NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|110626070|ref|NP_084097|]
View 

5-hydroxyisourate hydrolase isoform 2 [Mus musculus]

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

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

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 ...
 6-118 3.88e-62

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: 185.05  E-value: 3.88e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110626070   6 SPLTTHVLDTASGLPAQGLCLRLSRLEApcQQWMELRTSYTNLDGRCPGLLTPS-QIKPGTYKLFFDTERYWKERGQESF 84
Cdd:cd05822    1 GPLSTHVLDTATGKPAAGVAVTLYRLDG--NGWTLLATGVTNADGRCDDLLPPGaQLAAGTYKLTFDTGAYFAARGQESF 78

                         90       100       110
                 ....*....|....*....|....*....|....
gi 110626070  85 YPYVEVVFTITKETQKFHVPLLLSPWSYTTYRGS 118
Cdd:cd05822   79 YPEVEVRFTITDPTEHYHVPLLLSPFGYSTYRGS 112
 
Name Accession Description Interval E-value
TLP_HIUase cd05822
HIUase (5-hydroxyisourate hydrolase) catalyzes the second step in a three-step ureide pathway ...
 6-118 3.88e-62

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: 185.05  E-value: 3.88e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110626070   6 SPLTTHVLDTASGLPAQGLCLRLSRLEApcQQWMELRTSYTNLDGRCPGLLTPS-QIKPGTYKLFFDTERYWKERGQESF 84
Cdd:cd05822    1 GPLSTHVLDTATGKPAAGVAVTLYRLDG--NGWTLLATGVTNADGRCDDLLPPGaQLAAGTYKLTFDTGAYFAARGQESF 78

                         90       100       110
                 ....*....|....*....|....*....|....
gi 110626070  85 YPYVEVVFTITKETQKFHVPLLLSPWSYTTYRGS 118
Cdd:cd05822   79 YPEVEVRFTITDPTEHYHVPLLLSPFGYSTYRGS 112
hdxy_isourate TIGR02962
hydroxyisourate hydrolase; Members of this family, hydroxyisourate hydrolase, represent a ...
 6-118 3.66e-60

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: 180.05  E-value: 3.66e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110626070    6 SPLTTHVLDTASGLPAQGLCLRLSRLEApcQQWMELRTSYTNLDGRCPGLL-TPSQIKPGTYKLFFDTERYWKERGQESF 84
Cdd:TIGR02962   1 SPLSTHVLDTTSGKPAAGVPVTLYRLDG--GGWTPLATGVTNADGRCDGPLpEGEDLAPGIYKLRFDTGDYFAARGVESF 78

                          90       100       110
                  ....*....|....*....|....*....|....
gi 110626070   85 YPYVEVVFTITKETQKFHVPLLLSPWSYTTYRGS 118
Cdd:TIGR02962  79 YPEVEVVFTIADPGQHYHVPLLLSPYGYSTYRGS 112
Transthyretin pfam00576
HIUase/Transthyretin family; This family includes transthyretin that is a thyroid ...
 8-117 2.01e-58

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: 175.33  E-value: 2.01e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110626070    8 LTTHVLDTASGLPAQGLCLRLSRLEAPcqQWMELRTSYTNLDGRCPGLLTPS-QIKPGTYKLFFDTERYWKERGQESFYP 86
Cdd:pfam00576   1 LTTHVLDTARGRPAAGVRVTLYRLDGD--GWTLLAEGTTNADGRCDDLLLEGeALEPGTYRLVFDTGAYFAARGVESFYP 78

                          90       100       110
                  ....*....|....*....|....*....|.
gi 110626070   87 YVEVVFTITkETQKFHVPLLLSPWSYTTYRG 117
Cdd:pfam00576  79 EVEVRFGIT-DAEHYHVPLLLSPFGYSTYRG 108
HiuH COG2351
5-hydroxyisourate hydrolase (purine catabolism), transthyretin-related family [Nucleotide ...
 6-118 1.08e-51

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


Pssm-ID: 441918  Cd Length: 111  Bit Score: 158.38  E-value: 1.08e-51
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110626070   6 SPLTTHVLDTASGLPAQGLCLRLSRLEApcQQWMELRTSYTNLDGRCPGLlTPSQIKPGTYKLFFDTERYWKERGQESFY 85
Cdd:COG2351    2 GRLSTHVLDTARGRPAAGVRVELYRLDG--DGWTLLAEGVTNADGRIDAL-GGEALAAGTYRLVFDTGDYFAARGVPPFL 78

