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Conserved domains on  [gi|182724|gb|AAA58485|]
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dihydrofolate reductase [Homo sapiens]

Protein Classification

dihydrofolate reductase( domain architecture ID 10082841)

dihydrofolate reductase (DHFR) is involved in the biosynthesis of deoxythymidine phosphate; it reduces 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate with NADPH as a cofactor

CATH:  3.40.430.10
EC:  1.5.1.3
SCOP:  4000755

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
DHFR cd00209
Dihydrofolate reductase (DHFR). Reduces 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate with ...
5-184 1.27e-61

Dihydrofolate reductase (DHFR). Reduces 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate with NADPH as a cofactor. This is an essential step in the biosynthesis of deoxythymidine phosphate since 5,6,7,8-tetrahydrofolate is required to regenerate 5,10-methylenetetrahydrofolate which is then utilized by thymidylate synthase. Inhibition of DHFR interrupts thymidilate synthesis and DNA replication, inhibitors of DHFR (such as Methotrexate) are used in cancer chemotherapy. 5,6,7,8-tetrahydrofolate also is involved in glycine, serine, and threonine metabolism and aminoacyl-tRNA biosynthesis.


:

Pssm-ID: 238127 [Multi-domain]  Cd Length: 158  Bit Score: 188.12  E-value: 1.27e-61
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 182724     5 LNCIVAVSQNMGIGKNGDLPWPpLRNEFRYFQRMTTTssvegkqNLVIMGKKTWFSIPEknRPLKGRINLVLSRELKEPP 84
Cdd:cd00209   1 ISLIVAVDENGVIGKDNKLPWH-LPEDLKHFKKTTTG-------NPVIMGRKTFESIPR--RPLPGRTNIVLSRQLDYQD 70
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 182724    85 QGAHFLSRSLDDALKLteqpeLANKVDMVWIVGGSSVYKEAMNHPGhlKLFVTRIMQDFESDTFFPEIDLEKYKLLPEyp 164
Cdd:cd00209  71 AEGVEVVHSLEEALEL-----AENTVEEIFVIGGAEIYKQALPYAD--RLYLTRIHAEFEGDTFFPEIDESEWELVSE-- 141
                       170       180
                ....*....|....*....|
gi 182724   165 gvlSDVQEEKGIKYKFEVYE 184
Cdd:cd00209 142 ---EEVFEEDGYSYTFETYE 158
 
Name Accession Description Interval E-value
DHFR cd00209
Dihydrofolate reductase (DHFR). Reduces 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate with ...
5-184 1.27e-61

Dihydrofolate reductase (DHFR). Reduces 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate with NADPH as a cofactor. This is an essential step in the biosynthesis of deoxythymidine phosphate since 5,6,7,8-tetrahydrofolate is required to regenerate 5,10-methylenetetrahydrofolate which is then utilized by thymidylate synthase. Inhibition of DHFR interrupts thymidilate synthesis and DNA replication, inhibitors of DHFR (such as Methotrexate) are used in cancer chemotherapy. 5,6,7,8-tetrahydrofolate also is involved in glycine, serine, and threonine metabolism and aminoacyl-tRNA biosynthesis.


Pssm-ID: 238127 [Multi-domain]  Cd Length: 158  Bit Score: 188.12  E-value: 1.27e-61
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 182724     5 LNCIVAVSQNMGIGKNGDLPWPpLRNEFRYFQRMTTTssvegkqNLVIMGKKTWFSIPEknRPLKGRINLVLSRELKEPP 84
Cdd:cd00209   1 ISLIVAVDENGVIGKDNKLPWH-LPEDLKHFKKTTTG-------NPVIMGRKTFESIPR--RPLPGRTNIVLSRQLDYQD 70
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 182724    85 QGAHFLSRSLDDALKLteqpeLANKVDMVWIVGGSSVYKEAMNHPGhlKLFVTRIMQDFESDTFFPEIDLEKYKLLPEyp 164
Cdd:cd00209  71 AEGVEVVHSLEEALEL-----AENTVEEIFVIGGAEIYKQALPYAD--RLYLTRIHAEFEGDTFFPEIDESEWELVSE-- 141
                       170       180
                ....*....|....*....|
gi 182724   165 gvlSDVQEEKGIKYKFEVYE 184
Cdd:cd00209 142 ---EEVFEEDGYSYTFETYE 158
PTZ00164 PTZ00164
bifunctional dihydrofolate reductase-thymidylate synthase; Provisional
8-187 1.28e-46

