Oestrogen receptor;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1728949663  40 MYVETSKTGVFNYPEGATYDFGT----TAPVYSSTTLSYAPTSESFGSSSLAGFHSLNSVQPSPVVFLQTAPQLSPFIHH 115
Cdd:pfam02159   1 MYVESSKTAVYDYPEGATYDFAAaaaaSAPVYGSSTLSYSPPSEAFGSNSLGGFHSLNSVPPSPLVFLHPPPQLSPFLHP 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1728949663 116 HSQQVPYYLENEQGSFGMREAAAPAFYRPTSDNRRHNMRERLPTTNEKGSLSMESTKE 173
Cdd:pfam02159  81 PGQQVPYYLENEQSGYAVREAAPPAFYRPSSDNRRQSGRERLASTSDKGSLSMESAKE 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
                  ....*....|....*....|....*....|....*...
gi 1728949663 543 PAARSAAPMEEENQSQL-TTASASSHSMQSFYIGKEEE 579
Cdd:pfam12743   1 PANRGGAPMEEDNQSQLaTTGSTSSHSLQTYYITGEAE 38

Oestrogen receptor;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1728949663  40 MYVETSKTGVFNYPEGATYDFGT----TAPVYSSTTLSYAPTSESFGSSSLAGFHSLNSVQPSPVVFLQTAPQLSPFIHH 115
Cdd:pfam02159   1 MYVESSKTAVYDYPEGATYDFAAaaaaSAPVYGSSTLSYSPPSEAFGSNSLGGFHSLNSVPPSPLVFLHPPPQLSPFLHP 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1728949663 116 HSQQVPYYLENEQGSFGMREAAAPAFYRPTSDNRRHNMRERLPTTNEKGSLSMESTKE 173
Cdd:pfam02159  81 PGQQVPYYLENEQSGYAVREAAPPAFYRPSSDNRRQSGRERLASTSDKGSLSMESAKE 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1728949663 176 YCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMM 243
Cdd:pfam00105   1 LCKVCGDKASGYHYGVLTCEGCKGFFRRSIQKNIVYTCKFNKDCVIDKRNRNRCQYCRLKKCLEVGMS 68

Ligand binding domain of hormone receptors;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1728949663  341 ADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRN---QGKCVEGMVEIFD 417
Cdd:smart00430   1 AERQLLLTVEWAKSFPGFRELSLEDQIVLLKSFWFELLLLELAYRSVKLKKELLLAPDGTYIRPdavLELRKLFSPFLDR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1728949663  418 MLLATAARFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEkdyihrVLDKITDTLIHLMAKSGlsLQQQHRRLAQ 497
Cdd:smart00430  81 ILSELVKPLRELKLDDEEYALLKAIVLFNPAVPGLSEEGKEIVEK------LQEKYANALHDYYLKNY--PMNYPGRFAK 152

                          170
                   ....*....|.
gi 1728949663  498 LLLILSHIRHM 508
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
                  ....*....|....*....|....*....|....*...
gi 1728949663 543 PAARSAAPMEEENQSQL-TTASASSHSMQSFYIGKEEE 579
Cdd:pfam12743   1 PANRGGAPMEEDNQSQLaTTGSTSSHSLQTYYITGEAE 38

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 1728949663 306 MVRALLEAEPPIVYSEYDPNRPFNEASMMTLLTSLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWR 385
Cdd:cd07068     1 LLSALLVAEPDKLYAMNDPTGPDTEVSLLATLSDLADRELVHIISWAKHIPGFSDLSLNDQMHLLQSAWLEILMLGLVWR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1728949663 386 SMEHPGKLLFAPNLLLDRNQGKcVEGMVEIFDMLLATAARFRMMNLQGEEFVCLKSIILLNSGVYTflsstlksLEEKDY 465
Cdd:cd07068    81 SLPHPGKLVFAPDLLLDREQAR-VEGLLEIFDMLLQLVRRFRELGLQREEYVCLKAIILANSDVRH--------LEDREA 151

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1728949663 466 IHRVLDKITDTLIHLMAKSGLSlqQQHRRLAQLLLILSHIRHMSNKGMEHLYNMKCKNVVPLYDLLLEMLDA 537
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 1728949663 172 KETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDR 251
Cdd:cd07171     1 KDTHFCAVCSDYASGYHYGVWSCEGCKAFFKRSIQGHNDYICPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRRER 80

                  ..
gi 1728949663 252 RG 253
Cdd:cd07171    81 RG 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 1728949663 177 CAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDR 251
Cdd:cd07155     1 CLVCGDIASGYHYGVASCEACKAFFKRTIQGNLGYSCPSTSECEVDKKRRKSCQACRLQKCLKVGMLKEGVRLDR 75

Ligand-binding domain of nuclear receptor family 2; Ligand-binding domain (LBD) of nuclear receptor (NR) family 2: This is one of the major subfamily of nuclear receptors, including some well known nuclear receptors such as glucocorticoid receptor (GR), mineralocorticoid receptor (MR), estrogen receptor (ER), progesterone receptor (PR), and androgen receptor (AR), other related receptors. 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 non-conserved hinge and a C-terminal ligand binding domain (LBD).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1728949663 334 MTLLTSLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHP--GKLLFAPNLLLDRNQGKCvEG 411
Cdd:cd06930     1 PESLCELADRVLFKTVDWAKNLPAFRNLPLDDQLTLLQNSWAELLLLGLAQRSVHFElsELLLPSPLLVILTEREAL-LG 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1728949663 412 MVEIFDMLLATAARFRMMNLQGEEFVCLKSIILLNSGVytflsstlKSLEEKDYIHRVLDKITDTLIHLMAKSGlslQQQ 491
Cdd:cd06930    80 LAELVQRLQELLSKLRSLQLDPKEYACLKAIVLFNPDL--------PGLKNQQQVEELQEKAQQALQEYIRKRY---PQQ 148

                         170
                  ....*....|....*..
gi 1728949663 492 HRRLAQLLLILSHIRHM 508
Cdd:cd06930   149 PARFAKLLLRLPELRSI 165

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 1728949663 175 RYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDR-RG 253
Cdd:cd07170     5 RLCLVCGDIASGYHYGVASCEACKAFFKRTIQGNIEYSCPATNECEITKRRRKSCQACRFMKCLKVGMLKEGVRLDRvRG 84

                          90
                  ....*....|....*..
gi 1728949663 254 GRmMKQKRQkeePDSKN 270
Cdd:cd07170    85 GR-QKYKRR---IDAEN 97

c4 zinc finger in nuclear hormone receptors;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1728949663  177 CAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMK 244
Cdd:smart00399   2 CCVCGDHASGFHFGVCSCRACKAFFRRTVNLRYKYRCDRKNNCSINKRYRCRCRACRLKKCLGVGMDP 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 1728949663 177 CAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDR 251
Cdd:cd06960     1 CAVCGDRATGKHYGVLSCNGCKGFFRRSVRKNRTYTCRFGGNCVVDKDKRNACRYCRFKKCLEVGMDPEAVQNER 75

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 1728949663 174 TRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDRRG 253
Cdd:cd06964     4 YKPCFVCQDKSSGYHYGVSACEGCKGFFRRSIQKNMVYTCHRDKNCIINKVTRNRCQYCRLQKCFEVGMSKESVRNDRNK 83

                  ..
gi 1728949663 254 GR 255
Cdd:cd06964    84 KK 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 1728949663 169 ESTKETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIR 248
Cdd:cd07168     1 DEDESPKLCSICEDKATGLHYGIITCEGCKGFFKRTVQNKRVYTCVGDGRCEITKAQRNRCQYCRFRKCIRKGMMLAAVR 80

                  ....*...
gi 1728949663 249 KDRR-GGR 255
Cdd:cd07168    81 EDRMpGGR 88

DNA-binding domain of the orphan nuclear receptor, nerve growth factor-induced-B; DNA-binding domain (DBD) of the orphan nuclear receptor, nerve growth factor-induced-B (NGFI-B) 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. NGFI-B interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. NGFI-B is a member of the nuclear-steroid receptor superfamily. NGFI-B is classified as an orphan receptor because no ligand has yet been identified. NGFI-B is an early immediate gene product of embryo development that is rapidly produced in response to a variety of cellular signals including nerve growth factor. It is involved in T-cell-mediated apoptosis, as well as neuronal differentiation and function. NGFI-B regulates transcription by binding to a specific DNA target upstream of its target genes and regulating the rate of transcriptional initiation. NGFI-B binds to the NGFI-B response element (NBRE) 5'-(A/T)AAAGGTCA as a monomer. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, NGFI-B 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 1728949663 177 CAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIR 248
Cdd:cd06969     3 CAVCGDNAACQHYGVRTCEGCKGFFKRTVQKNAKYVCLANKNCPVDKRRRNRCQYCRFQKCLQVGMVKEVVR 74

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 1728949663 175 RYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGG 246
Cdd:cd07172     3 KICLVCSDEASGCHYGVLTCGSCKVFFKRAVEGQHNYLCAGRNDCIIDKIRRKNCPACRLRKCLQAGMNLGA 74

