAEVLQMTVDHLKMLHA 100
Cdd:cd11409     8 HR-LIEKKRRDRINECIAQLKDLLPEHLKLTTLGHLEKAVVLELTLKHLKALTA 60

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 1519314394  51 IEKRRRDRINSSLSELRRLVPTAFEKQGSSKLEKAEVLQMTVDHLKMLHAT 101
Cdd:cd11387     5 VERRRRDNINEKIQELGSLVPPSRLETKDLKPNKGSILSKAVEYIRELQNQ 55

basic helix-loop-helix-orange (bHLH-O) domain found in transcription factor HES-3 and similar proteins; HES-3, also termed Class B basic helix-loop-helix protein 43 (bHLHb43), or hairy and enhancer of split 3, is a bHLH-O transcription factor expressed in neural stem and progenitor cells that is involved in tissue regeneration. It regulates gene expression, cell growth, and insulin release. HES-3 is one mammalian counterpart of the Hairy and Enhancer of split proteins that play a critical role in many physiological processes including cellular differentiation, cell cycle arrest, apoptosis and self-renewal ability.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1519314394  51 IEKRRRDRINSSLSELRRLVPTAFEKQ-GSSKLEKAEVLQMTVDHLKMLHATG 102
Cdd:cd18933     1 MEKKRRARINVSLEQLKSLLEKHYSNNiRKRKLEKADILELTVKYLRSLQNSI 53

basic helix-loop-helix-orange (bHLH-O) domain found in transcription factor HES-6 and similar proteins; HES-6, also termed Class B basic helix-loop-helix protein 41 (bHLHb41), or hairy and enhancer of split 6, or C-HAIRY1, is a bHLH-O transcription factor that is expressed in developing muscle and involved in angiogenesis, myogenesis, neural differentiation and neurogenesis. HES-6 antagonizes Notch signaling but is not regulated by Notch signaling. It is a transcription co-factor associated with stem cell characteristics in neural tissue. It may act as an inhibitor of Hes-1 during neuronal development and forms a heterodimer with HES-1 to prevent its association with transcriptional co-repressors. The overexpression of HES-6 has been reported in metastatic cancers of different origins. HES-6 is one mammalian counterpart of the Hairy and Enhancer of split proteins that play a critical role in many physiological processes including cellular differentiation, cell cycle arrest, apoptosis and self-renewal ability.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1519314394  44 RKKHRGIIEKRRRDRINSSLSELRRLVPTAfEKQgsSKLEKAEVLQMTV 92
Cdd:cd11460     3 RKARKPLVEKKRRARINESLQELRLILADA-ELQ--SKMENAEVLELTV 48

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in MLX-interacting protein (MLXIP), MLX-interacting protein-like (MLXIPL) and similar proteins; The family includes MLXIP and MLXIPL. MLXIP, also termed Class E basic helix-loop-helix protein 36 (bHLHe36), or transcriptional activator MondoA, is a bHLHZip transcriptional activator that binds DNA as a heterodimer with Mlx. It binds to the canonical E box sequence 5'-CACGTG-3' and plays a role in transcriptional activation of glycolytic target genes. MLXIP is most highly expressed in skeletal muscle and functions as an indirect glucose sensor, by sensing glucose 6-phosphate and shuttling between the nucleus and the cytoplasm. MLXIPL, also termed carbohydrate-responsive element-binding protein (ChREBP), or Class D basic helix-loop-helix protein 14 (bHLHd14), or MLX interactor, or WS basic-helix-loop-helix leucine zipper protein (WS-bHLH), or Williams-Beuren syndrome chromosomal region 14 protein (WBSCR14), is a bHLHZip transcriptional factor integral to the regulation of glycolysis and lipogenesis in the liver. It forms heterodimers with the bHLHZip protein Mlx to bind the DNA sequence 5'-CACGTG-3'.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1519314394  52 EKRRRDRINSSLSELRRLVPTaFEKQGSSKLEKAEVLQMTVDHLKMLHA 100
Cdd:cd11405    11 EQKRRFNIKSGFDTLQSLIPS-LGQNPNQKVSKAAMLQKAAEYIKSLKR 58

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1519314394  42 QARKKHRgIIEKRRRDRINSSLSELRRLVPTAFEKQGSS------------KLEKAEVLQMTVDHLKML 98
Cdd:cd11395     2 RKRLPHN-AIEKRYRSNLNTKIERLRDAIPSLRSPEGKSddgglgglapttKLSKATILTKAIEYIRHL 69

basic helix-loop-helix (bHLH) domain found in the spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein (SOHLH) family; 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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1519314394  52 EKRRRDRINSSLSELRRLVPTAFEKqgssKLEKAEVLQMTVDHLKML 98
Cdd:cd18908    10 ERLRRERIKSSCDQLRDLLPYIKGR----KLDMASVLEMTVKYIRYI 52

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in aryl hydrocarbon receptor nuclear translocator-like protein 2 (ARNTL2) and similar proteins; 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. ARNT-2 heterodimerize with other bHLH-PAS proteins such as aryl hydrocarbon receptor (AhR), hypoxia-inducible factor (HIF), and single-minded (SIM).

