NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|285815373|tpg|DAA11265|]
View 

TPA: Mex67p [Saccharomyces cerevisiae S288C]

Protein Classification

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

 Name Accession Description Interval E-value
RRM_9 pfam18444
RNA recognition motif; The Mex67-Mtr2 complex (TAP-p15 or NXF1-NXT1 in metazoans) is the ...
 23-92 1.26e-32

RNA recognition motif; The Mex67-Mtr2 complex (TAP-p15 or NXF1-NXT1 in metazoans) is the principal mRNA export factor in Saccharomyces cerevisiae. Mex67 is a member of the NXF family of proteins and has conserved homologs through eukaryotes from yeast to humans. Although sequence conservation is poor between S. cerevisiae Mex67 and Homo sapiens NXF1, they do show functional complementarity. Mex67 and TAP/NXF1 are modular proteins that contain four structural domains: an N-terminal RNA recognition motif (RRM), a leucine rich repeat (LRR) domain, a nuclear transport factor 2-like domain (NTF2L) and an ubiquitin-associated domain (UBA). This entry describes the N-terminal RNA recognition motif (RRM) found in Mex67 proteins.


:

Pssm-ID: 408240  Cd Length: 70  Bit Score: 119.58  E-value: 1.26e-32
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 285815373   23 IKISVRNWQNATMNDLINFISRNARVAVYDAHVEGPLVIGYVNSKAEAESLMKWNGVRFAGSNLKFELLD 92
Cdd:pfam18444   1 VKVEIRGWQNATEQDLVSFISRKTRVALMNARVEGPVLVGYVNTRQDADQLLKWNGVRFAGNNLKIEILD 70
TAP_C smart00804
C-terminal domain of vertebrate Tap protein; The vertebrate Tap protein is a member of the NXF ...
 537-597 2.57e-21

C-terminal domain of vertebrate Tap protein; The vertebrate Tap protein is a member of the NXF family of shuttling transport receptors for the nuclear export of mRNA. Its most C-terminal domain is important for binding to FG repeat-containing nuclear pore proteins (FG-nucleoporins) and is sufficient to mediate shuttling. This domain forms a compact four-helix fold related to that of a UBA domain.


:

Pssm-ID: 197882  Cd Length: 63  Bit Score: 87.74  E-value: 2.57e-21
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 285815373   537 PPDVQSRLNPVQLELLNKLHLETKLNAEYTFMLAEQSNWNYEVAIKGFQS--SMNGIPREAFV 597
Cdd:smart00804   1 PASPKPTLSPEQQEMVQAFSAQTGMNAEYSQMCLEDNNWDYERALKNFTElkSEGSIPPEAFA 63
PPP1R42 super family cl42388
protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 ...
 155-256 9.52e-08

protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 (PPP1R42), also known as leucine-rich repeat-containing protein 67 (lrrc67) or testis leucine-rich repeat (TLRR) protein, plays a role in centrosome separation. PPP1R42 has been shown to interact with the well-conserved signaling protein phosphatase-1 (PP1) and thereby increasing PP1's activity, which counters centrosome separation. Inhibition of PPP1R42 expression increases the number of centrosomes per cell while its depletion reduces the activity of PP1 leading to activation of NEK2, the kinase responsible for phosphorylation of centrosomal linker proteins promoting centrosome separation.


The actual alignment was detected with superfamily member cd21340:

Pssm-ID: 455733 [Multi-domain]  Cd Length: 220  Bit Score: 52.87  E-value: 9.52e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 285815373 155 LASTEKSLIVesVNLADNQLKDISAISTLaqtfPNLKNLCLANNQIFRFRSLEVWKNKFKDLRELLMTNNPITTDKLYRT 234
Cdd:cd21340  115 LAALSNSLRV--LNISGNNIDSLEPLAPL----RNLEQLDASNNQISDLEELLDLLSSWPSLRELDLTGNPVCKKPKYRD 188

                         90       100
                 ....*....|....*....|..
gi 285815373 235 EMLRLFPKLVVLDNVIVRDEQK 256
Cdd:cd21340  189 KIILASKSLEVLDGKEITDTER 210
 
Name Accession Description Interval E-value
RRM_9 pfam18444
RNA recognition motif; The Mex67-Mtr2 complex (TAP-p15 or NXF1-NXT1 in metazoans) is the ...
 23-92 1.26e-32