DNA-binding domain of Germ cell nuclear factor (GCNF) F1 is composed of two C4-type zinc fingers; DNA-binding domain of Germ cell nuclear factor (GCNF) F1 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. GCNF is a transcription factor expressed in post-meiotic stages of developing male germ cells. In vitro, GCNF has the ability to bind to direct repeat elements of 5'-AGGTCA.AGGTCA-3', as well as to an extended half-site sequence 5'-TCA.AGGTCA-3'. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, GCNF 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 1728949663 172 KETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDR 251
Cdd:cd07169     4 AEQRTCLICGDRATGLHYGIISCEGCKGFFKRSICNKRVYRCSRDKNCVMSRKQRNRCQYCRLLKCLQMGMNRKAIREDG 83

                  ....*
gi 1728949663 252 -RGGR 255
Cdd:cd07169    84 mPGGR 88

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 1728949663 173 ETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGiRKDRR 252
Cdd:cd07173     2 PQKTCLICGDEASGCHYGALTCGSCKVFFKRAAEGKQKYLCASRNDCTIDKFRRKNCPSCRLRKCFEAGMTLGA-RKLKK 80

                  ..
gi 1728949663 253 GG 254
Cdd:cd07173    81 LG 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).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1728949663 177 CAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKdrrgGRM 256
Cdd:cd07165     1 CKVCGDKASGYHYGVTSCEGCKGFFRRSIQKQIEYRCLRDGKCEIIRLNRNRCQYCRFKKCLAAGMSKDSVRY----GRI 76

                  ....*
gi 1728949663 257 MKQKR 261
Cdd:cd07165    77 PNRQR 81

DNA-binding domain of vitamin D receptors (VDR) is composed of two C4-type zinc fingers; DNA-binding domain of vitamin D receptors (VDR) is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which coordinates a single zinc atom. VDR interacts with a VDR response element, a direct repeat of GGTTCA DNA site with 3 bp spacer upstream of the target gene, and modulates the rate of transcriptional initiation. VDR is a member of the nuclear receptor (NR) superfamily that functions as classical endocrine receptors. VDR controls a wide range of biological activities including calcium metabolism, cell proliferation and differentiation, and immunomodulation. VDR is a high-affinity receptor for the biologically most active Vitamin D metabolite, 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3). The binding of the ligand to the receptor induces a conformational change of the ligand binding domain (LBD) with consequent dissociation of corepressors. Upon ligand binding, VDR forms a heterodimer with the retinoid X receptor (RXR) that binds to vitamin D response elements (VDREs), recruits coactivators. This leads to the expression of a large number of genes. Approximately 200 human genes are considered to be primary targets of VDR and even more genes are regulated indirectly. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, VDR 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 1728949663 175 RYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDR--R 252
Cdd:cd06955     7 RICGVCGDRATGFHFNAMTCEGCKGFFRRSMKRKALFTCPFNGDCRITKDNRRHCQACRLKRCVDIGMMKEFILTDEevQ 86

                          90
                  ....*....|...
gi 1728949663 253 GGRMMKQKRQKEE 265
Cdd:cd06955    87 RKREMILKRKEEE 99

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 1728949663 176 YCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDRR 252
Cdd:cd06967     5 LCVVCGDKASGRHYGAVSCEGCKGFFKRSIRKNLGYSCRGSKDCVINKHHRNRCQYCRLQKCLAMGMKSDSVQCERK 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 1728949663 177 CAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGM 242
Cdd:cd06959     2 CVVCGDKASGFHYGVLSCEGCKGFFRRSVTKGAVYACKFGNKCEMDMYMRRKCQECRLRKCKAAGM 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 1728949663 177 CAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDR 251
Cdd:cd06956     3 CAICGDRASGKHYGVYSCEGCKGFFKRTVRKDLTYTCRDNKDCLIDKRQRNRCQYCRYQKCLAMGMKREAVQEER 77

