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PR00803

Identifier
AFETOPROTEIN  [View Relations]  [View Alignment]  
Accession
PR00803
No. of Motifs
7
Creation Date
13-FEB-1998  (UPDATE 02-FEB-2009)
Title
Alpha-fetoprotein signature
Database References
PRINTS; PR00802 SERUMALBUMIN
PROSITE; PS00212 ALBUMIN
PFAM; PF00273 Serum_albumin
PRODOM; PD002486
INTERPRO; IPR000264; IPR001703; IPR014760
MIM; 104150
Literature References
1. HAEFLIGER, D.N., MOSKAITIS, J.E., SCHOENBERG, D.R. AND WAHLI, W.
Amphibian albumins as members of the albumin, alpha-fetoprotein, 
vitamin-D-binding protein multigene family.
J.MOL.EVOL. 29 344-354 (1989).
 
2. SCHOENTGEN, F., METZ-BOUTIGUE, M.-H., JOLLES, J., CONSTANS, J.
AND JOLLES, P.
Complete amino-acid sequence of human vitamin-D-binding protein (group-
specific component) - evidence of a 3-fold internal homology as in serum-
albumin and alpha-fetoprotein.
BIOCHIM.BIOPHYS.ACTA 871 189-198 (1986).
 
3. LICHENSTEIN, H.S., LYONS, D.E., WURFEL, M.M., JOHNSON, D.A.,
MCGINLEY, M.D., LEIDLI, J.C., TROLLINGER, D.B., MAYER, J.P., WRIGHT, S.D.
AND ZUKOWSKI, M.M.
Afamin is a new member of the albumin, alpha-fetoprotein, and 
vitamin-D-binding protein gene family.
J.BIOL.CHEM. 269 18149-18154 (1994).
 
4. AOYAGI, Y., IKENAKA, T. AND ICHIDA, F.
Copper(II)-binding ability of human alpha-fetoprotein. 
CANCER RES. 38 3483-3486 (1978). 
 
5. AOYAGI, Y., IKENAKA, T. AND ICHIDA, F.
Alpha-fetoprotein as a carrier protein in plasma and its bilirubin-binding
ability.
CANCER RES. 39 3571-3574 (1979).
 
6. YACHNIN, S., HSU, R., HEINRIKSON, R.L. AND MILLER, J.B.
Studies on human alpha-fetoprotein. isolation and characterization of
monomeric and polymeric forms and amino-terminal sequence analysis. 
BIOCHIM.BIOPHYS.ACTA 493 418-428 (1977). 
 
7. MORINAGA, T., SAKAI, M., WEGMANN, T.G. AND TAMAOKI, T.
Primary structures of human alpha-fetoprotein and its mRNA.
PROC.NATL.ACAD.SCI.U.S.A. 80 4604-4608 (1983).
 
8. PUCCI, P., SICILIANO, R., MALORNI, A., MARINO, G., TECCE, M.F., 
CECCARINI, C. AND TERRANA, B.
Human alpha-fetoprotein primary structure: a mass spectrometric study. 
BIOCHEMISTRY 30 5061-5066 (1991). 

Documentation
A number of serum transport proteins are known to be evolutionarily related, 
including albumin, alpha-fetoprotein, vitamin D-binding protein and afamin
[1-3]. Albumin is the main protein of plasma; it binds water, cations (such
as Ca++, Na+ and  K+), fatty acids, hormones, bilirubin and drugs - its 
main gd; function is to regulate the colloidal osmotic pressure of blood. 
Vitamin D-binding protein binds to vitamin D and its metabolites, as well 
as to fatty acids. The biological role of afamin (alpha-albumin) has not 
yet been characterised.
 
Alpha-fetoprotein (AFP) (alpha-fetoglobulin) is a foetal plasma protein
that binds various cations, fatty acids and bilirubin [4,5]. The protein
appears in the plasma of 4-week old fetuses, reaches its highest levels in
the 12th-16th week of gestation, dropping to trace amounts after birth. It
is also found at high levels in the plasma and ascitic fluid of adults with
hepatoma [6]. 
 
The amino acid sequence contains a 19-amino acid signal peptide [7], and a 
591-residue mature protein [8]. Fifteen regularly-spaced disulphide bridges
generate a 3-domain folding structure, each domain containing ~190 amino
acids, with 5 or 6 internal disulphide bonds, as shown schematically below.
Sequence comparisons indicate that the greatest level of conservation 
resides in domain 3 and the lowest in domain 1 [4]. 
 
                   +---+          +----+                        +-----+
                   |   |          |    |                        |     |
xxCxxxxxxxxxxxxxxxxCCxxCxxxxCxxxxxCCxxxCxxxxxxxxxCxxxxxxxxxxxxxxCCxxxxCxxxx
  |                 |       |     |              |               |
  +-----------------+       +-----+              +---------------+
 
 
In addition to the monomeric form of AFP, dimeric and trimeric forms occur,
which dissociate only on exposure to disulphide-reducing reagents,
suggesting that polymer formation is mediated by inter-molecular disulphide
bond formation [6]. 
 
AFETOPROTEIN is an 7-element fingerprint that provides a signature for
alpha-fetoglobulins. The fingerprint was derived from an initial alignment
of 5 sequences: the motifs were drawn from conserved sections spanning 
the full length of the mature protein, focusing on those regions that
characterise the AFPs but distinguish them from related serum albumins -
motifs 1-3 lie in the first internal domain; motifs 4 and 5 lie in the
second domain; motif 6 lies in the third domain; and motif 7 resides at
the C-terminus. Two iterations on SPTR55_38f were required to reach 
convergence, at which point a true set comprising 13 sequences was 
identified.
Summary Information
13 codes involving  7 elements
0 codes involving 6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
713131313131313
60000000
50000000
40000000
30000000
20000000
1234567
True Positives
FETA_BOVIN    FETA_CANFA    FETA_GORGO    FETA_HORSE    
FETA_HUMAN FETA_MOUSE FETA_PIG FETA_RAT
Q28789 Q4QR90_RAT Q7TSF3_MARMO Q8BK56_MOUSE
Q8BK65_MOUSE
Sequence Titles
FETA_BOVIN  Alpha-fetoprotein precursor (Alpha-fetoglobulin) (Alpha-1- fetoprotein) - Bos taurus (Bovine). 
FETA_CANFA Alpha-fetoprotein precursor (Alpha-fetoglobulin) (Alpha-1- fetoprotein) - Canis familiaris (Dog).
FETA_GORGO Alpha-fetoprotein precursor (Alpha-fetoglobulin) (Alpha-1- fetoprotein) - Gorilla gorilla gorilla (Lowland gorilla).
FETA_HORSE Alpha-fetoprotein precursor (Alpha-fetoglobulin) (Alpha-1- fetoprotein) - Equus caballus (Horse).
FETA_HUMAN Alpha-fetoprotein precursor (Alpha-fetoglobulin) (Alpha-1- fetoprotein) - Homo sapiens (Human).
FETA_MOUSE Alpha-fetoprotein precursor (Alpha-fetoglobulin) (Alpha-1- fetoprotein) - Mus musculus (Mouse).
FETA_PIG Alpha-fetoprotein precursor (Alpha-fetoglobulin) (Alpha-1- fetoprotein) - Sus scrofa (Pig).
FETA_RAT Alpha-fetoprotein precursor (Alpha-fetoglobulin) (Alpha-1- fetoprotein) - Rattus norvegicus (Rat).
Q28789 ALPHA-FETOPROTEIN PRECURSOR - PAN TROGLODYTES (CHIMPANZEE).
Q4QR90_RAT Alpha-fetoprotein - Rattus norvegicus (Rat).
Q7TSF3_MARMO Alpha-fetoprotein - Marmota monax (Woodchuck).
Q8BK56_MOUSE 18 days pregnant adult female placenta and extra embryonic tissue cDNA, RIKEN full-length enriched library, clone:3830429G18 product:ALPHA-FETOPROTEIN, full insert sequence - Mus musculus (Mouse).
Q8BK65_MOUSE 11 days embryo whole body cDNA, RIKEN full-length enriched library, clone:2700028A11 product:ALPHA-FETOPROTEIN, full insert sequence - Mus musculus (Mouse).
Scan History
OWL29_6    2  100  NSINGLE    
SPTR37_9f 2 10 NSINGLE
SPTR55_38f 2 300 NSINGLE
Initial Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
HRNEYGIASILDSYQCTAE FETA_HUMAN 22 22 -
HRNEYGIASILDSYQCTAE FETA_GORGO 22 22 -
HENEFGIASTLDSSQCVTE FETA_MOUSE 22 22 -
HSNAYGIASALDSFQCSPE FETA_HORSE 22 22 -
HTNEFGIESTLDSSQCPTE FETA_RAT 28 28 -

Motif 2 width=16
Element Seqn Id St Int Rpt
FLEELCHEKEILEKYG FETA_HUMAN 94 53 -
FLEELCHEKEILEKYG FETA_GORGO 94 53 -
FLDEICHETELSNKYG FETA_MOUSE 90 49 -
FLEEICHEEEIPEKYG FETA_HORSE 94 53 -
FLDEICHETELSNKYG FETA_RAT 96 49 -

Motif 3 width=22
Element Seqn Id St Int Rpt
KAENAVECFQTKAATVTKELRE FETA_HUMAN 194 84 -
KAENAVECFQTKAATVTKELRE FETA_GORGO 194 84 -
KADNKEECFQTKRASIAKELRE FETA_MOUSE 190 84 -
KSENAVECFQSKAATITKELRE FETA_HORSE 194 84 -
KADNMEECFQTKRASMAKELRE FETA_RAT 196 84 -

