Oestrogen receptor;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 601984548   42 VYLDSSKPAVYNYPEGAAYEFNAAAAANAQVYGQTGLPYGPGSEAaaFGSNGLGGFPPLNSVSPSPLMLLHPPPQLSPFL 121
Cdd:pfam02159   1 MYVESSKTAVYDYPEGATYDFAAAAAASAPVYGSSTLSYSPPSEA--FGSNSLGGFHSLNSVPPSPLVFLHPPPQLSPFL 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 601984548  122 QPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQGGRERLASTNDKGSMAMESAKE 181
Cdd:pfam02159  79 HPPGQQVPYYLENEQSGYAVREAAPPAFYRPSSDNRRQSGRERLASTSDKGSLSMESAKE 138

Oestrogen-type nuclear receptor final C-terminal; This is the very C-terminal region of a subfamily of nuclear receptors that includes oestrogen receptors and other subfamily 3 group A members. The actual function of this region is not known, but the domain is absent from all the other types of nuclear receptors. Oestrogen receptors modulate AP-1-dependent transcription through two distinct mechanisms: via protein-protein interactions on DNA; and via non-genomic actions. The mechanism used depends on the cellular localization of the receptor. In addition to the more extensively studied cross-talk on DNA, additional non-genomic actions might be very important in target tissues in which membrane-associated ERs are found. These non-genomic actions probably contribute to the overall physiological responses mediated by ligand-bound ERs and might possibly be mediated via this C-terminal domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 601984548  554 PTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV 597
Cdd:pfam12743   1 PANRGGAPMEEDNQSQLATTGSTSSHSLQTYYITGEAESFPSTV 44

Oestrogen receptor;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 601984548   42 VYLDSSKPAVYNYPEGAAYEFNAAAAANAQVYGQTGLPYGPGSEAaaFGSNGLGGFPPLNSVSPSPLMLLHPPPQLSPFL 121
Cdd:pfam02159   1 MYVESSKTAVYDYPEGATYDFAAAAAASAPVYGSSTLSYSPPSEA--FGSNSLGGFHSLNSVPPSPLVFLHPPPQLSPFL 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 601984548  122 QPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQGGRERLASTNDKGSMAMESAKE 181
Cdd:pfam02159  79 HPPGQQVPYYLENEQSGYAVREAAPPAFYRPSSDNRRQSGRERLASTSDKGSLSMESAKE 138

Zinc finger, C4 type (two domains); In nearly all cases, this is the DNA binding domain of a nuclear hormone receptor. The alignment contains two Zinc finger domains that are too dissimilar to be aligned with each other.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 601984548  184 YCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGNRHndYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMM 253
Cdd:pfam00105   1 LCKVCGDKASGYHYGVLTCEGCKGFFRRSIQKNIV--YTCKFNKDCVIDKRNRNRCQYCRLKKCLEVGMS 68

Ligand binding domain of hormone receptors;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 601984548   352 ADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRN---QGKCVEGMVEIFD 428
Cdd:smart00430   1 AERQLLLTVEWAKSFPGFRELSLEDQIVLLKSFWFELLLLELAYRSVKLKKELLLAPDGTYIRPdavLELRKLFSPFLDR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 601984548   429 MLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEkdhihrVLDKITDTLIHLMAKAGltLQQQHQRLAQ 508
Cdd:smart00430  81 ILSELVKPLRELKLDDEEYALLKAIVLFNPAVPGLSEEGKEIVEK------LQEKYANALHDYYLKNY--PMNYPGRFAK 152

                          170
                   ....*....|.
gi 601984548   509 LLLILSHIRHM 519
Cdd:smart00430 153 LLLILPELRKI 163