RNA recognition motif; The Mex67-Mtr2 complex (TAP-p15 or NXF1-NXT1 in metazoans) is the principal mRNA export factor in Saccharomyces cerevisiae. Mex67 is a member of the NXF family of proteins and has conserved homologs through eukaryotes from yeast to humans. Although sequence conservation is poor between S. cerevisiae Mex67 and Homo sapiens NXF1, they do show functional complementarity. Mex67 and TAP/NXF1 are modular proteins that contain four structural domains: an N-terminal RNA recognition motif (RRM), a leucine rich repeat (LRR) domain, a nuclear transport factor 2-like domain (NTF2L) and an ubiquitin-associated domain (UBA). This entry describes the N-terminal RNA recognition motif (RRM) found in Mex67 proteins.


Pssm-ID: 408240  Cd Length: 70  Bit Score: 119.58  E-value: 1.26e-32
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 285815373   23 IKISVRNWQNATMNDLINFISRNARVAVYDAHVEGPLVIGYVNSKAEAESLMKWNGVRFAGSNLKFELLD 92
Cdd:pfam18444   1 VKVEIRGWQNATEQDLVSFISRKTRVALMNARVEGPVLVGYVNTRQDADQLLKWNGVRFAGNNLKIEILD 70
TAP_C smart00804
C-terminal domain of vertebrate Tap protein; The vertebrate Tap protein is a member of the NXF ...
 537-597 2.57e-21

C-terminal domain of vertebrate Tap protein; The vertebrate Tap protein is a member of the NXF family of shuttling transport receptors for the nuclear export of mRNA. Its most C-terminal domain is important for binding to FG repeat-containing nuclear pore proteins (FG-nucleoporins) and is sufficient to mediate shuttling. This domain forms a compact four-helix fold related to that of a UBA domain.


Pssm-ID: 197882  Cd Length: 63  Bit Score: 87.74  E-value: 2.57e-21
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 285815373   537 PPDVQSRLNPVQLELLNKLHLETKLNAEYTFMLAEQSNWNYEVAIKGFQS--SMNGIPREAFV 597
Cdd:smart00804   1 PASPKPTLSPEQQEMVQAFSAQTGMNAEYSQMCLEDNNWDYERALKNFTElkSEGSIPPEAFA 63
TAP_C pfam03943
TAP C-terminal domain; The vertebrate Tap protein is a member of the NXF family of shuttling ...
 550-596 2.48e-13

TAP C-terminal domain; The vertebrate Tap protein is a member of the NXF family of shuttling transport receptors for nuclear export of mRNA. Tap has a modular structure, and its most C-terminal domain is important for binding to FG repeat-containing nuclear pore proteins (FG-nucleoporins) and is sufficient to mediate nuclear shuttling. The structure of the C-terminal domain is composed of four helices. The structure is related to the UBA domain.


Pssm-ID: 461102  Cd Length: 49  Bit Score: 64.48  E-value: 2.48e-13
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 285815373  550 ELLNKLHLETKLNAEYTFMLAEQSNWNYEVAIKGFQSS--MNGIPREAF 596
Cdd:pfam03943   1 EMVQQFSQQTGMNLEWSEKCLEQNNWDYERALQNFTELkaQGKIPPEAF 49
UBA_TAP-C cd14342
UBA-like domain found in nuclear RNA export factor NXF1, NXF2 and similar proteins; The NXF ...
 548-596 1.12e-11

UBA-like domain found in nuclear RNA export factor NXF1, NXF2 and similar proteins; The NXF family of mRNA nuclear export factors including vertebrate NXF1 (also called tip-associated protein or mRNA export factor TAP), NXF2 (also called cancer/testis antigen CT39 or TAP-like protein TAPL-2), Caenorhabditis elegans NXF1 (ceNXF1), Saccharomyces cerevisiae mRNA nuclear export factor Mex67p and similar proteins. NXF proteins can stimulate nuclear export of mRNAs and facilitate the export of unspliced viral mRNA containing the constitutive transport element. It is a multi-domain protein with a nuclear localization sequence (NLS), a non-canonical mRNA-binding domain, and four leucine-rich repeats (LLR) at the N-terminal region. Its C-terminal part contains a NTF2-like domain and a ubiquitin-associated (UBA)-like domain, joined by flexible Pro-rich linker. Caenorhabditis elegans NXF1 are essential for the nuclear export of poly(A)+mRNA. In budding yeast, Mex67p binds mRNAs through its adaptor Yra1/REF. It also interacts directly with Nab2, an essential shuttling mRNA-binding protein required for export. Moreover, Mex67p associates with both nuclear pore protein (nucleoporin) FG repeats and Hpr1, a component of the TREX/THO complex linking transcription and export.


Pssm-ID: 270527  Cd Length: 51  Bit Score: 59.90  E-value: 1.12e-11
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 285815373 548 QLELLNKLHLETKLNAEYTFMLAEQSNWNYEVAIKGFQSSM--NGIPREAF 596
Cdd:cd14342    1 QQQMVQQLSAQTGMNLEWSQKCLEDNGWDYEKALANFEELKaqGKIPPEAF 51
PPP1R42 cd21340
protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 ...
 155-256 9.52e-08

protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 (PPP1R42), also known as leucine-rich repeat-containing protein 67 (lrrc67) or testis leucine-rich repeat (TLRR) protein, plays a role in centrosome separation. PPP1R42 has been shown to interact with the well-conserved signaling protein phosphatase-1 (PP1) and thereby increasing PP1's activity, which counters centrosome separation. Inhibition of PPP1R42 expression increases the number of centrosomes per cell while its depletion reduces the activity of PP1 leading to activation of NEK2, the kinase responsible for phosphorylation of centrosomal linker proteins promoting centrosome separation.


Pssm-ID: 411060 [Multi-domain]  Cd Length: 220  Bit Score: 52.87  E-value: 9.52e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 285815373 155 LASTEKSLIVesVNLADNQLKDISAISTLaqtfPNLKNLCLANNQIFRFRSLEVWKNKFKDLRELLMTNNPITTDKLYRT 234
Cdd:cd21340  115 LAALSNSLRV--LNISGNNIDSLEPLAPL----RNLEQLDASNNQISDLEELLDLLSSWPSLRELDLTGNPVCKKPKYRD 188

                         90       100
                 ....*....|....*....|..
gi 285815373 235 EMLRLFPKLVVLDNVIVRDEQK 256
Cdd:cd21340  189 KIILASKSLEVLDGKEITDTER 210
LRR COG4886
Leucine-rich repeat (LRR) protein [Transcription];
165-257 9.78e-05

Leucine-rich repeat (LRR) protein [Transcription];


Pssm-ID: 443914 [Multi-domain]  Cd Length: 414  Bit Score: 44.92  E-value: 9.78e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 285815373 165 ESVNLADNQLKDISAISTLaqtfPNLKNLCLANNQIFRFRSLEVWKNkfkdLRELLMTNNPITTDKLYRTEMLRLFPKLV 244
Cdd:COG4886  231 ETLDLSNNQLTDLPELGNL----TNLEELDLSNNQLTDLPPLANLTN----LKTLDLSNNQLTDLKLKELELLLGLNSLL 302

                         90
                 ....*....|...
gi 285815373 245 VLDNVIVRDEQKL 257
Cdd:COG4886  303 LLLLLLNLLELLI 315
LRR_9 pfam14580
Leucine-rich repeat;
183-247 1.48e-03

Leucine-rich repeat;


Pssm-ID: 405295 [Multi-domain]  Cd Length: 175  Bit Score: 39.75  E-value: 1.48e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 285815373  183 LAQTFPNLKNLCLANNQIFRFRSLEVWKNkFKDLRELLMTNNPITTDKLYRTEMLRLFPKLVVLD 247
Cdd:pfam14580  83 LGEALPNLTELILTNNNLQELGDLDPLAS-LKKLTFLSLLRNPVTNKPHYRLYVIYKVPQLRLLD 146
 
Name Accession Description Interval E-value
RRM_9 pfam18444
RNA recognition motif; The Mex67-Mtr2 complex (TAP-p15 or NXF1-NXT1 in metazoans) is the ...
 23-92 1.26e-32

RNA recognition motif; The Mex67-Mtr2 complex (TAP-p15 or NXF1-NXT1 in metazoans) is the principal mRNA export factor in Saccharomyces cerevisiae. Mex67 is a member of the NXF family of proteins and has conserved homologs through eukaryotes from yeast to humans. Although sequence conservation is poor between S. cerevisiae Mex67 and Homo sapiens NXF1, they do show functional complementarity. Mex67 and TAP/NXF1 are modular proteins that contain four structural domains: an N-terminal RNA recognition motif (RRM), a leucine rich repeat (LRR) domain, a nuclear transport factor 2-like domain (NTF2L) and an ubiquitin-associated domain (UBA). This entry describes the N-terminal RNA recognition motif (RRM) found in Mex67 proteins.


