NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|31543584|ref|NP_058542|]
View 

ral guanine nucleotide dissociation stimulator-like 1 isoform 3 [Mus musculus]

Protein Classification

RasGEF and RA_RGL domain-containing protein( domain architecture ID 13898961)

protein containing domains REM, RasGEF, and RA_RGL

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

Name Accession Description Interval E-value
RasGEF cd00155
Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of ...
228-497 6.80e-89

Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. Guanine-nucleotide-exchange factors (GEFs) positively regulate these GTP-binding proteins in response to a variety of signals. GEFs catalyze the dissociation of GDP from the inactive GTP-binding proteins. GTP can then bind and induce structural changes that allow interaction with effectors.


:

Pssm-ID: 238087 [Multi-domain]  Cd Length: 237  Bit Score: 279.52  E-value: 6.80e-89
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584 228 FTNFSEDLVAEQLTYMDAQLFKKVVPHHCLGCIWSQRDKKEnkHLAPTIRATISQFNTLTKCVVSTVLGSKELKtqQRAR 307
Cdd:cd00155   1 FLSLDPKELAEQLTLLDFELFRKIEPFELLGSLWSKKDKNI--HLSPNLERFIERFNNLSNWVASEILLCTNPK--KRAR 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584 308 VIEKWINIAHECRILKNFSSLRAIVSALQSNSIYRLKKAWAAVPKDRMLMFEELSDIFSDHNNHLTSRELLMKEGTSKFa 387
Cdd:cd00155  77 LLSKFIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEVLSSKLKKLFEELEELVDPSRNFKNYRKLLKSVGPNPP- 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584 388 nldssvkenqkrtqrrlqlqkdmgvmqgTVPYLGTFLTDLTMLDTALQDYIEGGLINFEKRRREFEVIAQIKLLQSacNS 467
Cdd:cd00155 156 ----------------------------CVPFLGVYLKDLTFLHEGNPDFLEGNLVNFEKRRKIAEILREIRQLQS--NS 205
                       250       260       270
                ....*....|....*....|....*....|..
gi 31543584 468 YCMGPDQKFIQWFQ--RQQLLSEEESYALSCE 497
Cdd:cd00155 206 YELNRDEDILAFLWklLELILNEDELYELSLE 237
RA_RGL cd17210
Ras-associating (RA) domain found in Ral guanine nucleotide dissociation stimulator-like 1 ...
647-733 2.01e-57

Ras-associating (RA) domain found in Ral guanine nucleotide dissociation stimulator-like 1 (RalGDS-like 1) and similar proteins; RalGDS-like 1 (RGL) is a Ral-specific guanine nucleotide exchange factor that belongs to RalGDS family, whose members are involved in Ras and Ral signaling pathways as downstream effector proteins. RGL has been identified as a possible effector protein of Ras. It also regulates c-fos promoter and the GDP/GTP exchange of Ral. Members in this family have similar structure: a central CDC25 homology domain with an upstream Ras Exchange motif (REM), and a C-terminal Ras-associating (RA) domain. The RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin; ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair.


:

Pssm-ID: 340730  Cd Length: 87  Bit Score: 190.20  E-value: 2.01e-57
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584 647 EDTCIIRISVEDNNGNMYKSIMLTSQDKTPAVIQRAMSKHNLESDPAEEYELVQVISEDKELVIPDSANVFYAMNSQVNF 726
Cdd:cd17210   1 EDTCIIRVSVEDNNGNMYKSIMLTSQDKTPAVIQRAMSKHNLESDPAEDYELVQVISEDRELVIPDNANVFYAMNSSVNF 80

                ....*..
gi 31543584 727 DFILRKK 733
Cdd:cd17210  81 DFILRKK 87
RasGEFN smart00229
Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif; A subset of guanine ...
65-196 2.26e-33

Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small GTPases appear to possess this domain N-terminal to the RasGef (Cdc25-like) domain. The recent crystal structureof Sos shows that this domain is alpha-helical and plays a "purely structural role" (Nature 394, 337-343).


:

Pssm-ID: 214571  Cd Length: 127  Bit Score: 124.37  E-value: 2.26e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584     65 KIRTIKAGTLEKLVENLLTAFGDNDFTYISIFLSTYRGFASTKEVLELLLDRYGNLTGPNCeddgsQSSPESKAVIRNAI 144
Cdd:smart00229   1 DGGLIKGGTLEALIEHLTEAFDKADPSFVETFLLTYRSFITTQELLQLLLYRYNAIPPESW-----VEEKVNPRRVKNRV 75
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 31543584    145 ASILRAWLDQCAEDFREPPH-FPCLQKLLEyLKQMMPGSDPERRAQNLLEQFQ 196
Cdd:smart00229  76 LNILRTWVENYWEDFEDDPKlISFLLEFLE-LVDDEKYPGLVTSLLNLLRRLS 127
 
Name Accession Description Interval E-value
RasGEF cd00155
Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of ...
228-497 6.80e-89

Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. Guanine-nucleotide-exchange factors (GEFs) positively regulate these GTP-binding proteins in response to a variety of signals. GEFs catalyze the dissociation of GDP from the inactive GTP-binding proteins. GTP can then bind and induce structural changes that allow interaction with effectors.


