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Conserved domains on  [gi|443297]
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Chain A, TRANSTHYRETIN

Protein Classification

peptidase associated/transthyretin-like domain-containing protein( domain architecture ID 229422)

peptidase associated/transthyretin-like domain-containing protein

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
Peptidase_M14NE-CP-C_like super family cl21470
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
 7-127 2.62e-82

Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, regulation, or interaction domain; This domain is found C-terminal to the M14 carboxypeptidase (CP) N/E subfamily containing zinc-binding enzymes that hydrolyze single C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. The N/E subfamily includes enzymatically active members (carboxypeptidase N, E, M, D, and Z), as well as non-active members (carboxypeptidase-like protein 1, -2, aortic CP-like protein, and adipocyte enhancer binding protein-1) which lack the critical active site and substrate-binding residues considered necessary for activity. The active N/E enzymes fulfill a variety of cellular functions, including prohormone processing, regulation of peptide hormone activity, alteration of protein-protein or protein-cell interactions and transcriptional regulation. For M14 CPs, it has been suggested that this domain may assist in folding of the CP domain, regulate enzyme activity, or be involved in interactions with other proteins or with membranes; for carboxypeptidase M, it may interact with the bradykinin 1 receptor at the cell surface. This domain may also be found in other peptidase families.


The actual alignment was detected with superfamily member smart00095:

Pssm-ID: 473874  Cd Length: 121  Bit Score: 236.70  E-value: 2.62e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 443297        7 ESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISP 86
Cdd:smart00095   1 DSKCPLMVKVLDAVRGSPAVNVAVKVFKKTEEGTWEPFASGKTNESGEIHELTTDEKFVEGLYKVEFDTKSYWKALGISP 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 443297       87 FHEHAEVVFTANDSGPRRYTIATLLSPYSYSTTAVVTNPKE 127
Cdd:smart00095  81 FHEYADVVFTANDSGHRHYTIAALLSPYSYSTTAVVSNPKE 121
 
Name Accession Description Interval E-value
TR_THY smart00095
Transthyretin;
7-127 2.62e-82

Transthyretin;


Pssm-ID: 128406  Cd Length: 121  Bit Score: 236.70  E-value: 2.62e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 443297        7 ESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISP 86
Cdd:smart00095   1 DSKCPLMVKVLDAVRGSPAVNVAVKVFKKTEEGTWEPFASGKTNESGEIHELTTDEKFVEGLYKVEFDTKSYWKALGISP 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 443297       87 FHEHAEVVFTANDSGPRRYTIATLLSPYSYSTTAVVTNPKE 127
Cdd:smart00095  81 FHEYADVVFTANDSGHRHYTIAALLSPYSYSTTAVVSNPKE 121
TLP_Transthyretin cd05821
Transthyretin (TTR) is a 55 kDa protein responsible for the transport of thyroid hormones and ...
 4-124 2.14e-79

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: 229.36  E-value: 2.14e-79
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 443297     4 GTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALG 83
Cdd:cd05821   1 GGGDSKCPLMVKVLDAVRGSPAANVAVKVFKKTADGSWEPFASGKTTETGEIHGLTTDEQFTEGVYKVEFDTKAYWKKLG 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 443297    84 ISPFHEHAEVVFTANDSGPRRYTIATLLSPYSYSTTAVVTN 124
Cdd:cd05821  81 ISPFHEYAEVVFTANDSGHRHYTIAALLSPYSYSTTAVVSN 121
Transthyretin pfam00576
HIUase/Transthyretin family; This family includes transthyretin that is a thyroid ...
 16-118 2.75e-25

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: 91.74  E-value: 2.75e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 443297      16 VLDAVRGSPAINVAVHVFRkAADDTWEPFASGKTSESGELHGLTTE-EEFVEGIYKVEIDTKSYWKALGISPFHEHAEVV 94
Cdd:pfam00576   5 VLDTARGRPAAGVRVTLYR-LDGDGWTLLAEGTTNADGRCDDLLLEgEALEPGTYRLVFDTGAYFAARGVESFYPEVEVR 83

                          90       100
                  ....*....|....*....|....
gi 443297      95 FTANDsgPRRYTIATLLSPYSYST 118
Cdd:pfam00576  84 FGITD--AEHYHVPLLLSPFGYST 105
HiuH COG2351
5-hydroxyisourate hydrolase (purine catabolism), transthyretin-related family [Nucleotide ...
 16-118 4.98e-25