bifunctional dihydrofolate reductase-thymidylate synthase; Provisional


Pssm-ID: 240299 [Multi-domain]  Cd Length: 514  Bit Score: 159.45  E-value: 1.28e-46
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 182724      8 IVAVSQNMGIGKNGDLPWPpLRNEFRYFQRMTTT------SSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVLSRELK 81
Cdd:PTZ00164  13 VVAVTLKRGIGIGNSLPWH-IPEDMKFFSKITTYvreekyEKSPKKQNAVIMGRKTWESIPKKFRPLKNRINVVLSRTLT 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 182724     82 EPPQGAH-FLSRSLDDALKLTEQPelaNKVDMVWIVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDLEKYKLl 160
Cdd:PTZ00164  92 EEEADPGvLVFGSLEDALRLLAED---LSIEKIFIIGGASVYREALSANLLDKIYLTRVNSEYECDVFFPKIPESFFIV- 167
                        170       180
                 ....*....|....*....|....*..
gi 182724    161 peypGVLSDVQEEKGIKYKFEVYEKND 187
Cdd:PTZ00164 168 ----AIVSQTFSTNGTSYDFVIYEKKN 190
DHFR_1 pfam00186
Dihydrofolate reductase;
8-185 1.58e-41

Dihydrofolate reductase;


Pssm-ID: 425512 [Multi-domain]  Cd Length: 159  Bit Score: 137.29  E-value: 1.58e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 182724       8 IVAVSQNMGIGKNGDLPWPpLRNEFRYFQRMTTtssveGKqnLVIMGKKTWFSIPeknRPLKGRINLVLSRELKEPPQGA 87
Cdd:pfam00186   5 IAAMDENGVIGKDNDLPWH-LPADLKHFKKLTT-----GK--PVIMGRKTFESIG---RPLPGRKNIVLTRNPDYKVDGV 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 182724      88 HFLSrSLDDALklteqpELANKVDMVWIVGGSSVYKEAMNHPGhlKLFVTRIMQDFESDTFFPEIDLEKYKLLPEYPGvl 167
Cdd:pfam00186  74 EVVH-SLEEAL------ALAAEAEEIFIIGGAEIYAQALPLAD--RLYITEIDAEFDGDTFFPEIDPSEWQLVSREEH-- 142
                         170
                  ....*....|....*...
gi 182724     168 sDVQEEKGIKYKFEVYEK 185
Cdd:pfam00186 143 -EADEKNPYPYTFVTYER 159
FolA COG0262
Dihydrofolate reductase [Coenzyme transport and metabolism]; Dihydrofolate reductase is part ...
5-155 1.01e-23

Dihydrofolate reductase [Coenzyme transport and metabolism]; Dihydrofolate reductase is part of the Pathway/BioSystem: Folate biosynthesis


Pssm-ID: 440032 [Multi-domain]  Cd Length: 168  Bit Score: 91.84  E-value: 1.01e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 182724     5 LNCIVAVSQNMGIG-KNGDLPW-PPLRNEFRYFQRMTTTSSVegkqnlVIMGKKTWFSIPEK--NRPLKGRINLVLSREL 80
Cdd:COG0262   3 LILIVAVSLDGVIGgPDGDLPWlFPDPEDLAHFKELTAGADA------VLMGRKTYESIAGYwpTRPLPGRPKIVLSRTL 76
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 182724    81 KEPP-QGAHFLSRSLDDALKLTEQPELANkvdmVWIVGGSSVYKEAMNHpGHL-KLFVTRIMQDFES-DTFFPEIDLE 155
Cdd:COG0262  77 DEADwEGVTVVSGDLEEALAALKAAGGKD----IWVIGGGELYRQLLPA-GLVdELYLTVVPVVLGEgDRLFPELDAP 149
dihyfolred_HdrA_Halo NF041386
dihydrofolate reductase HdrA;
10-162 8.51e-13

dihydrofolate reductase HdrA;


