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 528509163 218 EMPVEKILEAEMAVEQKTElhaDGSSGGSSPNDPVTNICQAADKQLFTLVEWAKRIPHFSELSLDDQVILLRAGWNELLI 297
Cdd:cd06943    1 DMPIERILEAELAVEPKSE---AVAMVPPEYRDPVSNICQAADKQLFQLVEWAKRIPHFSELPLDDQVILLRAGWNELLI 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509163 298 ASFSHRSITVKDGILLATGLHVHRNSAHSAGVGAIFDResahnaevgaifdrVLTELVSKMRDMQMDKTELGCLRAIILF 377
Cdd:cd06943   78 AAFAHRSIAVKDGILLATGLHLHRNSAHQAGVGAIFDR--------------ILTELVVKMRDLKMDRTELGCLRAIILF 143

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 528509163 378 NPDAKGLSSPSEVELLREKVYASLEAYCKQRYPDQQGRFAKLLLRLPALRSIGLKCLEHLFFFK 441
Cdd:cd06943  144 NPDVKGLKSRQEVESLREKVYASLEEYCRQKHPEQPGRFAKLLLRLPALRSIGLKCLEHLFFFK 207

Nuclear/hormone receptor activator site AF-1; Nuclear receptors (NRs) are a family of ligand-inducible transcription factors, and, like other transcription factors, they contain a distinct DNA binding domain that allows for target gene recognition and several activation domains that possess the ability to activate transcription. One of these activation domains is at the N-terminal, although there are two distinct motifs within this domain, between residues 20-36 and between 74 and the end of this domain, which are the binding regions. One of the co-activators is TIF1beta, which appears to bind at the first motif.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509163   25 PPLAPSAAAMTSLPPITSAVNSPISSMGSPFSVISSSLGSP--CLPGTPSVGYGPISSPQINStvsmsgLHAVSSSDDVK 102
Cdd:pfam11825  19 PSYISASGSSRSLHSPMSTLGSPMNGLGSPYSVITSSMGPHslSLPSTPGMNFGTLNSPQLNS------MNSVSSSEDIK 92

                          90       100
                  ....*....|....*....|.
gi 528509163  103 PPFGLKPL-----SSHSPGPM 118
Cdd:pfam11825  93 PPPGLNGVgnmnyPATSPGSL 113

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 528509163 218 EMPVEKILEAEMAVEQKTElhaDGSSGGSSPNDPVTNICQAADKQLFTLVEWAKRIPHFSELSLDDQVILLRAGWNELLI 297
Cdd:cd06943    1 DMPIERILEAELAVEPKSE---AVAMVPPEYRDPVSNICQAADKQLFQLVEWAKRIPHFSELPLDDQVILLRAGWNELLI 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509163 298 ASFSHRSITVKDGILLATGLHVHRNSAHSAGVGAIFDResahnaevgaifdrVLTELVSKMRDMQMDKTELGCLRAIILF 377
Cdd:cd06943   78 AAFAHRSIAVKDGILLATGLHLHRNSAHQAGVGAIFDR--------------ILTELVVKMRDLKMDRTELGCLRAIILF 143

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 528509163 378 NPDAKGLSSPSEVELLREKVYASLEAYCKQRYPDQQGRFAKLLLRLPALRSIGLKCLEHLFFFK 441
Cdd:cd06943  144 NPDVKGLKSRQEVESLREKVYASLEEYCRQKHPEQPGRFAKLLLRLPALRSIGLKCLEHLFFFK 207

Ligand binding domain of hormone receptors;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509163   259 ADKQLFTLVEWAKRIPHFSELSLDDQVILLRAGWNELLIASFSHRSITVKDGILLATGLHVHRNSAHsagvgaifdreSA 338
Cdd:smart00430   1 AERQLLLTVEWAKSFPGFRELSLEDQIVLLKSFWFELLLLELAYRSVKLKKELLLAPDGTYIRPDAV-----------LE 69

