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Conserved domains on  [gi|115534555|ref|NP_503496|]
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putative 5-hydroxyisourate hydrolase ZK697.8 [Caenorhabditis elegans]

Protein Classification

hydroxyisourate hydrolase( domain architecture ID 10146731)

hydroxyisourate hydrolase catalyzes the hydrolysis of 5-hydroxyisourate (HIU) to 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (OHCU) in the second step of a three-step ureide pathway

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
TLP_HIUase cd05822
HIUase (5-hydroxyisourate hydrolase) catalyzes the second step in a three-step ureide pathway ...
 28-136 3.37e-53

HIUase (5-hydroxyisourate hydrolase) catalyzes the second step in a three-step ureide pathway in which 5-hydroxyisourate (HIU), a product of the uricase (urate oxidase) reaction, is hydrolyzed to 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (OHCU). HIUase has high sequence similarity with transthyretins and is a member of the transthyretin-like protein (TLP) family. HIUase is distinguished from transthyretins by a conserved signature motif at its C-terminus that forms part of the active site. In HIUase, this motif is YRGS, while transthyretins have a conserved TAVV sequence in the same location. Most HIUases are cytosolic but in plants and slime molds, they are peroxisomal based on the presence of N-terminal periplasmic localization sequences. HIUase forms a homotetramer with each subunit consisting of eight beta-strands arranged in two sheets and a short alpha-helix. The central channel of the tetramer contains two independent binding sites, each located between a pair of subunits.


:

Pssm-ID: 100114  Cd Length: 112  Bit Score: 163.10  E-value: 3.37e-53
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115534555  28 ISAHVLDISGGSPAGGIQILAFILLNNGWTNIGSQFTQDNGRVD-WVSPDFTLIPGTYRLVYITEPYYTAKNVESFYPYV 106
Cdd:cd05822    3 LSTHVLDTATGKPAAGVAVTLYRLDGNGWTLLATGVTNADGRCDdLLPPGAQLAAGTYKLTFDTGAYFAARGQESFYPEV 82

                         90       100       110
                 ....*....|....*....|....*....|
gi 115534555 107 EVVFNIRNATQHYHVPLTLSPWGYSTYRGS 136
Cdd:cd05822   83 EVRFTITDPTEHYHVPLLLSPFGYSTYRGS 112
 
Name Accession Description Interval E-value
TLP_HIUase cd05822
HIUase (5-hydroxyisourate hydrolase) catalyzes the second step in a three-step ureide pathway ...
 28-136 3.37e-53

HIUase (5-hydroxyisourate hydrolase) catalyzes the second step in a three-step ureide pathway in which 5-hydroxyisourate (HIU), a product of the uricase (urate oxidase) reaction, is hydrolyzed to 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (OHCU). HIUase has high sequence similarity with transthyretins and is a member of the transthyretin-like protein (TLP) family. HIUase is distinguished from transthyretins by a conserved signature motif at its C-terminus that forms part of the active site. In HIUase, this motif is YRGS, while transthyretins have a conserved TAVV sequence in the same location. Most HIUases are cytosolic but in plants and slime molds, they are peroxisomal based on the presence of N-terminal periplasmic localization sequences. HIUase forms a homotetramer with each subunit consisting of eight beta-strands arranged in two sheets and a short alpha-helix. The central channel of the tetramer contains two independent binding sites, each located between a pair of subunits.


Pssm-ID: 100114  Cd Length: 112  Bit Score: 163.10  E-value: 3.37e-53
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115534555  28 ISAHVLDISGGSPAGGIQILAFILLNNGWTNIGSQFTQDNGRVD-WVSPDFTLIPGTYRLVYITEPYYTAKNVESFYPYV 106
Cdd:cd05822    3 LSTHVLDTATGKPAAGVAVTLYRLDGNGWTLLATGVTNADGRCDdLLPPGAQLAAGTYKLTFDTGAYFAARGQESFYPEV 82