                         90       100       110
                 ....*....|....*....|....*....|...
gi 110626070  86 PYVEVVFTITKETQKFHVPLLLSPWSYTTYRGS 118
Cdd:COG2351   79 PEVPVRFGIADPEEHYHVPLLLSPWGYSTYRGS 111
PRK15036 PRK15036
hydroxyisourate hydrolase; Provisional
 1-118 8.36e-28

hydroxyisourate hydrolase; Provisional


Pssm-ID: 184996  Cd Length: 137  Bit Score: 98.90  E-value: 8.36e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110626070   1 MATESSPLTTHVLDTASGLPAQGLCLRLSRLEApcQQWMELRTSYTNLDGRCPGLLTPSQIKPGTYKLFFDTERYWKERG 80
Cdd:PRK15036  22 YAAQQNILSVHILNQQTGKPAADVTVTLEKKAD--NGWLQLNTAKTDKDGRIKALWPEQTATTGDYRVVFKTGDYFKKQN 99

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 110626070  81 QESFYPYVEVVFTITKETQKFHVPLLLSPWSYTTYRGS 118
Cdd:PRK15036 100 LESFFPEIPVEFHINKVNEHYHVPLLLSQYGYSTYRGS 137
TR_THY smart00095
Transthyretin;
7-114 1.82e-16

Transthyretin;


Pssm-ID: 128406  Cd Length: 121  Bit Score: 69.53  E-value: 1.82e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110626070     7 PLTTHVLDTASGLPAQGLCLRLSRLEAPcQQWMELRTSYTNLDGRCPGLLTPSQIKPGTYKLFFDTERYWKERGQESFYP 86
Cdd:smart00095   5 PLMVKVLDAVRGSPAVNVAVKVFKKTEE-GTWEPFASGKTNESGEIHELTTDEKFVEGLYKVEFDTKSYWKALGISPFHE 83

                           90       100
                   ....*....|....*....|....*....
gi 110626070    87 YVEVVFTITKETQK-FHVPLLLSPWSYTT 114
Cdd:smart00095  84 YADVVFTANDSGHRhYTIAALLSPYSYST 112
 
Name Accession Description Interval E-value
TLP_HIUase cd05822
HIUase (5-hydroxyisourate hydrolase) catalyzes the second step in a three-step ureide pathway ...
 6-118 3.88e-62

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: 185.05  E-value: 3.88e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110626070   6 SPLTTHVLDTASGLPAQGLCLRLSRLEApcQQWMELRTSYTNLDGRCPGLLTPS-QIKPGTYKLFFDTERYWKERGQESF 84
Cdd:cd05822    1 GPLSTHVLDTATGKPAAGVAVTLYRLDG--NGWTLLATGVTNADGRCDDLLPPGaQLAAGTYKLTFDTGAYFAARGQESF 78

                         90       100       110
                 ....*....|....*....|....*....|....
gi 110626070  85 YPYVEVVFTITKETQKFHVPLLLSPWSYTTYRGS 118
Cdd:cd05822   79 YPEVEVRFTITDPTEHYHVPLLLSPFGYSTYRGS 112
hdxy_isourate TIGR02962
hydroxyisourate hydrolase; Members of this family, hydroxyisourate hydrolase, represent a ...
 6-118 3.66e-60

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: 180.05  E-value: 3.66e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110626070    6 SPLTTHVLDTASGLPAQGLCLRLSRLEApcQQWMELRTSYTNLDGRCPGLL-TPSQIKPGTYKLFFDTERYWKERGQESF 84
Cdd:TIGR02962   1 SPLSTHVLDTTSGKPAAGVPVTLYRLDG--GGWTPLATGVTNADGRCDGPLpEGEDLAPGIYKLRFDTGDYFAARGVESF 78

                          90       100       110
                  ....*....|....*....|....*....|....
gi 110626070   85 YPYVEVVFTITKETQKFHVPLLLSPWSYTTYRGS 118
Cdd:TIGR02962  79 YPEVEVVFTIADPGQHYHVPLLLSPYGYSTYRGS 112
Transthyretin pfam00576
HIUase/Transthyretin family; This family includes transthyretin that is a thyroid ...
 8-117 2.01e-58

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: 175.33  E-value: 2.01e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110626070    8 LTTHVLDTASGLPAQGLCLRLSRLEAPcqQWMELRTSYTNLDGRCPGLLTPS-QIKPGTYKLFFDTERYWKERGQESFYP 86
Cdd:pfam00576   1 LTTHVLDTARGRPAAGVRVTLYRLDGD--GWTLLAEGTTNADGRCDDLLLEGeALEPGTYRLVFDTGAYFAARGVESFYP 78

                          90       100       110
                  ....*....|....*....|....*....|.
gi 110626070   87 YVEVVFTITkETQKFHVPLLLSPWSYTTYRG 117
Cdd:pfam00576  79 EVEVRFGIT-DAEHYHVPLLLSPFGYSTYRG 108
HiuH COG2351
5-hydroxyisourate hydrolase (purine catabolism), transthyretin-related family [Nucleotide ...
 6-118 1.08e-51

