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Conserved domains on  [gi|1022432070|ref|NP_001310966|]
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uroporphyrinogen-III synthase isoform 3 [Homo sapiens]

Protein Classification

uroporphyrinogen-III synthase( domain architecture ID 10159118)

uroporphyrinogen-III synthase catalyzes cyclization of the linear tetrapyrrole, hydroxymethylbilane, to the macrocyclic uroporphyrinogen III

CATH:  3.40.50.10090
EC:  4.2.1.75
Gene Ontology:  GO:0006782|GO:0006780|GO:0004852
PubMed:  12196144
SCOP:  4003361

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
HemD cd06578
Uroporphyrinogen-III synthase (HemD) catalyzes the asymmetrical cyclization of tetrapyrrole ...
3-255 5.35e-35

Uroporphyrinogen-III synthase (HemD) catalyzes the asymmetrical cyclization of tetrapyrrole (linear) to uroporphyrinogen-III, the fourth step in the biosynthesis of heme. This ubiquitous enzyme is present in eukaryotes, bacteria and archaea. Mutations in the human uroporphyrinogen-III synthase gene cause congenital erythropoietic porphyria, a recessive inborn error of metabolism also known as Gunther disease.


:

Pssm-ID: 119440 [Multi-domain]  Cd Length: 239  Bit Score: 125.50  E-value: 5.35e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1022432070   3 VLLLKDAKEDDcgqdPYIRELGLYGLEATLIPVLSFEFLSLPSFSEKLSHPEDYGGLIFTSPRAVEAAELCLEQNNktev 82
Cdd:cd06578     1 VLVTRPRPQAD----ELAALLEALGAEVLELPLIEIEPLDDAELDAALADLDEYDWLIFTSPNAVEAFFEALEELG---- 72
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1022432070  83 werslKEKWNAKSVYVVGNATASLVSKIGLDTE-GETCGNAEKLAEYI-------------CSRIAME------------ 136
Cdd:cd06578    73 -----LRALAGLKIAAVGPKTAEALREAGLTADfVPEEGDSEGLLELLelqdgkgkrilrpRGGRAREdlaealrergae 147
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1022432070 137 --SITVYQTVAHPGIQGNLNSYysQQGVPASITFFSPSGLTYSLKHIQELSGDNIDQIKtqgpqhpkknclqleplrkdc 214
Cdd:cd06578   148 vdEVEVYRTVPPDLDAELLELL--EEGAIDAVLFTSPSTVRNLLELLGKEGRALLKNVK--------------------- 204
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|.
gi 1022432070 215 tdtavmFAAIGPTTARALAAQGLPVSCTAESPTPQALATGI 255
Cdd:cd06578   205 ------IAAIGPRTAEALRELGLKVVIVAESPTLEALLEAL 239
 
Name Accession Description Interval E-value
HemD cd06578
Uroporphyrinogen-III synthase (HemD) catalyzes the asymmetrical cyclization of tetrapyrrole ...
3-255 5.35e-35

Uroporphyrinogen-III synthase (HemD) catalyzes the asymmetrical cyclization of tetrapyrrole (linear) to uroporphyrinogen-III, the fourth step in the biosynthesis of heme. This ubiquitous enzyme is present in eukaryotes, bacteria and archaea. Mutations in the human uroporphyrinogen-III synthase gene cause congenital erythropoietic porphyria, a recessive inborn error of metabolism also known as Gunther disease.