Pssm-ID: 238087 [Multi-domain]  Cd Length: 237  Bit Score: 279.52  E-value: 6.80e-89
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584 228 FTNFSEDLVAEQLTYMDAQLFKKVVPHHCLGCIWSQRDKKEnkHLAPTIRATISQFNTLTKCVVSTVLGSKELKtqQRAR 307
Cdd:cd00155   1 FLSLDPKELAEQLTLLDFELFRKIEPFELLGSLWSKKDKNI--HLSPNLERFIERFNNLSNWVASEILLCTNPK--KRAR 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584 308 VIEKWINIAHECRILKNFSSLRAIVSALQSNSIYRLKKAWAAVPKDRMLMFEELSDIFSDHNNHLTSRELLMKEGTSKFa 387
Cdd:cd00155  77 LLSKFIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEVLSSKLKKLFEELEELVDPSRNFKNYRKLLKSVGPNPP- 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584 388 nldssvkenqkrtqrrlqlqkdmgvmqgTVPYLGTFLTDLTMLDTALQDYIEGGLINFEKRRREFEVIAQIKLLQSacNS 467
Cdd:cd00155 156 ----------------------------CVPFLGVYLKDLTFLHEGNPDFLEGNLVNFEKRRKIAEILREIRQLQS--NS 205
                       250       260       270
                ....*....|....*....|....*....|..
gi 31543584 468 YCMGPDQKFIQWFQ--RQQLLSEEESYALSCE 497
Cdd:cd00155 206 YELNRDEDILAFLWklLELILNEDELYELSLE 237
RasGEF smart00147
Guanine nucleotide exchange factor for Ras-like small GTPases;
228-499 2.10e-86

Guanine nucleotide exchange factor for Ras-like small GTPases;


Pssm-ID: 214539  Cd Length: 242  Bit Score: 272.97  E-value: 2.10e-86
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584    228 FTNFSEDLVAEQLTYMDAQLFKKVVPHHCLGCIWSQRDKKENKHLapTIRATISQFNTLTKCVVSTVLGSKELKtqQRAR 307
Cdd:smart00147   1 LLLLDPKELAEQLTLLDFELFRKIDPSELLGSVWGKRSKKSPSPL--NLEAFIRRFNEVSNWVATEILKQTTPK--DRAE 76
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584    308 VIEKWINIAHECRILKNFSSLRAIVSALQSNSIYRLKKAWAAVPKDRMLMFEELSDIFSDHNNHLTSRELLMKEgtskfa 387
Cdd:smart00147  77 LLSKFIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEKLPSKYKKLFEELEELLSPERNYKNYREALSSC------ 150
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584    388 nldssvkenqkrtqrrlqlqkdmgVMQGTVPYLGTFLTDLTMLDTALQDYIEGGLINFEKRRREFEVIAQIKLLQSAcnS 467
Cdd:smart00147 151 ------------------------NLPPCIPFLGVLLKDLTFIDEGNPDFLENGLVNFEKRRQIAEILREIRQLQSQ--P 204
                          250       260       270
                   ....*....|....*....|....*....|....*
gi 31543584    468 YCMGPDQKFIQWFQRQ---QLLSEEESYALSCEIE 499
Cdd:smart00147 205 YNLRPNRSDIQSLLQQlldHLDEEEELYQLSLKIE 239
RasGEF pfam00617
RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.
236-449 3.51e-70

RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.


Pssm-ID: 425780  Cd Length: 178  Bit Score: 227.86  E-value: 3.51e-70
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584   236 VAEQLTYMDAQLFKKVVPHHCLGCIWSQRDKKEnkhlAPTIRATISQFNTLTKCVVSTVLgsKELKTQQRARVIEKWINI 315
Cdd:pfam00617   2 LARQLTLIEFELFRKIKPRELLGSAWSKKDKKE----SPNIEAMIARFNRLSNWVASEIL--SEEDPKKRAKVIKKFIKI 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584   316 AHECRILKNFSSLRAIVSALQSNSIYRLKKAWAAVPKDRMLMFEELSDIFSDHNNHLTSRELLMKegtskfanldssvke 395
Cdd:pfam00617  76 AEHCRELNNFNSLMAILSGLNSSPISRLKKTWELVSKKSKKLFEELEKLMSPSRNFKNYREALKS--------------- 140
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 31543584   396 nqkrtqrrlqlqkdmgVMQGTVPYLGTFLTDLTMLDTALQDYIEGGLINFEKRR 449
Cdd:pfam00617 141 ----------------ASPPCIPFLGLYLTDLTFIEEGNPDFLDGGLINFEKRR 178
RA_RGL cd17210
Ras-associating (RA) domain found in Ral guanine nucleotide dissociation stimulator-like 1 ...
647-733 2.01e-57

Ras-associating (RA) domain found in Ral guanine nucleotide dissociation stimulator-like 1 (RalGDS-like 1) and similar proteins; RalGDS-like 1 (RGL) is a Ral-specific guanine nucleotide exchange factor that belongs to RalGDS family, whose members are involved in Ras and Ral signaling pathways as downstream effector proteins. RGL has been identified as a possible effector protein of Ras. It also regulates c-fos promoter and the GDP/GTP exchange of Ral. Members in this family have similar structure: a central CDC25 homology domain with an upstream Ras Exchange motif (REM), and a C-terminal Ras-associating (RA) domain. The RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin; ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair.


Pssm-ID: 340730  Cd Length: 87  Bit Score: 190.20  E-value: 2.01e-57
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584 647 EDTCIIRISVEDNNGNMYKSIMLTSQDKTPAVIQRAMSKHNLESDPAEEYELVQVISEDKELVIPDSANVFYAMNSQVNF 726
Cdd:cd17210   1 EDTCIIRVSVEDNNGNMYKSIMLTSQDKTPAVIQRAMSKHNLESDPAEDYELVQVISEDRELVIPDNANVFYAMNSSVNF 80

                ....*..
gi 31543584 727 DFILRKK 733
Cdd:cd17210  81 DFILRKK 87
RasGEFN smart00229
Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif; A subset of guanine ...
65-196 2.26e-33

Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small GTPases appear to possess this domain N-terminal to the RasGef (Cdc25-like) domain. The recent crystal structureof Sos shows that this domain is alpha-helical and plays a "purely structural role" (Nature 394, 337-343).


Pssm-ID: 214571  Cd Length: 127  Bit Score: 124.37  E-value: 2.26e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584     65 KIRTIKAGTLEKLVENLLTAFGDNDFTYISIFLSTYRGFASTKEVLELLLDRYGNLTGPNCeddgsQSSPESKAVIRNAI 144
Cdd:smart00229   1 DGGLIKGGTLEALIEHLTEAFDKADPSFVETFLLTYRSFITTQELLQLLLYRYNAIPPESW-----VEEKVNPRRVKNRV 75
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 31543584    145 ASILRAWLDQCAEDFREPPH-FPCLQKLLEyLKQMMPGSDPERRAQNLLEQFQ 196
Cdd:smart00229  76 LNILRTWVENYWEDFEDDPKlISFLLEFLE-LVDDEKYPGLVTSLLNLLRRLS 127
REM cd06224
Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also ...
73-197 6.03e-27

Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also called REM domain (Ras exchanger motif). This domain is common in nucleotide exchange factors for Ras-like small GTPases and is typically found immediately N-terminal to the RasGef (Cdc25-like) domain. REM contacts the GTPase and is assumed to participate in the catalytic activity of the exchange factor. Proteins with the REM domain include Sos1 and Sos2, which relay signals from tyrosine-kinase mediated signalling to Ras, RasGRP1-4, RasGRF1,2, CNrasGEF, and RAP-specific nucleotide exchange factors, to name a few.


Pssm-ID: 100121  Cd Length: 122  Bit Score: 105.96  E-value: 6.03e-27
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584  73 TLEKLVENLLTAFGDNDFTYISIFLSTYRGFASTKEVLELLLDRYGNLtgPNCEDDGSQSSPESKAVIRNAIASILRAWL 152
Cdd:cd06224   1 TLEALIEHLTSTFDMPDPSFVSTFLLTYRSFTTPTELLEKLIERYEIA--PPENLEYNDWDKKKSKPIRLRVLNVLRTWV 78
                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 31543584 153 DQCAEDFRepPHFPCLQKLLEYLKQMMPGSDPERRAQNLLEQFQK 197
Cdd:cd06224  79 ENYPYDFF--DDEELLELLEEFLNRLVQEGALLQELKKLLRKLLK 121
RasGEF_N pfam00618
RasGEF N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small ...
68-173 1.02e-23

RasGEF N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small GTPases appear to possess this motif/domain N-terminal to the RasGef (Cdc25-like) domain.


Pssm-ID: 425781  Cd Length: 104  Bit Score: 96.22  E-value: 1.02e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584    68 TIKAGTLEKLVENLLTAFGDNDFTYISIFLSTYRGFASTKEVLELLLDRYGNLTGPNCEDDGSQSSpESKAVIRNAIASI 147
Cdd:pfam00618   1 QVKAGTLEKLVEYLTSTRIMLDDSFLSTFLLTYRSFTTPAELLELLIERYNIPPPLDLSSDSYWIS-KKTLPIRIRVLSV 79
                          90       100
                  ....*....|....*....|....*.
gi 31543584   148 LRAWLDQCAEDFREPPHfpCLQKLLE 173
Cdd:pfam00618  80 LRHWVENYFSDFNDDPV--LLSRLEK 103
RA smart00314
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
648-734 1.64e-23

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Kalhammer et al. have shown that not all RA domains bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase. Predicted RA domains in PLC210 and nore1 found to bind RasGTP. Included outliers (Grb7, Grb14, adenylyl cyclases etc.)


Pssm-ID: 214612  Cd Length: 90  Bit Score: 95.06  E-value: 1.64e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584    648 DTCIIRISVEDNNGNMYKSIMLTSQDKTPAVIQRAMSKHNLESDPaEEYELVQVISEDKELVIPDSANVFYAMN----SQ 723
Cdd:smart00314   1 DTFVLRVYVDDLPGGTYKTLRVSSRTTARDVIQQLLEKFHLTDDP-EEYVLVEVLPDGKERVLPDDENPLQLQKlwprRG 79
                           90
                   ....*....|.
gi 31543584    724 VNFDFILRKKN 734
Cdd:smart00314  80 PNLRFVLRKRD 90
RA pfam00788
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
648-734 3.72e-13

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Recent evidence (not yet in MEDLINE) shows that some RA domains do NOT bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase.


Pssm-ID: 425871  Cd Length: 93  Bit Score: 65.82  E-value: 3.72e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584   648 DTCIIRISVEDNN-GNMYKSIMLTSQDKTPAVIQRAMSKHNLESDPaEEYELVQVI-SEDKELVIPDSANVFYAMN---- 721
Cdd:pfam00788   1 DDGVLKVYTEDGKpGTTYKTILVSSSTTAEEVIEALLEKFGLEDDP-RDYVLVEVLeRGGGERRLPDDECPLQIQLqwpr 79
                          90
                  ....*....|...
gi 31543584   722 SQVNFDFILRKKN 734
Cdd:pfam00788  80 DASDSRFLLRKRD 92
 
Name Accession Description Interval E-value
RasGEF cd00155
Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of ...
228-497 6.80e-89

Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. Guanine-nucleotide-exchange factors (GEFs) positively regulate these GTP-binding proteins in response to a variety of signals. GEFs catalyze the dissociation of GDP from the inactive GTP-binding proteins. GTP can then bind and induce structural changes that allow interaction with effectors.


Pssm-ID: 238087 [Multi-domain]  Cd Length: 237  Bit Score: 279.52  E-value: 6.80e-89
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584 228 FTNFSEDLVAEQLTYMDAQLFKKVVPHHCLGCIWSQRDKKEnkHLAPTIRATISQFNTLTKCVVSTVLGSKELKtqQRAR 307
Cdd:cd00155   1 FLSLDPKELAEQLTLLDFELFRKIEPFELLGSLWSKKDKNI--HLSPNLERFIERFNNLSNWVASEILLCTNPK--KRAR 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584 308 VIEKWINIAHECRILKNFSSLRAIVSALQSNSIYRLKKAWAAVPKDRMLMFEELSDIFSDHNNHLTSRELLMKEGTSKFa 387
Cdd:cd00155  77 LLSKFIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEVLSSKLKKLFEELEELVDPSRNFKNYRKLLKSVGPNPP- 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584 388 nldssvkenqkrtqrrlqlqkdmgvmqgTVPYLGTFLTDLTMLDTALQDYIEGGLINFEKRRREFEVIAQIKLLQSacNS 467
Cdd:cd00155 156 ----------------------------CVPFLGVYLKDLTFLHEGNPDFLEGNLVNFEKRRKIAEILREIRQLQS--NS 205
                       250       260       270
                ....*....|....*....|....*....|..
gi 31543584 468 YCMGPDQKFIQWFQ--RQQLLSEEESYALSCE 497
Cdd:cd00155 206 YELNRDEDILAFLWklLELILNEDELYELSLE 237
RasGEF smart00147
Guanine nucleotide exchange factor for Ras-like small GTPases;
228-499 2.10e-86

Guanine nucleotide exchange factor for Ras-like small GTPases;