Pssm-ID: 408240  Cd Length: 70  Bit Score: 119.58  E-value: 1.26e-32
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 285815373   23 IKISVRNWQNATMNDLINFISRNARVAVYDAHVEGPLVIGYVNSKAEAESLMKWNGVRFAGSNLKFELLD 92
Cdd:pfam18444   1 VKVEIRGWQNATEQDLVSFISRKTRVALMNARVEGPVLVGYVNTRQDADQLLKWNGVRFAGNNLKIEILD 70
TAP_C smart00804
C-terminal domain of vertebrate Tap protein; The vertebrate Tap protein is a member of the NXF ...
 537-597 2.57e-21

C-terminal domain of vertebrate Tap protein; The vertebrate Tap protein is a member of the NXF family of shuttling transport receptors for the nuclear export of mRNA. Its most C-terminal domain is important for binding to FG repeat-containing nuclear pore proteins (FG-nucleoporins) and is sufficient to mediate shuttling. This domain forms a compact four-helix fold related to that of a UBA domain.


Pssm-ID: 197882  Cd Length: 63  Bit Score: 87.74  E-value: 2.57e-21
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 285815373   537 PPDVQSRLNPVQLELLNKLHLETKLNAEYTFMLAEQSNWNYEVAIKGFQS--SMNGIPREAFV 597
Cdd:smart00804   1 PASPKPTLSPEQQEMVQAFSAQTGMNAEYSQMCLEDNNWDYERALKNFTElkSEGSIPPEAFA 63
TAP_C pfam03943
TAP C-terminal domain; The vertebrate Tap protein is a member of the NXF family of shuttling ...
 550-596 2.48e-13

TAP C-terminal domain; The vertebrate Tap protein is a member of the NXF family of shuttling transport receptors for nuclear export of mRNA. Tap has a modular structure, and its most C-terminal domain is important for binding to FG repeat-containing nuclear pore proteins (FG-nucleoporins) and is sufficient to mediate nuclear shuttling. The structure of the C-terminal domain is composed of four helices. The structure is related to the UBA domain.


Pssm-ID: 461102  Cd Length: 49  Bit Score: 64.48  E-value: 2.48e-13
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 285815373  550 ELLNKLHLETKLNAEYTFMLAEQSNWNYEVAIKGFQSS--MNGIPREAF 596
Cdd:pfam03943   1 EMVQQFSQQTGMNLEWSEKCLEQNNWDYERALQNFTELkaQGKIPPEAF 49
UBA_TAP-C cd14342
UBA-like domain found in nuclear RNA export factor NXF1, NXF2 and similar proteins; The NXF ...
 548-596 1.12e-11

UBA-like domain found in nuclear RNA export factor NXF1, NXF2 and similar proteins; The NXF family of mRNA nuclear export factors including vertebrate NXF1 (also called tip-associated protein or mRNA export factor TAP), NXF2 (also called cancer/testis antigen CT39 or TAP-like protein TAPL-2), Caenorhabditis elegans NXF1 (ceNXF1), Saccharomyces cerevisiae mRNA nuclear export factor Mex67p and similar proteins. NXF proteins can stimulate nuclear export of mRNAs and facilitate the export of unspliced viral mRNA containing the constitutive transport element. It is a multi-domain protein with a nuclear localization sequence (NLS), a non-canonical mRNA-binding domain, and four leucine-rich repeats (LLR) at the N-terminal region. Its C-terminal part contains a NTF2-like domain and a ubiquitin-associated (UBA)-like domain, joined by flexible Pro-rich linker. Caenorhabditis elegans NXF1 are essential for the nuclear export of poly(A)+mRNA. In budding yeast, Mex67p binds mRNAs through its adaptor Yra1/REF. It also interacts directly with Nab2, an essential shuttling mRNA-binding protein required for export. Moreover, Mex67p associates with both nuclear pore protein (nucleoporin) FG repeats and Hpr1, a component of the TREX/THO complex linking transcription and export.