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509163   339 HNAEVGAIFDRVLTELVSKMRDMQMDKTELGCLRAIILFNPDAKGLSSPS--EVELLREKVYASLEAYCKQRYPDQQ-GR 415
Cdd:smart00430  70 LRKLFSPFLDRILSELVKPLRELKLDDEEYALLKAIVLFNPAVPGLSEEGkeIVEKLQEKYANALHDYYLKNYPMNYpGR 149

                          170
                   ....*....|....
gi 528509163   416 FAKLLLRLPALRSI 429
Cdd:smart00430 150 FAKLLLILPELRKI 163

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 528509163  252 VTNICQAADKQLFTLVEWAKRIPHFSELSLDDQVILLRAGWNELLIASFSHRSITVKDGILLATGLHVHRNSAHSAGVGA 331
Cdd:pfam00104  13 KEELCELWERDLLLVAEWAKHFPEFQELPLEDQMALLKSFWLEWLRLEKAARSAKLRRKKILGEDVLMISDDDAMKFVED 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509163  332 IFDRESAHNAEVGAIF----DRVLTELVSKMRDMQMDKTELGCLRAIILFNPDAKGLSSPSE--VELLREKVYASLEAYC 405
Cdd:pfam00104  93 DSSWCTNYDLEQLLFFlpffNSYFFELVKPLRELNPDDEELAYLLAQLLFDYAGDGLSGEILeiVEKLQEKLANELHDYY 172

                         170       180
                  ....*....|....*....|....
gi 528509163  406 KQRYPDqqgRFAKLLLRLPALRSI 429
Cdd:pfam00104 173 VNKYSG---RLAKLLKILPSLRKI 193

Nuclear/hormone receptor activator site AF-1; Nuclear receptors (NRs) are a family of ligand-inducible transcription factors, and, like other transcription factors, they contain a distinct DNA binding domain that allows for target gene recognition and several activation domains that possess the ability to activate transcription. One of these activation domains is at the N-terminal, although there are two distinct motifs within this domain, between residues 20-36 and between 74 and the end of this domain, which are the binding regions. One of the co-activators is TIF1beta, which appears to bind at the first motif.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509163   25 PPLAPSAAAMTSLPPITSAVNSPISSMGSPFSVISSSLGSP--CLPGTPSVGYGPISSPQINStvsmsgLHAVSSSDDVK 102
Cdd:pfam11825  19 PSYISASGSSRSLHSPMSTLGSPMNGLGSPYSVITSSMGPHslSLPSTPGMNFGTLNSPQLNS------MNSVSSSEDIK 92

                          90       100
                  ....*....|....*....|.
gi 528509163  103 PPFGLKPL-----SSHSPGPM 118
Cdd:pfam11825  93 PPPGLNGVgnmnyPATSPGSL 113

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 528509163 218 EMPVEKILEAEMAVEQKTElhaDGSSGGSSPNDPVTNICQAADKQLFTLVEWAKRIPHFSELSLDDQVILLRAGWNELLI 297
Cdd:cd06943    1 DMPIERILEAELAVEPKSE---AVAMVPPEYRDPVSNICQAADKQLFQLVEWAKRIPHFSELPLDDQVILLRAGWNELLI 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509163 298 ASFSHRSITVKDGILLATGLHVHRNSAHSAGVGAIFDResahnaevgaifdrVLTELVSKMRDMQMDKTELGCLRAIILF 377
Cdd:cd06943   78 AAFAHRSIAVKDGILLATGLHLHRNSAHQAGVGAIFDR--------------ILTELVVKMRDLKMDRTELGCLRAIILF 143

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 528509163 378 NPDAKGLSSPSEVELLREKVYASLEAYCKQRYPDQQGRFAKLLLRLPALRSIGLKCLEHLFFFK 441
Cdd:cd06943  144 NPDVKGLKSRQEVESLREKVYASLEEYCRQKHPEQPGRFAKLLLRLPALRSIGLKCLEHLFFFK 207

Ligand binding domain of chicken ovalbumin upstream promoter transcription factors, a member of the nuclear receptor family; The ligand binding domain of chicken ovalbumin upstream promoter transcription factors (COUP-TFs): 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. In mammals two isoforms named COUP-TFI and COUP-TFII have been identified. Both genes show an exceptional homology and overlapping expression patterns, suggesting that they may serve redundant functions. Although COUP-TF was originally characterized as a transcriptional activator of the chicken ovalbumin gene, 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 cons erved 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 528509163 254 NICQAADKQLFTLVEWAKRIPHFSELSLDDQVILLRAGWNELLIASFSHRSITVKDGILLATglhvhrNSAHSAGVGAif 333
Cdd:cd06948   34 NICELAARLLFSAVEWARNIPFFPDLQVTDQVALLRLSWSELFVLNAAQCCMPLHVAPLLAA------AGLHASPMSA-- 105

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509163 334 DRESAHNAEVgaifdRVLTELVSKMRDMQMDKTELGCLRAIILFNPDAKGLSSPSEVELLREKVYASLEAYCKQRYPDQQ 413
Cdd:cd06948  106 DRVVAFMDHI-----RIFQEQVEKLKALHVDSAEFSCLKAIVLFTSDACGLSDPAHIESLQEKSQCALEEYVRTQYPNQP 180

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 528509163 414 GRFAKLLLRLPALRSIGLKCLEHLFFFKLIGDTPIDTFLMEML 456
Cdd:cd06948  181 TRFGKLLLRLPSLRTVSSSVIEQLFFVRLVGKTPIETLIRDML 223

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).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 528509163 124 LCAICGDRSSGKHYGVYSCEGCKGFFKRTVRKDLSYTCRDNKDCLVDKRQRNRCQYCRYQKCLAMGMKREAVQEER 199
Cdd:cd06956    2 ICAICGDRASGKHYGVYSCEGCKGFFKRTVRKDLTYTCRDNKDCLIDKRQRNRCQYCRYQKCLAMGMKREAVQEER 77

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 528509163 242 SSGGSSPNDPVTNICQAADKQLFTLVEWAKRIPHFSELSLDDQVILLRAGWNELLIASFSHRSIT--VKDGILLATGLHV 319
Cdd:cd06944   30 TYNRGEELDTFGLMCKMADQTLFSIVEWARNSVFFKELKVDDQMKLLQNCWSELLVLDHIYRQVHhgKEDSILLVTGQEV 109

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509163 320 HRNS-AHSAGVGaifdresahnaeVGAIFDRvLTELVSKMRDMQMDKTELGCLRAIILFNPDAKGLSSPSEVELLREKVY 398
Cdd:cd06944  110 DLSTlASQAGLG------------LSSLVDR-AQELVNKLRELQFDRQEFVCLKFLILFNPDVKGLENRQLVESVQEQVN 176

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509163 399 ASLEAYCKQRYPDQQGRFAKLLLRLPALRSIGLKCLEHLFFFKLIGDTPIDTFLMEMLEA 458
Cdd:cd06944  177 AALLDYTLCNYPQQTDKFGQLLLRLPEIRAISMQAEEYLYYKHLNGEVPCNNLLIEMLHA 236

Ligand binding domain of hormone receptors;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509163   259 ADKQLFTLVEWAKRIPHFSELSLDDQVILLRAGWNELLIASFSHRSITVKDGILLATGLHVHRNSAHsagvgaifdreSA 338
Cdd:smart00430   1 AERQLLLTVEWAKSFPGFRELSLEDQIVLLKSFWFELLLLELAYRSVKLKKELLLAPDGTYIRPDAV-----------LE 69

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509163   339 HNAEVGAIFDRVLTELVSKMRDMQMDKTELGCLRAIILFNPDAKGLSSPS--EVELLREKVYASLEAYCKQRYPDQQ-GR 415
Cdd:smart00430  70 LRKLFSPFLDRILSELVKPLRELKLDDEEYALLKAIVLFNPAVPGLSEEGkeIVEKLQEKYANALHDYYLKNYPMNYpGR 149

                          170
                   ....*....|....
gi 528509163   416 FAKLLLRLPALRSI 429
Cdd:smart00430 150 FAKLLLILPELRKI 163