Pssm-ID: 214539  Cd Length: 242  Bit Score: 272.97  E-value: 2.10e-86
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584    228 FTNFSEDLVAEQLTYMDAQLFKKVVPHHCLGCIWSQRDKKENKHLapTIRATISQFNTLTKCVVSTVLGSKELKtqQRAR 307
Cdd:smart00147   1 LLLLDPKELAEQLTLLDFELFRKIDPSELLGSVWGKRSKKSPSPL--NLEAFIRRFNEVSNWVATEILKQTTPK--DRAE 76
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584    308 VIEKWINIAHECRILKNFSSLRAIVSALQSNSIYRLKKAWAAVPKDRMLMFEELSDIFSDHNNHLTSRELLMKEgtskfa 387
Cdd:smart00147  77 LLSKFIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEKLPSKYKKLFEELEELLSPERNYKNYREALSSC------ 150
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584    388 nldssvkenqkrtqrrlqlqkdmgVMQGTVPYLGTFLTDLTMLDTALQDYIEGGLINFEKRRREFEVIAQIKLLQSAcnS 467
Cdd:smart00147 151 ------------------------NLPPCIPFLGVLLKDLTFIDEGNPDFLENGLVNFEKRRQIAEILREIRQLQSQ--P 204
                          250       260       270
                   ....*....|....*....|....*....|....*
gi 31543584    468 YCMGPDQKFIQWFQRQ---QLLSEEESYALSCEIE 499
Cdd:smart00147 205 YNLRPNRSDIQSLLQQlldHLDEEEELYQLSLKIE 239
RasGEF pfam00617
RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.
236-449 3.51e-70

RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.


Pssm-ID: 425780  Cd Length: 178  Bit Score: 227.86  E-value: 3.51e-70
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584   236 VAEQLTYMDAQLFKKVVPHHCLGCIWSQRDKKEnkhlAPTIRATISQFNTLTKCVVSTVLgsKELKTQQRARVIEKWINI 315
Cdd:pfam00617   2 LARQLTLIEFELFRKIKPRELLGSAWSKKDKKE----SPNIEAMIARFNRLSNWVASEIL--SEEDPKKRAKVIKKFIKI 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584   316 AHECRILKNFSSLRAIVSALQSNSIYRLKKAWAAVPKDRMLMFEELSDIFSDHNNHLTSRELLMKegtskfanldssvke 395
Cdd:pfam00617  76 AEHCRELNNFNSLMAILSGLNSSPISRLKKTWELVSKKSKKLFEELEKLMSPSRNFKNYREALKS--------------- 140
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 31543584   396 nqkrtqrrlqlqkdmgVMQGTVPYLGTFLTDLTMLDTALQDYIEGGLINFEKRR 449
Cdd:pfam00617 141 ----------------ASPPCIPFLGLYLTDLTFIEEGNPDFLDGGLINFEKRR 178
RA_RGL cd17210
Ras-associating (RA) domain found in Ral guanine nucleotide dissociation stimulator-like 1 ...
647-733 2.01e-57

Ras-associating (RA) domain found in Ral guanine nucleotide dissociation stimulator-like 1 (RalGDS-like 1) and similar proteins; RalGDS-like 1 (RGL) is a Ral-specific guanine nucleotide exchange factor that belongs to RalGDS family, whose members are involved in Ras and Ral signaling pathways as downstream effector proteins. RGL has been identified as a possible effector protein of Ras. It also regulates c-fos promoter and the GDP/GTP exchange of Ral. Members in this family have similar structure: a central CDC25 homology domain with an upstream Ras Exchange motif (REM), and a C-terminal Ras-associating (RA) domain. The RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin; ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair.


Pssm-ID: 340730  Cd Length: 87  Bit Score: 190.20  E-value: 2.01e-57
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584 647 EDTCIIRISVEDNNGNMYKSIMLTSQDKTPAVIQRAMSKHNLESDPAEEYELVQVISEDKELVIPDSANVFYAMNSQVNF 726
Cdd:cd17210   1 EDTCIIRVSVEDNNGNMYKSIMLTSQDKTPAVIQRAMSKHNLESDPAEDYELVQVISEDRELVIPDNANVFYAMNSSVNF 80

                ....*..
gi 31543584 727 DFILRKK 733
Cdd:cd17210  81 DFILRKK 87
RA_RalGDS_like cd00153
Ras-associating (RA) domain of RalGDS family; The RalGDS family RA domains can interact with ...
648-733 8.17e-43

Ras-associating (RA) domain of RalGDS family; The RalGDS family RA domains can interact with activated Ras and may function as effectors for other Ras family. Ras proteins are small GTPases that are involved in cellular signal transduction. The RA domain has the beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin (Ub); Ub is a protein modifier in eukaryotes and is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair. The RalGDS family includes RalGDS, RGL, RGL2/Rlf and RGL3. All family members have similar domain structure: a central CDC25 homology domain with an upstream Ras Exchange motif (REM), and a C-terminal RA domain. The RA domain mediates the GTP-dependent interaction with Ras and Ras-related proteins.