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1519314394  44 RKKHRGIiEKRRRDRINSSLSELRRLVPTAfeKQGSSKLEKAEVLQMTVDHLKML 98
Cdd:cd11469     2 REAHSQT-EKRRRDKMNNLIEELSAMIPQC--NPMARKLDKLTVLRMAVQHLKSL 53

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
                  ....*....|....*....|....*....|....*....|....*..
gi 1519314394  52 EKRRRDRINSSLSELRRLVPTAfekqgSSKLEKAEVLQMTVDHLKML 98
Cdd:cd19683    10 ERQRRERIKIACDQLRKLVPGC-----SRKTDKATVFEFTVAYIKFL 51

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in the aryl hydrocarbon receptor (AhR) family; The AhR family includes AhR, AhR repressor (AhRR) and Drosophila melanogaster protein spineless. AhR, also termed Ah receptor, or Dioxin receptor (DR), or Class E basic helix-loop-helix protein 76 (bHLHe76), is the only member of bHLH-PAS transcription regulators that bind and be activated by small chemical ligands. It is activated by Dioxin to control the expression of certain genes to influence biological processes such as apoptosis, proliferation, cell growth and differentiation. To form active DNA binding complexes AhR dimerizes with a bHLH-PAS factor ARNT (Aryl hydrocarbon Nuclear Receptor Translocator). AhRR, also termed Class E basic helix-loop-helix protein 77 (bHLHe77), is a member of bHLH-PAS transcription factors that acts as a negative regulator of AhR, playing key roles in development and environmental sensing. AhRR functions by competing with AhR for its partner ARNT. AhRR-ARNT complexes are transcriptionally inactive. Spineless is a bHLH-PAS transcription factor that plays an important role in fly morphogenesis. It is both necessary and sufficient for the formation of the ommatidial mosaic.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1519314394  53 KRRRDRINSSLSELRRLVPtaFEKQGSSKLEKAEVLQMTVDHLK 96
Cdd:cd19696     9 KRHRDRLNSELDELASLLP--FPEDVISKLDKLSVLRLSVSYLR 50

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana phytochrome interacting factors (PIFs) and similar proteins; The family includes several bHLH transcription factors from Arabidopsis thaliana, such as PIFs, ALC, PIL1, SPATULA, and UNE10. PIFs (PIF1, PIF3, PIF4, PIF5, PIF6 and PIF7) have been shown to control light-regulated gene expression. They directly bind to the photoactivated phytochromes and are degraded in response to light signals. ALC, also termed AtbHLH73, or protein ALCATRAZ, or EN 98, is required for the dehiscence of fruit, especially for the separation of the valve cells from the replum. It promotes the differentiation of a strip of labile non-lignified cells sandwiched between layers of lignified cells. PIL1, also termed AtbHLH124, or protein phytochrome interacting factor 3-like 1, or EN 110, is involved in responses to transient and long-term shade. It is required for the light-mediated inhibition of hypocotyl elongation and necessary for rapid light-induced expression of the photomorphogenesis- and circadian-related gene APRR9. PIL1 seems to play a role in multiple PHYB responses, such as flowering transition and petiole elongation. SPATULA, also termed AtbHLH24, or EN 99, plays a role in floral organogenesis. It promotes the growth of carpel margins and of pollen tract tissues derived from them. UNE10, also termed AtbHLH16, or protein UNFERTILIZED EMBRYO SAC 10, or EN 99, is required during the fertilization of ovules by pollen.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1519314394  52 EKRRRDRINSSLSELRRLVPTafekqgSSKLEKAEVLQMTVDHLKML 98
Cdd:cd11445    10 ERRRRDRINEKMKALQELIPN------CNKTDKASMLDEAIEYLKSL 50

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in Drosophila melanogaster Circadian locomotor output cycles protein kaput (dCLOCK) and similar proteins; dCLOCK, also termed dPAS1, is a bHLH-PAS Circadian regulator that acts as a transcription factor and generates a rhythmic output with a period of about 24 hours.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1519314394  43 ARKKHRGIIEKRRRDRINSSLSELRRLVPTafekqGSSKLEKAEVLQMTVDHLK 96
Cdd:cd19735     9 IKRKSRNLSEKKRRDQFNVLINELCSMVST-----SNRKMDKSTVLKSTIAFLK 57