Oestrogen-type nuclear receptor final C-terminal; This is the very C-terminal region of a subfamily of nuclear receptors that includes oestrogen receptors and other subfamily 3 group A members. The actual function of this region is not known, but the domain is absent from all the other types of nuclear receptors. Oestrogen receptors modulate AP-1-dependent transcription through two distinct mechanisms: via protein-protein interactions on DNA; and via non-genomic actions. The mechanism used depends on the cellular localization of the receptor. In addition to the more extensively studied cross-talk on DNA, additional non-genomic actions might be very important in target tissues in which membrane-associated ERs are found. These non-genomic actions probably contribute to the overall physiological responses mediated by ligand-bound ERs and might possibly be mediated via this C-terminal domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 601984548  554 PTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV 597
Cdd:pfam12743   1 PANRGGAPMEEDNQSQLATTGSTSSHSLQTYYITGEAESFPSTV 44

The ligand binding domain of estrogen receptor and estrogen receptor-related receptors; The ligand binding domain of estrogen receptor (ER) and estrogen receptor-related receptors (ERRs): Estrogen receptors are a group of receptors which are activated by the hormone estrogen. Estrogen regulates many physiological processes including reproduction, bone integrity, cardiovascular health, and behavior. The main mechanism of action of the estrogen receptor is as a transcription factor by binding to the estrogen response element of target genes upon activation by estrogen and then recruiting coactivator proteins which are responsible for the transcription of target genes. Additionally some ERs may associate with other membrane proteins and can be rapidly activated by exposure of cells to estrogen. ERRs are closely related to the estrogen receptor (ER) family. But, it lacks the ability to bind estrogen. ERRs can interfere with the classic ER-mediated estrogen signaling pathway, positively or negatively. ERRs share target genes, co-regulators and promoters with the estrogen receptor (ER) family. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, ER and ERRs have a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a non-conserved hinge and a C-terminal ligand binding domain (LBD).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 601984548 317 MVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWR 396
Cdd:cd07068    1 LLSALLVAEPDKLYAMNDPTGPDTEVSLLATLSDLADRELVHIISWAKHIPGFSDLSLNDQMHLLQSAWLEILMLGLVWR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 601984548 397 SMEHPGKLLFAPNLLLDRNQGKcVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTflsstlksLEEKDH 476
Cdd:cd07068   81 SLPHPGKLVFAPDLLLDREQAR-VEGLLEIFDMLLQLVRRFRELGLQREEYVCLKAIILANSDVRH--------LEDREA 151

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 601984548 477 IHRVLDKITDTLIHLMAKAGLTlqQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEMLDA 548
Cdd:cd07068  152 VQQLRDAILDALVDVEAKRHGS--QQPRRLAQLLLLLPHLRQASNKGVRHLYSVKCEGKVPMYKLFLEMLEA 221

DNA-binding domain of estrogen receptors (ER) is composed of two C4-type zinc fingers; DNA-binding domain of estrogen receptors (ER) is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which coordinates a single zinc atom. ER interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. Estrogen receptor is a transcription regulator that mediates the biological effects of hormone estrogen. The binding of estrogen to the receptor triggers the dimerization and the binding of the receptor dimer to estrogen response element, which is a palindromic inverted repeat: 5'GGTCAnnnTGACC-3', of target genes. Through ER, estrogen regulates development, reproduction and homeostasis. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, ER has a central well-conserved DNA binding domain (DBD), a variable N-terminal domain, a non-conserved hinge and a C-terminal ligand binding domain (LBD).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 601984548 180 KETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGnrHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRK 259
Cdd:cd07171    1 KDTHFCAVCSDYASGYHYGVWSCEGCKAFFKRSIQG--HNDYICPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRR 78

                 ....
gi 601984548 260 DRRG 263
Cdd:cd07171   79 ERRG 82

DNA-binding domain of estrogen receptor (ER) and estrogen related receptors (ERR) is composed of two C4-type zinc fingers; DNA-binding domains of estrogen receptor (ER) and estrogen related receptors (ERR) are composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. ER and ERR interact with the palindromic inverted repeat, 5'GGTCAnnnTGACC-3', upstream of the target gene and modulate the rate of transcriptional initiation. ERR and ER are closely related and share sequence similarity, target genes, co-regulators and promoters. While ER is activated by endogenous estrogen, ERR lacks the ability to bind to estrogen. Estrogen receptor mediates the biological effects of hormone estrogen by the binding of the receptor dimer to estrogen response element of target genes. However, ERRs seem to interfere with the classic ER-mediated estrogen responsive signaling by targeting the same set of genes. ERRs and ERs exhibit the common modular structure with other nuclear receptors. They have a central highly conserved DNA binding domain (DBD), a non-conserved N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 601984548 185 CAVCNDYASGYHYGVWSCEGCKAFFKRSIQGnrHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDR 261
Cdd:cd07155    1 CLVCGDIASGYHYGVASCEACKAFFKRTIQG--NLGYSCPSTSECEVDKKRRKSCQACRLQKCLKVGMLKEGVRLDR 75

DNA-binding domain of nuclear receptors is composed of two C4-type zinc fingers; DNA-binding domain of nuclear receptors is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. It interacts with a specific DNA site upstream of the target gene and modulates the rate of transcriptional initiation. Nuclear receptors form a superfamily of ligand-activated transcription regulators, which regulate various physiological functions, from development, reproduction, to homeostasis and metabolism in animals (metazoans). The family contains not only receptors for known ligands but also orphan receptors for which ligands do not exist or have not been identified. NRs share a common structural organization with a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD). Most nuclear receptors bind as homodimers or heterodimers to their target sites, which consist of two hexameric half-sites. Specificity is determined by the half-site sequence, the relative orientation of the half-sites and the number of spacer nucleotides between the half-sites. However, a growing number of nuclear receptors have been reported to bind to DNA as monomers.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 601984548 185 CAVCNDYASGYHYGVWSCEGCKAFFKRSIQGNRHndYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIR 258
Cdd:cd06916    1 CAVCGDKASGYHYGVLTCEGCKGFFRRSVRRNLE--YTCPAGGNCVIDKRNRNRCQACRLKKCLAVGMRKEAVR 72

DNA-binding domain of estrogen related receptors (ERR) is composed of two C4-type zinc fingers; DNA-binding domain of estrogen related receptors (ERRs) is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which coordinates a single zinc atom. ERR interacts with the palindromic inverted repeat, 5'GGTCAnnnTGACC-3', upstream of the target gene and modulates the rate of transcriptional initiation. The estrogen receptor-related receptors (ERRs) are transcriptional regulators, which are closely related to the estrogen receptor (ER) family. Although ERRs lack the ability to bind to estrogen and are so-called orphan receptors, they share target genes, co-regulators and promoters with the estrogen receptor (ER) family. By targeting the same set of genes, ERRs seem to interfere with the classic ER-mediated estrogen response in various ways. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, ERR has a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a non-conserved hinge and a C-terminal ligand binding domain (LBD).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 601984548 183 RYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGNRhnDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDR- 261
Cdd:cd07170    5 RLCLVCGDIASGYHYGVASCEACKAFFKRTIQGNI--EYSCPATNECEITKRRRKSCQACRFMKCLKVGMLKEGVRLDRv 82

                         90
                 ....*....|...
gi 601984548 262 RGGRMlKHKRQRD 274
Cdd:cd07170   83 RGGRQ-KYKRRID 94

c4 zinc finger in nuclear hormone receptors;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 601984548   185 CAVCNDYASGYHYGVWSCEGCKAFFKRSIQGNRhnDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMK 254
Cdd:smart00399   2 CCVCGDHASGFHFGVCSCRACKAFFRRTVNLRY--KYRCDRKNNCSINKRYRCRCRACRLKKCLGVGMDP 69

DNA-binding domain of heptocyte nuclear factor 4 (HNF4) is composed of two C4-type zinc fingers; DNA-binding domain of hepatocyte nuclear factor 4 (HNF4) is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. HNF4 interacts with a DNA site, composed of two direct repeats of AGTTCA with 1 bp spacer, which is upstream of target genes and modulates the rate of transcriptional initiation. HNF4 is a member of the nuclear receptor superfamily. HNF4 plays a key role in establishing and maintenance of hepatocyte differentiation in the liver. It is also expressed in gut, kidney, and pancreatic beta cells. HNF4 was originally classified as an orphan receptor, but later it is found that HNF4 binds with very high affinity to a variety of fatty acids. However, unlike other nuclear receptors, the ligands do not act as a molecular switch for HNF4. They seem to constantly bind to the receptor, which is constitutively active as a transcription activator. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, HNF4 has a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 601984548 185 CAVCNDYASGYHYGVWSCEGCKAFFKRSIQGNRhnDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDR 261
Cdd:cd06960    1 CAVCGDRATGKHYGVLSCNGCKGFFRRSVRKNR--TYTCRFGGNCVVDKDKRNACRYCRFKKCLEVGMDPEAVQNER 75

The ligand binding domain of the retinoid X receptor and Ultraspiracle, members of nuclear receptor superfamily; The ligand binding domain of the retinoid X receptor (RXR) and Ultraspiracle (USP): This family includes two evolutionary related nuclear receptors: retinoid X receptor (RXR) and Ultraspiracle (USP). RXR is a nuclear receptor in mammalian and USP is its counterpart in invertebrates. The native ligand of retinoid X receptor is 9-cis retinoic acid (RA). RXR functions as a DNA binding partner by forming heterodimers with other nuclear receptors including CAR, FXR, LXR, PPAR, PXR, RAR, TR, and VDR. RXRs can play different roles in these heterodimers. It acts either as a structural component of the heterodimer complex, required for DNA binding but not acting as a receptor or as both a structural and a functional component of the heterodimer, allowing 9-cis RA to signal through the corresponding heterodimer. In addition, RXR can also form homodimers, functioning as a receptor for 9-cis RA, independently of other nuclear receptors. Ultraspiracle (USP) plays similar roles as DNA binding partner of other nuclear rec eptors in invertebrates. USP has no known high-affinity ligand and is thought to be a silent component in the heterodimeric complex with partner receptors. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, RXR and USP have a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 601984548 318 VSALLDAEppILYSEYDPTRPFSEASMMGLLTNL---ADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLV 394
Cdd:cd06943    4 IERILEAE--LAVEPKSEAVAMVPPEYRDPVSNIcqaADKQLFQLVEWAKRIPHFSELPLDDQVILLRAGWNELLIAAFA 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 601984548 395 WRSMEHPGKLLFAPNLLLDRNQGKCVeGMVEIFDMLLAT-SSRFRMMNLQGEEFVCLKSIILLNSGVytflsstlKSLEE 473
Cdd:cd06943   82 HRSIAVKDGILLATGLHLHRNSAHQA-GVGAIFDRILTElVVKMRDLKMDRTELGCLRAIILFNPDV--------KGLKS 152

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 601984548 474 KDHIHRVLDKITDTlihLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMK 531
Cdd:cd06943  153 RQEVESLREKVYAS---LEEYCRQKHPEQPGRFAKLLLRLPALRSIGLKCLEHLFFFK 207

DNA-binding domain of retinoic acid receptor (RAR) is composed of two C4-type zinc fingers; DNA-binding domain of retinoic acid receptor (RAR) is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. RAR interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. RARs mediate the biological effect of retinoids, including both natural dietary vitamin A (retinol) metabolites and active synthetic analogs. Retinoids play key roles in a wide variety of essential biological processes, such as vertebrate embryonic morphogenesis and organogenesis, differentiation and apoptosis, and homeostasis. RAR function as a heterodimer with retinoic X receptor by binding to specific RAR response elements (RAREs), which are composed of two direct repeats of the consensus sequence 5'-AGGTCA-3' separated by one to five base pair and found in the promoter regions of retinoid target genes. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, retinoic acid receptors have a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a non-conserved hinge and a C-terminal ligand binding domain (LBD).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 601984548 182 TRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGNRHndYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDR 261
Cdd:cd06964    4 YKPCFVCQDKSSGYHYGVSACEGCKGFFRRSIQKNMV--YTCHRDKNCIINKVTRNRCQYCRLQKCFEVGMSKESVRNDR 81

                 ....
gi 601984548 262 RGGR 265
Cdd:cd06964   82 NKKK 85

DNA-binding domain of ecdysone-induced DHR4 orphan nuclear receptor is composed of two C4-type zinc fingers; DNA-binding domain of ecdysone-induced DHR4 orphan nuclear receptor is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which coordinates a single zinc atom. This domain interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. Ecdysone-induced orphan receptor DHR4 is a member of the nuclear receptor family. DHR4 is expressed during the early Drosophila larval development and is induced by ecdysone. DHR4 coordinates growth and maturation in Drosophila by mediating endocrine response to the attainment of proper body size during larval development. Mutations in DHR4 result in shorter larval development which translates into smaller and lighter flies. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, DHR4 has a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 601984548 177 ESAKETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGNRHndYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGG 256
Cdd:cd07168    1 DEDESPKLCSICEDKATGLHYGIITCEGCKGFFKRTVQNKRV--YTCVGDGRCEITKAQRNRCQYCRFRKCIRKGMMLAA 78

                         90
                 ....*....|
gi 601984548 257 IRKDRR-GGR 265
Cdd:cd07168   79 VREDRMpGGR 88

DNA-binding domain of Tailless (TLX) is composed of two C4-type zinc fingers; DNA-binding domain of Tailless (TLX) is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. TLX interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. TLX is an orphan receptor that is expressed by neural stem/progenitor cells in the adult brain of the subventricular zone (SVZ) and the dentate gyrus (DG). It plays a key role in neural development by promoting cell cycle progression and preventing apoptosis in the developing brain. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, TLX has a central well conserved DNA-binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 601984548 185 CAVCNDYASGYHYGVWSCEGCKAFFKRSIQGNRHndYMCPATNQ--CTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDR 261
Cdd:cd07163    9 CKVCGDRSSGKHYGIYACDGCSGFFKRSIRRNRQ--YVCKSKGQggCPVDKTHRNQCRACRLKKCFEVGMNKDAVQHER 85

DNA-binding domain of glucocorticoid receptor (GR) is composed of two C4-type zinc fingers; DNA-binding domains of glucocorticoid receptor (GR) and progesterone receptor (PR) are composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinate a single zinc atom. The DBD from both receptors interact with the same hormone response element (HRE), which is an imperfect palindrome GGTACAnnnTGTTCT, upstream of target genes and modulates the rate of transcriptional initiation. GR is a transcriptional regulator that mediates the biological effects of glucocorticoids and PR regulates genes controlled by progesterone. GR is expressed in almost every cell in the body and regulates genes controlling a wide variety of processes including the development, metabolism, and immune response of the organism. PR functions in a variety of biological processes including development of the mammary gland, regulating cell cycle progression, protein processing, and metabolism. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, GR and PR have a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a non-conserved hinge and a C-terminal ligand binding domain (LBD).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 601984548 183 RYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGnrHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGG 256
Cdd:cd07172    3 KICLVCSDEASGCHYGVLTCGSCKVFFKRAVEG--QHNYLCAGRNDCIIDKIRRKNCPACRLRKCLQAGMNLGA 74

The DNA-binding domain of the photoreceptor cell-specific nuclear receptor (PNR) nuclear receptor-like family; The DNA-binding domain of the photoreceptor cell-specific nuclear receptor (PNR) nuclear receptor-like family is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which coordinates a single zinc atom. PNR interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. This family includes nuclear receptor Tailless (TLX), photoreceptor cell-specific nuclear receptor (PNR) and related receptors. TLX is an orphan receptor that plays a key role in neural development by regulating cell cycle progression and exit of neural stem cells in the developing brain. PNR is expressed only in the outer layer of retinal photoreceptor cells. It may be involved in the signaling pathway regulating photoreceptor differentiation and/or maintenance. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, PNR-like receptors have a central well-conserved DNA-binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 601984548 185 CAVCNDYASGYHYGVWSCEGCKAFFKRSIQGNRhnDYMCPATN-QCTIDKNRRKSCQACRLRKCYEVGMMKGGIR 258
Cdd:cd07154    1 CKVCGDRSSGKHYGVYACDGCSGFFKRSIRRNL--LYTCKAGNgSCVVDKARRNQCQACRLKKCLEVSMNKDAVQ 73

DNA-binding domain of androgen receptor (AR) is composed of two C4-type zinc fingers; DNA-binding domain of androgen receptor (AR) is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. To regulate gene expression, AR interacts with a palindrome of the core sequence 5'-TGTTCT-3' with a 3-bp spacer. It also binds to the direct repeat 5'-TGTTCT-3' hexamer in some androgen controlled genes. AR is activated by the androgenic hormones, testosterone or dihydrotestosterone, which are responsible for primary and for secondary male characteristics, respectively. The primary mechanism of action of ARs is by direct regulation of gene transcription. The binding of androgen results in a conformational change in the androgen receptor which causes its transport from the cytosol into the cell nucleus, and dimerization. The receptor dimer binds to a hormone response element of AR regulated genes and modulates their expression. Another mode of action of androgen receptor is independent of their interactions with DNA. The receptor interacts directly with signal transduction proteins in the cytoplasm, causing rapid changes in cell function, such as ion transport. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, AR has a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 601984548 181 ETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGNRhnDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGiRKD 260
Cdd:cd07173    2 PQKTCLICGDEASGCHYGALTCGSCKVFFKRAAEGKQ--KYLCASRNDCTIDKFRRKNCPSCRLRKCFEAGMTLGA-RKL 78

                 ....
gi 601984548 261 RRGG 264
Cdd:cd07173   79 KKLG 82

DNA-binding domain of Drosophila ecdysone-induced protein 78 (E78) like is composed of two C4-type zinc fingers; DNA-binding domain of proteins similar to Drosophila ecdysone-induced protein 78 (E78) is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which coordinates a single zinc atom. E78 interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. Drosophila ecdysone-induced protein 78 (E78) is a transcription factor belonging to the nuclear receptor superfamily. E78 is a product of the ecdysone-inducible gene found in an early late puff locus at position 78C during the onset of Drosophila metamorphosis. An E78 orthologue from the Platyhelminth Schistosoma mansoni (SmE78) has also been identified. It is the first E78 orthologue known outside of the molting animals--the Ecdysozoa. The SmE78 may be involved in transduction of an ecdysone signal in S. mansoni, consistent with its function in Drosophila. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, E78-like receptors have a central well conserved DNA-binding domain (DBD), a variable N-terminal domain, a non-conserved hinge and a C-terminal ligand binding domain (LBD).

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gi 601984548 185 CAVCNDYASGYHYGVWSCEGCKAFFKRSIQgnRHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDRRGG 264
Cdd:cd07165    1 CKVCGDKASGYHYGVTSCEGCKGFFRRSIQ--KQIEYRCLRDGKCEIIRLNRNRCQYCRFKKCLAAGMSKDSVRYGRIPN 78

                 ..
gi 601984548 265 RM 266
Cdd:cd07165   79 RQ 80

The DNA binding domain of GR_like nuclear receptors is composed of two C4-type zinc fingers; The DNA binding domain of GR_like nuclear receptors is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. It interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. This family of NRs includes four types of nuclear hormone receptors: glucocorticoid receptor (GR), mineralocorticoid receptor (MR), progesterone receptor (PR), and androgen receptor (AR). The receptors bind to common DNA elements containing a partial palindrome of the core sequence 5'-TGTTCT-3' with a 3bp spacer. These four receptors regulate some of the most fundamental physiological functions such as the stress response, metabolism, electrolyte homeostasis, immune function, growth, development, and reproduction. The NRs in this family have high sequence homology and share similar functional mechanisms. The dominant mechanism of function is by direct DNA binding and transcriptional regulation of target genes . The GR, MR, PR, and AR exhibit same modular structure. They have a central highly conserved DNA binding domain (DBD), a non-conserved N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD).

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gi 601984548 185 CAVCNDYASGYHYGVWSCEGCKAFFKRSIQGnRHNdYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGG 256
Cdd:cd06963    1 CLICGDEASGCHYGVLTCGSCKVFFKRAAEG-QHN-YLCAGRNDCIIDKIRRKNCPACRLRKCYQAGMTLGA 70

DNA-binding domain of Retinoid-related orphan receptors (RORs) is composed of two C4-type zinc fingers; DNA-binding domain of Retinoid-related orphan receptors (RORs) is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which coordinates a single zinc atom. ROR interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. RORS are key regulators of many physiological processes during embryonic development. RORs bind as monomers to specific ROR response elements (ROREs) consisting of the consensus core motif AGGTCA preceded by a 5-bp A/T-rich sequence. There are three subtypes of retinoid-related orphan receptors (RORs), alpha, beta, and gamma, which differ only in N-terminal sequence and are distributed in distinct tissues. RORalpha plays a key role in the development of the cerebellum particularly in the regulation of the maturation and survival of Purkinje cells. RORbeta expression is largely restricted to several regions of the brain, the retina, and pineal gland. RORgamma is essential for lymph node organogenesis. Recently, it has been suggested that cholesterol or a cholesterol derivative are the natural ligands of RORalpha. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, retinoid-related orphan receptors have a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a non-conserved hinge and a C-terminal ligand binding domain (LBD).

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gi 601984548 185 CAVCNDYASGYHYGVWSCEGCKAFFKRSIQGNRhnDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKdrrgG 264
Cdd:cd06968    8 CKICGDKSSGIHYGVITCEGCKGFFRRSQQNNV--SYSCPRQKNCLIDRTNRNRCQHCRLQKCLALGMSRDAVKF----G 81

                         90
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gi 601984548 265 RMLKHKRQRDDGE 277
Cdd:cd06968   82 RMSKKQRDSLYAE 94

DNA-binding domain of constitutive androstane receptor (CAR) is composed of two C4-type zinc fingers; DNA-binding domain (DBD) of constitutive androstane receptor (CAR) is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. CAR DBD interacts with CAR response element, a perfect repeat of two AGTTCA motifs with a 4 bp spacer upstream of the target gene, and modulates the rate of transcriptional initiation. The constitutive androstane receptor (CAR) is a ligand-regulated transcription factor that responds to a diverse array of chemically distinct ligands, including many endogenous compounds and clinical drugs. It functions as a heterodimer with RXR. The CAR/RXR heterodimer binds many common response elements in the promoter regions of a diverse set of target genes involved in the metabolism, transport, and ultimately, elimination of these molecules from the body. CAR is a closest mammalian relative of PXR and is activated by some of the same ligands as PXR and regulates a subset of common genes. The sequence homology and functional similarity suggests that the CAR gene arose from a duplication of an ancestral PXR gene. Like other nuclear receptors, CAR has a central well conserved DNA binding domain, a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain.

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gi 601984548 183 RYCAVCNDYASGYHYGVWSCEGCKAFFKRSiqGNRHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRkdRR 262
Cdd:cd06966    1 KICGVCGDKALGYNFNAITCESCKAFFRRN--ALKNKEFKCPFNESCEINVVTRRFCQKCRLDKCFAIGMKKEWIM--SE 76

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gi 601984548 263 GGRMLKHKR 271
Cdd:cd06966   77 EDKSEKRQK 85

DNA-binding domain of the TR2 and TR4 (human testicular receptor 2 and 4) is composed of two C4-type zinc fingers; DNA-binding domain of the TR2 and TR4 (human testicular receptor 2 and 4) is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which coordinates a single zinc atom. TR2 and TR4 interact with specific DNA sites upstream of the target gene and modulate the rate of transcriptional initiation. TR4 and TR2 are orphan nuclear receptors; the physiological ligand is as yet unidentified. TR2 is abundantly expressed in the androgen-sensitive prostate. TR4 transcripts are expressed in many tissues, including central nervous system, adrenal gland, spleen, thyroid gland, and prostate. It has been shown that human TR2 binds to a wide spectrum of natural hormone response elements (HREs) with distinct affinities suggesting that TR2 may cross-talk with other gene expression regulation systems. The genes responding to TR2 or TR4 include genes that are regulated by retinoic acid receptor, vitamin D receptor, and peroxisome proliferator-activated receptor. TR4/2 binds to HREs as dimers. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, TR2-like receptors have a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD).

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gi 601984548 184 YCAVCNDYASGYHYGVWSCEGCKAFFKRSIQgnRHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDRR 262
Cdd:cd06967    5 LCVVCGDKASGRHYGAVSCEGCKGFFKRSIR--KNLGYSCRGSKDCVINKHHRNRCQYCRLQKCLAMGMKSDSVQCERK 81

The DNA-binding domain of Ecdysone receptor (EcR) like nuclear receptor family is composed of two C4-type zinc fingers; The DNA-binding domain of Ecdysone receptor (EcR) like nuclear receptor family is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. EcR interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. This family includes three types of nuclear receptors: Ecdysone receptor (EcR), Liver X receptor (LXR) and Farnesoid X receptor (FXR). The DNA binding activity is regulated by their corresponding ligands. The ligands for EcR are ecdysteroids; LXR is regulated by oxidized cholesterol derivatives or oxysterols; and bile acids control FXR's activities. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, EcR-like receptors have a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD).

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gi 601984548 185 CAVCNDYASGYHYGVWSCEGCKAFFKRSIqgNRHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGM 252
Cdd:cd06959    2 CVVCGDKASGFHYGVLSCEGCKGFFRRSV--TKGAVYACKFGNKCEMDMYMRRKCQECRLRKCKAAGM 67

DNA-binding domain of retinoid X receptor (RXR) is composed of two C4-type zinc fingers; DNA-binding domain of retinoid X receptor (RXR) is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. RXR functions as a DNA binding partner by forming heterodimers with other nuclear receptors including CAR, FXR, LXR, PPAR, PXR, RAR, TR, and VDR. All RXR heterodimers preferentially bind response elements composed of direct repeats of two AGGTCA sites with a 1-5 bp spacer. RXRs can play different roles in these heterodimers. RXR acts either as a structural component of the heterodimer complex, required for DNA binding but not acting as a receptor, or as both a structural and a functional component of the heterodimer, allowing 9-cis RA to signal through the corresponding heterodimer. In addition, RXR can also form homodimers, functioning as a receptor for 9-cis RA, independently of other nuclear receptors. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, RXR has a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD).

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gi 601984548 185 CAVCNDYASGYHYGVWSCEGCKAFFKRSIQgnRHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDR 261
Cdd:cd06956    3 CAICGDRASGKHYGVYSCEGCKGFFKRTVR--KDLTYTCRDNKDCLIDKRQRNRCQYCRYQKCLAMGMKREAVQEER 77