NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|738192376|ref|WP_036148366|]
View 

MULTISPECIES: cAMP-activated global transcriptional regulator CRP [Gammaproteobacteria]

Protein Classification

Crp/Fnr family transcriptional regulator( domain architecture ID 11485491)

Crp/Fnr family transcriptional regulator such as Escherichia coli cAMP-activated global transcriptional regulator CRP, which complexes with cyclic AMP (cAMP) to allosterically activate DNA binding (to consensus sequence 5'-AAATGTGATCTAGATCACATTT-3') and to directly regulate the transcription of about 300 genes in about 200 operons and indirectly regulate the expression of about half the genome

Gene Ontology:  GO:0003677|GO:0006355
PubMed:  29146813|24914983

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

 Name Accession Description Interval E-value
PRK11753 PRK11753
cAMP-activated global transcriptional regulator CRP;
13-221 9.29e-122

cAMP-activated global transcriptional regulator CRP;


:

Pssm-ID: 236969 [Multi-domain]  Cd Length: 211  Bit Score: 343.89  E-value: 9.29e-122
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738192376  13 PDGATIERFLAHCHRRRYPSRTDVFRPGDPASTLYYVVSGSVSIITEEEDGRELVLGYFGPGEFVGELGLFIESDHREVI 92
Cdd:PRK11753   8 QTDPTLEWFLSHCHIHKYPAKSTLIHAGEKAETLYYIVKGSVAVLIKDEEGKEMILSYLNQGDFIGELGLFEEGQERSAW 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738192376  93 LRTRSTCELAEIGHERLYDLlltrlSLDAPKLLYAIGAQISRRLLDTSRKAGRLAFLDVTDRIVRALHDLAKEPEAMSHP 172
Cdd:PRK11753  88 VRAKTACEVAEISYKKFRQL-----IQVNPDILMALSAQMARRLQNTSRKVGDLAFLDVTGRIAQTLLDLAKQPDAMTHP 162

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 738192376 173 QGTQLRVSRQELSRLVGCSREMAGRVLKKLQADGKLHARGKTVVLYGTR 221
Cdd:PRK11753 163 DGMQIKITRQEIGRIVGCSREMVGRVLKMLEDQGLISAHGKTIVVYGTR 211
 
Name Accession Description Interval E-value
PRK11753 PRK11753
cAMP-activated global transcriptional regulator CRP;
13-221 9.29e-122

cAMP-activated global transcriptional regulator CRP;


Pssm-ID: 236969 [Multi-domain]  Cd Length: 211  Bit Score: 343.89  E-value: 9.29e-122
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738192376  13 PDGATIERFLAHCHRRRYPSRTDVFRPGDPASTLYYVVSGSVSIITEEEDGRELVLGYFGPGEFVGELGLFIESDHREVI 92
Cdd:PRK11753   8 QTDPTLEWFLSHCHIHKYPAKSTLIHAGEKAETLYYIVKGSVAVLIKDEEGKEMILSYLNQGDFIGELGLFEEGQERSAW 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738192376  93 LRTRSTCELAEIGHERLYDLlltrlSLDAPKLLYAIGAQISRRLLDTSRKAGRLAFLDVTDRIVRALHDLAKEPEAMSHP 172
Cdd:PRK11753  88 VRAKTACEVAEISYKKFRQL-----IQVNPDILMALSAQMARRLQNTSRKVGDLAFLDVTGRIAQTLLDLAKQPDAMTHP 162

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 738192376 173 QGTQLRVSRQELSRLVGCSREMAGRVLKKLQADGKLHARGKTVVLYGTR 221
Cdd:PRK11753 163 DGMQIKITRQEIGRIVGCSREMVGRVLKMLEDQGLISAHGKTIVVYGTR 211
Crp COG0664
cAMP-binding domain of CRP or a regulatory subunit of cAMP-dependent protein kinases [Signal ...
 16-217 3.83e-41

cAMP-binding domain of CRP or a regulatory subunit of cAMP-dependent protein kinases [Signal transduction mechanisms];