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


Pssm-ID: 441918  Cd Length: 111  Bit Score: 158.38  E-value: 1.08e-51
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110626070   6 SPLTTHVLDTASGLPAQGLCLRLSRLEApcQQWMELRTSYTNLDGRCPGLlTPSQIKPGTYKLFFDTERYWKERGQESFY 85
Cdd:COG2351    2 GRLSTHVLDTARGRPAAGVRVELYRLDG--DGWTLLAEGVTNADGRIDAL-GGEALAAGTYRLVFDTGDYFAARGVPPFL 78

                         90       100       110
                 ....*....|....*....|....*....|...
gi 110626070  86 PYVEVVFTITKETQKFHVPLLLSPWSYTTYRGS 118
Cdd:COG2351   79 PEVPVRFGIADPEEHYHVPLLLSPWGYSTYRGS 111
Transthyretin_like cd05469
Transthyretin_like. This domain is present in the transthyretin-like protein (TLP) family ...
 6-118 2.37e-38

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: 124.96  E-value: 2.37e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110626070   6 SPLTTHVLDTASGLPAQGLCLRLSRLeAPCQQWMELRTSYTNLDGRCPGLLTPSQIKPGTYKLFFDTERYWKERGQESFY 85
Cdd:cd05469    1 CPLMVKVLDAVRGSPAANVAIKVFRK-TADGSWEIFATGKTNEDGELHGLITEEEF*AGVYRVEFDTKSYWKALGITPFH 79

                         90       100       110
                 ....*....|....*....|....*....|....
gi 110626070  86 PYVEVVFTITKET-QKFHVPLLLSPWSYTTYRGS 118
Cdd:cd05469   80 EYAEVVFTANDSGhRHYTIALLLSPFSYSTTAVV 113
PRK15036 PRK15036
hydroxyisourate hydrolase; Provisional
 1-118 8.36e-28

hydroxyisourate hydrolase; Provisional


Pssm-ID: 184996  Cd Length: 137  Bit Score: 98.90  E-value: 8.36e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110626070   1 MATESSPLTTHVLDTASGLPAQGLCLRLSRLEApcQQWMELRTSYTNLDGRCPGLLTPSQIKPGTYKLFFDTERYWKERG 80
Cdd:PRK15036  22 YAAQQNILSVHILNQQTGKPAADVTVTLEKKAD--NGWLQLNTAKTDKDGRIKALWPEQTATTGDYRVVFKTGDYFKKQN 99

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 110626070  81 QESFYPYVEVVFTITKETQKFHVPLLLSPWSYTTYRGS 118
Cdd:PRK15036 100 LESFFPEIPVEFHINKVNEHYHVPLLLSQYGYSTYRGS 137
TLP_Transthyretin cd05821
Transthyretin (TTR) is a 55 kDa protein responsible for the transport of thyroid hormones and ...
 5-114 3.25e-22

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: 84.14  E-value: 3.25e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110626070   5 SSPLTTHVLDTASGLPAQGLCLRLSRLEAPcQQWMELRTSYTNLDGRCPGLLTPSQIKPGTYKLFFDTERYWKERGQESF 84
Cdd:cd05821    6 KCPLMVKVLDAVRGSPAANVAVKVFKKTAD-GSWEPFASGKTTETGEIHGLTTDEQFTEGVYKVEFDTKAYWKKLGISPF 84

                         90       100       110
                 ....*....|....*....|....*....|.
gi 110626070  85 YPYVEVVFTITKETQK-FHVPLLLSPWSYTT 114
Cdd:cd05821   85 HEYAEVVFTANDSGHRhYTIAALLSPYSYST 115
TR_THY smart00095
Transthyretin;
7-114 1.82e-16

Transthyretin;


Pssm-ID: 128406  Cd Length: 121  Bit Score: 69.53  E-value: 1.82e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110626070     7 PLTTHVLDTASGLPAQGLCLRLSRLEAPcQQWMELRTSYTNLDGRCPGLLTPSQIKPGTYKLFFDTERYWKERGQESFYP 86
Cdd:smart00095   5 PLMVKVLDAVRGSPAVNVAVKVFKKTEE-GTWEPFASGKTNESGEIHELTTDEKFVEGLYKVEFDTKSYWKALGISPFHE 83

                           90       100
                   ....*....|....*....|....*....
gi 110626070    87 YVEVVFTITKETQK-FHVPLLLSPWSYTT 114
Cdd:smart00095  84 YADVVFTANDSGHRhYTIAALLSPYSYST 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.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH