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Conserved domains on  [gi|1139421645]
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Chain A, Dihydrofolate reductase

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 ...
4-183 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 1139421645   4 LNCIVAVSQNMGIGKNGDLPWPpLRNEFRYFQRMTTTssvegkqNLVIMGKKTWFSIPEknRPLKGRINLVLSRELKEPP 83
Cdd:cd00209     1 ISLIVAVDENGVIGKDNKLPWH-LPEDLKHFKKTTTG-------NPVIMGRKTFESIPR--RPLPGRTNIVLSRQLDYQD 70
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421645  84 QGAHFLSRSLDDALKLteqpeLANKVDMVWIVGGSSVYKEAMNHPGhlKLFVTRIMQDFESDTFFPEIDLEKYKLLPEyp 163
Cdd:cd00209    71 AEGVEVVHSLEEALEL-----AENTVEEIFVIGGAEIYKQALPYAD--RLYLTRIHAEFEGDTFFPEIDESEWELVSE-- 141
                         170       180
                  ....*....|....*....|
gi 1139421645 164 gvlSDVQEEKGIKYKFEVYE 183
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 ...
4-183 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 1139421645   4 LNCIVAVSQNMGIGKNGDLPWPpLRNEFRYFQRMTTTssvegkqNLVIMGKKTWFSIPEknRPLKGRINLVLSRELKEPP 83
Cdd:cd00209     1 ISLIVAVDENGVIGKDNKLPWH-LPEDLKHFKKTTTG-------NPVIMGRKTFESIPR--RPLPGRTNIVLSRQLDYQD 70
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421645  84 QGAHFLSRSLDDALKLteqpeLANKVDMVWIVGGSSVYKEAMNHPGhlKLFVTRIMQDFESDTFFPEIDLEKYKLLPEyp 163
Cdd:cd00209    71 AEGVEVVHSLEEALEL-----AENTVEEIFVIGGAEIYKQALPYAD--RLYLTRIHAEFEGDTFFPEIDESEWELVSE-- 141
                         170       180
                  ....*....|....*....|
gi 1139421645 164 gvlSDVQEEKGIKYKFEVYE 183
Cdd:cd00209   142 ---EEVFEEDGYSYTFETYE 158
PTZ00164 PTZ00164
bifunctional dihydrofolate reductase-thymidylate synthase; Provisional
7-186 1.09e-46

bifunctional dihydrofolate reductase-thymidylate synthase; Provisional


Pssm-ID: 240299 [Multi-domain]  Cd Length: 514  Bit Score: 159.84  E-value: 1.09e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421645   7 IVAVSQNMGIGKNGDLPWPpLRNEFRYFQRMTTT------SSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVLSRELK 80
Cdd:PTZ00164   13 VVAVTLKRGIGIGNSLPWH-IPEDMKFFSKITTYvreekyEKSPKKQNAVIMGRKTWESIPKKFRPLKNRINVVLSRTLT 91
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421645  81 EPPQGAH-FLSRSLDDALKLTEQPelaNKVDMVWIVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDLEKYKLl 159
Cdd:PTZ00164   92 EEEADPGvLVFGSLEDALRLLAED---LSIEKIFIIGGASVYREALSANLLDKIYLTRVNSEYECDVFFPKIPESFFIV- 167
                         170       180
                  ....*....|....*....|....*..
gi 1139421645 160 peypGVLSDVQEEKGIKYKFEVYEKND 186
Cdd:PTZ00164  168 ----AIVSQTFSTNGTSYDFVIYEKKN 190
DHFR_1 pfam00186
Dihydrofolate reductase;
7-184 1.52e-41

Dihydrofolate reductase;


Pssm-ID: 425512 [Multi-domain]  Cd Length: 159  Bit Score: 137.29  E-value: 1.52e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421645   7 IVAVSQNMGIGKNGDLPWPpLRNEFRYFQRMTTtssveGKqnLVIMGKKTWFSIPeknRPLKGRINLVLSRELKEPPQGA 86
Cdd:pfam00186   5 IAAMDENGVIGKDNDLPWH-LPADLKHFKKLTT-----GK--PVIMGRKTFESIG---RPLPGRKNIVLTRNPDYKVDGV 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421645  87 HFLSrSLDDALklteqpELANKVDMVWIVGGSSVYKEAMNHPGhlKLFVTRIMQDFESDTFFPEIDLEKYKLLPEYPGvl 166
Cdd:pfam00186  74 EVVH-SLEEAL------ALAAEAEEIFIIGGAEIYAQALPLAD--RLYITEIDAEFDGDTFFPEIDPSEWQLVSREEH-- 142
                         170
                  ....*....|....*...
gi 1139421645 167 sDVQEEKGIKYKFEVYEK 184
Cdd:pfam00186 143 -EADEKNPYPYTFVTYER 159
FolA COG0262
Dihydrofolate reductase [Coenzyme transport and metabolism]; Dihydrofolate reductase is part ...
4-154 9.77e-24

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: 9.77e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421645   4 LNCIVAVSQNMGIG-KNGDLPW-PPLRNEFRYFQRMTTTSSVegkqnlVIMGKKTWFSIPEK--NRPLKGRINLVLSREL 79
Cdd:COG0262     3 LILIVAVSLDGVIGgPDGDLPWlFPDPEDLAHFKELTAGADA------VLMGRKTYESIAGYwpTRPLPGRPKIVLSRTL 76
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1139421645  80 KEPP-QGAHFLSRSLDDALKLTEQPELANkvdmVWIVGGSSVYKEAMNHpGHL-KLFVTRIMQDFES-DTFFPEIDLE 154
Cdd:COG0262    77 DEADwEGVTVVSGDLEEALAALKAAGGKD----IWVIGGGELYRQLLPA-GLVdELYLTVVPVVLGEgDRLFPELDAP 149
dihyfolred_HdrA_Halo NF041386
dihydrofolate reductase HdrA;
9-161 8.33e-13

dihydrofolate reductase HdrA;


Pssm-ID: 469277 [Multi-domain]  Cd Length: 158  Bit Score: 63.05  E-value: 8.33e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421645   9 AVSQNMGIGKNGDLPWPPLRNEFR-YFQRMTTTSsvegkqnlVIMGKKTWFSIPEKnrpLKGRINLVLSRELKEPPQGAH 87
Cdd:NF041386    8 AVAENGVIGRDGELPWPSIPADKRqYRERVADDP--------VILGRRTFESMRDD---LPGSAQIVLSRSEREFDVETA 76
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1139421645  88 FLSRSLDDALKLTEQPElankVDMVWIVGGSSVYkeAMNHPGHLKLFVTRIMQDFESDTFFPEIDLEKYKLLPE 161
Cdd:NF041386   77 HHAGGVDEAIEIAESLG----AERAYVLGGAAIY--ELFQPHVDRMVLSRVPGEYEGDAYYPEWDEDEWELVEE 144
trim_DfrL NF041668
trimethoprim-resistant dihydrofolate reductase DfrL;
16-184 1.32e-04

trimethoprim-resistant dihydrofolate reductase DfrL;


Pssm-ID: 469550 [Multi-domain]  Cd Length: 176  Bit Score: 40.79  E-value: 1.32e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421645  16 IGKNGDLPWPpLRNEFRYFQRMtttssveGKQNLVIMGKKTWFSIPekNRPLKGRINLVLSRELKEPPQGAhFLSRSLDD 95
Cdd:NF041668   13 IGKPGDLFVN-AEDDMGHFGNS-------GDDDVNLMGDKKHEKIP--TMDDKNRIGIKLTENIPVRADGA-IICHSKED 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421645  96 ALKLTEQPELankVDMVWIVGGSSVYKEAMNHPGHlkLFVTRIMQDFESDTFFPEIDlekYKLLPEYPGVLSDVQEEKGI 175
Cdd:NF041668   82 NKNYLADGAI---ECHIHEDGGISAFEMFIDEPIH--LHGGIIAEEFEGDEVMIEHD---TIIDECFDGADGMPDEDNKY 153

                  ....*....
gi 1139421645 176 KYKFEVYEK 184
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 ...
4-183 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 1139421645   4 LNCIVAVSQNMGIGKNGDLPWPpLRNEFRYFQRMTTTssvegkqNLVIMGKKTWFSIPEknRPLKGRINLVLSRELKEPP 83
Cdd:cd00209     1 ISLIVAVDENGVIGKDNKLPWH-LPEDLKHFKKTTTG-------NPVIMGRKTFESIPR--RPLPGRTNIVLSRQLDYQD 70
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421645  84 QGAHFLSRSLDDALKLteqpeLANKVDMVWIVGGSSVYKEAMNHPGhlKLFVTRIMQDFESDTFFPEIDLEKYKLLPEyp 163
Cdd:cd00209    71 AEGVEVVHSLEEALEL-----AENTVEEIFVIGGAEIYKQALPYAD--RLYLTRIHAEFEGDTFFPEIDESEWELVSE-- 141
                         170       180
                  ....*....|....*....|
gi 1139421645 164 gvlSDVQEEKGIKYKFEVYE 183
Cdd:cd00209   142 ---EEVFEEDGYSYTFETYE 158
PTZ00164 PTZ00164
bifunctional dihydrofolate reductase-thymidylate synthase; Provisional
7-186 1.09e-46

bifunctional dihydrofolate reductase-thymidylate synthase; Provisional


Pssm-ID: 240299 [Multi-domain]  Cd Length: 514  Bit Score: 159.84  E-value: 1.09e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421645   7 IVAVSQNMGIGKNGDLPWPpLRNEFRYFQRMTTT------SSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVLSRELK 80
Cdd:PTZ00164   13 VVAVTLKRGIGIGNSLPWH-IPEDMKFFSKITTYvreekyEKSPKKQNAVIMGRKTWESIPKKFRPLKNRINVVLSRTLT 91
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421645  81 EPPQGAH-FLSRSLDDALKLTEQPelaNKVDMVWIVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDLEKYKLl 159
Cdd:PTZ00164   92 EEEADPGvLVFGSLEDALRLLAED---LSIEKIFIIGGASVYREALSANLLDKIYLTRVNSEYECDVFFPKIPESFFIV- 167
                         170       180
                  ....*....|....*....|....*..
gi 1139421645 160 peypGVLSDVQEEKGIKYKFEVYEKND 186
Cdd:PTZ00164  168 ----AIVSQTFSTNGTSYDFVIYEKKN 190
DHFR_1 pfam00186
Dihydrofolate reductase;
7-184 1.52e-41

Dihydrofolate reductase;


Pssm-ID: 425512 [Multi-domain]  Cd Length: 159  Bit Score: 137.29  E-value: 1.52e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421645   7 IVAVSQNMGIGKNGDLPWPpLRNEFRYFQRMTTtssveGKqnLVIMGKKTWFSIPeknRPLKGRINLVLSRELKEPPQGA 86
Cdd:pfam00186   5 IAAMDENGVIGKDNDLPWH-LPADLKHFKKLTT-----GK--PVIMGRKTFESIG---RPLPGRKNIVLTRNPDYKVDGV 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421645  87 HFLSrSLDDALklteqpELANKVDMVWIVGGSSVYKEAMNHPGhlKLFVTRIMQDFESDTFFPEIDLEKYKLLPEYPGvl 166
Cdd:pfam00186  74 EVVH-SLEEAL------ALAAEAEEIFIIGGAEIYAQALPLAD--RLYITEIDAEFDGDTFFPEIDPSEWQLVSREEH-- 142
                         170
                  ....*....|....*...
gi 1139421645 167 sDVQEEKGIKYKFEVYEK 184
Cdd:pfam00186 143 -EADEKNPYPYTFVTYER 159
FolA COG0262
Dihydrofolate reductase [Coenzyme transport and metabolism]; Dihydrofolate reductase is part ...
4-154 9.77e-24

