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PR00189

Identifier
TRNSTHYRETIN  [View Relations]  [View Alignment]  
Accession
PR00189
No. of Motifs
4
Creation Date
12-OCT-1993  (UPDATE 28-JUN-1999)
Title
Transthyretin signature
Database References

PROSITE; PS00768 TRANSTHYRETIN_1; PS00769 TRANSTHYRETIN_2
BLOCKS; BL00768
PFAM; PF00576 Transthyretin
INTERPRO; IPR000895
PDB; 2PAB
SCOP; 2PAB
CATH; 2PAB
Literature References
1. DUAN, W., ACHEN, M.G., RICHARDSON, S.J., LAWRENCE, M.C., WETTENHALL,
R.E.H., JAWOROWSKI, A. AND SCHREIBER, G.
Isolation, characterization, cDNA cloning and gene expression of an avian
transthyretin - Implications for the evolution of structure and function of
transthyretin in vertebrates.
EUR.J.BIOCHEMISTRY 200(3) 679-687 (1991).
 
2. SASAKI, H., YOSHIOKA, N., TAKAGI, Y. AND SAKAKI, Y.
Structure of the chromosomal gene for human serum prealbumin.
GENE 37 191-197 (1985).

Documentation
Transthyretin (formerly prealbumin) is one of 3 thyroid hormone-binding
proteins found in the blood of vertebrates [1]. It is produced in the liver
and circulates in the bloodstream, where it binds retinol and thyroxine
(T4) [2]. It differs from the other 2 hormone-binding proteins (T4-binding
globulin and albumin) in 3 distinct ways: (1) the gene is expressed at a
high rate in the brain choroid plexus; (2) it is enriched in cerebrospinal 
fluid; and (3) no genetically caused absence has been observed, suggesting 
an essential role in brain function, distinct from that played in the blood-
stream [1]. The protein consists of around 130 amino acids, which assemble 
as a homotetramer that contains an internal channel in which T4 is bound
[1]. Within this complex, T4 appears to be transported across the blood-
brain barrier, where, in the choroid plexus, the hormone stimulates further
synthesis of transthyretin: the protein then diffuses back into the blood-
stream, where it binds T4 for transport back to the brain [1].  
 
TRNSTHYRETIN is a 4-element fingerprint that provides a signature for
transthyretins. The fingerprint was derived from an initial alignment of 4
sequences: the motifs correspond to highly conserved regions spanning the
full alignment length, 1 and 4 including N- and C-terminal domains encoded
by PROSITE patterns TRANSTHYRETIN_1 (PS00768) and TRANSTHYRETIN_2 (PS00769),
both of which contain residues known to bind T4 (in the former a Lys
residue, and in the latter a Ser-Thr dipeptide). Two iterations on OWL21.1
were required to reach convergence, at which point a true set comprising 7
sequences was identified. Two partial matches were also found, both of
which lack motifs 1 and 4.
 
An update on SPTR37_9f identified a true set of 21 sequences, and 3
partial matches.
Summary Information
  21 codes involving  4 elements
2 codes involving 3 elements
1 codes involving 2 elements
Composite Feature Index
421212121
32022
21001
1234
True Positives
O46654        O74492        O85301        O93330        
O93483 TTHY_BOVIN TTHY_CHICK TTHY_CROPO
TTHY_HUMAN TTHY_MACEU TTHY_MACGI TTHY_MONDO
TTHY_MOUSE TTHY_PETBR TTHY_PIG TTHY_RABIT
TTHY_RAT TTHY_SHEEP TTHY_SMIMA TTHY_TILRU
YEDX_ECOLI
True Positive Partials
Codes involving 3 elements
TTH1_CAEEL TTH2_CAEEL
Codes involving 2 elements
YUNM_BACSU
Sequence Titles
O46654      TRANSTHYRETIN (PREALBUMIN) PRECURSOR - SOREX ARANEUS (EURASIAN COMMON SHREW) (EUROPEAN SHREW). 
O74492 PUTATIVE TRANSTHYRETIN PRECURSOR - SCHIZOSACCHAROMYCES POMBE (FISSION YEAST).
O85301 HYPOTHETICAL 18.9 KD PROTEIN - SALMONELLA DUBLIN.
O93330 TRANSTHYRETIN PRECURSOR - SPARUS AURATA (GILTHEAD SEA BREAM).
O93483 TRANSTHYRETIN - RANA CATESBEIANA (BULL FROG).
TTHY_BOVIN TRANSTHYRETIN PRECURSOR (PREALBUMIN) - BOS TAURUS (BOVINE).
TTHY_CHICK TRANSTHYRETIN PRECURSOR (PREALBUMIN) (TBPA) - GALLUS GALLUS (CHICKEN).
TTHY_CROPO TRANSTHYRETIN PRECURSOR (PREALBUMIN) - CROCODYLUS POROSUS (CROCODILE).
TTHY_HUMAN TRANSTHYRETIN PRECURSOR (PREALBUMIN) (TBPA) (TTR) (ATTR) - HOMO SAPIENS (HUMAN).
TTHY_MACEU TRANSTHYRETIN PRECURSOR (PREALBUMIN) - MACROPUS EUGENII (TAMMAR WALLABY).
TTHY_MACGI TRANSTHYRETIN PRECURSOR (PREALBUMIN) - MACROPUS GIGANTEUS (EASTERN GRAY KANGAROO).
TTHY_MONDO TRANSTHYRETIN PRECURSOR (PREALBUMIN) - MONODELPHIS DOMESTICA (SHORT-TAILED GREY OPOSSUM).
TTHY_MOUSE TRANSTHYRETIN PRECURSOR (PREALBUMIN) - MUS MUSCULUS (MOUSE).
TTHY_PETBR TRANSTHYRETIN PRECURSOR (PREALBUMIN) - PETAURUS BREVICEPS (AUSTRALIAN SUGAR GLIDER).
TTHY_PIG TRANSTHYRETIN PRECURSOR (PREALBUMIN) - SUS SCROFA (PIG).
TTHY_RABIT TRANSTHYRETIN (PREALBUMIN) - ORYCTOLAGUS CUNICULUS (RABBIT).
TTHY_RAT TRANSTHYRETIN PRECURSOR (PREALBUMIN) (TBPA) (ALLERGEN RAT N 1) (RAT N I) - RATTUS NORVEGICUS (RAT).
TTHY_SHEEP TRANSTHYRETIN PRECURSOR (PREALBUMIN) - OVIS ARIES (SHEEP).
TTHY_SMIMA TRANSTHYRETIN PRECURSOR (PREALBUMIN) - SMINTHOPSIS MACROURA (STRIPE-FACED DUNNART).
TTHY_TILRU TRANSTHYRETIN PRECURSOR (PREALBUMIN) (TBPA) - TILIQUA RUGOSA (STUMP-TAILED SKINK).
YEDX_ECOLI HYPOTHETICAL TRANSTHYRETIN-LIKE PROTEIN PRECURSOR - ESCHERICHIA COLI.

TTH1_CAEEL HYPOTHETICAL TRANSTHYRETIN-LIKE PROTEIN R09H10.3 IN CHROMOSOME IV - CAENORHABDITIS ELEGANS.
TTH2_CAEEL HYPOTHETICAL TRANSTHYRETIN-LIKE PROTEIN ZK697.8 IN CHROMOSOME V - CAENORHABDITIS ELEGANS.

YUNM_BACSU HYPOTHETICAL TRANSTHYRETIN-LIKE PROTEIN IN HOM-MRGA INTERGENIC REGION - BACILLUS SUBTILIS.
Scan History
OWL21_1    2  100  NSINGLE    
OWL26_0 1 100 NSINGLE
SPTR37_9f 3 100 NSINGLE
Initial Motifs
Motif 1  width=21
Element Seqn Id St Int Rpt
PLMVKVLDAVRGSPAVDVAVK TTHY_MOUSE 31 31 -
PLMVKVLDAVRGSPAANVGVK TTHY_SHEEP 31 31 -
PLMVKVLDAVRGSPAANVAVK TTHY_CHICK 34 34 -
PLMVKVLDAVRGRPATSIAVK TTHY_TILRU 34 34 -

Motif 2 width=26
Element Seqn Id St Int Rpt
FASGKTAESGELHGLTTDEKFVEGVY TTHY_MOUSE 64 12 -
FASGKTSDSGELHGLTTEDKFVEGLY TTHY_SHEEP 64 12 -
FATGKTTEFGEIHELTTEEQFVEGVY TTHY_CHICK 67 12 -
FANGKTNEFGEIHELTTDEQFVQGLY TTHY_TILRU 67 12 -

Motif 3 width=30
Element Seqn Id St Int Rpt
RVELDTKSYWKTLGISPFHEFADVVFTAND TTHY_MOUSE 90 0 -
KVELDTKSYWKSLGISPFHEYAEVVFTAND TTHY_SHEEP 90 0 -
RVEFDTSSYWKGLGLSPFHEYADVVFTAND TTHY_CHICK 93 0 -
KVEFDTSSYWKALGVSPFHEYADVVFSAND TTHY_TILRU 93 0 -

Motif 4 width=23
Element Seqn Id St Int Rpt
SGHRHYTIAALLSPYSYSTTAVV TTHY_MOUSE 120 0 -
SGLRHYTIAALLSPYSYSTTALV TTHY_SHEEP 120 0 -
SGHRHYTIAALLSPFSYSTTAVV TTHY_CHICK 123 0 -
SGHRHYTIAALLSPFSYSTTAVV TTHY_TILRU 123 0 -
Final Motifs
Motif 1  width=21
Element Seqn Id St Int Rpt
PLMVKVLDAVRGSPAVDVAVK TTHY_RAT 31 31 -
PLMVKVLDAVRGSPAVNVGVK TTHY_PIG 31 31 -
PLMVKVLDAVRGSPAVDVAVK TTHY_MOUSE 31 31 -
PLMVKVLDAVRGSPAANVGVK TTHY_SHEEP 31 31 -
PLMVKVLDAVRGSPAANVAVK TTHY_CHICK 34 34 -
PLMVKVLDAVRGSPAANVGVK TTHY_BOVIN 31 31 -
PLMVKVLDAVRGRPAVNVDVK TTHY_MACEU 33 33 -
PLMVKVLDAVRGSPAVNVNVK TTHY_MONDO 33 33 -
PLMVKVLDAVRGSPAANVAIK TTHY_CROPO 34 34 -
PLMVKVLDAVRGRPAVNVDVK TTHY_MACGI 33 33 -
PLMVKVLDAVRGRPAVNVDVK TTHY_PETBR 33 33 -
PLMVKVLDAVRGSPAVDVSVH TTHY_RABIT 11 11 -
PLMVKVLDAVRGSPAINVAVH TTHY_HUMAN 31 31 -
PLMVKVLDAVRGRPATSIAVK TTHY_TILRU 34 34 -
PLMVKVLDAVQGSPAVNVAVR O46654 31 31 -
PLMVKVLDSVRGSPAVNVDVK TTHY_SMIMA 33 33 -
PLMVKVLDAVRGIPAAKLPVK O93483 34 34 -
PLMVKILDAVKGTPAGSVALK O93330 34 34 -
ILSVHILNQQTGKPAADVTVT YEDX_ECOLI 28 28 -
ILSVHILDQQTGKPAPGVEVV O85301 27 27 -
ALTAHILNTMSGIPAAGVQVA O74492 12 12 -

Motif 2 width=26
Element Seqn Id St Int Rpt
FASGKTAESGELHGLTTDEKFTEGVY TTHY_RAT 64 12 -
FALGKTSEFGELHGLTTDEKFVEGIY TTHY_PIG 64 12 -
FASGKTAESGELHGLTTDEKFVEGVY TTHY_MOUSE 64 12 -
FASGKTSDSGELHGLTTEDKFVEGLY TTHY_SHEEP 64 12 -
FATGKTTEFGEIHELTTEEQFVEGVY TTHY_CHICK 67 12 -
FASGKTSESGELHGLTTEDKFVEGLY TTHY_BOVIN 64 12 -
FAAGKTNDNGEIHELTTDDKFGEGLY TTHY_MACEU 66 12 -
FATGKTNDYGEIHELTNDEKFGEGLY TTHY_MONDO 66 12 -
FAAGKTTEFGEVHELTSDEKFVEGIY TTHY_CROPO 67 12 -
FAAGKTNDNGEIHELTTDDKFGEGLY TTHY_MACGI 66 12 -
FASGKTNDNGEIHELTSDDKFGEGLY TTHY_PETBR 66 12 -
FASGKTSKTGELHGLTTSEKFVEGVY TTHY_RABIT 44 12 -
FASGKTSESGELHGLTTEEEFVEGIY TTHY_HUMAN 64 12 -
FANGKTNEFGEIHELTTDEQFVQGLY TTHY_TILRU 67 12 -
FASGKTSEFGELHGLTTDEKFVEGII O46654 64 12 -
FASGKTNNNGEIHELTSDDQFGEGLY TTHY_SMIMA 66 12 -
ISSGTTSSDGEIHNLATEEQFVEGIY O93483 67 12 -
IATGVTDATGEIHNLITEQQFPAGVY O93330 67 12 -
LNTAKTDKDGRIKALWPEQTATTGDY YEDX_ECOLI 60 11 -
LNTGHTDQDGRIKALWPEKAAAPGDY O85301 59 11 -
IATTETNANGRVTSWNVDLSTVESGI O74492 47 14 -