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
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1519314394  44 RKKHRGII-EKRRRDRINSSLSELRRLVPTAFEKqgssKLEKAEVLQMTVDHLKMLHAT 101
Cdd:cd11404     1 QRRLNHVRsEKKRRELIKKGYDELCALVPGLDPQ----KRTKADILQKAADWIQELKEE 55

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1519314394  52 EKRRRDRINSSLSELRRLVPTAfekqgsSKLEKAEVLQMTVDHLKML 98
Cdd:cd11443     7 ERRRRKKLNDRLYMLRSVVPKI------TKMDRASILGDAIDYVKEL 47

large tegument protein UL36; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1519314394  136 EGPSSRADPVRIRLLSHLNSYAAEMEPSPTPTGPL--AFPAWPWSFFHSC----PGLPALSNQLAILGRVPSPVLPGVSS 209
Cdd:PHA03247  2650 ERPRDDPAPGRVSRPRRARRLGRAAQASSPPQRPRrrAARPTVGSLTSLAdpppPPPTPEPAPHALVSATPLPPGPAAAR 2729

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1519314394  210 PAYPIPALRTAPLRRATGIILPARRNVLPSRGASSTRRArplerPATP-VPVAPSSRAARSSHIAPLLQSSSPTPPGPTG 288
Cdd:PHA03247  2730 QASPALPAAPAPPAVPAGPATPGGPARPARPPTTAGPPA-----PAPPaAPAAGPPRRLTRPAVASLSESRESLPSPWDP 2804

                          170       180
                   ....*....|....*....|...
gi 1519314394  289 SAAYVAVPTPNSSSPgPAGRPAG 311
Cdd:PHA03247  2805 ADPPAAVLAPAAALP-PAASPAG 2826

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in Circadian locomotor output cycles protein kaput (CLOCK) and similar proteins; CLOCK, also termed Class E basic helix-loop-helix protein 8 (bHLHe8), is a bHLH-PAS transcriptional activator which forms a core component of the circadian clock. It forms heterodimers with another bHLH-PAS protein, Brain-Muscle-Arnt-Like (also known as BMAL or ARNT3 or mop3), which regulates circadian rhythm. BMAL1-CLOCK heterodimer complex activates transcription from E-box (CANNTG) elements found in the promoter of circadian responsive genes.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1519314394  42 QARKKHRGIIEKRRRDRINSSLSELRRLVPTafekqGSSKLEKAEVLQMTVDHLK 96
Cdd:cd19734     5 KAKRVSRNKSEKKRRDQFNVLIKELGSMLPG-----NARKMDKSTVLQKSIDFLR 54

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
                  ....*....|....*....|....*....|....*....|....*....|
gi 1519314394  52 EKRRRDRINSSLSELRRLVPTafekqgSSKLEKAEVLQMTVDHLKMLHAT 101
Cdd:cd18918     5 ERERREKLNEKFSDLRNLIPN------PTKNDRASILSDAIKYINELQRT 48

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in aryl hydrocarbon receptor repressor (AhRR) and similar proteins; AhRR, also termed AhR repressor, or Class E basic helix-loop-helix protein 77 (bHLHe77), is a member of bHLH-PAS transcription factors that acts as a negative regulator of AhR (or Dioxin Receptor), playing key roles in development and environmental sensing. AhR is activated by Dioxin to control the expression of certain genes to influence biological processes such as apoptosis, proliferation, cell growth and differentiation. To form active DNA binding complexes, AhR dimerizes with a bHLH-PAS factor ARNT (Aryl hydrocarbon Nuclear Receptor Translocator). AhRR functions by competing with AhR for its partner ARNT. AhRR-ARNT complexes are transcriptionally inactive.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1519314394  53 KRRRDRINSSLSELRRLVPtaFEKQGSSKLEKAEVLQMTVDHLKM 97
Cdd:cd11435     9 KRHRDRLNAELDHLASLLP--FPPDIISKLDKLSVLRLSVSYLRV 51

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
                  ....*....|....*....|....*....|....*....|....*....|
gi 1519314394  52 EKRRRDRINSSLSELRRLVPTAfekqGSSKLEKAEVLQMTVDHLKMLHAT 101
Cdd:cd11419    12 ERRRMQSINAGFQSLRTLLPHC----DGEKLSKAAILQQTAEYIFSLEQE 57