The ligand binding domain of Tailless-like proteins, orphan nuclear receptors; The ligand binding domain of the photoreceptor cell-specific nuclear receptor (PNR) like family: This family includes photoreceptor cell-specific nuclear receptor (PNR), Tailless (TLX), and related receptors. 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. 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, TLX and PNR 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 528509163 246 SSPNDPVTNICQAADKQLFTLVEWAKRIPHFSELSLDDQVILLRAGWNELLIASFSHRSITVkDGILLATGLHVHRNSAH 325
Cdd:cd06950   22 SSYEVSPESVCESAARLLFMAVKWAKSIPAFSTLPFRDQLILLEESWSELFLLGAAQWSLPL-DSCPLLAVPGLSPDNTE 100

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509163 326 sagvgaifdRESAHNAEVgaifdRVLTELVSKMRDMQMDKTELGCLRAIILFNPDAKGLSSPSEVELLREKVYASLEAYC 405
Cdd:cd06950  101 ---------AERTFLSEV-----RALQETLSRFRQLRVDATEFACLKAIVLFKPETRGLKDPAQVEALQDQAQLMLNKHI 166

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 528509163 406 KQRYPDQQGRFAKLLLRLPALRSIGLKCLEHLFFFKLIGD 445
Cdd:cd06950  167 RTRYPTQPARFGKLLLLLPSLRFISSSTIEELFFKKTIGN 206

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).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 528509163 124 LCAICGDRSSGKHYGVYSCEGCKGFFKRTVRKDLSYTCRDNKDCLVDKRQRNRCQYCRYQKCLAMGMKREAVQEERQ 200
Cdd:cd06967    5 LCVVCGDKASGRHYGAVSCEGCKGFFKRSIRKNLGYSCRGSKDCVINKHHRNRCQYCRLQKCLAMGMKSDSVQCERK 81

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 528509163 125 CAICGDRSSGKHYGVYSCEGCKGFFKRTVRKDLSYTCRDNKDCLVDKRQRNRCQYCRYQKCLAMGMKREAVQEER 199
Cdd:cd06960    1 CAVCGDRATGKHYGVLSCNGCKGFFRRSVRKNRTYTCRFGGNCVVDKDKRNACRYCRFKKCLEVGMDPEAVQNER 75

DNA-binding domain of the photoreceptor cell-specific nuclear receptor (PNR) like proteins is composed of two C4-type zinc fingers; DNA-binding domain of the photoreceptor cell-specific nuclear receptor (PNR) like proteins 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. PNR interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. PNR is a member of nuclear receptor superfamily of the ligand-activated transcription factors. 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. It most likely binds to DNA as a homodimer. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, PNR 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 528509163 125 CAICGDRSSGKHYGVYSCEGCKGFFKRTVRKDLSYTCRDNKDCLVDKRQRNRCQYCRYQKCLAMGMKREAVQEERQ 200
Cdd:cd07164    1 CRVCGDRASGKHYGVPSCDGCRGFFKRSIRRNLAYVCKENGSCVVDVARRNQCQACRFKKCLQVNMNRDAVQHERA 76

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 528509163 125 CAICGDRSSGKHYGVYSCEGCKGFFKRTVRKDLSYTCRDNKDCLVDKRQRNRCQYCRYQKCLAMGMKREAVQ 196
Cdd:cd06958    1 CVVCGDKSSGKHYGQFTCEGCKSFFKRSVRRNLTYTCRGNRNCPIDQHHRNQCQYCRLKKCLKVGMRREAVQ 72

c4 zinc finger in nuclear hormone receptors;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509163   124 LCAICGDRSSGKHYGVYSCEGCKGFFKRTVRKDLSYTCRDNKDCLVDKRQRNRCQYCRYQKCLAMGMKRE 193
Cdd:smart00399   1 LCCVCGDHASGFHFGVCSCRACKAFFRRTVNLRYKYRCDRKNNCSINKRYRCRCRACRLKKCLGVGMDPE 70

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 528509163 123 RLCAICGDRSSGKHYGVYSCEGCKGFFKRTVRKDLSYTCRDNKDCLVDKRQRNRCQYCRYQKCLAMGMKREAVQEERQRN 202
Cdd:cd06964    5 KPCFVCQDKSSGYHYGVSACEGCKGFFRRSIQKNMVYTCHRDKNCIINKVTRNRCQYCRLQKCFEVGMSKESVRNDRNKK 84

                 .
gi 528509163 203 K 203
Cdd:cd06964   85 K 85

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 528509163 120 SQKRLCAICGDRSSGKHYGVYSCEGCKGFFKRTVRKDLSYTCRDNKDCLVDKRQRNRCQYCRYQKCLAMGMKREAVQEER 199
Cdd:cd07169    4 AEQRTCLICGDRATGLHYGIISCEGCKGFFKRSICNKRVYRCSRDKNCVMSRKQRNRCQYCRLLKCLQMGMNRKAIREDG 83

                 ....*..
gi 528509163 200 Q---RNK 203
Cdd:cd07169   84 MpggRNK 90

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).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509163 125 CAICGDRSSGKHYGVYSCEGCKGFFKRTVRKDLSYTCRDNKDCLVDKRQRNRCQYCRYQKCLAMGMKREAVQEERQRNKE 204
Cdd:cd06968    8 CKICGDKSSGIHYGVITCEGCKGFFRRSQQNNVSYSCPRQKNCLIDRTNRNRCQHCRLQKCLALGMSRDAVKFGRMSKKQ 87

                 ..
gi 528509163 205 RD 206
Cdd:cd06968   88 RD 89

The ligand binding domain of nuclear receptor steroidogenic factor 1, a member of nuclear receptor superfamily; The ligand binding domain of nuclear receptor steroidogenic factor 1 (SF-1): SF-1, a member of the nuclear hormone receptor superfamily, is an essential regulator of endocrine development and function and is considered a master regulator of reproduction. Most nuclear receptors function as homodimer or heterodimers, however SF-1 binds to its target genes as a monomer, recognizing the variations of the DNA sequence motif, T/CCA AGGTCA. SF-1 functions cooperatively with other transcription factors to modulate gene expression. Phospholipids have been determined as potential ligands of SF-1. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, SF-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 528509163 237 LHADGSSGGSSPNdPVTNICQAADKQLFTLVEWAKRIPHFSELSLDDQVILLRAGWNELLIASFSHRSI--TVKDGILLA 314
Cdd:cd07070   26 LQEPQKSRPDQPA-PFGLLCRMADQTFISIVDWARRCMVFKELEVADQMTLLQNCWSELLVFDHIYRQVqhGKEGSILLV 104

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509163 315 TGLHVHRnSAHSAGVGAIFdresaHNAEVGAifdrvlTELVSKMRDMQMDKTELGCLRAIILFNPDAKGLSSPSEVELLR 394
Cdd:cd07070  105 TGQEVEL-STVAAQAGSLL-----HSLVLRA------QELVLQLHALQLDRQEFVCLKFLILFSLDVKFLNNHSLVKDAQ 172

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 528509163 395 EKVYASLEAYCKQRYPDQQGRFAKLLLRLPALRSIGLKCLEHLFFFKLIGDTPIDTFLMEMLEA 458
Cdd:cd07070  173 EKANAALLDYTLCHYPHCGDKFQQLLLRLVEVRALSMQAKEYLYHKHLGNEMPRNNLLIEMLQA 236

