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 755496358 111 SMPKRLCLVCGDIASGYHYGVASCEACKAFFKRTIQGNIEYSCPATNECEITKRRRKSCQACRFMKCLKVGMLKEGVRLD 190
Cdd:cd07170    1 TIPKRLCLVCGDIASGYHYGVASCEACKAFFKRTIQGNIEYSCPATNECEITKRRRKSCQACRFMKCLKVGMLKEGVRLD 80

                         90
                 ....*....|....*..
gi 755496358 191 RVRGGRQKYKRRIDAEN 207
Cdd:cd07170   81 RVRGGRQKYKRRIDAEN 97

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 755496358 111 SMPKRLCLVCGDIASGYHYGVASCEACKAFFKRTIQGNIEYSCPATNECEITKRRRKSCQACRFMKCLKVGMLKEGVRLD 190
Cdd:cd07170    1 TIPKRLCLVCGDIASGYHYGVASCEACKAFFKRTIQGNIEYSCPATNECEITKRRRKSCQACRFMKCLKVGMLKEGVRLD 80

                         90
                 ....*....|....*..
gi 755496358 191 RVRGGRQKYKRRIDAEN 207
Cdd:cd07170   81 RVRGGRQKYKRRIDAEN 97

c4 zinc finger in nuclear hormone receptors;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755496358   116 LCLVCGDIASGYHYGVASCEACKAFFKRTIQGNIEYSCPATNECEITKRRRKSCQACRFMKCLKVGMLKE 185
Cdd:smart00399   1 LCCVCGDHASGFHFGVCSCRACKAFFRRTVNLRYKYRCDRKNNCSINKRYRCRCRACRLKKCLGVGMDPE 70

Ligand-binding domain of nuclear hormone receptor; This all helical domain is involved in binding the hormone in these receptors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755496358  255 TTLCDLADRELVVIIGWAKHIPGFSTLSLADQMSLLQSAWMEILILGVVYRSLSFEDELVYADDYIMDEDQSKLAGLLDL 334
Cdd:pfam00104  14 EELCELWERDLLLVAEWAKHFPEFQELPLEDQMALLKSFWLEWLRLEKAARSAKLRRKKILGEDVLMISDDDAMKFVEDD 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755496358  335 -------------------NNAILQLVKKYKSMKLEKEEFVTLKAIAL--ANSDSMHIEDVEAVQKLQDVLHEALQDYEA 393
Cdd:pfam00104  94 sswctnydleqllfflpffNSYFFELVKPLRELNPDDEELAYLLAQLLfdYAGDGLSGEILEIVEKLQEKLANELHDYYV 173

                         170       180
                  ....*....|....*....|....
gi 755496358  394 GQHmedPRRAGKMLMTLPLLRQTS 417
Cdd:pfam00104 174 NKY---SGRLAKLLKILPSLRKIS 194

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 755496358 226 IVSHLLVAEPEKIYAMPDPTVPDSDIKALTTLCDLADRELVVIIGWAKHIPGFSTLSLADQMSLLQSAWMEILILGVVYR 305
Cdd:cd07068    1 LLSALLVAEPDKLYAMNDPTGPDTEVSLLATLSDLADRELVHIISWAKHIPGFSDLSLNDQMHLLQSAWLEILMLGLVWR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755496358 306 SLSFEDELVYADDYIMDEDQSKLAGLLDLNNAILQLVKKYKSMKLEKEEFVTLKAIALANSDSMHIEDVEAVQKLQDVLH 385
Cdd:cd07068   81 SLPHPGKLVFAPDLLLDREQARVEGLLEIFDMLLQLVRRFRELGLQREEYVCLKAIILANSDVRHLEDREAVQQLRDAIL 160

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 755496358 386 EALQDYEAGQHM-EDPRRAGKMLMTLPLLRQTSTKAVQHFYNIKLEGKVPMHKLFLEMLEA 445
Cdd:cd07068  161 DALVDVEAKRHGsQQPRRLAQLLLLLPHLRQASNKGVRHLYSVKCEGKVPMYKLFLEMLEA 221