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1519314394  42 QARKKHRGIiEKRRRDRINSSLSELRRLVPTAfekqgSSKLEKAEVLQMTVDHLKMLHAT 101
Cdd:cd18921     5 EKRTAHNAI-EKRYRSSINDKIIELKDLVVGT-----EAKLNKSAVLRKAIDYIRFLQQS 58

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in upstream stimulatory factor 2 (USF2) and similar proteins; USF2, also termed Class B basic helix-loop-helix protein 12 (bHLHb12), or major late transcription factor 2, or FOS-interacting protein (FIP), or upstream transcription factor 2, 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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1519314394  42 QARKKHRGIIEKRRRDRINSSLSELRRLVPTAFEKQGSSKLEKAEVLQMTVDHLKMLHAT 101
Cdd:cd18923     6 ERRRAQHNEVERRRRDKINNWIVQLSKIIPDCNTDNSKTGASKGGILSKACDYIRELRQT 65

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
                  ....*....|....*....|....*....|....*....|....*..
gi 1519314394  52 EKRRRDRINSSLSELRRLVPTafeKQGSSKLEKAEVLQMTVDHLKML 98
Cdd:cd19708     9 ERWRQQNVNGAFAELRKLVPT---HPPDKKLSKNEILRLAIKYIRLL 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
                  ....*....|....*....|....*....|....*....|....*...
gi 1519314394  52 EKRRRDRINSSLSELRRLVPT-AFEKqgssKLEKAEVLQMTVDHLKML 98
Cdd:cd19686     9 ERKRMRSINDAFDGLRRHIPTfPYEK----RLSKVDTLRLAIQYINFL 52

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Saccharomyces cerevisiae transcription factor HMS1 and similar proteins; HMS1, also termed high-copy MEP suppressor protein 1, is a putative bHLHzip transcription factor involved in exit from mitosis and pseudohyphal differentiation.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1519314394  50 IIEKRRRDRINSSLSELRRLVPT-------------AFEKQG----SSKLEKAEVLQMTVDHLKML 98
Cdd:cd11399     9 MIEKRYRSNINDRIAELRDSVPAlreayksargedeDEEDLGgltpATKLNKATILSKATEYIRHL 74

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in single-minded (SIM) family; The SIM family includes Drosophila melanogaster protein SIM and its homologs from vertebrates, single-minded homolog 1 (SIM1) and single-minded homolog 2 (SIM2). SIM is a nuclear bHLH-PAS transcription factor that functions as a master developmental regulator controlling midline development of the ventral nerve cord in Drosophila. SIM1, also termed Class E basic helix-loop-helix protein 14 (bHLHe14), is a bHLH-PAS transcription factor that may have pleiotropic effects during embryogenesis and in the adult. SIM2, also termed Class E basic helix-loop-helix protein 15 (bHLHe15), is a bHLH-PAS transcription factor that may be a master gene of central nervous system (CNS) development in cooperation with ARNT. It may have pleiotropic effects in the tissues expressed during development.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1519314394  53 KRRRDRINSSLSELRRLVPtaFEKQGSSKLEKAEVLQMTVDHLKMLH 99
Cdd:cd11434    10 RTRREKENAEFYELAKLLP--LPSAITSQLDKASIIRLTTSYLKMRA 54

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
                  ....*....|....*....|....*....|....*....|....*..
gi 1519314394  52 EKRRRDRINSSLSELRRLVPtafEKQGSSKLEKAEVLQMTVDHLKML 98
Cdd:cd11430     9 ERRRMNGLNRAFDQLRSVVP---SIGNDKKLSKYETLQMAQIYIETL 52

large tegument protein UL36; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1519314394  155 SYAAEMEPSPTPTGPLAFPAWPwsffhscPGLPALSNQLAILGRVPSPVLP---GVSSPAYPIPALRTAPLRRATGIILP 231
Cdd:PHA03247  2607 DPRGPAPPSPLPPDTHAPDPPP-------PSPSPAANEPDPHPPPTVPPPErprDDPAPGRVSRPRRARRLGRAAQASSP 2679

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1519314394  232 A---RRNVLPSRGASSTRRARPLERPATP-------VPVAPSSRAARSSHIAPLLQSSSPTPPGPTGSAAYVAVPTPNSS 301
Cdd:PHA03247  2680 PqrpRRRAARPTVGSLTSLADPPPPPPTPepaphalVSATPLPPGPAAARQASPALPAAPAPPAVPAGPATPGGPARPAR 2759

                          170
                   ....*....|.
gi 1519314394  302 SPGPAGRPAGA 312
Cdd:PHA03247  2760 PPTTAGPPAPA 2770