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


Pssm-ID: 441918  Cd Length: 111  Bit Score: 91.35  E-value: 4.98e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 443297    16 VLDAVRGSPAINVAVHVFRkAADDTWEPFASGKTSESGELHGLTtEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVF 95
Cdd:COG2351   8 VLDTARGRPAAGVRVELYR-LDGDGWTLLAEGVTNADGRIDALG-GEALAAGTYRLVFDTGDYFAARGVPPFLPEVPVRF 85

                        90       100
                ....*....|....*....|...
gi 443297    96 TANDSGpRRYTIATLLSPYSYST 118
Cdd:COG2351  86 GIADPE-EHYHVPLLLSPWGYST 107
hdxy_isourate TIGR02962
hydroxyisourate hydrolase; Members of this family, hydroxyisourate hydrolase, represent a ...
 11-118 4.31e-23

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: 86.45  E-value: 4.31e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 443297      11 PLMVKVLDAVRGSPAINVAVHVFRKAADDtWEPFASGKTSESGELHG-LTTEEEFVEGIYKVEIDTKSYWKALGISPFHE 89
Cdd:TIGR02962   2 PLSTHVLDTTSGKPAAGVPVTLYRLDGGG-WTPLATGVTNADGRCDGpLPEGEDLAPGIYKLRFDTGDYFAARGVESFYP 80

                          90       100
                  ....*....|....*....|....*....
gi 443297      90 HAEVVFTANDSGpRRYTIATLLSPYSYST 118
Cdd:TIGR02962  81 EVEVVFTIADPG-QHYHVPLLLSPYGYST 108
PRK15036 PRK15036
hydroxyisourate hydrolase; Provisional
 12-118 5.74e-13

hydroxyisourate hydrolase; Provisional


Pssm-ID: 184996  Cd Length: 137  Bit Score: 61.15  E-value: 5.74e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 443297     12 LMVKVLDAVRGSPAINVAVhVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHA 91
Cdd:PRK15036  29 LSVHILNQQTGKPAADVTV-TLEKKADNGWLQLNTAKTDKDGRIKALWPEQTATTGDYRVVFKTGDYFKKQNLESFFPEI 107

                         90       100
                 ....*....|....*....|....*..
gi 443297     92 EVVFTANDSGpRRYTIATLLSPYSYST 118
Cdd:PRK15036 108 PVEFHINKVN-EHYHVPLLLSQYGYST 133
 
Name Accession Description Interval E-value
TR_THY smart00095
Transthyretin;
7-127 2.62e-82

Transthyretin;


Pssm-ID: 128406  Cd Length: 121  Bit Score: 236.70  E-value: 2.62e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 443297        7 ESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISP 86
Cdd:smart00095   1 DSKCPLMVKVLDAVRGSPAVNVAVKVFKKTEEGTWEPFASGKTNESGEIHELTTDEKFVEGLYKVEFDTKSYWKALGISP 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 443297       87 FHEHAEVVFTANDSGPRRYTIATLLSPYSYSTTAVVTNPKE 127
Cdd:smart00095  81 FHEYADVVFTANDSGHRHYTIAALLSPYSYSTTAVVSNPKE 121
TLP_Transthyretin cd05821
Transthyretin (TTR) is a 55 kDa protein responsible for the transport of thyroid hormones and ...
 4-124 2.14e-79

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: 229.36  E-value: 2.14e-79
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 443297     4 GTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALG 83
Cdd:cd05821   1 GGGDSKCPLMVKVLDAVRGSPAANVAVKVFKKTADGSWEPFASGKTTETGEIHGLTTDEQFTEGVYKVEFDTKAYWKKLG 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 443297    84 ISPFHEHAEVVFTANDSGPRRYTIATLLSPYSYSTTAVVTN 124
Cdd:cd05821  81 ISPFHEYAEVVFTANDSGHRHYTIAALLSPYSYSTTAVVSN 121
Transthyretin_like cd05469
Transthyretin_like. This domain is present in the transthyretin-like protein (TLP) family ...
 10-122 1.91e-67

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: 198.91  E-value: 1.91e-67
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 443297    10 CPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHE 89
Cdd:cd05469   1 CPLMVKVLDAVRGSPAANVAIKVFRKTADGSWEIFATGKTNEDGELHGLITEEEF*AGVYRVEFDTKSYWKALGITPFHE 80

                        90       100       110
                ....*....|....*....|....*....|...
gi 443297    90 HAEVVFTANDSGPRRYTIATLLSPYSYSTTAVV 122
Cdd:cd05469  81 YAEVVFTANDSGHRHYTIALLLSPFSYSTTAVV 113
Transthyretin pfam00576
HIUase/Transthyretin family; This family includes transthyretin that is a thyroid ...
 16-118 2.75e-25

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: 91.74  E-value: 2.75e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 443297      16 VLDAVRGSPAINVAVHVFRkAADDTWEPFASGKTSESGELHGLTTE-EEFVEGIYKVEIDTKSYWKALGISPFHEHAEVV 94
Cdd:pfam00576   5 VLDTARGRPAAGVRVTLYR-LDGDGWTLLAEGTTNADGRCDDLLLEgEALEPGTYRLVFDTGAYFAARGVESFYPEVEVR 83

                          90       100
                  ....*....|....*....|....
gi 443297      95 FTANDsgPRRYTIATLLSPYSYST 118
Cdd:pfam00576  84 FGITD--AEHYHVPLLLSPFGYST 105
HiuH COG2351
5-hydroxyisourate hydrolase (purine catabolism), transthyretin-related family [Nucleotide ...
 16-118 4.98e-25

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


Pssm-ID: 441918  Cd Length: 111  Bit Score: 91.35  E-value: 4.98e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 443297    16 VLDAVRGSPAINVAVHVFRkAADDTWEPFASGKTSESGELHGLTtEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVF 95
Cdd:COG2351   8 VLDTARGRPAAGVRVELYR-LDGDGWTLLAEGVTNADGRIDALG-GEALAAGTYRLVFDTGDYFAARGVPPFLPEVPVRF 85

                        90       100
                ....*....|....*....|...
gi 443297    96 TANDSGpRRYTIATLLSPYSYST 118
Cdd:COG2351  86 GIADPE-EHYHVPLLLSPWGYST 107
TLP_HIUase cd05822
HIUase (5-hydroxyisourate hydrolase) catalyzes the second step in a three-step ureide pathway ...
 11-118 1.56e-23

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: 87.60  E-value: 1.56e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 443297    11 PLMVKVLDAVRGSPAINVAVHVFRkAADDTWEPFASGKTSESGELHGLTTEEEFVE-GIYKVEIDTKSYWKALGISPFHE 89
Cdd:cd05822   2 PLSTHVLDTATGKPAAGVAVTLYR-LDGNGWTLLATGVTNADGRCDDLLPPGAQLAaGTYKLTFDTGAYFAARGQESFYP 80

                        90       100
                ....*....|....*....|....*....
gi 443297    90 HAEVVFTANDSGpRRYTIATLLSPYSYST 118
Cdd:cd05822  81 EVEVRFTITDPT-EHYHVPLLLSPFGYST 108
hdxy_isourate TIGR02962
hydroxyisourate hydrolase; Members of this family, hydroxyisourate hydrolase, represent a ...
 11-118 4.31e-23

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: 86.45  E-value: 4.31e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 443297      11 PLMVKVLDAVRGSPAINVAVHVFRKAADDtWEPFASGKTSESGELHG-LTTEEEFVEGIYKVEIDTKSYWKALGISPFHE 89
Cdd:TIGR02962   2 PLSTHVLDTTSGKPAAGVPVTLYRLDGGG-WTPLATGVTNADGRCDGpLPEGEDLAPGIYKLRFDTGDYFAARGVESFYP 80

                          90       100
                  ....*....|....*....|....*....
gi 443297      90 HAEVVFTANDSGpRRYTIATLLSPYSYST 118
Cdd:TIGR02962  81 EVEVVFTIADPG-QHYHVPLLLSPYGYST 108
PRK15036 PRK15036
hydroxyisourate hydrolase; Provisional
 12-118 5.74e-13

hydroxyisourate hydrolase; Provisional


Pssm-ID: 184996  Cd Length: 137  Bit Score: 61.15  E-value: 5.74e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 443297     12 LMVKVLDAVRGSPAINVAVhVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHA 91
Cdd:PRK15036  29 LSVHILNQQTGKPAADVTV-TLEKKADNGWLQLNTAKTDKDGRIKALWPEQTATTGDYRVVFKTGDYFKKQNLESFFPEI 107

                         90       100
                 ....*....|....*....|....*..
gi 443297     92 EVVFTANDSGpRRYTIATLLSPYSYST 118
Cdd:PRK15036 108 PVEFHINKVN-EHYHVPLLLSQYGYST 133
 
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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