Ligand binding domain of Estrogen receptor, which are activated by the hormone 17beta-estradiol (estrogen); The ligand binding domain (LBD) of Estrogen receptor (ER): Estrogen receptor, a member of nuclear receptor superfamily, is 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. 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 flexible hinge and a C-terminal ligand binding domain (LBD). The C-terminal LBD also contains AF-2 activation motif, the dimerization motif, and part of the nuclear localization region. Estrogen receptor has been linked to aging, cancer, obesity and other diseases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755496358 226 IVSHLLVAEPEKIYAMPDPTVPDSDIKALTTLCDLADRELVVIIGWAKHIPGFSTLSLADQMSLLQSAWMEILILGVVYR 305
Cdd:cd06949    6 LISALLEAEPPHIYSEYDPTRPFTEASLMMLLTNLADRELVHMINWAKKIPGFVDLSLHDQVHLLESAWLELLMLGLVWR 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755496358 306 SLSFEDELVYADDYIMDEDQSK-LAGLLDLNNAILQLVKKYKSMKLEKEEFVTLKAIALANSDSM-----HIEDVEAVQK 379
Cdd:cd06949   86 SMEHPGKLLFAPDLLLDRNQGScVEGMVEIFDMLLATASRFRELQLQREEYVCLKAIILLNSSVYtflleSLESRRQVQR 165

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 755496358 380 LQDVLHEALQDYEAGQHM---EDPRRAGKMLMTLPLLRQTSTKAVQHFYNIKLEGKVPMHKLFLEMLEA 445
Cdd:cd06949  166 LLDKITDALVHACSKRGLslqQQSRRLAQLLLILSHIRHVSNKGMEHLYSMKCKNVVPLYDLLLEMLDA 234

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 755496358 254 LTTLCDLADRELVVIIGWAKHIPGFSTLSLADQMSLLQSAWMEILILGVVYRSLSFE--DELVYADDYIMDEDQSKLAGL 331
Cdd:cd06930    1 PESLCELADRVLFKTVDWAKNLPAFRNLPLDDQLTLLQNSWAELLLLGLAQRSVHFElsELLLPSPLLVILTEREALLGL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755496358 332 LDLNNAILQLVKKYKSMKLEKEEFVTLKAIALANSDSMHIEDVEAVQKLQDVLHEALQDYEAGQHMEDPRRAGKMLMTLP 411
Cdd:cd06930   81 AELVQRLQELLSKLRSLQLDPKEYACLKAIVLFNPDLPGLKNQQQVEELQEKAQQALQEYIRKRYPQQPARFAKLLLRLP 160

                 ....*
gi 755496358 412 LLRQT 416
Cdd:cd06930  161 ELRSI 165

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 755496358 113 PKRLCLVCGDIASGYHYGVASCEACKAFFKRTIQGNIEYSCPATNECEITKRRRKSCQACRFMKCLKVGMLKEGVRLDRV 192
Cdd:cd07171    2 DTHFCAVCSDYASGYHYGVWSCEGCKAFFKRSIQGHNDYICPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRRERR 81

                 .
gi 755496358 193 R 193
Cdd:cd07171   82 G 82

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 755496358  116 LCLVCGDIASGYHYGVASCEACKAFFKRTIQGNIEYSCPATNECEITKRRRKSCQACRFMKCLKVGM 182
Cdd:pfam00105   1 LCKVCGDKASGYHYGVLTCEGCKGFFRRSIQKNIVYTCKFNKDCVIDKRNRNRCQYCRLKKCLEVGM 67

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 755496358 234 EPEKIYAMPDPTVPDSDIK---ALTTLCDLADRELVVIIGWAKHIPGFSTLSLADQMSLLQSAWMEILILGVVYRSLSFE 310
Cdd:cd06943    9 EAELAVEPKSEAVAMVPPEyrdPVSNICQAADKQLFQLVEWAKRIPHFSELPLDDQVILLRAGWNELLIAAFAHRSIAVK 88

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755496358 311 DELVYADDYIMDEDQSKLAGLLDLNNAIL-QLVKKYKSMKLEKEEFVTLKAIALANSDSMHIEDVEAVQKLQDVLHEALQ 389
Cdd:cd06943   89 DGILLATGLHLHRNSAHQAGVGAIFDRILtELVVKMRDLKMDRTELGCLRAIILFNPDVKGLKSRQEVESLREKVYASLE 168

                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 755496358 390 DYEAGQHMEDPRRAGKMLMTLPLLRQTSTKAVQHFYNIK 428
Cdd:cd06943  169 EYCRQKHPEQPGRFAKLLLRLPALRSIGLKCLEHLFFFK 207