                         90       100       110
                 ....*....|....*....|....*....|
gi 115534555 107 EVVFNIRNATQHYHVPLTLSPWGYSTYRGS 136
Cdd:cd05822   83 EVRFTITDPTEHYHVPLLLSPFGYSTYRGS 112
hdxy_isourate TIGR02962
hydroxyisourate hydrolase; Members of this family, hydroxyisourate hydrolase, represent a ...
 26-136 1.71e-52

hydroxyisourate hydrolase; Members of this family, hydroxyisourate hydrolase, represent a distinct clade of transthyretin-related proteins. Bacterial members typically are encoded next to ureidoglycolate hydrolase and often near either xanthine dehydrogenase or xanthine/uracil permease genes and have been demonstrated to have hydroxyisourate hydrolase activity. In eukaryotes, a clade separate from the transthyretins (a family of thyroid-hormone binding proteins) has also been shown to have HIU hydrolase activity in urate catabolizing organisms. Transthyretin, then, would appear to be the recently diverged paralog of the more ancient HIUH family. [Purines, pyrimidines, nucleosides, and nucleotides, Other]


Pssm-ID: 274364  Cd Length: 112  Bit Score: 161.18  E-value: 1.71e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115534555   26 ASISAHVLDISGGSPAGGIQILAFILLNNGWTNIGSQFTQDNGRVD-WVSPDFTLIPGTYRLVYITEPYYTAKNVESFYP 104
Cdd:TIGR02962   1 SPLSTHVLDTTSGKPAAGVPVTLYRLDGGGWTPLATGVTNADGRCDgPLPEGEDLAPGIYKLRFDTGDYFAARGVESFYP 80

                          90       100       110
                  ....*....|....*....|....*....|..
gi 115534555  105 YVEVVFNIRNATQHYHVPLTLSPWGYSTYRGS 136
Cdd:TIGR02962  81 EVEVVFTIADPGQHYHVPLLLSPYGYSTYRGS 112
Transthyretin pfam00576
HIUase/Transthyretin family; This family includes transthyretin that is a thyroid ...
 28-135 9.85e-49

HIUase/Transthyretin family; This family includes transthyretin that is a thyroid hormone-binding protein that transports thyroxine from the bloodstream to the brain. However, most of the sequences listed in this family do not bind thyroid hormones. They are actually enzymes of the purine catabolism that catalyze the conversion of 5-hydroxyisourate (HIU) to OHCU. HIU hydrolysis is the original function of the family and is conserved from bacteria to mammals; transthyretins arose by gene duplications in the vertebrate lineage. HIUases are distinguished in the alignment from the conserved C-terminal YRGS sequence.


Pssm-ID: 459857  Cd Length: 108  Bit Score: 151.83  E-value: 9.85e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115534555   28 ISAHVLDISGGSPAGGIQILAFILLNNGWTNIGSQFTQDNGRVD-WVSPDFTLIPGTYRLVYITEPYYTAKNVESFYPYV 106
Cdd:pfam00576   1 LTTHVLDTARGRPAAGVRVTLYRLDGDGWTLLAEGTTNADGRCDdLLLEGEALEPGTYRLVFDTGAYFAARGVESFYPEV 80

                          90       100
                  ....*....|....*....|....*....
gi 115534555  107 EVVFNIRNAtQHYHVPLTLSPWGYSTYRG 135
Cdd:pfam00576  81 EVRFGITDA-EHYHVPLLLSPFGYSTYRG 108
HiuH COG2351
5-hydroxyisourate hydrolase (purine catabolism), transthyretin-related family [Nucleotide ...
 26-136 1.06e-45

5-hydroxyisourate hydrolase (purine catabolism), transthyretin-related family [Nucleotide transport and metabolism];


Pssm-ID: 441918  Cd Length: 111  Bit Score: 144.13  E-value: 1.06e-45
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115534555  26 ASISAHVLDISGGSPAGGIQILAFILLNNGWTNIGSQFTQDNGRVDWVSPDfTLIPGTYRLVYITEPYYTAKNVESFYPY 105
Cdd:COG2351    2 GRLSTHVLDTARGRPAAGVRVELYRLDGDGWTLLAEGVTNADGRIDALGGE-ALAAGTYRLVFDTGDYFAARGVPPFLPE 80

                         90       100       110
                 ....*....|....*....|....*....|.
gi 115534555 106 VEVVFNIRNATQHYHVPLTLSPWGYSTYRGS 136
Cdd:COG2351   81 VPVRFGIADPEEHYHVPLLLSPWGYSTYRGS 111
PRK15036 PRK15036
hydroxyisourate hydrolase; Provisional
 1-136 2.69e-36

hydroxyisourate hydrolase; Provisional


Pssm-ID: 184996  Cd Length: 137  Bit Score: 121.25  E-value: 2.69e-36
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115534555   1 MIKFLLFLAIAAATVISNAELAVPTASISAHVLDISGGSPAGGIQILAFILLNNGWTNIGSQFTQDNGRVDWVSPDFTLI 80
Cdd:PRK15036   2 LKRYLVLSVITAAFSLPSLVYAAQQNILSVHILNQQTGKPAADVTVTLEKKADNGWLQLNTAKTDKDGRIKALWPEQTAT 81