Pssm-ID: 270527  Cd Length: 51  Bit Score: 59.90  E-value: 1.12e-11
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 285815373 548 QLELLNKLHLETKLNAEYTFMLAEQSNWNYEVAIKGFQSSM--NGIPREAF 596
Cdd:cd14342    1 QQQMVQQLSAQTGMNLEWSQKCLEDNGWDYEKALANFEELKaqGKIPPEAF 51
PPP1R42 cd21340
protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 ...
 155-256 9.52e-08

protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 (PPP1R42), also known as leucine-rich repeat-containing protein 67 (lrrc67) or testis leucine-rich repeat (TLRR) protein, plays a role in centrosome separation. PPP1R42 has been shown to interact with the well-conserved signaling protein phosphatase-1 (PP1) and thereby increasing PP1's activity, which counters centrosome separation. Inhibition of PPP1R42 expression increases the number of centrosomes per cell while its depletion reduces the activity of PP1 leading to activation of NEK2, the kinase responsible for phosphorylation of centrosomal linker proteins promoting centrosome separation.


Pssm-ID: 411060 [Multi-domain]  Cd Length: 220  Bit Score: 52.87  E-value: 9.52e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 285815373 155 LASTEKSLIVesVNLADNQLKDISAISTLaqtfPNLKNLCLANNQIFRFRSLEVWKNKFKDLRELLMTNNPITTDKLYRT 234
Cdd:cd21340  115 LAALSNSLRV--LNISGNNIDSLEPLAPL----RNLEQLDASNNQISDLEELLDLLSSWPSLRELDLTGNPVCKKPKYRD 188

                         90       100
                 ....*....|....*....|..
gi 285815373 235 EMLRLFPKLVVLDNVIVRDEQK 256
Cdd:cd21340  189 KIILASKSLEVLDGKEITDTER 210
LRR COG4886
Leucine-rich repeat (LRR) protein [Transcription];
165-257 9.78e-05

Leucine-rich repeat (LRR) protein [Transcription];


Pssm-ID: 443914 [Multi-domain]  Cd Length: 414  Bit Score: 44.92  E-value: 9.78e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 285815373 165 ESVNLADNQLKDISAISTLaqtfPNLKNLCLANNQIFRFRSLEVWKNkfkdLRELLMTNNPITTDKLYRTEMLRLFPKLV 244
Cdd:COG4886  231 ETLDLSNNQLTDLPELGNL----TNLEELDLSNNQLTDLPPLANLTN----LKTLDLSNNQLTDLKLKELELLLGLNSLL 302

                         90
                 ....*....|...
gi 285815373 245 VLDNVIVRDEQKL 257
Cdd:COG4886  303 LLLLLLNLLELLI 315
LRR_9 pfam14580
Leucine-rich repeat;
183-247 1.48e-03

Leucine-rich repeat;


Pssm-ID: 405295 [Multi-domain]  Cd Length: 175  Bit Score: 39.75  E-value: 1.48e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 285815373  183 LAQTFPNLKNLCLANNQIFRFRSLEVWKNkFKDLRELLMTNNPITTDKLYRTEMLRLFPKLVVLD 247
Cdd:pfam14580  83 LGEALPNLTELILTNNNLQELGDLDPLAS-LKKLTFLSLLRNPVTNKPHYRLYVIYKVPQLRLLD 146
LRR COG4886
Leucine-rich repeat (LRR) protein [Transcription];
165-228 3.60e-03

Leucine-rich repeat (LRR) protein [Transcription];


Pssm-ID: 443914 [Multi-domain]  Cd Length: 414  Bit Score: 39.92  E-value: 3.60e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 285815373 165 ESVNLADNQLKDISaiSTLAQtFPNLKNLCLANNQIfrfRSLEVWKNKFKDLRELLMTNNPITT 228
Cdd:COG4886  139 KELDLSNNQLTDLP--EPLGN-LTNLKSLDLSNNQL---TDLPEELGNLTNLKELDLSNNQITD 196
LRR COG4886
Leucine-rich repeat (LRR) protein [Transcription];
165-228 6.50e-03

Leucine-rich repeat (LRR) protein [Transcription];


Pssm-ID: 443914 [Multi-domain]  Cd Length: 414  Bit Score: 39.15  E-value: 6.50e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 285815373 165 ESVNLADNQLKDISAisTLAQtFPNLKNLCLANNQIFRFRSLEvwknKFKDLRELLMTNNPITT 228
Cdd:COG4886  208 EELDLSGNQLTDLPE--PLAN-LTNLETLDLSNNQLTDLPELG----NLTNLEELDLSNNQLTD 264
 
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