DNA-binding domain of thyroid hormone receptors (TRs) is composed of two C4-type zinc fingers; DNA-binding domain of thyroid hormone receptors (TRs) 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. TR interacts with the thyroid response element, which is a DNA site with direct repeats of the consensus sequence 5'-AGGTCA-3' separated by one to five base pairs, upstream of target genes and modulates the rate of transcriptional initiation. Thyroid hormone receptor (TR) mediates the actions of thyroid hormones, which play critical roles in growth, development, and homeostasis in mammals. They regulate overall metabolic rate, cholesterol and triglyceride levels, and heart rate, and affect mood. TRs are expressed from two separate genes (alpha and beta) in human and each gene generates two isoforms of the receptor through differential promoter usage or splicing. TRalpha functions in the heart to regulate heart rate and rhythm and TRbeta is active in the liver and other tissues. The unliganded TRs function as transcription repressors, by binding to thyroid hormone response elements (TRE) predominantly as homodimers, or as heterodimers with retinoid X-receptors (RXR), and being associated with a complex of proteins containing corepressor proteins. Ligand binding promotes corepressor dissociation and binding of a coactivator to activate transcription. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, TR 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 755496358 116 LCLVCGDIASGYHYGVASCEACKAFFKRTIQGNIEYSCPATNECEITKRRRKSCQACRFMKCLKVGMLKEGVRLDRVRGG 195
Cdd:cd06961    1 PCVVCGDKATGYHYRCITCEGCKGFFRRTVQKKLSYSCKGEGKCEIDKVTRNQCQECRFKKCIAVGMAKDLVLDDRKRGA 80

                 ....*
gi 755496358 196 RQKYK 200
Cdd:cd06961   81 KRKLI 85

Ligand binding domain of hormone receptors;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755496358   261 ADRELVVIIGWAKHIPGFSTLSLADQMSLLQSAWMEILILGVVYRSLSFEDELVYADDYIMDEDQ----SKLAGLLDLNN 336
Cdd:smart00430   1 AERQLLLTVEWAKSFPGFRELSLEDQIVLLKSFWFELLLLELAYRSVKLKKELLLAPDGTYIRPDavleLRKLFSPFLDR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755496358   337 AILQLVKKYKSMKLEKEEFVTLKAIALANSDSMHIED--VEAVQKLQDVLHEALQDYEAGQH-MEDPRRAGKMLMTLPLL 413
Cdd:smart00430  81 ILSELVKPLRELKLDDEEYALLKAIVLFNPAVPGLSEegKEIVEKLQEKYANALHDYYLKNYpMNYPGRFAKLLLILPEL 160

                   ...
gi 755496358   414 RQT 416
Cdd:smart00430 161 RKI 163

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 755496358 116 LCLVCGDIASGYHYGVASCEACKAFFKRTIQGNIEYSCPATNECEITKRRRKSCQACRFMKCLKVGMLKEGVR 188
Cdd:cd06969    2 LCAVCGDNAACQHYGVRTCEGCKGFFKRTVQKNAKYVCLANKNCPVDKRRRNRCQYCRFQKCLQVGMVKEVVR 74

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 755496358 115 RLCLVCGDIASGYHYGVASCEACKAFFKRTIQGNIEYSCPATNECEITKRRRKSCQACRFMKCLKVGMLKEGVRLDR 191
Cdd:cd06964    5 KPCFVCQDKSSGYHYGVSACEGCKGFFRRSIQKNMVYTCHRDKNCIINKVTRNRCQYCRLQKCFEVGMSKESVRNDR 81

The ligand binding domain of the liver receptor homolog-1, a member of nuclear receptor superfamily,; The ligand binding domain (LBD) of the liver receptor homolog-1 (LRH-1): LRH-1 belongs to nuclear hormone receptor superfamily, and is expressed mainly in the liver, intestine, exocrine pancreas, and ovary. Most nuclear receptors function as homodimer or heterodimers. However, LRH-1 binds DNA as a monomer, and is a regulator of bile-acid homeostasis, steroidogenesis, reverse cholesterol transport and the initial stages of embryonic development. Recently, phospholipids have been identified as potential ligand for LRH-1 and steroidogenic factor-1 (SF-1). Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, LRH-1 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 755496358 251 IKALTTLCDLADRELVVIIGWAKHIPGFSTLSLADQMSLLQSAWMEILILGVVYRSLSFEDE----LVYAD--DYIMDED 324
Cdd:cd07069   39 LSTFGLMCKMADQTLFSIVEWARSSIFFRELKVDDQMKLLQNCWSELLILDHIYRQVVHGKEgsifLVTGQqvDYSIIAS 118