Ligand-binding domain of nuclear receptor family 1; Ligand-binding domain (LBD) of nuclear receptor (NR) family 1: This is one of the major subfamily of nuclear receptors, including thyroid receptor, retinoid acid receptor, ecdysone receptor, farnesoid X receptor, vitamin D receptor, and 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 flexible hinge and a C-terminal ligand binding domain (LBD).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509163 266 LVEWAKRIPHFSELSLDDQVILLRAGWNELLIASFSHRSITVKDGILLATGLHVHRNSAHSAGVGAIFDResahnaevga 345
Cdd:cd06929   18 VVEFAKRIPGFRELSQEDQIALLKGGCFEILLLRSATLYDPEKNSLTFGDGKGNSRDVLLNGGFGEFIEP---------- 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509163 346 ifdrvLTELVSKMRDMQMDKTELGCLRAIILFNPDAKGLSSPSEVELLREKVYASLEAYCKQRYPDQQGRFAKLLLRLPA 425
Cdd:cd06929   88 -----LFEFAEKMNKLQLDDNEYALLTAIVLFSPDRPGLQDVDTVEKLQERLLEALQRYLKVNHPDAPQMFAKLLKKLTE 162

                        170
                 ....*....|..
gi 528509163 426 LRSIGLKCLEHL 437
Cdd:cd06929  163 LRTLNELHAELL 174

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 528509163 125 CAICGDRSSGKHYGVYSCEGCKGFFKRTVRKDLSYTCRDNKDCLVDKRQRNRCQYCRYQKCLAMGMKREAVQEERQRNKE 204
Cdd:cd07165    1 CKVCGDKASGYHYGVTSCEGCKGFFRRSIQKQIEYRCLRDGKCEIIRLNRNRCQYCRFKKCLAAGMSKDSVRYGRIPNRQ 80

                 .
gi 528509163 205 R 205
Cdd:cd07165   81 R 81

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).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509163 124 LCAICGDRSSGKHYGVYSCEGCKGFFKRTVRKDLSY-TCRDNkdCLVDKRQRNRCQYCRYQKCLAMGMKREAVQEERQRN 202
Cdd:cd06965    1 ECRVCGDKASGFHYGVHACEGCKGFFRRTIRLKLVYkPCDLS--CKIHKKSRNKCQYCRFQKCLNVGMSHNAIRFGRMPR 78

                 ...
gi 528509163 203 KER 205
Cdd:cd06965   79 VEK 81

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).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509163 124 LCAICGDRSSGKHYGVYSCEGCKGFFKRTVRKDLSY-TCRDNKDCLVDKRQRNRCQYCRYQKCLAMGMKREAVQEERQRN 202
Cdd:cd07166    5 LCKVCGDKASGFHYGVHACEGCKGFFRRSIQQKIQYrKCTKNETCSIMRINRNRCQYCRFKKCLAVGMSRDAVRFGRIPK 84

                 ...
gi 528509163 203 KER 205
Cdd:cd07166   85 REK 87

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 528509163 122 KRLCAICGDRSSGKHYGVYSCEGCKGFFKRTVRKDLSYTCRDNKDCLVDKRQRNRCQYCRYQKCLAMGMKREAVQEERQR 201
Cdd:cd07170    4 KRLCLVCGDIASGYHYGVASCEACKAFFKRTIQGNIEYSCPATNECEITKRRRKSCQACRFMKCLKVGMLKEGVRLDRVR 83

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 528509163 252 VTNIcqaADKQLFTLVEWAKRIPHFSELSLDDQVILLRAGWNELLIASFSHRSITVKDGILLATGLHVHRNsahsagvga 331
Cdd:cd06949   37 LTNL---ADRELVHMINWAKKIPGFVDLSLHDQVHLLESAWLELLMLGLVWRSMEHPGKLLFAPDLLLDRN--------- 104

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509163 332 ifdrESAHNAEVGAIFDRVLtELVSKMRDMQMDKTELGCLRAIILFNPDAKG-----LSSPSEVELLREKVYASLEAYCK 406
Cdd:cd06949  105 ----QGSCVEGMVEIFDMLL-ATASRFRELQLQREEYVCLKAIILLNSSVYTfllesLESRRQVQRLLDKITDALVHACS 179

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 528509163 407 QRY---PDQQGRFAKLLLRLPALRSIGLKCLEHLFFFKLIGDTPIDTFLMEMLEAP 459
Cdd:cd06949  180 KRGlslQQQSRRLAQLLLILSHIRHVSNKGMEHLYSMKCKNVVPLYDLLLEMLDAH 235