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: 9.77e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421645   4 LNCIVAVSQNMGIG-KNGDLPW-PPLRNEFRYFQRMTTTSSVegkqnlVIMGKKTWFSIPEK--NRPLKGRINLVLSREL 79
Cdd:COG0262     3 LILIVAVSLDGVIGgPDGDLPWlFPDPEDLAHFKELTAGADA------VLMGRKTYESIAGYwpTRPLPGRPKIVLSRTL 76
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1139421645  80 KEPP-QGAHFLSRSLDDALKLTEQPELANkvdmVWIVGGSSVYKEAMNHpGHL-KLFVTRIMQDFES-DTFFPEIDLE 154
Cdd:COG0262    77 DEADwEGVTVVSGDLEEALAALKAAGGKD----IWVIGGGELYRQLLPA-GLVdELYLTVVPVVLGEgDRLFPELDAP 149
folA PRK10769
type 3 dihydrofolate reductase;
7-184 1.79e-15

type 3 dihydrofolate reductase;


Pssm-ID: 182714 [Multi-domain]  Cd Length: 159  Bit Score: 70.15  E-value: 1.79e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421645   7 IVAVSQNMGIGKNGDLPWPpLRNEFRYFQRMTTTSSVegkqnlvIMGKKTWFSIpekNRPLKGRINLVLSRElkepPQGA 86
Cdd:PRK10769    5 IAALAVDRVIGMENAMPWN-LPADLAWFKRNTLNKPV-------IMGRHTWESI---GRPLPGRKNIVISSQ----PGTD 69
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421645  87 HFLS--RSLDDALklteqpELANKVDMVWIVGGSSVYKEAMnhPGHLKLFVTRIMQDFESDTFFPEIDLEkykllpEYPG 164
Cdd:PRK10769   70 DRVTwvKSVDEAL------AAAGDVPEIMVIGGGRVYEQFL--PKAQRLYLTHIDAEVEGDTHFPDYEPD------EWES 135
                         170       180
                  ....*....|....*....|...
gi 1139421645 165 VLS---DVQEEKGIKYKFEVYEK 184
Cdd:PRK10769  136 VFSefhDADEQNSHSYCFEILER 158
dihyfolred_HdrA_Halo NF041386
dihydrofolate reductase HdrA;
9-161 8.33e-13

dihydrofolate reductase HdrA;


Pssm-ID: 469277 [Multi-domain]  Cd Length: 158  Bit Score: 63.05  E-value: 8.33e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421645   9 AVSQNMGIGKNGDLPWPPLRNEFR-YFQRMTTTSsvegkqnlVIMGKKTWFSIPEKnrpLKGRINLVLSRELKEPPQGAH 87
Cdd:NF041386    8 AVAENGVIGRDGELPWPSIPADKRqYRERVADDP--------VILGRRTFESMRDD---LPGSAQIVLSRSEREFDVETA 76
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1139421645  88 FLSRSLDDALKLTEQPElankVDMVWIVGGSSVYkeAMNHPGHLKLFVTRIMQDFESDTFFPEIDLEKYKLLPE 161
Cdd:NF041386   77 HHAGGVDEAIEIAESLG----AERAYVLGGAAIY--ELFQPHVDRMVLSRVPGEYEGDAYYPEWDEDEWELVEE 144
trim_DfrL NF041668
trimethoprim-resistant dihydrofolate reductase DfrL;
16-184 1.32e-04

trimethoprim-resistant dihydrofolate reductase DfrL;


Pssm-ID: 469550 [Multi-domain]  Cd Length: 176  Bit Score: 40.79  E-value: 1.32e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421645  16 IGKNGDLPWPpLRNEFRYFQRMtttssveGKQNLVIMGKKTWFSIPekNRPLKGRINLVLSRELKEPPQGAhFLSRSLDD 95
Cdd:NF041668   13 IGKPGDLFVN-AEDDMGHFGNS-------GDDDVNLMGDKKHEKIP--TMDDKNRIGIKLTENIPVRADGA-IICHSKED 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421645  96 ALKLTEQPELankVDMVWIVGGSSVYKEAMNHPGHlkLFVTRIMQDFESDTFFPEIDlekYKLLPEYPGVLSDVQEEKGI 175
Cdd:NF041668   82 NKNYLADGAI---ECHIHEDGGISAFEMFIDEPIH--LHGGIIAEEFEGDEVMIEHD---TIIDECFDGADGMPDEDNKY 153

                  ....*....
gi 1139421645 176 KYKFEVYEK 184
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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