Pssm-ID: 440428 [Multi-domain]  Cd Length: 207  Bit Score: 138.97  E-value: 3.83e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738192376  16 ATIERFLAHCHRRRYPSRTDVFRPGDPASTLYYVVSGSVSIITEEEDGRELVLGYFGPGEFVGELGLFiESDHREVILRT 95
Cdd:COG0664    7 EELEALLAHLELRTLKKGEVLFREGDPADHLYFVLSGLVKLYRISEDGREQILGFLGPGDFFGELSLL-GGEPSPATAEA 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738192376  96 RSTCELAEIGHERLYDLLLTRlsldaPKLLYAIGAQISRRLLDTSRKAGRLAFLDVTDRIVRALHDLAKEpeamsHPQGT 175
Cdd:COG0664   86 LEDSELLRIPREDLEELLERN-----PELARALLRLLARRLRQLQERLVSLAFLSAEERLARFLLELADR-----LDGRI 155

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 738192376 176 QLRVSRQELSRLVGCSREMAGRVLKKLQADGKLHARGKTVVL 217
Cdd:COG0664  156 DLPLTQEEIASYLGLTRETVSRILKKLEKEGLIELERGRITI 197
CAP_ED cd00038
effector domain of the CAP family of transcription factors; members include CAP (or cAMP ...
 16-119 2.53e-21

effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO sensor. In all cases binding of the effector leads to conformational changes and the ability to activate transcription. Cyclic nucleotide-binding domain similar to CAP are also present in cAMP- and cGMP-dependent protein kinases (cAPK and cGPK) and vertebrate cyclic nucleotide-gated ion-channels. Cyclic nucleotide-monophosphate binding domain; proteins that bind cyclic nucleotides (cAMP or cGMP) share a structural domain of about 120 residues; the best studied is the prokaryotic catabolite gene activator, CAP, where such a domain is known to be composed of three alpha-helices and a distinctive eight-stranded, antiparallel beta-barrel structure; three conserved glycine residues are thought to be essential for maintenance of the structural integrity of the beta-barrel; CooA is a homodimeric transcription factor that belongs to CAP family; cAMP- and cGMP-dependent protein kinases (cAPK and cGPK) contain two tandem copies of the cyclic nucleotide-binding domain; cAPK's are composed of two different subunits, a catalytic chain and a regulatory chain, which contains both copies of the domain; cGPK's are single chain enzymes that include the two copies of the domain in their N-terminal section; also found in vertebrate cyclic nucleotide-gated ion-channels


Pssm-ID: 237999 [Multi-domain]  Cd Length: 115  Bit Score: 85.07  E-value: 2.53e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738192376  16 ATIERFLAHCHRRRYPSRTDVFRPGDPASTLYYVVSGSVSIITEEEDGRELVLGYFGPGEFVGELGLFiESDHREVILRT 95
Cdd:cd00038    8 EELEELADALEERRFPAGEVIIRQGDPADSLYIVLSGSVEVYKLDEDGREQIVGFLGPGDLFGELALL-GNGPRSATVRA 86

                         90       100
                 ....*....|....*....|....
gi 738192376  96 RSTCELAEIGHERLYDLLLTRLSL 119
Cdd:cd00038   87 LTDSELLVLPRSDFRRLLQEYPEL 110
cNMP_binding pfam00027
Cyclic nucleotide-binding domain; This domain sensor domain can bind cAMP, cGMP, c-di-GMP, ...
 27-115 5.41e-21

Cyclic nucleotide-binding domain; This domain sensor domain can bind cAMP, cGMP, c-di-GMP, oxygen and 2-oxoglutarate (Matilla et. al., FEMS Microbiology Reviews, fuab043, 45, 2021, 1. https://doi.org/10.1093/femsre/fuab043).


Pssm-ID: 459637 [Multi-domain]  Cd Length: 89  Bit Score: 83.43  E-value: 5.41e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738192376   27 RRRYPSRTDVFRPGDPASTLYYVVSGSVSIITEEEDGRELVLGYFGPGEFVGELGLFiESDHREVILRTRSTCELAEIGH 106
Cdd:pfam00027   1 LRSYKAGEVIFREGDPADSLYIVLSGKVKVYRTLEDGREQILAVLGPGDFFGELALL-GGEPRSATVVALTDSELLVIPR 79


                  ....*....
gi 738192376  107 ERLYDLLLT 115
Cdd:pfam00027  80 EDFLELLER 88
cNMP smart00100
Cyclic nucleotide-monophosphate binding domain; Catabolite gene activator protein (CAP) is a ...
 14-116 7.54e-18

Cyclic nucleotide-monophosphate binding domain; Catabolite gene activator protein (CAP) is a prokaryotic homologue of eukaryotic cNMP-binding domains, present in ion channels, and cNMP-dependent kinases.


Pssm-ID: 197516 [Multi-domain]  Cd Length: 120  Bit Score: 76.29  E-value: 7.54e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738192376    14 DGATIERFLAHCHRRRYPSRTDVFRPGDPASTLYYVVSGSVSIITEEEDGRELVLGYFGPGEFVGELGLFI-ESDHREVI 92
Cdd:smart00100   6 DAEELRELADALEPVRYPAGEVIIRQGDVGDSFYIIVSGEVEVYKVLEDGEEQIVGTLGPGDFFGELALLTnSRRAASAA 85

                           90       100
                   ....*....|....*....|....
gi 738192376    93 LRTRSTCELAEIGHERLYDLLLTR 116
Cdd:smart00100  86 AVALELATLLRIDFRDFLQLLPEL 109
 
Name Accession Description Interval E-value
PRK11753 PRK11753
cAMP-activated global transcriptional regulator CRP;
13-221 9.29e-122

cAMP-activated global transcriptional regulator CRP;


Pssm-ID: 236969 [Multi-domain]  Cd Length: 211  Bit Score: 343.89  E-value: 9.29e-122
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738192376  13 PDGATIERFLAHCHRRRYPSRTDVFRPGDPASTLYYVVSGSVSIITEEEDGRELVLGYFGPGEFVGELGLFIESDHREVI 92
Cdd:PRK11753   8 QTDPTLEWFLSHCHIHKYPAKSTLIHAGEKAETLYYIVKGSVAVLIKDEEGKEMILSYLNQGDFIGELGLFEEGQERSAW 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738192376  93 LRTRSTCELAEIGHERLYDLlltrlSLDAPKLLYAIGAQISRRLLDTSRKAGRLAFLDVTDRIVRALHDLAKEPEAMSHP 172
Cdd:PRK11753  88 VRAKTACEVAEISYKKFRQL-----IQVNPDILMALSAQMARRLQNTSRKVGDLAFLDVTGRIAQTLLDLAKQPDAMTHP 162

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 738192376 173 QGTQLRVSRQELSRLVGCSREMAGRVLKKLQADGKLHARGKTVVLYGTR 221
Cdd:PRK11753 163 DGMQIKITRQEIGRIVGCSREMVGRVLKMLEDQGLISAHGKTIVVYGTR 211
Crp COG0664
cAMP-binding domain of CRP or a regulatory subunit of cAMP-dependent protein kinases [Signal ...
 16-217 3.83e-41

cAMP-binding domain of CRP or a regulatory subunit of cAMP-dependent protein kinases [Signal transduction mechanisms];


Pssm-ID: 440428 [Multi-domain]  Cd Length: 207  Bit Score: 138.97  E-value: 3.83e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738192376  16 ATIERFLAHCHRRRYPSRTDVFRPGDPASTLYYVVSGSVSIITEEEDGRELVLGYFGPGEFVGELGLFiESDHREVILRT 95
Cdd:COG0664    7 EELEALLAHLELRTLKKGEVLFREGDPADHLYFVLSGLVKLYRISEDGREQILGFLGPGDFFGELSLL-GGEPSPATAEA 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738192376  96 RSTCELAEIGHERLYDLLLTRlsldaPKLLYAIGAQISRRLLDTSRKAGRLAFLDVTDRIVRALHDLAKEpeamsHPQGT 175
Cdd:COG0664   86 LEDSELLRIPREDLEELLERN-----PELARALLRLLARRLRQLQERLVSLAFLSAEERLARFLLELADR-----LDGRI 155

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 738192376 176 QLRVSRQELSRLVGCSREMAGRVLKKLQADGKLHARGKTVVL 217
Cdd:COG0664  156 DLPLTQEEIASYLGLTRETVSRILKKLEKEGLIELERGRITI 197
CAP_ED cd00038
effector domain of the CAP family of transcription factors; members include CAP (or cAMP ...
 16-119 2.53e-21

effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO sensor. In all cases binding of the effector leads to conformational changes and the ability to activate transcription. Cyclic nucleotide-binding domain similar to CAP are also present in cAMP- and cGMP-dependent protein kinases (cAPK and cGPK) and vertebrate cyclic nucleotide-gated ion-channels. Cyclic nucleotide-monophosphate binding domain; proteins that bind cyclic nucleotides (cAMP or cGMP) share a structural domain of about 120 residues; the best studied is the prokaryotic catabolite gene activator, CAP, where such a domain is known to be composed of three alpha-helices and a distinctive eight-stranded, antiparallel beta-barrel structure; three conserved glycine residues are thought to be essential for maintenance of the structural integrity of the beta-barrel; CooA is a homodimeric transcription factor that belongs to CAP family; cAMP- and cGMP-dependent protein kinases (cAPK and cGPK) contain two tandem copies of the cyclic nucleotide-binding domain; cAPK's are composed of two different subunits, a catalytic chain and a regulatory chain, which contains both copies of the domain; cGPK's are single chain enzymes that include the two copies of the domain in their N-terminal section; also found in vertebrate cyclic nucleotide-gated ion-channels


Pssm-ID: 237999 [Multi-domain]  Cd Length: 115  Bit Score: 85.07  E-value: 2.53e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738192376  16 ATIERFLAHCHRRRYPSRTDVFRPGDPASTLYYVVSGSVSIITEEEDGRELVLGYFGPGEFVGELGLFiESDHREVILRT 95
Cdd:cd00038    8 EELEELADALEERRFPAGEVIIRQGDPADSLYIVLSGSVEVYKLDEDGREQIVGFLGPGDLFGELALL-GNGPRSATVRA 86

                         90       100
                 ....*....|....*....|....
gi 738192376  96 RSTCELAEIGHERLYDLLLTRLSL 119
Cdd:cd00038   87 LTDSELLVLPRSDFRRLLQEYPEL 110
cNMP_binding pfam00027
Cyclic nucleotide-binding domain; This domain sensor domain can bind cAMP, cGMP, c-di-GMP, ...
 27-115 5.41e-21

Cyclic nucleotide-binding domain; This domain sensor domain can bind cAMP, cGMP, c-di-GMP, oxygen and 2-oxoglutarate (Matilla et. al., FEMS Microbiology Reviews, fuab043, 45, 2021, 1. https://doi.org/10.1093/femsre/fuab043).


Pssm-ID: 459637 [Multi-domain]  Cd Length: 89  Bit Score: 83.43  E-value: 5.41e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738192376   27 RRRYPSRTDVFRPGDPASTLYYVVSGSVSIITEEEDGRELVLGYFGPGEFVGELGLFiESDHREVILRTRSTCELAEIGH 106
Cdd:pfam00027   1 LRSYKAGEVIFREGDPADSLYIVLSGKVKVYRTLEDGREQILAVLGPGDFFGELALL-GGEPRSATVVALTDSELLVIPR 79


                  ....*....
gi 738192376  107 ERLYDLLLT 115
Cdd:pfam00027  80 EDFLELLER 88
cNMP smart00100
Cyclic nucleotide-monophosphate binding domain; Catabolite gene activator protein (CAP) is a ...
 14-116 7.54e-18

Cyclic nucleotide-monophosphate binding domain; Catabolite gene activator protein (CAP) is a prokaryotic homologue of eukaryotic cNMP-binding domains, present in ion channels, and cNMP-dependent kinases.


Pssm-ID: 197516 [Multi-domain]  Cd Length: 120  Bit Score: 76.29  E-value: 7.54e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738192376    14 DGATIERFLAHCHRRRYPSRTDVFRPGDPASTLYYVVSGSVSIITEEEDGRELVLGYFGPGEFVGELGLFI-ESDHREVI 92
Cdd:smart00100   6 DAEELRELADALEPVRYPAGEVIIRQGDVGDSFYIIVSGEVEVYKVLEDGEEQIVGTLGPGDFFGELALLTnSRRAASAA 85

                           90       100
                   ....*....|....*....|....
gi 738192376    93 LRTRSTCELAEIGHERLYDLLLTR 116
Cdd:smart00100  86 AVALELATLLRIDFRDFLQLLPEL 109
PRK13918 PRK13918
CRP/FNR family transcriptional regulator; Provisional
 34-206 3.94e-09

CRP/FNR family transcriptional regulator; Provisional


Pssm-ID: 237557 [Multi-domain]  Cd Length: 202  Bit Score: 54.44  E-value: 3.94e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738192376  34 TDVFRPGD---------PASTLYYVVSGSVSIITEEEDGRELVLGYFGPGEFVGELGLFiesdhrevilrtrstcelaei 104
Cdd:PRK13918   8 TVTYRPGAvilypgvpgPSDMLYRVRSGLVRLHTVDDEGNALTLRYVRPGEYFGEEALA--------------------- 66

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738192376 105 GHERLY---DLLLTRLSLDAPKLLYA-----IGAQISRRLLDTSRKAGRLAFLDVTDRIVRALHDLAKEPEAMSHPQG-T 175
Cdd:PRK13918  67 GAERAYfaeAVTDSRIDVLNPALMSAednlvLTQHLVRTLARAYESIYRLVGQRLKNRIAAALLELSDTPLATQEDSGeT 146

                        170       180       190
                 ....*....|....*....|....*....|.
gi 738192376 176 QLRVSRQELSRLVGCSREMAGRVLKKLQADG 206
Cdd:PRK13918 147 MIYATHDELAAAVGSVRETVTKVIGELSREG 177
HTH_CRP smart00419
helix_turn_helix, cAMP Regulatory protein;
171-218 1.52e-07

helix_turn_helix, cAMP Regulatory protein;


Pssm-ID: 128696 [Multi-domain]  Cd Length: 48  Bit Score: 46.66  E-value: 1.52e-07
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 738192376   171 HPQGTQLRVSRQELSRLVGCSREMAGRVLKKLQADGKLHARGKTVVLY 218
Cdd:smart00419   1 EGIRVRLPLTRQEIAELLGLTRETVSRTLKRLEKEGLISREGGRIVIL 48
Crp pfam00325
Bacterial regulatory proteins, crp family;
177-206 1.19e-05

Bacterial regulatory proteins, crp family;


Pssm-ID: 425608  Cd Length: 32  Bit Score: 41.13  E-value: 1.19e-05
                          10        20        30
                  ....*....|....*....|....*....|
gi 738192376  177 LRVSRQELSRLVGCSREMAGRVLKKLQADG 206
Cdd:pfam00325   1 LRMSRQDIANYLGLTRETVSRVLGKLQEKG 30
HTH_CRP cd00092
helix_turn_helix, cAMP Regulatory protein C-terminus; DNA binding domain of prokaryotic ...
 151-216 1.19e-04

helix_turn_helix, cAMP Regulatory protein C-terminus; DNA binding domain of prokaryotic regulatory proteins belonging to the catabolite activator protein family.


Pssm-ID: 238044 [Multi-domain]  Cd Length: 67  Bit Score: 39.19  E-value: 1.19e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 738192376 151 VTDRIVRALHDLAKEPEAmshPQGTQLRVSRQELSRLVGCSREMAGRVLKKLQADGKLHARGKTVV 216
Cdd:cd00092    1 AKERLASFLLNLSLRYGA---GDLVQLPLTRQEIADYLGLTRETVSRTLKELEEEGLISRRGRGKY 63
HTH_Crp_2 pfam13545
Crp-like helix-turn-helix domain; This family represents a crp-like helix-turn-helix domain ...
 154-217 1.47e-04

Crp-like helix-turn-helix domain; This family represents a crp-like helix-turn-helix domain that is likely to bind DNA.


Pssm-ID: 463917 [Multi-domain]  Cd Length: 68  Bit Score: 38.98  E-value: 1.47e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 738192376  154 RIVRALHDLAKEPEAMShpqgTQLRVSRQELSRLVGCSREMAGRVLKKLQADGkLHARGKTVVL 217
Cdd:pfam13545   2 RLARFLLELAARDGGGR----IDLPLTQEDLADLLGTTRETVSRVLSELRREG-LIERGRITIL 60
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH