Conserved Protein Domain Family
TLP_Transthyretin

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cd05821: TLP_Transthyretin 
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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.
Statistics
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PSSM-Id: 100113
View PSSM: cd05821
Aligned: 7 rows
Threshold Bit Score: 221.268
Threshold Setting Gi: 51247415
Created: 5-Sep-2007
Updated: 17-Jan-2013
Structure
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Program:
Drawing:
Aligned Rows:
 
active sitehomotetramer
Conserved site includes 8 residues -Click on image for an interactive view with Cn3D
Feature 1:active site [active site]
Evidence:
  • Structure:1KGJ_A; Rattus norvegicus transthyretin binds 3', 5'-dibromoflavone. Contacts determined at 3.5 Angstroms.
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  • Structure:1SN5_D; Sparus aurata transthyretin binds triiodothyronine. Contacts determined at 5 Angstroms.
    View structure with Cn3D
  • Comment:The homotetrameric thyretin structure contains two independent binding sites within the central core of the tetramer, each formed by a pair of monomers.
  • Structure:1IE4_A; Rattus norvegicus transthyretin binds two molecules of thyroxine in two independent binding sites, each formed by a pair of subunits. Contacts determined at 3.5 Angstroms.
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  • Structure:1TYR_A; Homo sapiens transthyretin binds retinol. Contacts determined at 3.5 Angstroms.
    View structure with Cn3D
  • Citation:PMID 8536704

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                   # #                                    #                             
1KGJ_A         4 GAGESKCPLMVKVLDAVRGSPAVDVAVKVFKKTADGSWEPFASGKTAESGELHGLTTDEKFTEGVYRVELDTKSYWKALG 83
1SN5_D         7 GGSDTRCPLMVKILDAVKGTPAGSVALKVSQKTADGGWTQIATGVTDATGEIHNLITEQQFPAGVYRVEFDTKAYWTNQG 86
1TYR_A         4 GTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALG 83
1IE4_A         4 GAGESKCPLMVKVLDAVRGSPAVDVAVKVFKKTADGSWEPFASGKTAESGELHGLTTDEKFTEGVYRVELDTKSYWKALG 83
1TFP_A         7 GSVDSKCPLMVKVLDAVRGSPAANVAVKVFKKAADGTWQDFATGKTTEFGEIHELTTEEQFVEGVYRVEFDTSSYWKGLG 86
gi 4808470    28 GEADSKCPLMVKVLDAVRGIPAANLLVNVFRQTESGKWEQITSGKTTELGEIHNLTTDEQFTEGVYKIEFATKAFWGKLG 107
gi 115293348  32 GGVKDSCPLMVKAIDSVRGKPAAGVKLSVMKKQEDASWKEVATGVTGKTGESHHLIGDKDFTEGTYKVRFDTQAYWTKAG 111
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
Feature 1                              # # #      # #     
1KGJ_A        84 ISPFHEYAEVVFTANDSGHRHYTIAALLSPYSYSTTAVVSN 124
1SN5_D        87 STPFHEVAEVVFDAHPEGHRHYTLALLLSPFSYTTTAVVSS 127
1TYR_A        84 ISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTN 124
1IE4_A        84 ISPFHEYAEVVFTANDSGHRHYTIAALLSPYSYSTTAVVSN 124
1TFP_A        87 LSPFHEYADVVFTANDSGHRHYTIAALLSPFSYSTTAVVSD 127
gi 4808470   108 LSPFHEYVDVVFTANDAGHRQYTIAVLLTPYSFSSTAIVSE 148
gi 115293348 112 ITPFHEAAEVVFMAHGAGHKHYHIPMLLSPFFYATGTIVGD 152

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