Pssm-ID: 469277 [Multi-domain]  Cd Length: 158  Bit Score: 63.05  E-value: 8.51e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 182724     10 AVSQNMGIGKNGDLPWPPLRNEFR-YFQRMTTTSsvegkqnlVIMGKKTWFSIPEKnrpLKGRINLVLSRELKEPPQGAH 88
Cdd:NF041386   8 AVAENGVIGRDGELPWPSIPADKRqYRERVADDP--------VILGRRTFESMRDD---LPGSAQIVLSRSEREFDVETA 76
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 182724     89 FLSRSLDDALKLTEQPElankVDMVWIVGGSSVYkeAMNHPGHLKLFVTRIMQDFESDTFFPEIDLEKYKLLPE 162
Cdd:NF041386  77 HHAGGVDEAIEIAESLG----AERAYVLGGAAIY--ELFQPHVDRMVLSRVPGEYEGDAYYPEWDEDEWELVEE 144
trim_DfrL NF041668
trimethoprim-resistant dihydrofolate reductase DfrL;
17-185 1.51e-04

trimethoprim-resistant dihydrofolate reductase DfrL;


Pssm-ID: 469550 [Multi-domain]  Cd Length: 176  Bit Score: 40.41  E-value: 1.51e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 182724     17 IGKNGDLPWPpLRNEFRYFQRMtttssveGKQNLVIMGKKTWFSIPekNRPLKGRINLVLSRELKEPPQGAhFLSRSLDD 96
Cdd:NF041668  13 IGKPGDLFVN-AEDDMGHFGNS-------GDDDVNLMGDKKHEKIP--TMDDKNRIGIKLTENIPVRADGA-IICHSKED 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 182724     97 ALKLTEQPELankVDMVWIVGGSSVYKEAMNHPGHlkLFVTRIMQDFESDTFFPEIDlekYKLLPEYPGVLSDVQEEKGI 176
Cdd:NF041668  82 NKNYLADGAI---ECHIHEDGGISAFEMFIDEPIH--LHGGIIAEEFEGDEVMIEHD---TIIDECFDGADGMPDEDNKY 153

                 ....*....
gi 182724    177 KYKFEVYEK 185
Cdd:NF041668 154 FHCFDIADG 162
 
Name Accession Description Interval E-value
DHFR cd00209
Dihydrofolate reductase (DHFR). Reduces 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate with ...
5-184 1.27e-61

Dihydrofolate reductase (DHFR). Reduces 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate with NADPH as a cofactor. This is an essential step in the biosynthesis of deoxythymidine phosphate since 5,6,7,8-tetrahydrofolate is required to regenerate 5,10-methylenetetrahydrofolate which is then utilized by thymidylate synthase. Inhibition of DHFR interrupts thymidilate synthesis and DNA replication, inhibitors of DHFR (such as Methotrexate) are used in cancer chemotherapy. 5,6,7,8-tetrahydrofolate also is involved in glycine, serine, and threonine metabolism and aminoacyl-tRNA biosynthesis.


Pssm-ID: 238127 [Multi-domain]  Cd Length: 158  Bit Score: 188.12  E-value: 1.27e-61
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 182724     5 LNCIVAVSQNMGIGKNGDLPWPpLRNEFRYFQRMTTTssvegkqNLVIMGKKTWFSIPEknRPLKGRINLVLSRELKEPP 84
Cdd:cd00209   1 ISLIVAVDENGVIGKDNKLPWH-LPEDLKHFKKTTTG-------NPVIMGRKTFESIPR--RPLPGRTNIVLSRQLDYQD 70
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 182724    85 QGAHFLSRSLDDALKLteqpeLANKVDMVWIVGGSSVYKEAMNHPGhlKLFVTRIMQDFESDTFFPEIDLEKYKLLPEyp 164
Cdd:cd00209  71 AEGVEVVHSLEEALEL-----AENTVEEIFVIGGAEIYKQALPYAD--RLYLTRIHAEFEGDTFFPEIDESEWELVSE-- 141
                       170       180
                ....*....|....*....|
gi 182724   165 gvlSDVQEEKGIKYKFEVYE 184
Cdd:cd00209 142 ---EEVFEEDGYSYTFETYE 158
PTZ00164 PTZ00164
bifunctional dihydrofolate reductase-thymidylate synthase; Provisional
8-187 1.28e-46