Pssm-ID: 119440 [Multi-domain]  Cd Length: 239  Bit Score: 125.50  E-value: 5.35e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1022432070   3 VLLLKDAKEDDcgqdPYIRELGLYGLEATLIPVLSFEFLSLPSFSEKLSHPEDYGGLIFTSPRAVEAAELCLEQNNktev 82
Cdd:cd06578     1 VLVTRPRPQAD----ELAALLEALGAEVLELPLIEIEPLDDAELDAALADLDEYDWLIFTSPNAVEAFFEALEELG---- 72
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1022432070  83 werslKEKWNAKSVYVVGNATASLVSKIGLDTE-GETCGNAEKLAEYI-------------CSRIAME------------ 136
Cdd:cd06578    73 -----LRALAGLKIAAVGPKTAEALREAGLTADfVPEEGDSEGLLELLelqdgkgkrilrpRGGRAREdlaealrergae 147
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1022432070 137 --SITVYQTVAHPGIQGNLNSYysQQGVPASITFFSPSGLTYSLKHIQELSGDNIDQIKtqgpqhpkknclqleplrkdc 214
Cdd:cd06578   148 vdEVEVYRTVPPDLDAELLELL--EEGAIDAVLFTSPSTVRNLLELLGKEGRALLKNVK--------------------- 204
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|.
gi 1022432070 215 tdtavmFAAIGPTTARALAAQGLPVSCTAESPTPQALATGI 255
Cdd:cd06578   205 ------IAAIGPRTAEALRELGLKVVIVAESPTLEALLEAL 239
HEM4 pfam02602
Uroporphyrinogen-III synthase HemD; This family consists of uroporphyrinogen-III synthase HemD ...
19-251 5.26e-28

Uroporphyrinogen-III synthase HemD; This family consists of uroporphyrinogen-III synthase HemD EC:4.2.1.75 also known as Hydroxymethylbilane hydrolyase (cyclizing) from eukaryotes, bacteria and archaea. This enzyme catalyzes the reaction: Hydroxymethylbilane <=> uroporphyrinogen-III + H(2)O. Some members of this family are multi-functional proteins possessing other enzyme activities related to porphyrin biosynthesis, such as HemD with pfam00590, however the aligned region corresponds with the uroporphyrinogen-III synthase EC:4.2.1.75 activity only. Uroporphyrinogen-III synthase is the fourth enzyme in the heme pathway. Mutant forms of the Uroporphyrinogen-III synthase gene cause congenital erythropoietic porphyria in humans a recessive inborn error of metabolism also known as Gunther disease.


Pssm-ID: 426866  Cd Length: 230  Bit Score: 107.02  E-value: 5.26e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1022432070  19 YIRELGLYGLEATLIPVLSFEFLSLPSF-SEKLSHPEDYGGLIFTSPRAVEAAELCLEqnnktevWERSLKEKWNAKSVY 97
Cdd:pfam02602   2 LAELLEALGAEPLELPLIEIVPPEDRAElDEALKDLGEYDWLIFTSANAVRAFFEALK-------LEGEDLRALANIKIA 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1022432070  98 VVGNATASLVSKIGL--DTEGETCGNAEKLAEYICSRIA--------------------------MESITVYQTVAHPGI 149
Cdd:pfam02602  75 AVGPKTARALREAGLtpDFVPSEEGTAEGLAEELAELLAgkrvlllrgnigrddlaealrergaeVTEVVVYRTVPPEEL 154
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1022432070 150 QGNLNSYYSQQGVPAsITFFSPSGLTYSLKHIQELSGDNIDQIKtqgpqhpkknclqleplrkdctdtavmFAAIGPTTA 229
Cdd:pfam02602 155 PEELREALKDGEIDA-VTFTSPSTVRNLLELLKDEGLDWLKSVK---------------------------AAAIGPTTA 206
                         250       260
                  ....*....|....*....|..
gi 1022432070 230 RALAAQGLPVSCTAESPTPQAL 251
Cdd:pfam02602 207 EALKELGLKVDVVAERPTMEAL 228
HemD COG1587
Uroporphyrinogen-III synthase [Coenzyme transport and metabolism];
1-260 1.71e-16

Uroporphyrinogen-III synthase [Coenzyme transport and metabolism];


Pssm-ID: 224503  Cd Length: 248  Bit Score: 76.66  E-value: 1.71e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1022432070   1 MKVLLLK-DAKEDdcgqdPYIRELGLYGLEATLIPVLSFEflSLPSFSEKLSHPEDYGGLIFTSPRAVEAA-ELCLEQNN 78
Cdd:COG1587     2 MRVLVTRpREQAE-----ELAALLRKAGAEPLELPLIEIE--PLPDLEVALEDLDSADWVVFTSPNAVRFFfEALKEQGL 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1022432070  79 KtevWERSLKekwnaksVYVVGNATASLVSKIGLDTE-GETCGNAEKLAE-------------YICSRIA---------- 134
Cdd:COG1587    75 D---ALKNKK-------IAAVGEKTAEALRKLGIKVDfIPEDGDSEGLLEelpellkggkrvlILRGNGGrevleeklee 144
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1022432070 135 ----MESITVYQTVAHPGIQGNLNSYYSQQGVPAsITFFSPSGLtyslkhiqelsgdnidqiktqgpqhpkKNCLQLEPL 210
Cdd:COG1587   145 rgaeVREVEVYRTEPPPLDEATLIELLKLGEVDA-VVFTSSSAV---------------------------RALLALAPE 196
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 1022432070 211 RKDCTDTAVMFAAIGPTTARALAAQGLPVSCTAESPTPQALATGIRKALQ 260
Cdd:COG1587   197 SGIEFLERKRVASIGPRTAETLKELGITVDIAAEKPTLEALADALAKLLR 246
hemD PRK05928
uroporphyrinogen-III synthase; Reviewed
1-260 1.66e-11

uroporphyrinogen-III synthase; Reviewed


Pssm-ID: 235647  Cd Length: 249  Bit Score: 62.29  E-value: 1.66e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1022432070   1 MKVLLLKDAK--EDDCgqdPYIRELGLyglEATLIPVLSFEFLSLPSFSEKLSHPEDYGGLIFTSPRAVEAAElcleqnn 78
Cdd:PRK05928    2 MKILVTRPSPkaEELV---ELLRELGF---VALHFPLIEIEPGRQLPQLAAQLAALGADWVIFTSKNAVEFLL------- 68
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1022432070  79 ktEVWERSLKEKWNAKSVYVVGNATASLVSKIGL-----DTEGETCGNAEKLAEYICS--RIAM---------------- 135
Cdd:PRK05928   69 --SALKKKKLKWPKNKKYAAIGEKTALALKKLGGkvvfvPEDGESSELLLELPELLLKgkRVLYlrgnggrevlgdtlee 146
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1022432070 136 -----ESITVYQTVAHPGIQGNLNSYYSQQGVPAsITFFSPSGLTYSLKHIqelsgdnidqiktqgPQHPKKNCLqlepl 210
Cdd:PRK05928  147 rgaevDECEVYERVPPKLDGAELLARLQSGEVDA-VIFTSPSTVRAFFSLA---------------PELGRREWL----- 205
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 1022432070 211 rKDCTdtavmFAAIGPTTARALAAQGLPVSCTAESPTPQALATGIRKALQ 260
Cdd:PRK05928  206 -LSCK-----AVVIGERTAEALRELGIKVIIVPDSADNEALLRALKELLK 249
 
Name Accession Description Interval E-value
HemD cd06578
Uroporphyrinogen-III synthase (HemD) catalyzes the asymmetrical cyclization of tetrapyrrole ...
3-255 5.35e-35

Uroporphyrinogen-III synthase (HemD) catalyzes the asymmetrical cyclization of tetrapyrrole (linear) to uroporphyrinogen-III, the fourth step in the biosynthesis of heme. This ubiquitous enzyme is present in eukaryotes, bacteria and archaea. Mutations in the human uroporphyrinogen-III synthase gene cause congenital erythropoietic porphyria, a recessive inborn error of metabolism also known as Gunther disease.