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755496358 325 QSKlAGLLDLNNAILQLVKKYKSMKLEKEEFVTLKAIALANSDSMHIEDVEAVQKLQDVLHEALQDYEAGQHMEDPRRAG 404
Cdd:cd07069  119 QAG-ATLNNLMSHAQELVAKLRSLQFDQREFVCLKFLVLFSLDVKNLENFQLVEGVQEQVNAALLDYTMCNYPQQTEKFG 197

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 755496358 405 KMLMTLPLLRQTSTKAVQHFYNIKLEGKVPMHKLFLEMLEAK 446
Cdd:cd07069  198 QLLLRLPEIRAISMQAEEYLYYKHLNGDVPYNNLLIEMLHAK 239

The ligand binding domain of FTZ-F1 like nuclear receptors; The ligand binding domain of FTZ-F1 like nuclear receptors: This nuclear receptor family includes at least three subgroups of receptors that function in embryo development and differentiation, and other processes. FTZ-F1 interacts with the cis-acting DNA motif of ftz gene, which required at several stages of development. Particularly, FTZ-F1 genes are strongly linked to steroid biosynthesis and sex-determination; LRH-1 is a regulator of bile-acid homeostasis, steroidogenesis, reverse cholesterol transport and the initial stages of embryonic development. SF-1 is an essential regulator of endocrine development and function and is considered a master regulator of reproduction; SF-1 functions cooperatively with other transcription factors to modulate gene expression. Phospholipids have been identified as potential ligand for LRH-1 and steroidogenic factor-1 (SF-1). However, the ligand for FTZ-F1 has not yet been identified. Most nuclear receptors function as homodimer or heterodimers. However, LRH-1 and SF-1 bind to DNA as a monomer. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, receptors in this family 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 755496358 257 LCDLADRELVVIIGWAKHIPGFSTLSLADQMSLLQSAWMEILILGVVYRSL--SFEDELVYADDYIMDEDQSKLAGLLDL 334
Cdd:cd06944   43 MCKMADQTLFSIVEWARNSVFFKELKVDDQMKLLQNCWSELLVLDHIYRQVhhGKEDSILLVTGQEVDLSTLASQAGLGL 122

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755496358 335 NNAILQ---LVKKYKSMKLEKEEFVTLKAIALANSDSMHIEDVEAVQKLQDVLHEALQDYEAGQHMEDPRRAGKMLMTLP 411
Cdd:cd06944  123 SSLVDRaqeLVNKLRELQFDRQEFVCLKFLILFNPDVKGLENRQLVESVQEQVNAALLDYTLCNYPQQTDKFGQLLLRLP 202

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 755496358 412 LLRQTSTKAVQHFYNIKLEGKVPMHKLFLEMLEAK 446
Cdd:cd06944  203 EIRAISMQAEEYLYYKHLNGEVPCNNLLIEMLHAK 237

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 755496358 117 CLVCGDIASGYHYGVASCEACKAFFKRTIQGNIEYSCPATNECEITKRRRKSCQACRFMKCLKVGMLKEGVRLDRVR 193
Cdd:cd07165    1 CKVCGDKASGYHYGVTSCEGCKGFFRRSIQKQIEYRCLRDGKCEIIRLNRNRCQYCRFKKCLAAGMSKDSVRYGRIP 77

The ligand binding domain (LBD) of retinoic acid receptor (RAR), a members of the nuclear receptor superfamily; The ligand binding domain (LBD) of retinoic acid receptor (RAR): Retinoic acid receptors are members of the nuclear receptor (NR) superfamily of ligand-regulated transcription factors. RARs mediate the biological effect of retinoids, including both naturally 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. RARs function as heterodimers with retinoic X receptors by binding to specific RAR response elements (RAREs) found in the promoter regions of retinoid target genes. In the absence of ligand, the RAR-RXR heterodimer recruits the corepressor proteins NCoR or AMRT, and associated factors such as histone deacetylases or DNA-methyltransferases, leading to an inactive condensed chromatin structure, preventing transcription. Upon ligand binding, the corepressors are released, and coactivator complexes such as histone acetyltransferase or histone arginine methyltransferases are recruited to activate transcription. There are three RAR subtypes (alpha, beta, gamma), originating from three distinct genes. For each subtype, several isoforms exist that differ in their N-terminal region, allowing retinoids to exert their pleiotropic effects. 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 755496358 248 DSDIKALTTLCDLADRELVVIIGWAKHIPGFSTLSLADQMSLLQSAWMEILILGVVYRSLSFEDELVYADDYIMDEDQSK 327
Cdd:cd06937   34 RLDLGLWDKFSELSTKCIIKIVEFAKRLPGFTTLTIADQITLLKAACLDILILRICTRYTPEQDTMTFSDGLTLNRTQMH 113

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755496358 328 LAGLLDLNNAILQLVKKYKSMKLEKEEFVTLKAIALANSDSMHIEDVEAVQKLQDVLHEALQDYEAGQHMEDPRRAGKML 407
Cdd:cd06937  114 NAGFGPLTDLVFTFANQLLPLEMDDTEIGLLSAICLICGDRQDLEEPDRVEKLQEPLLEALKIYARKRRPDKPHMFPKML 193

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 755496358 408 MTLPLLRQTSTKAVQHFYNIKLEGKVPMHKLFLEMLE 444
Cdd:cd06937  194 MKITDLRSISAKGAERVITLKMEIPGPMPPLISEMLE 230

The ligand binding domain of heptocyte nuclear factor 4, which is explosively expanded in nematodes; The ligand binding domain of hepatocyte nuclear factor 4 (HNF4) like proteins: 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). The LBD domain is also responsible for recruiting co-activator proteins. More than 280 nuclear receptors are found in C. ele gans, most of which are originated from an explosive burst of duplications of HNF4.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755496358 227 VSHLLVAEPEKIYAMPDPTVPDSDIK-----ALTTLCDLADRELVVIIGWAKHIPGFSTLSLADQMSLLQSAWMEILILG 301
Cdd:cd06931    2 ISVLLQAEALSRQQSSPIPTCSGDIRpkkiaSINDVCESMKQQLLVLVEWAKYIPAFCELPLDDQVALLRAHAGEHLLLG 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755496358 302 VVYRSLSFEDELVYADDYIMDEDQSKLAGLLDLNNAILQLVKKYKSMKLEKEEFVTLKAIALANSDSMHIEDVEAVQKLQ 381
Cdd:cd06931   82 VARRSMPYKDILLLGNDLIIPRHCPEPEISRVANRILDELVLPLRDLNIDDNEYACLKAIVFFDPDAKGLSDPQKIKRLR 161

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 755496358 382 DVLHEALQDYEAGQHMEDPRRAGKMLMTLPLLRQTSTKAVQHFYNIKLEGKVPMHKLFLEM 442
Cdd:cd06931  162 FQVQVSLEDYINDRQYDSRGRFGELLLLLPTLQSITWQMIEQIQFARLFGVAKIDNLLQEM 222

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 755496358 117 CLVCGDIASGYHYGVASCEACKAFFKRTIQGNIEYSCPATNECEITKRRRKSCQACRFMKCLKVGMLKEGVRL 189
Cdd:cd07179    1 CRVCGGKSSGFHFGALTCEGCKGFFRRTELSSNSYVCPGGQNCAITPATRNACKSCRFRRCLAVGMSKTGSRI 73

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).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 755496358 117 CLVCGDIASGYHYGVASCEACKAFFKRTIQGNIEYS-CPATNECEITKRRRKSCQACRFMKCLKVGMLKEGVR 188
Cdd:cd07158    1 CKVCGDKASGFHYGVHSCEGCKGFFRRTIQHNLTYRrCLNGGKCVIQRKNRNRCQYCRFKKCLSVGMSRNAVR 73

DNA-binding domain of chicken ovalbumin upstream promoter transcription factors (COUP-TFs) is composed of two C4-type zinc fingers; DNA-binding domain of chicken ovalbumin upstream promoter transcription factors (COUP-TFs) 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. COUP-TFs are orphan members of the steroid/thyroid hormone receptor superfamily. They are expressed in many tissues and are involved in the regulation of several important biological processes, such as neurogenesis, organogenesis, cell fate determination, and metabolic homeostasis. COUP-TFs homodimerize or heterodimerize with retinoid X receptor (RXR) and a few other nuclear receptors and bind to a variety of response elements that are composed of imperfect AGGTCA direct or inverted repeats with various spacings. COUP-TFs are generally considered to be repressors of transcription for other nuclear hormone receptors such as retinoic acid receptor (RAR), thyroid hormone receptor (TR), vitamin D receptor (VDR), peroxisome proliferator activated receptor (PPAR), and hepatocyte nuclear factor 4 (HNF4). Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, COUP-TFs 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 755496358 117 CLVCGDIASGYHYGVASCEACKAFFKRTIQGNIEYSCPATNECEITKRRRKSCQACRFMKCLKVGMLKEGVR 188
Cdd:cd06958    1 CVVCGDKSSGKHYGQFTCEGCKSFFKRSVRRNLTYTCRGNRNCPIDQHHRNQCQYCRLKKCLKVGMRREAVQ 72

