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Conserved domains on  [gi|19075833|ref|NP_588333|]
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transthyretin/hydroxyisourate hydrolase domain-containing protein [Schizosaccharomyces pombe]

Protein Classification

hydroxyisourate hydrolase( domain architecture ID 10456803)

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
Transthyretin pfam00576
HIUase/Transthyretin family; This family includes transthyretin that is a thyroid ...
 13-123 1.06e-53

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: 163.77  E-value: 1.06e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19075833    13 LTAHILNTMSGIPAAGVQVALFKLNESPTpsqQFIATTETNANGRVTSWNVDLSTVESGIYTFRFETGAYFDSLGVTSFY 92
Cdd:pfam00576   1 LTTHVLDTARGRPAAGVRVTLYRLDGDGW---TLLAEGTTNADGRCDDLLLEGEALEPGTYRLVFDTGAYFAARGVESFY 77

                          90       100       110
                  ....*....|....*....|....*....|.
gi 19075833    93 PYVEMAVRINKGQHYHIPLLLAPYGYTTYRG 123
Cdd:pfam00576  78 PEVEVRFGITDAEHYHVPLLLSPFGYSTYRG 108
 
Name Accession Description Interval E-value
Transthyretin pfam00576
HIUase/Transthyretin family; This family includes transthyretin that is a thyroid ...
 13-123 1.06e-53

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: 163.77  E-value: 1.06e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19075833    13 LTAHILNTMSGIPAAGVQVALFKLNESPTpsqQFIATTETNANGRVTSWNVDLSTVESGIYTFRFETGAYFDSLGVTSFY 92
Cdd:pfam00576   1 LTTHVLDTARGRPAAGVRVTLYRLDGDGW---TLLAEGTTNADGRCDDLLLEGEALEPGTYRLVFDTGAYFAARGVESFY 77

                          90       100       110
                  ....*....|....*....|....*....|.
gi 19075833    93 PYVEMAVRINKGQHYHIPLLLAPYGYTTYRG 123
Cdd:pfam00576  78 PEVEVRFGITDAEHYHVPLLLSPFGYSTYRG 108
hdxy_isourate TIGR02962
hydroxyisourate hydrolase; Members of this family, hydroxyisourate hydrolase, represent a ...
 13-124 4.36e-53

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: 162.33  E-value: 4.36e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19075833    13 LTAHILNTMSGIPAAGVQVALFKLNESPtpsQQFIATTETNANGRVTSWNVDLSTVESGIYTFRFETGAYFDSLGVTSFY 92
Cdd:TIGR02962   3 LSTHVLDTTSGKPAAGVPVTLYRLDGGG---WTPLATGVTNADGRCDGPLPEGEDLAPGIYKLRFDTGDYFAARGVESFY 79

                          90       100       110
                  ....*....|....*....|....*....|...
gi 19075833    93 PYVEMAVRI-NKGQHYHIPLLLAPYGYTTYRGS 124
Cdd:TIGR02962  80 PEVEVVFTIaDPGQHYHVPLLLSPYGYSTYRGS 112
TLP_HIUase cd05822
HIUase (5-hydroxyisourate hydrolase) catalyzes the second step in a three-step ureide pathway ...
 11-124 4.68e-51

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: 157.32  E-value: 4.68e-51
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19075833  11 PALTAHILNTMSGIPAAGVQVALFKLNESptpSQQFIATTETNANGRVTSWNVDLSTVESGIYTFRFETGAYFDSLGVTS 90
Cdd:cd05822   1 GPLSTHVLDTATGKPAAGVAVTLYRLDGN---GWTLLATGVTNADGRCDDLLPPGAQLAAGTYKLTFDTGAYFAARGQES 77

                        90       100       110
                ....*....|....*....|....*....|....*
gi 19075833  91 FYPYVEMAVRINK-GQHYHIPLLLAPYGYTTYRGS 124
Cdd:cd05822  78 FYPEVEVRFTITDpTEHYHVPLLLSPFGYSTYRGS 112
HiuH COG2351
5-hydroxyisourate hydrolase (purine catabolism), transthyretin-related family [Nucleotide ...
 13-124 9.06e-46

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


Pssm-ID: 441918  Cd Length: 111  Bit Score: 143.74  E-value: 9.06e-46
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19075833  13 LTAHILNTMSGIPAAGVQVALFKLNESptpSQQFIATTETNANGRVTSWNVDlsTVESGIYTFRFETGAYFDSLGVTSFY 92
Cdd:COG2351   4 LSTHVLDTARGRPAAGVRVELYRLDGD---GWTLLAEGVTNADGRIDALGGE--ALAAGTYRLVFDTGDYFAARGVPPFL 78