Pssm-ID: 340449  Cd Length: 88  Bit Score: 149.65  E-value: 8.17e-43
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584 648 DTCIIRISVED--NNGNMYKSIMLTSQDKTPAVIQRAMSKHNLESDPAEEYELVQVISEDKELVIPDSANVFYAMNSQVN 725
Cdd:cd00153   1 DSRIIRVSLEDgsEDGNLYKSILLTNQDRTPSVIRRALEKHNLEDEDPDDFSLVQILPDDKELVIPDNANVFYAMNSSAN 80

                ....*...
gi 31543584 726 FDFILRKK 733
Cdd:cd00153  81 LNFILRKK 88
RA_RalGDS cd17209
Ras-associating (RA) domain found in Ral guanine nucleotide dissociation stimulator (RalGDS) ...
648-733 2.22e-42

Ras-associating (RA) domain found in Ral guanine nucleotide dissociation stimulator (RalGDS) and similar proteins; RalGDS, also termed Ral guanine nucleotide exchange factor (RalGEF), is a guanine exchange factor (GEF) for the Ral family of small GTPases. It is the prototype of RalGDS family proteins that are involved in Ras and Ral signaling pathways as downstream effector proteins. RalGDS stimulates the dissociation of GDP from the Ras-related RalA and RalB GTPases which allows GTP binding and activation of the GTPases. It interacts and acts as an effector molecule for R-Ras, H-Ras, K-Ras, and Rap. Moreover, RalGDS functions as a novel interacting partner for Rab7-interacting lysosomal protein (RILP), a key regulator for late endosomal/lysosomal trafficking. RILP suppresses invasion of breast cancer cells by inhibiting the GEF activity for RalA of RalGDS. RalGDS also plays a vital role in the regulation of Ral-dependent Weibel-Palade bodies (WPB) exocytosis from endothelial cells. In addition, RalGDS couples growth factor signaling to Akt activation by promoting PDK1-induced Akt phosphorylation. Members in this family have similar domain structure: a central CDC25 homology domain with an upstream Ras Exchange motif (REM), and a C-terminal Ras-associating (RA) domain. The RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin; ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair.


Pssm-ID: 340729  Cd Length: 86  Bit Score: 148.56  E-value: 2.22e-42
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584 648 DTCIIRISVEDNNGNMYKSIMLTSQDKTPAVIQRAMSKHNLESDPAEEYELVQVISEDKELVIPDSANVFYAMNSQVNFD 727
Cdd:cd17209   1 DCCIIRVSLDVDNGNMYKSILVTSQDKTPVVIRKAMAKHNLDEEEPEDYELLQILSEDRELKIPDNANVFYAMNSTANYD 80

                ....*.
gi 31543584 728 FILRKK 733
Cdd:cd17209  81 FVLKKR 86
RA_RGL3 cd17212
Ras-associating (RA) domain found in Ral guanine nucleotide dissociation stimulator-like 3 ...
651-733 2.85e-34

Ras-associating (RA) domain found in Ral guanine nucleotide dissociation stimulator-like 3 (RalGDS-like 3) and similar proteins; RalGDS-like 3 (RGL3), also termed Ras pathway modulator (RPM), interacts in a GTP- and effector loop-dependent manner with Rit and Ras. As a novel potential effector of both p21 Ras and M-Ras, RGL3 negatively regulates Elk-1-dependent gene induction downstream of p21 Ras or mitogen activated protein/extracellular signal regulated kinase Kinase 1 (MEKK1). It also functions as a potential binding partner for Rap-family small G-proteins and profilin II. RGL3 belongs to RalGDS family, whose members are involved in Ras and Ral signaling pathways as downstream effector proteins. Members in this family have similar domain structure: a central CDC25 homology domain with an upstream Ras Exchange motif (REM), and a C-terminal Ras-associating (RA) domain. The RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin; ubiquitin is a protein modifier (Ubiquitination) in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair.


Pssm-ID: 340732  Cd Length: 87  Bit Score: 125.82  E-value: 2.85e-34
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584 651 IIRISVEDNNGNMYKSIMLTSQDKTPAVIQRAMSKHNLESDPAEEYELVQVISEDKELVIPDSANVFYAMNSQVNFDFIL 730
Cdd:cd17212   5 VIRVSIDNDHGNLYRSILLTSQDKAPSVVQRALQKHNVPQPWARDYQLFQVLPGDRELLIPDNANVFYAMSPAAPGDFML 84

                ...
gi 31543584 731 RKK 733
Cdd:cd17212  85 RRK 87
RasGEFN smart00229
Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif; A subset of guanine ...
65-196 2.26e-33

Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small GTPases appear to possess this domain N-terminal to the RasGef (Cdc25-like) domain. The recent crystal structureof Sos shows that this domain is alpha-helical and plays a "purely structural role" (Nature 394, 337-343).


Pssm-ID: 214571  Cd Length: 127  Bit Score: 124.37  E-value: 2.26e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584     65 KIRTIKAGTLEKLVENLLTAFGDNDFTYISIFLSTYRGFASTKEVLELLLDRYGNLTGPNCeddgsQSSPESKAVIRNAI 144
Cdd:smart00229   1 DGGLIKGGTLEALIEHLTEAFDKADPSFVETFLLTYRSFITTQELLQLLLYRYNAIPPESW-----VEEKVNPRRVKNRV 75
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 31543584    145 ASILRAWLDQCAEDFREPPH-FPCLQKLLEyLKQMMPGSDPERRAQNLLEQFQ 196
Cdd:smart00229  76 LNILRTWVENYWEDFEDDPKlISFLLEFLE-LVDDEKYPGLVTSLLNLLRRLS 127
RA_RGL2 cd17211
Ras-associating (RA) domain found in Ral guanine nucleotide dissociation stimulator-like 2 ...
651-733 7.34e-32

Ras-associating (RA) domain found in Ral guanine nucleotide dissociation stimulator-like 2 (RalGDS-like 2) and similar proteins; RalGDS-like 2 (RGL2), also termed RalGDS-like factor (RLF), or Ras-associated protein RAB2L, is a novel Ras and Rap 1A-associating protein that belongs to RalGDS family, whose members are involved in Ras and Ral signaling pathways as downstream effector proteins. RGL2 exhibits guanine nucleotide exchange activity towards the small GTPase Ral. Members in this family have similar domain structure: a central CDC25 homology domain with an upstream Ras Exchange motif (REM), and a C-terminal Ras-associating (RA) domain. The RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin; ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair. The RA domain of RGL2 is phosphorylated by protein kinase A and the phosphorylation affects the ability of RGL2 to bind both Ras and Rap1.


Pssm-ID: 340731  Cd Length: 86  Bit Score: 118.77  E-value: 7.34e-32
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584 651 IIRISVEDNNGNMYKSIMLTSQDKTPAVIQRAMSKHNLESDPAEEYELVQVISEDKELVIPDSANVFYAMNSQvNFDFIL 730
Cdd:cd17211   5 IIRVRMELHDGSVYKSILVTSQDKTPAVISRALEKHNQSSQAASPYELVQLLPEGKELTIPPTANVFYAMSSA-SLDFIL 83

                ...
gi 31543584 731 RKK 733
Cdd:cd17211  84 RPR 86
REM cd06224
Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also ...
73-197 6.03e-27

Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also called REM domain (Ras exchanger motif). This domain is common in nucleotide exchange factors for Ras-like small GTPases and is typically found immediately N-terminal to the RasGef (Cdc25-like) domain. REM contacts the GTPase and is assumed to participate in the catalytic activity of the exchange factor. Proteins with the REM domain include Sos1 and Sos2, which relay signals from tyrosine-kinase mediated signalling to Ras, RasGRP1-4, RasGRF1,2, CNrasGEF, and RAP-specific nucleotide exchange factors, to name a few.


Pssm-ID: 100121  Cd Length: 122  Bit Score: 105.96  E-value: 6.03e-27
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584  73 TLEKLVENLLTAFGDNDFTYISIFLSTYRGFASTKEVLELLLDRYGNLtgPNCEDDGSQSSPESKAVIRNAIASILRAWL 152
Cdd:cd06224   1 TLEALIEHLTSTFDMPDPSFVSTFLLTYRSFTTPTELLEKLIERYEIA--PPENLEYNDWDKKKSKPIRLRVLNVLRTWV 78
                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 31543584 153 DQCAEDFRepPHFPCLQKLLEYLKQMMPGSDPERRAQNLLEQFQK 197
Cdd:cd06224  79 ENYPYDFF--DDEELLELLEEFLNRLVQEGALLQELKKLLRKLLK 121
RasGEF_N pfam00618
RasGEF N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small ...
68-173 1.02e-23

RasGEF N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small GTPases appear to possess this motif/domain N-terminal to the RasGef (Cdc25-like) domain.