Motif 4 width=17
Element Seqn Id St Int Rpt
CIIHAENDEKPEGLSPN FETA_HUMAN 313 97 -
CIIHAENDEKPEGLSPN FETA_GORGO 313 97 -
CIIHAENGVKPEGLSLN FETA_MOUSE 309 97 -
CIIHAENDDKPEGLSPN FETA_HORSE 313 97 -
CIIHAENGDKPEGLTLN FETA_RAT 315 97 -

Motif 5 width=19
Element Seqn Id St Int Rpt
LGDRDFNQFSSGEKNIFLA FETA_HUMAN 334 4 -
LGDRDFNQFSSGEKNIFLA FETA_GORGO 334 4 -
LGDRNFAQFSSEEKIMFMA FETA_MOUSE 330 4 -
LGERDFNQFSSKEKDLFMA FETA_HORSE 334 4 -
LGDRNFAQFSSEEKLLFMA FETA_RAT 336 4 -

Motif 6 width=17
Element Seqn Id St Int Rpt
QAQGVALQTMKQEFLIN FETA_HUMAN 539 186 -
QAQGVALQTMKQEFLIN FETA_GORGO 539 186 -
QAQGKALQTMKQELLIN FETA_MOUSE 535 186 -
QAQGVALQTMKQQFLIN FETA_HORSE 539 186 -
QAQGRALQTMKQELLIN FETA_RAT 541 186 -

Motif 7 width=14
Element Seqn Id St Int Rpt
EGQKLISKTRAALG FETA_HUMAN 595 39 -
EGQKLISKTRTALG FETA_GORGO 595 39 -
EGPKLISKTRDALG FETA_MOUSE 591 39 -
EGPQLISKTRAALG FETA_HORSE 595 39 -
EGPKLISKTREALG FETA_RAT 597 39 -
Final Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
HRNEYGIASILDSYQCTAE FETA_HUMAN 22 22 -
HRNAYGIASILDSSQCSAE FETA_CANFA 22 22 -
HRNEYGIASILDSYQCTAE FETA_GORGO 22 22 -
HRNEYGIASILDSYQCTAE Q28789 22 22 -
HENEFGIASTLDSSQCVTE FETA_MOUSE 22 22 -
HENEFGIASTLDSSQCVTE Q8BK56_MOUSE 22 22 -
HENAYGIASILDSSQCSAE FETA_PIG 22 22 -
HENEFGIASTLDSSQCVTE Q8BK65_MOUSE 22 22 -
HNNAYGIASTLDSSQCSAE Q7TSF3_MARMO 22 22 -
HSNAYGIASALDSFQCSPE FETA_HORSE 22 22 -
HTNEFGIESTLDSSQCPTE FETA_RAT 28 28 -
HTNEFGIESTLDSSQCPTE Q4QR90_RAT 28 28 -
HKNAYGIDSILDSSPCSSG FETA_BOVIN 22 22 -

Motif 2 width=16
Element Seqn Id St Int Rpt
FLEELCHEKEILEKYG FETA_HUMAN 94 53 -
FLEEICHEKEISEKYG FETA_CANFA 94 53 -
FLEELCHEKEILEKYG FETA_GORGO 94 53 -
FLEELCREKEILEKYG Q28789 94 53 -
FLDEICHETELSNKYG FETA_MOUSE 90 49 -
FLDEICHETELSNKYG Q8BK56_MOUSE 90 49 -
FLEEICHEEEIPEKYG FETA_PIG 94 53 -
FLDEICHETELSNKYG Q8BK65_MOUSE 90 49 -
FLEEICHEKEIFEKYG Q7TSF3_MARMO 94 53 -
FLEEICHEEEIPEKYG FETA_HORSE 94 53 -
FLDEICHETELSNKYG FETA_RAT 96 49 -
FLDEICHETELFNKYG Q4QR90_RAT 96 49 -
FLEEICREKEIPEKYG FETA_BOVIN 94 53 -

Motif 3 width=22
Element Seqn Id St Int Rpt
KAENAVECFQTKAATVTKELRE FETA_HUMAN 194 84 -
KAENAVECFQTKTSLITKELRE FETA_CANFA 194 84 -
KAENAVECFQTKAATVTKELRE FETA_GORGO 194 84 -
KAENAVECFQTKAATVTKELRE Q28789 194 84 -
KADNKEECFQTKRASIAKELRE FETA_MOUSE 190 84 -
KADNKEECFQTKRASIAKELRE Q8BK56_MOUSE 190 84 -
KAENAVECFQTKAASITKELRE FETA_PIG 194 84 -
KADNKEECFQTKRASIAKELRE Q8BK65_MOUSE 190 84 -
KAENAAECFQTKTASITKELKE Q7TSF3_MARMO 193 83 -
KSENAVECFQSKAATITKELRE FETA_HORSE 194 84 -
KADNMEECFQTKRASMAKELRE FETA_RAT 196 84 -
KADNMEECFQTKRASMAKELRE Q4QR90_RAT 196 84 -
KAENATECFETKVTSITKELRE FETA_BOVIN 194 84 -

Motif 4 width=17
Element Seqn Id St Int Rpt
CIIHAENDEKPEGLSPN FETA_HUMAN 313 97 -
CIIHAENDGKPEGLSPN FETA_CANFA 313 97 -
CIIHAENDEKPEGLSPN FETA_GORGO 313 97 -
CIIHAENDEKPEGLSPN Q28789 313 97 -
CIIHAENGVKPEGLSLN FETA_MOUSE 309 97 -
CIIHAENGVKPEGLSLN Q8BK56_MOUSE 309 97 -
CIIHAENDDKPEGLSPN FETA_PIG 314 98 -
CIIHAENGVKPEGLSLN Q8BK65_MOUSE 309 97 -
CIIHAENDDKPEGLSPT Q7TSF3_MARMO 312 97 -
CIIHAENDDKPEGLSPN FETA_HORSE 313 97 -
CIIHAENGDKPEGLTLN FETA_RAT 315 97 -
CIIHAENGDKPEGLTLN Q4QR90_RAT 315 97 -
CIIHAENDDKPEGLSPN FETA_BOVIN 314 98 -

Motif 5 width=19
Element Seqn Id St Int Rpt
LGDRDFNQFSSGEKNIFLA FETA_HUMAN 334 4 -
LEERDFNQFSSREKDLFMA FETA_CANFA 334 4 -
LGDRDFNQFSSGEKNIFLA FETA_GORGO 334 4 -
LGDRDFNQFSSGEKNIFLA Q28789 334 4 -
LGDRNFAQFSSEEKIMFMA FETA_MOUSE 330 4 -
LGDRNFAQFSSEEKIMFMA Q8BK56_MOUSE 330 4 -
LGERDFNQLSSREKDLSMA FETA_PIG 335 4 -
LGDRNFAQFSSEEKIMFMA Q8BK65_MOUSE 330 4 -
LGDRDFNQFSSAERNIFLA Q7TSF3_MARMO 333 4 -
LGERDFNQFSSKEKDLFMA FETA_HORSE 334 4 -
LGDRNFAQFSSEEKLLFMA FETA_RAT 336 4 -
LGDRNFAQFSSEEKLLFMA Q4QR90_RAT 336 4 -
LGDRDFNQLSSRDKDLSMA FETA_BOVIN 335 4 -

Motif 6 width=17
Element Seqn Id St Int Rpt
QAQGVALQTMKQEFLIN FETA_HUMAN 539 186 -
QAQGVALQTMKQQFLIN FETA_CANFA 539 186 -
QAQGVALQTMKQEFLIN FETA_GORGO 539 186 -
QAQGVALQTMKQEFLIN Q28789 539 186 -
QAQGKALQTMKQELLIN FETA_MOUSE 535 186 -
QAQGKALQTMKQELLIN Q8BK56_MOUSE 535 186 -
QAQGVALQTMKQQFLIN FETA_PIG 540 186 -
QAHGKALQTMKQELLIN Q8BK65_MOUSE 535 186 -
QPQGVALQTMKQEFLIN Q7TSF3_MARMO 538 186 -
QAQGVALQTMKQQFLIN FETA_HORSE 539 186 -
QAQGRALQTMKQELLIN FETA_RAT 541 186 -
QAQGRALQTMKQELLIN Q4QR90_RAT 541 186 -
QVQGVPLQTMKQQFLIN FETA_BOVIN 540 186 -

Motif 7 width=14
Element Seqn Id St Int Rpt
EGQKLISKTRAALG FETA_HUMAN 595 39 -
EGPKLISKTRAALG FETA_CANFA 595 39 -
EGQKLISKTRTALG FETA_GORGO 595 39 -
EGQKLISKTRAALG Q28789 595 39 -
EGPKLISKTRDALG FETA_MOUSE 591 39 -
EGPKLISKTRDALG Q8BK56_MOUSE 591 39 -
EGPALISKTRASLG FETA_PIG 596 39 -
EGPKLISKTRDALG Q8BK65_MOUSE 591 39 -
EGPKLISKTRDALG Q7TSF3_MARMO 594 39 -
EGPQLISKTRAALG FETA_HORSE 595 39 -
EGPKLISKTREALG FETA_RAT 597 39 -
EGPKLISKTREALG Q4QR90_RAT 597 39 -
EGPALISKTRAALG FETA_BOVIN 596 39 -