                        90       100       110
                ....*....|....*....|....*....|...
gi 19075833  93 PYVEMAVRI-NKGQHYHIPLLLAPYGYTTYRGS 124
Cdd:COG2351  79 PEVPVRFGIaDPEEHYHVPLLLSPWGYSTYRGS 111
PRK15036 PRK15036
hydroxyisourate hydrolase; Provisional
 9-124 8.19e-24

hydroxyisourate hydrolase; Provisional


Pssm-ID: 184996  Cd Length: 137  Bit Score: 88.89  E-value: 8.19e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19075833    9 QGPALTAHILNTMSGIPAAGVQVALFKLNESptpSQQFIATTETNANGRVTS-WnvDLSTVESGIYTFRFETGAYFDSLG 87
Cdd:PRK15036  25 QQNILSVHILNQQTGKPAADVTVTLEKKADN---GWLQLNTAKTDKDGRIKAlW--PEQTATTGDYRVVFKTGDYFKKQN 99

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 19075833   88 VTSFYPYVEMAVRINKGQ-HYHIPLLLAPYGYTTYRGS 124
Cdd:PRK15036 100 LESFFPEIPVEFHINKVNeHYHVPLLLSQYGYSTYRGS 137
TR_THY smart00095
Transthyretin;
13-120 3.81e-13

Transthyretin;


Pssm-ID: 128406  Cd Length: 121  Bit Score: 61.05  E-value: 3.81e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19075833     13 LTAHILNTMSGIPAAGVQVALFKLNESPTpsQQFIATTETNANGRVTSWNVDLSTVEsGIYTFRFETGAYFDSLGVTSFY 92
Cdd:smart00095   6 LMVKVLDAVRGSPAVNVAVKVFKKTEEGT--WEPFASGKTNESGEIHELTTDEKFVE-GLYKVEFDTKSYWKALGISPFH 82

                           90       100       110
                   ....*....|....*....|....*....|
gi 19075833     93 PYVEMAVRINKG--QHYHIPLLLAPYGYTT 120
Cdd:smart00095  83 EYADVVFTANDSghRHYTIAALLSPYSYST 112
 
Name Accession Description Interval E-value
Transthyretin pfam00576
HIUase/Transthyretin family; This family includes transthyretin that is a thyroid ...
 13-123 1.06e-53

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: 163.77  E-value: 1.06e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19075833    13 LTAHILNTMSGIPAAGVQVALFKLNESPTpsqQFIATTETNANGRVTSWNVDLSTVESGIYTFRFETGAYFDSLGVTSFY 92
Cdd:pfam00576   1 LTTHVLDTARGRPAAGVRVTLYRLDGDGW---TLLAEGTTNADGRCDDLLLEGEALEPGTYRLVFDTGAYFAARGVESFY 77

                          90       100       110
                  ....*....|....*....|....*....|.
gi 19075833    93 PYVEMAVRINKGQHYHIPLLLAPYGYTTYRG 123
Cdd:pfam00576  78 PEVEVRFGITDAEHYHVPLLLSPFGYSTYRG 108
hdxy_isourate TIGR02962
hydroxyisourate hydrolase; Members of this family, hydroxyisourate hydrolase, represent a ...
 13-124 4.36e-53

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: 162.33  E-value: 4.36e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19075833    13 LTAHILNTMSGIPAAGVQVALFKLNESPtpsQQFIATTETNANGRVTSWNVDLSTVESGIYTFRFETGAYFDSLGVTSFY 92
Cdd:TIGR02962   3 LSTHVLDTTSGKPAAGVPVTLYRLDGGG---WTPLATGVTNADGRCDGPLPEGEDLAPGIYKLRFDTGDYFAARGVESFY 79

                          90       100       110
                  ....*....|....*....|....*....|...
gi 19075833    93 PYVEMAVRI-NKGQHYHIPLLLAPYGYTTYRGS 124
Cdd:TIGR02962  80 PEVEVVFTIaDPGQHYHVPLLLSPYGYSTYRGS 112
TLP_HIUase cd05822
HIUase (5-hydroxyisourate hydrolase) catalyzes the second step in a three-step ureide pathway ...
 11-124 4.68e-51

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: 157.32  E-value: 4.68e-51
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19075833  11 PALTAHILNTMSGIPAAGVQVALFKLNESptpSQQFIATTETNANGRVTSWNVDLSTVESGIYTFRFETGAYFDSLGVTS 90
Cdd:cd05822   1 GPLSTHVLDTATGKPAAGVAVTLYRLDGN---GWTLLATGVTNADGRCDDLLPPGAQLAAGTYKLTFDTGAYFAARGQES 77

                        90       100       110
                ....*....|....*....|....*....|....*
gi 19075833  91 FYPYVEMAVRINK-GQHYHIPLLLAPYGYTTYRGS 124
Cdd:cd05822  78 FYPEVEVRFTITDpTEHYHVPLLLSPFGYSTYRGS 112
HiuH COG2351
5-hydroxyisourate hydrolase (purine catabolism), transthyretin-related family [Nucleotide ...
 13-124 9.06e-46

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


Pssm-ID: 441918  Cd Length: 111  Bit Score: 143.74  E-value: 9.06e-46
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19075833  13 LTAHILNTMSGIPAAGVQVALFKLNESptpSQQFIATTETNANGRVTSWNVDlsTVESGIYTFRFETGAYFDSLGVTSFY 92
Cdd:COG2351   4 LSTHVLDTARGRPAAGVRVELYRLDGD---GWTLLAEGVTNADGRIDALGGE--ALAAGTYRLVFDTGDYFAARGVPPFL 78

                        90       100       110
                ....*....|....*....|....*....|...
gi 19075833  93 PYVEMAVRI-NKGQHYHIPLLLAPYGYTTYRGS 124
Cdd:COG2351  79 PEVPVRFGIaDPEEHYHVPLLLSPWGYSTYRGS 111
Transthyretin_like cd05469
Transthyretin_like. This domain is present in the transthyretin-like protein (TLP) family ...
 13-124 2.74e-29

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: 102.23  E-value: 2.74e-29
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19075833  13 LTAHILNTMSGIPAAGVQVALFKLNESPTPSQqfIATTETNANGRVTSwnvdLSTVE---SGIYTFRFETGAYFDSLGVT 89
Cdd:cd05469   3 LMVKVLDAVRGSPAANVAIKVFRKTADGSWEI--FATGKTNEDGELHG----LITEEef*AGVYRVEFDTKSYWKALGIT 76

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 19075833  90 SFYPYVEMAVRIN--KGQHYHIPLLLAPYGYTTYRGS 124
Cdd:cd05469  77 PFHEYAEVVFTANdsGHRHYTIALLLSPFSYSTTAVV 113
PRK15036 PRK15036
hydroxyisourate hydrolase; Provisional
 9-124 8.19e-24

hydroxyisourate hydrolase; Provisional


Pssm-ID: 184996  Cd Length: 137  Bit Score: 88.89  E-value: 8.19e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19075833    9 QGPALTAHILNTMSGIPAAGVQVALFKLNESptpSQQFIATTETNANGRVTS-WnvDLSTVESGIYTFRFETGAYFDSLG 87
Cdd:PRK15036  25 QQNILSVHILNQQTGKPAADVTVTLEKKADN---GWLQLNTAKTDKDGRIKAlW--PEQTATTGDYRVVFKTGDYFKKQN 99

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 19075833   88 VTSFYPYVEMAVRINKGQ-HYHIPLLLAPYGYTTYRGS 124
Cdd:PRK15036 100 LESFFPEIPVEFHINKVNeHYHVPLLLSQYGYSTYRGS 137
TLP_Transthyretin cd05821
Transthyretin (TTR) is a 55 kDa protein responsible for the transport of thyroid hormones and ...
 13-120 3.55e-17

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: 71.43  E-value: 3.55e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19075833  13 LTAHILNTMSGIPAAGVQVALFKLNESPTPSQqfIATTETNANGRVTSWNVDLSTVEsGIYTFRFETGAYFDSLGVTSFY 92
Cdd:cd05821   9 LMVKVLDAVRGSPAANVAVKVFKKTADGSWEP--FASGKTTETGEIHGLTTDEQFTE-GVYKVEFDTKAYWKKLGISPFH 85

                        90       100       110
                ....*....|....*....|....*....|
gi 19075833  93 PYVEMAVRINKG--QHYHIPLLLAPYGYTT 120
Cdd:cd05821  86 EYAEVVFTANDSghRHYTIAALLSPYSYST 115
TR_THY smart00095
Transthyretin;
13-120 3.81e-13

Transthyretin;


Pssm-ID: 128406  Cd Length: 121  Bit Score: 61.05  E-value: 3.81e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19075833     13 LTAHILNTMSGIPAAGVQVALFKLNESPTpsQQFIATTETNANGRVTSWNVDLSTVEsGIYTFRFETGAYFDSLGVTSFY 92
Cdd:smart00095   6 LMVKVLDAVRGSPAVNVAVKVFKKTEEGT--WEPFASGKTNESGEIHELTTDEKFVE-GLYKVEFDTKSYWKALGISPFH 82

                           90       100       110
                   ....*....|....*....|....*....|
gi 19075833     93 PYVEMAVRINKG--QHYHIPLLLAPYGYTT 120
Cdd:smart00095  83 EYADVVFTANDSghRHYTIAALLSPYSYST 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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