Pssm-ID: 425781  Cd Length: 104  Bit Score: 96.22  E-value: 1.02e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584    68 TIKAGTLEKLVENLLTAFGDNDFTYISIFLSTYRGFASTKEVLELLLDRYGNLTGPNCEDDGSQSSpESKAVIRNAIASI 147
Cdd:pfam00618   1 QVKAGTLEKLVEYLTSTRIMLDDSFLSTFLLTYRSFTTPAELLELLIERYNIPPPLDLSSDSYWIS-KKTLPIRIRVLSV 79
                          90       100
                  ....*....|....*....|....*.
gi 31543584   148 LRAWLDQCAEDFREPPHfpCLQKLLE 173
Cdd:pfam00618  80 LRHWVENYFSDFNDDPV--LLSRLEK 103
RA smart00314
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
648-734 1.64e-23

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Kalhammer et al. have shown that not all RA domains bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase. Predicted RA domains in PLC210 and nore1 found to bind RasGTP. Included outliers (Grb7, Grb14, adenylyl cyclases etc.)


Pssm-ID: 214612  Cd Length: 90  Bit Score: 95.06  E-value: 1.64e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584    648 DTCIIRISVEDNNGNMYKSIMLTSQDKTPAVIQRAMSKHNLESDPaEEYELVQVISEDKELVIPDSANVFYAMN----SQ 723
Cdd:smart00314   1 DTFVLRVYVDDLPGGTYKTLRVSSRTTARDVIQQLLEKFHLTDDP-EEYVLVEVLPDGKERVLPDDENPLQLQKlwprRG 79
                           90
                   ....*....|.
gi 31543584    724 VNFDFILRKKN 734
Cdd:smart00314  80 PNLRFVLRKRD 90
RA cd17043
Ras-associating (RA) domain, structurally similar to a beta-grasp ubiquitin-like fold; RA ...
651-732 2.50e-13

Ras-associating (RA) domain, structurally similar to a beta-grasp ubiquitin-like fold; RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in various functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. The RA domain has the beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin (Ub); Ub is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair. RA-containing proteins include RalGDS, AF6, RIN, RASSF1, SNX27, CYR1, STE50, and phospholipase C epsilon.


Pssm-ID: 340563  Cd Length: 87  Bit Score: 65.80  E-value: 2.50e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584 651 IIRISVEDNNGN-MYKSIMLTSQDKTPAVIQRAMSKHNLESDPaEEYELVQVI-SEDKELVIPDSANVFYAMNSQVN--- 725
Cdd:cd17043   1 VLKVYDDDLAPGsAYKSILVSSTTTAREVVQLLLEKYGLEEDP-EDYSLYEVSeKQETERVLHDDECPLLIQLEWGPqgt 79

                ....*...
gi 31543584 726 -FDFILRK 732
Cdd:cd17043  80 eFRFVLKR 87
RA pfam00788
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
648-734 3.72e-13

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Recent evidence (not yet in MEDLINE) shows that some RA domains do NOT bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase.


Pssm-ID: 425871  Cd Length: 93  Bit Score: 65.82  E-value: 3.72e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543584   648 DTCIIRISVEDNN-GNMYKSIMLTSQDKTPAVIQRAMSKHNLESDPaEEYELVQVI-SEDKELVIPDSANVFYAMN---- 721
Cdd:pfam00788   1 DDGVLKVYTEDGKpGTTYKTILVSSSTTAEEVIEALLEKFGLEDDP-RDYVLVEVLeRGGGERRLPDDECPLQIQLqwpr 79
                          90
                  ....*....|...
gi 31543584   722 SQVNFDFILRKKN 734
Cdd:pfam00788  80 DASDSRFLLRKRD 92
RA2_Afadin cd01781
Ras-associating (RA) domain 2 found in Afadin; Afadin, also termed ALL1-fused gene from ...
664-701 3.56e-03

Ras-associating (RA) domain 2 found in Afadin; Afadin, also termed ALL1-fused gene from chromosome 6 protein (AF-6), or canoe, is involved in many fundamental signaling cascades in cells. In addition, it is involved in oncogenesis and metastasis. Afadin has multiple domains: from the N-terminus to the C-terminus it has two Ras-associated (RA) domains, a forkhead-associated domain, a dilute domain, a PDZ domain, three proline-rich domains, and an F-actin binding domain. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in several different functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. The RA domain has a beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin (Ub). Ub is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes. Afadin is abundant at cadherin-based adherens junctions in epithelial cells, endothelial cells, and fibroblasts. This family corresponds to the second RA domain of afadin.


Pssm-ID: 340479  Cd Length: 102  Bit Score: 37.64  E-value: 3.56e-03
                        10        20        30
                ....*....|....*....|....*....|....*...
gi 31543584 664 YKSIMLTSQDKTPAVIQRAMSKHNLESDPAEEYELVQV 701
Cdd:cd01781  17 YKTLLLSTNDTADFVVREALEKYGLEKENPKDYCLVQV 54
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.20
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