bifunctional dihydrofolate reductase-thymidylate synthase; Provisional


Pssm-ID: 240299 [Multi-domain]  Cd Length: 514  Bit Score: 159.45  E-value: 1.28e-46
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 182724      8 IVAVSQNMGIGKNGDLPWPpLRNEFRYFQRMTTT------SSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVLSRELK 81
Cdd:PTZ00164  13 VVAVTLKRGIGIGNSLPWH-IPEDMKFFSKITTYvreekyEKSPKKQNAVIMGRKTWESIPKKFRPLKNRINVVLSRTLT 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 182724     82 EPPQGAH-FLSRSLDDALKLTEQPelaNKVDMVWIVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDLEKYKLl 160
Cdd:PTZ00164  92 EEEADPGvLVFGSLEDALRLLAED---LSIEKIFIIGGASVYREALSANLLDKIYLTRVNSEYECDVFFPKIPESFFIV- 167
                        170       180
                 ....*....|....*....|....*..
gi 182724    161 peypGVLSDVQEEKGIKYKFEVYEKND 187
Cdd:PTZ00164 168 ----AIVSQTFSTNGTSYDFVIYEKKN 190
DHFR_1 pfam00186
Dihydrofolate reductase;
8-185 1.58e-41

Dihydrofolate reductase;


Pssm-ID: 425512 [Multi-domain]  Cd Length: 159  Bit Score: 137.29  E-value: 1.58e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 182724       8 IVAVSQNMGIGKNGDLPWPpLRNEFRYFQRMTTtssveGKqnLVIMGKKTWFSIPeknRPLKGRINLVLSRELKEPPQGA 87
Cdd:pfam00186   5 IAAMDENGVIGKDNDLPWH-LPADLKHFKKLTT-----GK--PVIMGRKTFESIG---RPLPGRKNIVLTRNPDYKVDGV 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 182724      88 HFLSrSLDDALklteqpELANKVDMVWIVGGSSVYKEAMNHPGhlKLFVTRIMQDFESDTFFPEIDLEKYKLLPEYPGvl 167
Cdd:pfam00186  74 EVVH-SLEEAL------ALAAEAEEIFIIGGAEIYAQALPLAD--RLYITEIDAEFDGDTFFPEIDPSEWQLVSREEH-- 142
                         170
                  ....*....|....*...
gi 182724     168 sDVQEEKGIKYKFEVYEK 185
Cdd:pfam00186 143 -EADEKNPYPYTFVTYER 159
FolA COG0262
Dihydrofolate reductase [Coenzyme transport and metabolism]; Dihydrofolate reductase is part ...
5-155 1.01e-23

Dihydrofolate reductase [Coenzyme transport and metabolism]; Dihydrofolate reductase is part of the Pathway/BioSystem: Folate biosynthesis


Pssm-ID: 440032 [Multi-domain]  Cd Length: 168  Bit Score: 91.84  E-value: 1.01e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 182724     5 LNCIVAVSQNMGIG-KNGDLPW-PPLRNEFRYFQRMTTTSSVegkqnlVIMGKKTWFSIPEK--NRPLKGRINLVLSREL 80
Cdd:COG0262   3 LILIVAVSLDGVIGgPDGDLPWlFPDPEDLAHFKELTAGADA------VLMGRKTYESIAGYwpTRPLPGRPKIVLSRTL 76
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 182724    81 KEPP-QGAHFLSRSLDDALKLTEQPELANkvdmVWIVGGSSVYKEAMNHpGHL-KLFVTRIMQDFES-DTFFPEIDLE 155
Cdd:COG0262  77 DEADwEGVTVVSGDLEEALAALKAAGGKD----IWVIGGGELYRQLLPA-GLVdELYLTVVPVVLGEgDRLFPELDAP 149
folA PRK10769
type 3 dihydrofolate reductase;
8-185 1.99e-15

type 3 dihydrofolate reductase;