Ligand binding domain of the progesterone receptor, a member of the nuclear hormone receptor; The ligand binding domain of the progesterone receptor (PR): PR is a member of the nuclear receptor superfamily of ligand dependent transcription factors, mediating the biological actions of progesterone. PR functions in a variety of biological processes including development of the mammary gland, regulating cell cycle progression, protein processing, and metabolism. When no binding hormone is present the carboxyl terminal inhibits transcription. Binding to a hormone induces a structural change that removes the inhibitory action. After progesterone binds to the receptor, PR forms a dimer and the complex enters the nucleus where it interacts with the hormone response element (HRE) in the promoters of progesterone responsive genes and alters their transcription. In addition, rapid actions of PR that occur independent of transcription, have also been observed in several tissues like brain, liver, mammary gland and spermatozoa. There are two natural PR isoforms called PR-A and PR-B. PR-B has an additional stretc h of 164 amino acids at the N terminus. The extra domain in PR-B performs activation functions by recruiting coactivators that could not be recruited by PR-A. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, PR 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). The LBD is not only involved in binding to progesterone, but also involved in coactivator binding and dimerization.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1728949663 305 QMVRALLEAEPPIVYSEYDPNRPFNEASMMTLLTSLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVW 384
Cdd:cd07074     1 PLINLLMSIEPDVVYAGYDNTKPETPSSLLTSLNQLCERQLLSVVKWSKSLPGFRNLHIDDQITLIQYSWMSLMVFGLGW 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1728949663 385 RSMEH--PGKLLFAPNLLLDRNQGKcvegMVEIFDMLLAT---AARFRMMNLQGEEFVCLKSIILLNS 447
Cdd:cd07074    81 RSYKHvsGQMLYFAPDLILNEQRMK----ESSFYSLCLTMwqiPQEFVKLQVSQEEFLCMKALLLLNT 144

DNA-binding domain of peroxisome proliferator-activated receptors (PPAR) is composed of two C4-type zinc fingers; DNA-binding domain of peroxisome proliferator-activated receptors (PPAR) 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. PPAR interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily of ligand-activated transcription factors. PPARs play important roles in regulating cellular differentiation, development and lipid metabolism. Activated PPAR forms a heterodimer with the retinoid X receptor (RXR) that binds to the hormone response elements, which are composed of two direct repeats of the consensus sequence 5'-AGGTCA-3' separated by one to five base pair located upstream of the peroxisome proliferator responsive genes, and interacts with co-activators. Several essential fatty acids, oxidized lipids and prostaglandin J derivatives can bind and activate PPAR. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, PPAR has a central well conserved DNA binding domain (DBD), a variable N-terminal regulatory domain, a flexible hinge and a C-terminal ligand binding domain (LBD).

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1728949663 177 CAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMcPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKdrrgGRM 256
Cdd:cd06965     2 CRVCGDKASGFHYGVHACEGCKGFFRRTIRLKLVYK-PCDLSCKIHKKSRNKCQYCRFQKCLNVGMSHNAIRF----GRM 76

                  ....*..
gi 1728949663 257 MKQKRQK 263
Cdd:cd06965    77 PRVEKEK 83

The second DNA-binding domain (DBD) of the 2DBD nuclear receptor is composed of two C4-type zinc fingers; The second DNA-binding domain (DBD) of the 2DBD nuclear receptor (NR) 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. NRs interact with specific DNA sites upstream of the target gene and modulate the rate of transcriptional initiation. The proteins contain two DBDs in tandem, probably resulting from an ancient recombination event. The 2DBD-NRs are found only in flatworm species, mollusks and arthropods. Their biological function is unknown.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1728949663 177 CAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIR 248
Cdd:cd07179     1 CRVCGGKSSGFHFGALTCEGCKGFFRRTELSSNSYVCPGGQNCAITPATRNACKSCRFRRCLAVGMSKTGSR 72

DNA-binding domain of REV-ERB receptor-like is composed of two C4-type zinc fingers; DNA-binding domain of REV-ERB receptor- like 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. REV-ERB receptors are transcriptional regulators belonging to the nuclear receptor superfamily. They regulate a number of physiological functions including the circadian rhythm, lipid metabolism, and cellular differentiation. REV-ERB receptors bind as a monomer to a (A/G)GGTCA half-site with a 5' AT-rich extension or as a homodimer to a direct repeat 2 element (AGGTCA sequence with a 2-bp spacer), indicating functional diversity. When bound to the DNA, they recruit corepressors (NcoR/histone deacetylase 3) to the promoter, resulting in repression of the target genes. The porphyrin heme has been demonstrated to function as a ligand for REV-ERB receptor. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, REV-ERB 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 1728949663 177 CAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDY-MCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKdrrgGR 255
Cdd:cd07166     6 CKVCGDKASGFHYGVHACEGCKGFFRRSIQQKIQYrKCTKNETCSIMRINRNRCQYCRFKKCLAVGMSRDAVRF----GR 81

                  ....*...
gi 1728949663 256 MMKQKRQK 263
Cdd:cd07166    82 IPKREKAR 89

The DNA-binding domain of peroxisome proliferator-activated receptors (PPAR) like nuclear receptor family; The DNA-binding domain of peroxisome proliferator-activated receptors (PPAR) 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. These domains interact with specific DNA sites upstream of the target gene and modulate the rate of transcriptional initiation. This family includes three known types of nuclear receptors: peroxisome proliferator-activated receptors (PPAR), REV-ERB receptors and Drosophila ecdysone-induced protein 78 (E78). Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, PPAR-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).