Pssm-ID: 119440 [Multi-domain]  Cd Length: 239  Bit Score: 125.50  E-value: 5.35e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1022432070   3 VLLLKDAKEDDcgqdPYIRELGLYGLEATLIPVLSFEFLSLPSFSEKLSHPEDYGGLIFTSPRAVEAAELCLEQNNktev 82
Cdd:cd06578     1 VLVTRPRPQAD----ELAALLEALGAEVLELPLIEIEPLDDAELDAALADLDEYDWLIFTSPNAVEAFFEALEELG---- 72
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1022432070  83 werslKEKWNAKSVYVVGNATASLVSKIGLDTE-GETCGNAEKLAEYI-------------CSRIAME------------ 136
Cdd:cd06578    73 -----LRALAGLKIAAVGPKTAEALREAGLTADfVPEEGDSEGLLELLelqdgkgkrilrpRGGRAREdlaealrergae 147
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1022432070 137 --SITVYQTVAHPGIQGNLNSYysQQGVPASITFFSPSGLTYSLKHIQELSGDNIDQIKtqgpqhpkknclqleplrkdc 214
Cdd:cd06578   148 vdEVEVYRTVPPDLDAELLELL--EEGAIDAVLFTSPSTVRNLLELLGKEGRALLKNVK--------------------- 204
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|.
gi 1022432070 215 tdtavmFAAIGPTTARALAAQGLPVSCTAESPTPQALATGI 255
Cdd:cd06578   205 ------IAAIGPRTAEALRELGLKVVIVAESPTLEALLEAL 239
HEM4 pfam02602
Uroporphyrinogen-III synthase HemD; This family consists of uroporphyrinogen-III synthase HemD ...
19-251 5.26e-28

Uroporphyrinogen-III synthase HemD; This family consists of uroporphyrinogen-III synthase HemD EC:4.2.1.75 also known as Hydroxymethylbilane hydrolyase (cyclizing) from eukaryotes, bacteria and archaea. This enzyme catalyzes the reaction: Hydroxymethylbilane <=> uroporphyrinogen-III + H(2)O. Some members of this family are multi-functional proteins possessing other enzyme activities related to porphyrin biosynthesis, such as HemD with pfam00590, however the aligned region corresponds with the uroporphyrinogen-III synthase EC:4.2.1.75 activity only. Uroporphyrinogen-III synthase is the fourth enzyme in the heme pathway. Mutant forms of the Uroporphyrinogen-III synthase gene cause congenital erythropoietic porphyria in humans a recessive inborn error of metabolism also known as Gunther disease.


Pssm-ID: 426866  Cd Length: 230  Bit Score: 107.02  E-value: 5.26e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1022432070  19 YIRELGLYGLEATLIPVLSFEFLSLPSF-SEKLSHPEDYGGLIFTSPRAVEAAELCLEqnnktevWERSLKEKWNAKSVY 97
Cdd:pfam02602   2 LAELLEALGAEPLELPLIEIVPPEDRAElDEALKDLGEYDWLIFTSANAVRAFFEALK-------LEGEDLRALANIKIA 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1022432070  98 VVGNATASLVSKIGL--DTEGETCGNAEKLAEYICSRIA--------------------------MESITVYQTVAHPGI 149
Cdd:pfam02602  75 AVGPKTARALREAGLtpDFVPSEEGTAEGLAEELAELLAgkrvlllrgnigrddlaealrergaeVTEVVVYRTVPPEEL 154
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1022432070 150 QGNLNSYYSQQGVPAsITFFSPSGLTYSLKHIQELSGDNIDQIKtqgpqhpkknclqleplrkdctdtavmFAAIGPTTA 229
Cdd:pfam02602 155 PEELREALKDGEIDA-VTFTSPSTVRNLLELLKDEGLDWLKSVK---------------------------AAAIGPTTA 206
                         250       260
                  ....*....|....*....|..
gi 1022432070 230 RALAAQGLPVSCTAESPTPQAL 251
Cdd:pfam02602 207 EALKELGLKVDVVAERPTMEAL 228
HemD COG1587
Uroporphyrinogen-III synthase [Coenzyme transport and metabolism];
1-260 1.71e-16

Uroporphyrinogen-III synthase [Coenzyme transport and metabolism];


Pssm-ID: 224503  Cd Length: 248  Bit Score: 76.66  E-value: 1.71e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1022432070   1 MKVLLLK-DAKEDdcgqdPYIRELGLYGLEATLIPVLSFEflSLPSFSEKLSHPEDYGGLIFTSPRAVEAA-ELCLEQNN 78
Cdd:COG1587     2 MRVLVTRpREQAE-----ELAALLRKAGAEPLELPLIEIE--PLPDLEVALEDLDSADWVVFTSPNAVRFFfEALKEQGL 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1022432070  79 KtevWERSLKekwnaksVYVVGNATASLVSKIGLDTE-GETCGNAEKLAE-------------YICSRIA---------- 134
Cdd:COG1587    75 D---ALKNKK-------IAAVGEKTAEALRKLGIKVDfIPEDGDSEGLLEelpellkggkrvlILRGNGGrevleeklee 144
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1022432070 135 ----MESITVYQTVAHPGIQGNLNSYYSQQGVPAsITFFSPSGLtyslkhiqelsgdnidqiktqgpqhpkKNCLQLEPL 210
Cdd:COG1587   145 rgaeVREVEVYRTEPPPLDEATLIELLKLGEVDA-VVFTSSSAV---------------------------RALLALAPE 196
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 1022432070 211 RKDCTDTAVMFAAIGPTTARALAAQGLPVSCTAESPTPQALATGIRKALQ 260
Cdd:COG1587   197 SGIEFLERKRVASIGPRTAETLKELGITVDIAAEKPTLEALADALAKLLR 246
hemD PRK05928
uroporphyrinogen-III synthase; Reviewed
1-260 1.66e-11

uroporphyrinogen-III synthase; Reviewed


Pssm-ID: 235647  Cd Length: 249  Bit Score: 62.29  E-value: 1.66e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1022432070   1 MKVLLLKDAK--EDDCgqdPYIRELGLyglEATLIPVLSFEFLSLPSFSEKLSHPEDYGGLIFTSPRAVEAAElcleqnn 78
Cdd:PRK05928    2 MKILVTRPSPkaEELV---ELLRELGF---VALHFPLIEIEPGRQLPQLAAQLAALGADWVIFTSKNAVEFLL------- 68
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1022432070  79 ktEVWERSLKEKWNAKSVYVVGNATASLVSKIGL-----DTEGETCGNAEKLAEYICS--RIAM---------------- 135
Cdd:PRK05928   69 --SALKKKKLKWPKNKKYAAIGEKTALALKKLGGkvvfvPEDGESSELLLELPELLLKgkRVLYlrgnggrevlgdtlee 146
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1022432070 136 -----ESITVYQTVAHPGIQGNLNSYYSQQGVPAsITFFSPSGLTYSLKHIqelsgdnidqiktqgPQHPKKNCLqlepl 210
Cdd:PRK05928  147 rgaevDECEVYERVPPKLDGAELLARLQSGEVDA-VIFTSPSTVRAFFSLA---------------PELGRREWL----- 205
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 1022432070 211 rKDCTdtavmFAAIGPTTARALAAQGLPVSCTAESPTPQALATGIRKALQ 260
Cdd:PRK05928  206 -LSCK-----AVVIGERTAEALRELGIKVIIVPDSADNEALLRALKELLK 249
HemD cd06578
Uroporphyrinogen-III synthase (HemD) catalyzes the asymmetrical cyclization of tetrapyrrole ...
221-263 4.34e-04

Uroporphyrinogen-III synthase (HemD) catalyzes the asymmetrical cyclization of tetrapyrrole (linear) to uroporphyrinogen-III, the fourth step in the biosynthesis of heme. This ubiquitous enzyme is present in eukaryotes, bacteria and archaea. Mutations in the human uroporphyrinogen-III synthase gene cause congenital erythropoietic porphyria, a recessive inborn error of metabolism also known as Gunther disease.


Pssm-ID: 119440 [Multi-domain]  Cd Length: 239  Bit Score: 40.75  E-value: 4.34e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1022432070 221 FAAIGPTTARALAAQGLPVSCTAESPTPQALATGIRKALQPHG 263
Cdd:cd06578    81 IAAVGPKTAEALREAGLTADFVPEEGDSEGLLELLELQDGKGK 123
 
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.
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