Pssm-ID: 182714 [Multi-domain]  Cd Length: 159  Bit Score: 69.77  E-value: 1.99e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 182724      8 IVAVSQNMGIGKNGDLPWPpLRNEFRYFQRMTTTSSVegkqnlvIMGKKTWFSIpekNRPLKGRINLVLSRElkepPQGA 87
Cdd:PRK10769   5 IAALAVDRVIGMENAMPWN-LPADLAWFKRNTLNKPV-------IMGRHTWESI---GRPLPGRKNIVISSQ----PGTD 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 182724     88 HFLS--RSLDDALklteqpELANKVDMVWIVGGSSVYKEAMnhPGHLKLFVTRIMQDFESDTFFPEIDLEkykllpEYPG 165
Cdd:PRK10769  70 DRVTwvKSVDEAL------AAAGDVPEIMVIGGGRVYEQFL--PKAQRLYLTHIDAEVEGDTHFPDYEPD------EWES 135
                        170       180
                 ....*....|....*....|...
gi 182724    166 VLS---DVQEEKGIKYKFEVYEK 185
Cdd:PRK10769 136 VFSefhDADEQNSHSYCFEILER 158
dihyfolred_HdrA_Halo NF041386
dihydrofolate reductase HdrA;
10-162 8.51e-13

dihydrofolate reductase HdrA;


Pssm-ID: 469277 [Multi-domain]  Cd Length: 158  Bit Score: 63.05  E-value: 8.51e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 182724     10 AVSQNMGIGKNGDLPWPPLRNEFR-YFQRMTTTSsvegkqnlVIMGKKTWFSIPEKnrpLKGRINLVLSRELKEPPQGAH 88
Cdd:NF041386   8 AVAENGVIGRDGELPWPSIPADKRqYRERVADDP--------VILGRRTFESMRDD---LPGSAQIVLSRSEREFDVETA 76
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 182724     89 FLSRSLDDALKLTEQPElankVDMVWIVGGSSVYkeAMNHPGHLKLFVTRIMQDFESDTFFPEIDLEKYKLLPE 162
Cdd:NF041386  77 HHAGGVDEAIEIAESLG----AERAYVLGGAAIY--ELFQPHVDRMVLSRVPGEYEGDAYYPEWDEDEWELVEE 144
trim_DfrL NF041668
trimethoprim-resistant dihydrofolate reductase DfrL;
17-185 1.51e-04

trimethoprim-resistant dihydrofolate reductase DfrL;


Pssm-ID: 469550 [Multi-domain]  Cd Length: 176  Bit Score: 40.41  E-value: 1.51e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 182724     17 IGKNGDLPWPpLRNEFRYFQRMtttssveGKQNLVIMGKKTWFSIPekNRPLKGRINLVLSRELKEPPQGAhFLSRSLDD 96
Cdd:NF041668  13 IGKPGDLFVN-AEDDMGHFGNS-------GDDDVNLMGDKKHEKIP--TMDDKNRIGIKLTENIPVRADGA-IICHSKED 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 182724     97 ALKLTEQPELankVDMVWIVGGSSVYKEAMNHPGHlkLFVTRIMQDFESDTFFPEIDlekYKLLPEYPGVLSDVQEEKGI 176
Cdd:NF041668  82 NKNYLADGAI---ECHIHEDGGISAFEMFIDEPIH--LHGGIIAEEFEGDEVMIEHD---TIIDECFDGADGMPDEDNKY 153

                 ....*....
gi 182724    177 KYKFEVYEK 185
Cdd:NF041668 154 FHCFDIADG 162
 
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.
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