Motif 3 width=30
Element Seqn Id St Int Rpt
RVELDTKSYWKALGISPFHEYAEVVFTAND TTHY_RAT 90 0 -
KVELDTKSYWKALGISPFHEYAEVVFTAND TTHY_PIG 90 0 -
RVELDTKSYWKTLGISPFHEFADVVFTAND TTHY_MOUSE 90 0 -
KVELDTKSYWKSLGISPFHEYAEVVFTAND TTHY_SHEEP 90 0 -
RVEFDTSSYWKGLGLSPFHEYADVVFTAND TTHY_CHICK 93 0 -
KVELDTKSYWKSLGISPFHEFAEVVFTAND TTHY_BOVIN 90 0 -
KVEFDTISYWKALGVSPFHEYADVVFTAND TTHY_MACEU 92 0 -
KVEFDTFSYWNALGVSPFHEYADVVFKAND TTHY_MONDO 92 0 -
RVEFDTSSYWKALGLSPFHEYADVVFTAND TTHY_CROPO 93 0 -
KVEFDTISYWKALGVSPFHEYADVVFTAND TTHY_MACGI 92 0 -
KVEFDTISYWKALGVSPFHEYADVVFTAND TTHY_PETBR 92 0 -
KVELDTKSYWKALGISPFHEYAEVVFTAND TTHY_RABIT 70 0 -
KVEIDTKSYWKALGISPFHEHAEVVFTAND TTHY_HUMAN 90 0 -
KVEFDTSSYWKALGVSPFHEYADVVFSAND TTHY_TILRU 93 0 -
KVELDTKTYWKALGISPFHEYVEVVFHAND O46654 90 0 -
KVEFDTVSYWKTFGISPFHEYADVVFTAND TTHY_SMIMA 92 0 -
KLEFATKRFWSKLGLTPFHEYVDVVFTAND O93483 93 0 -
RVEFDTKAYWTNQGSTPFHEVAEVVFDAHP O93330 93 0 -
RVVFKTGDYFKKQNLESFFPEIPVEFHINK YEDX_ECOLI 86 0 -
RVIFKTGQYFESKKLDTFFPEIPVEFHISK O85301 85 0 -
TFRFETGAYFDSLGVTSFYPYVEMAVRINK O74492 74 1 -

Motif 4 width=23
Element Seqn Id St Int Rpt
SGHRHYTIAALLSPYSYSTTAVV TTHY_RAT 120 0 -
SGRRHYTIAALLSPYSYSTTALV TTHY_PIG 120 0 -
SGHRHYTIAALLSPYSYSTTAVV TTHY_MOUSE 120 0 -
SGLRHYTIAALLSPYSYSTTALV TTHY_SHEEP 120 0 -
SGHRHYTIAALLSPFSYSTTAVV TTHY_CHICK 123 0 -
SGPRHYTIAALLSPYSYSTTALV TTHY_BOVIN 120 0 -
AGHRHYTIAALLSPYSFSTTAIV TTHY_MACEU 122 0 -
AGHRHYTIAALLSPYSYSTTAVV TTHY_MONDO 122 0 -
SGHRHYTIAALLSPFSYSTTAVV TTHY_CROPO 123 0 -
AGHRHYTIAAQLSPYSFSTTAIV TTHY_MACGI 122 0 -
AGHRHYTIAAQLSPYSFSTTAIV TTHY_PETBR 122 0 -
SGHRSYTIAALLSPFSYSTTAVV TTHY_RABIT 100 0 -
SGPRRYTIAALLSPYSYSTTAVV TTHY_HUMAN 120 0 -
SGHRHYTIAALLSPFSYSTTAVV TTHY_TILRU 123 0 -
SGKRRYTIAALLSPYSYSTTALV O46654 120 0 -
AGHRHYTIAAQLSPFSFSTTAVV TTHY_SMIMA 122 0 -
AGHRHYTTAVLLTPYSFSTTAVV O93483 123 0 -
EGHGHYTLALLLSPFSYTTTAVV O93330 123 0 -
KVNEHYHVPLLLSQYGYSTYRGS YEDX_ECOLI 115 -1 -
KTNEHYHVPLLLSQYGYSTYRGA O85301 114 -1 -
NKGQHYHIPLLLAPYGYTTYRGS O74492 102 -2 -