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 115534555  81 PGTYRLVYITEPYYTAKNVESFYPYVEVVFNIRNATQHYHVPLTLSPWGYSTYRGS 136
Cdd:PRK15036  82 TGDYRVVFKTGDYFKKQNLESFFPEIPVEFHINKVNEHYHVPLLLSQYGYSTYRGS 137
TR_THY smart00095
Transthyretin;
32-132 1.99e-10

Transthyretin;


Pssm-ID: 128406  Cd Length: 121  Bit Score: 54.50  E-value: 1.99e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115534555    32 VLDISGGSPAGGIQILAFILLNNG-WTNIGSQFTQDNGRVDWVSPDFTLIPGTYRLVYITEPYYTAKNVESFYPYVEVVF 110
Cdd:smart00095  10 VLDAVRGSPAVNVAVKVFKKTEEGtWEPFASGKTNESGEIHELTTDEKFVEGLYKVEFDTKSYWKALGISPFHEYADVVF 89

                           90       100
                   ....*....|....*....|...
gi 115534555   111 NIRNA-TQHYHVPLTLSPWGYST 132
Cdd:smart00095  90 TANDSgHRHYTIAALLSPYSYST 112
 
Name Accession Description Interval E-value
TLP_HIUase cd05822
HIUase (5-hydroxyisourate hydrolase) catalyzes the second step in a three-step ureide pathway ...
 28-136 3.37e-53

HIUase (5-hydroxyisourate hydrolase) catalyzes the second step in a three-step ureide pathway in which 5-hydroxyisourate (HIU), a product of the uricase (urate oxidase) reaction, is hydrolyzed to 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (OHCU). HIUase has high sequence similarity with transthyretins and is a member of the transthyretin-like protein (TLP) family. HIUase is distinguished from transthyretins by a conserved signature motif at its C-terminus that forms part of the active site. In HIUase, this motif is YRGS, while transthyretins have a conserved TAVV sequence in the same location. Most HIUases are cytosolic but in plants and slime molds, they are peroxisomal based on the presence of N-terminal periplasmic localization sequences. HIUase forms a homotetramer with each subunit consisting of eight beta-strands arranged in two sheets and a short alpha-helix. The central channel of the tetramer contains two independent binding sites, each located between a pair of subunits.


Pssm-ID: 100114  Cd Length: 112  Bit Score: 163.10  E-value: 3.37e-53
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115534555  28 ISAHVLDISGGSPAGGIQILAFILLNNGWTNIGSQFTQDNGRVD-WVSPDFTLIPGTYRLVYITEPYYTAKNVESFYPYV 106
Cdd:cd05822    3 LSTHVLDTATGKPAAGVAVTLYRLDGNGWTLLATGVTNADGRCDdLLPPGAQLAAGTYKLTFDTGAYFAARGQESFYPEV 82

                         90       100       110
                 ....*....|....*....|....*....|
gi 115534555 107 EVVFNIRNATQHYHVPLTLSPWGYSTYRGS 136
Cdd:cd05822   83 EVRFTITDPTEHYHVPLLLSPFGYSTYRGS 112
hdxy_isourate TIGR02962
hydroxyisourate hydrolase; Members of this family, hydroxyisourate hydrolase, represent a ...
 26-136 1.71e-52

hydroxyisourate hydrolase; Members of this family, hydroxyisourate hydrolase, represent a distinct clade of transthyretin-related proteins. Bacterial members typically are encoded next to ureidoglycolate hydrolase and often near either xanthine dehydrogenase or xanthine/uracil permease genes and have been demonstrated to have hydroxyisourate hydrolase activity. In eukaryotes, a clade separate from the transthyretins (a family of thyroid-hormone binding proteins) has also been shown to have HIU hydrolase activity in urate catabolizing organisms. Transthyretin, then, would appear to be the recently diverged paralog of the more ancient HIUH family. [Purines, pyrimidines, nucleosides, and nucleotides, Other]


Pssm-ID: 274364  Cd Length: 112  Bit Score: 161.18  E-value: 1.71e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115534555   26 ASISAHVLDISGGSPAGGIQILAFILLNNGWTNIGSQFTQDNGRVD-WVSPDFTLIPGTYRLVYITEPYYTAKNVESFYP 104
Cdd:TIGR02962   1 SPLSTHVLDTTSGKPAAGVPVTLYRLDGGGWTPLATGVTNADGRCDgPLPEGEDLAPGIYKLRFDTGDYFAARGVESFYP 80

                          90       100       110
                  ....*....|....*....|....*....|..
gi 115534555  105 YVEVVFNIRNATQHYHVPLTLSPWGYSTYRGS 136
Cdd:TIGR02962  81 EVEVVFTIADPGQHYHVPLLLSPYGYSTYRGS 112
Transthyretin pfam00576
HIUase/Transthyretin family; This family includes transthyretin that is a thyroid ...
 28-135 9.85e-49

HIUase/Transthyretin family; This family includes transthyretin that is a thyroid hormone-binding protein that transports thyroxine from the bloodstream to the brain. However, most of the sequences listed in this family do not bind thyroid hormones. They are actually enzymes of the purine catabolism that catalyze the conversion of 5-hydroxyisourate (HIU) to OHCU. HIU hydrolysis is the original function of the family and is conserved from bacteria to mammals; transthyretins arose by gene duplications in the vertebrate lineage. HIUases are distinguished in the alignment from the conserved C-terminal YRGS sequence.


Pssm-ID: 459857  Cd Length: 108  Bit Score: 151.83  E-value: 9.85e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115534555   28 ISAHVLDISGGSPAGGIQILAFILLNNGWTNIGSQFTQDNGRVD-WVSPDFTLIPGTYRLVYITEPYYTAKNVESFYPYV 106
Cdd:pfam00576   1 LTTHVLDTARGRPAAGVRVTLYRLDGDGWTLLAEGTTNADGRCDdLLLEGEALEPGTYRLVFDTGAYFAARGVESFYPEV 80

                          90       100
                  ....*....|....*....|....*....
gi 115534555  107 EVVFNIRNAtQHYHVPLTLSPWGYSTYRG 135
Cdd:pfam00576  81 EVRFGITDA-EHYHVPLLLSPFGYSTYRG 108
HiuH COG2351
5-hydroxyisourate hydrolase (purine catabolism), transthyretin-related family [Nucleotide ...
 26-136 1.06e-45

5-hydroxyisourate hydrolase (purine catabolism), transthyretin-related family [Nucleotide transport and metabolism];


Pssm-ID: 441918  Cd Length: 111  Bit Score: 144.13  E-value: 1.06e-45
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115534555  26 ASISAHVLDISGGSPAGGIQILAFILLNNGWTNIGSQFTQDNGRVDWVSPDfTLIPGTYRLVYITEPYYTAKNVESFYPY 105
Cdd:COG2351    2 GRLSTHVLDTARGRPAAGVRVELYRLDGDGWTLLAEGVTNADGRIDALGGE-ALAAGTYRLVFDTGDYFAARGVPPFLPE 80

                         90       100       110
                 ....*....|....*....|....*....|.
gi 115534555 106 VEVVFNIRNATQHYHVPLTLSPWGYSTYRGS 136
Cdd:COG2351   81 VPVRFGIADPEEHYHVPLLLSPWGYSTYRGS 111
PRK15036 PRK15036
hydroxyisourate hydrolase; Provisional
 1-136 2.69e-36

hydroxyisourate hydrolase; Provisional


Pssm-ID: 184996  Cd Length: 137  Bit Score: 121.25  E-value: 2.69e-36
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115534555   1 MIKFLLFLAIAAATVISNAELAVPTASISAHVLDISGGSPAGGIQILAFILLNNGWTNIGSQFTQDNGRVDWVSPDFTLI 80
Cdd:PRK15036   2 LKRYLVLSVITAAFSLPSLVYAAQQNILSVHILNQQTGKPAADVTVTLEKKADNGWLQLNTAKTDKDGRIKALWPEQTAT 81

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 115534555  81 PGTYRLVYITEPYYTAKNVESFYPYVEVVFNIRNATQHYHVPLTLSPWGYSTYRGS 136
Cdd:PRK15036  82 TGDYRVVFKTGDYFKKQNLESFFPEIPVEFHINKVNEHYHVPLLLSQYGYSTYRGS 137
Transthyretin_like cd05469
Transthyretin_like. This domain is present in the transthyretin-like protein (TLP) family ...
 28-136 6.54e-26

Transthyretin_like. This domain is present in the transthyretin-like protein (TLP) family which includes transthyretin (TTR) and a transthyretin-related protein called 5-hydroxyisourate hydrolase (HIUase). TTR and HIUase are homotetrameric proteins with each subunit consisting of eight beta-strands arranged in two sheets and a short alpha-helix. The central channel of the tetramer contains two independent binding sites, each located between a pair of subunits. TTR transports thyroid hormones and retinol in the blood serum of vertebrates while HIUase catalyzes the second step in a three-step ureide pathway. TTRs are highly conserved and found only in vertebrates while the HIUases are found in a wide range of bacterial, plant, fungal, slime mold and vertebrate organisms.


Pssm-ID: 100112  Cd Length: 113  Bit Score: 94.14  E-value: 6.54e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115534555  28 ISAHVLDISGGSPAGGIQILAFIL-LNNGWTNIGSQFTQDNGRVDWVSPDFTLIPGTYRLVYITEPYYTAKNVESFYPYV 106
Cdd:cd05469    3 LMVKVLDAVRGSPAANVAIKVFRKtADGSWEIFATGKTNEDGELHGLITEEEF*AGVYRVEFDTKSYWKALGITPFHEYA 82

                         90       100       110
                 ....*....|....*....|....*....|.
gi 115534555 107 EVVFNIRN-ATQHYHVPLTLSPWGYSTYRGS 136
Cdd:cd05469   83 EVVFTANDsGHRHYTIALLLSPFSYSTTAVV 113
TLP_Transthyretin cd05821
Transthyretin (TTR) is a 55 kDa protein responsible for the transport of thyroid hormones and ...
 32-132 2.15e-14

Transthyretin (TTR) is a 55 kDa protein responsible for the transport of thyroid hormones and retinol in vertebrates. TTR distributes the two thyroid hormones T3 (3,5,3'-triiodo-L-thyronine) and T4 (Thyroxin, or 3,5,3',5'-tetraiodo-L-thyronine), as well as retinol (vitamin A) through the formation of a macromolecular complex that includes each of these as well as retinol-binding protein. Misfolded forms of TTR are implicated in the amyloid diseases familial amyloidotic polyneuropathy and senile systemic amyloidosis. TTR forms a homotetramer with each subunit consisting of eight beta-strands arranged in two sheets and a short alpha-helix. The central channel of the tetramer contains two independent binding sites, each located between a pair of subunits, which differ in their ligand binding affinity. A negative cooperativity has been observed for the binding of T4 and other TTR ligands. A fraction of plasma TTR is carried in high density lipoproteins by binding to apolipoprotein AI (apoA-I). TTR is able to proteolytically process apoA-I by cleaving its C-terminus; therefore TTR has protease activity in addition to its function in protein transport.


Pssm-ID: 100113  Cd Length: 121  Bit Score: 64.88  E-value: 2.15e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115534555  32 VLDISGGSPAGGIQILAFILLNNG-WTNIGSQFTQDNGRVDWVSPDFTLIPGTYRLVYITEPYYTAKNVESFYPYVEVVF 110
Cdd:cd05821   13 VLDAVRGSPAANVAVKVFKKTADGsWEPFASGKTTETGEIHGLTTDEQFTEGVYKVEFDTKAYWKKLGISPFHEYAEVVF 92

                         90       100
                 ....*....|....*....|...
gi 115534555 111 NIRNAT-QHYHVPLTLSPWGYST 132
Cdd:cd05821   93 TANDSGhRHYTIAALLSPYSYST 115
TR_THY smart00095
Transthyretin;
32-132 1.99e-10

Transthyretin;


Pssm-ID: 128406  Cd Length: 121  Bit Score: 54.50  E-value: 1.99e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115534555    32 VLDISGGSPAGGIQILAFILLNNG-WTNIGSQFTQDNGRVDWVSPDFTLIPGTYRLVYITEPYYTAKNVESFYPYVEVVF 110
Cdd:smart00095  10 VLDAVRGSPAVNVAVKVFKKTEEGtWEPFASGKTNESGEIHELTTDEKFVEGLYKVEFDTKSYWKALGISPFHEYADVVF 89

                           90       100
                   ....*....|....*....|...
gi 115534555   111 NIRNA-TQHYHVPLTLSPWGYST 132
Cdd:smart00095  90 TANDSgHRHYTIAALLSPYSYST 112
 
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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