The ligand binding domain of Nurr1 and related nuclear receptor proteins, members of nuclear receptor superfamily; The ligand binding domain of nuclear receptor Nurr1_like: This family of nuclear receptors, including Nurr1, Nerve growth factor-induced-B (NGFI-B) and DHR38 are involved in the embryo development. Nurr1 is a transcription factor that is expressed in the embryonic ventral midbrain and is critical for the development of dopamine (DA) neurons. Structural studies have shown that the ligand binding pocket of Nurr1 is filled by bulky hydrophobic residues, making it unable to bind to ligands. Therefore, it belongs to the class of orphan receptors. However, Nurr1 forms heterodimers with RXR and can promote signaling via its partner, RXR. 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 tr anscriptional initiation. Another group of receptor in this family is DHR38. DHR38 is the Drosophila homolog to the vertebrate NGFI-B-type orphan receptor. It interacts with the USP component of the ecdysone receptor complex, suggesting that DHR38 might modulate ecdysone-triggered signals in the fly, in addition to the ECR/USP pathway. Nurr1_like proteins exhibit a modular structure that is characteristic for nuclear receptors; they 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 755496358 237 KIYAMPDPTVPDSDIKALTTLCDLADRELVVIIGWAKHIPGFSTLSLADQMSLLQSAWMEILILGVVYRSLSFEDELVYA 316
Cdd:cd06945   26 KIQENVDPVPPKPDSQQVQQFYDLLTGSVDVIRQWAEKIPGFKDLHREDQDLLLESAFLELFVLRLAYRSNPVDGKLVFC 105

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755496358 317 DDYIMDEDQSkLAGLLDLNNAILQLVKKYKSMKLEKEEFVTLKAIALANSDSMHIEDVEAVQKLQDVLHEALQDYEAGQH 396
Cdd:cd06945  106 NGLVLHRLQC-VRGFGEWLDSILAFSSSLQSLLLDDISAFCCLALLLLITERHGLKEPKKVEELQNKIISCLRDHVTSNY 184

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 755496358 397 --MEDPRRAGKMLMTLPLLRQTSTKAVQHFYNIKLEGKVPMHKLFLEMLEAKV 447
Cdd:cd06945  185 pgQDKPNRLSKLLLKLPELRTLSKKGLQRIFFLKLEDLLPPPPLIDKRFLDTL 237

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 755496358 115 RLCLVCGDIASGYHYGVASCEACKAFFKRTIQGNIEYSCPATNECEITKRRRKSCQACRFMKCLKVGMLKE 185
Cdd:cd06966    1 KICGVCGDKALGYNFNAITCESCKAFFRRNALKNKEFKCPFNESCEINVVTRRFCQKCRLDKCFAIGMKKE 71

DNA-binding domain of pregnane X receptor (PXRs) is composed of two C4-type zinc fingers; DNA-binding domain (DBD)of pregnane X receptor (PXR) 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. PXR DBD interacts with the PXR 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 pregnane X receptor (PXR) is a ligand-regulated transcription factor that responds to a diverse array of chemically distinct ligands, including many endogenous compounds and clinical drugs. PXR functions as a heterodimer with retinoic X receptor-alpha (RXRa) and binds to a variety of promoter regions of a diverse set of target genes involved in the metabolism, transport, and ultimately, elimination of these molecules from the body. Like other nuclear receptors, PXR has a central well conserved DNA-binding domain, a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755496358 116 LCLVCGDIASGYHYGVASCEACKAFFKRTIQGNIEYSCPATNECEITKRRRKSCQACRFMKCLKVGMLKEGVRLDRVRGG 195
Cdd:cd07162    1 ICRVCGDRATGYHFNAMTCEGCKGFFRRAMKRNARLCCPFQKGCVITKSNRRQCQACRLRKCLSIGMKKELIMSDEAVEK 80

                 ....*..
gi 755496358 196 RQKYKRR 202
Cdd:cd07162   81 RRALIKR 87