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PR00804

Identifier
VITAMNDBNDNG  [View Relations]  [View Alignment]  
Accession
PR00804
No. of Motifs
9
Creation Date
10-FEB-1998  (UPDATE 07-JUN-1999)
Title
Vitamin D-binding protein signature
Database References
PRINTS; PR00802 SERUMALBUMIN
INTERPRO; IPR000213
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. COOKE, N.E.
rat vitaminD binding protein. determination of the full-length primary 
structure from cloned cDNA. 
J.BIOL.CHEM. 261 3441-3450 (1986). 

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
function is to regulate the colloidal osmotic pressure of blood. Alphafeto-
protein (alpha-fetoglobulin) is a foetal plasma protein that binds various
cations, fatty acids and bilirubin. The biological role of afamin 
(alpha-albumin) has not yet been characterised.
 
Vitamin D-binding protein (DBP) is an abundant serum glycoprotein secreted
by the liver; the protein transports vitamin D sterols, binds to actin, and 
is found on the surface of B-lymphocytes and subpopulations of T-lymphocytes
[4]. The full length DBP contains 476-amino acids, including a 16-amino
acid signal sequence. Sequence analysis reveals 23% similarity to albumin
and to alpha-fetoprotein [4]. DBP contains a characteristic placement of
cysteine residues, identical to that in albumin, suggesting a similar
folding structure. Albumin and alpha-fetoprotein contain three internally
repeated domains [4]. DBP shows similarity to the first two domains and
has a truncated third domain, supporting the view that DBP is a member of
the albumin/alpha-fetoprotein multigene family [4]. 
 
Within the sequence, regularly-spaced disulphide bridges generate a 3-domain
folding structure, each domain containing ~170 amino acids, with 5 or 6
internal disulphide bonds, as shown schematically below: 
 
                   +---+          +----+                        +-----+
                   |   |          |    |                        |     |
xxCxxxxxxxxxxxxxxxxCCxxCxxxxCxxxxxCCxxxCxxxxxxxxxCxxxxxxxxxxxxxxCCxxxxCxxxx
  |                 |       |     |              |               |
  +-----------------+       +-----+              +---------------+
 
 
VITAMNDBNDNG is a 9-element fingerprint that provides a signature for
vitamin D-binding proteins. The fingerprint was derived from an initial
alignment of 3 sequences: the motifs were drawn from conserved regions
spanning virtually the full alignment length, focusing on those sections
that characterise the DBPs but distinguish them from related serum albumins
- motifs 1-5 lie in the first repeat; motifs 6 and 7 lie in the second 
repeat; and motifs 8 and 9 reside in the third repeat. Two iterations on 
OWL29.6 were required to reach convergence, at which point a true set
comprising 7 sequences was identified.
 
An update on SPTR37_9f identified a true set of 3 sequences.
Summary Information
3 codes involving  9 elements
0 codes involving 8 elements
0 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
9333333333
8000000000
7000000000
6000000000
5000000000
4000000000
3000000000
2000000000
123456789
True Positives
VTDB_HUMAN    VTDB_RABIT    VTDB_RAT      
Sequence Titles
VTDB_HUMAN  VITAMIN D-BINDING PROTEIN PRECURSOR (DBP) (GROUP-SPECIFIC COMPONENT) (GC-GLOBULIN) (VDB) - HOMO SAPIENS (HUMAN). 
VTDB_RABIT VITAMIN D-BINDING PROTEIN PRECURSOR (DBP) (GROUP-SPECIFIC COMPONENT) (GC-GLOBULIN) (VDB) - ORYCTOLAGUS CUNICULUS (RABBIT).
VTDB_RAT VITAMIN D-BINDING PROTEIN PRECURSOR (DBP) (GROUP-SPECIFIC COMPONENT) (GC-GLOBULIN) (VDB) - RATTUS NORVEGICUS (RAT).
Scan History
OWL29_6    2  50   NSINGLE    
SPTR37_9f 2 4 NSINGLE
Initial Motifs
Motif 1  width=18
Element Seqn Id St Int Rpt
GHALERGRDYEKNKVCKE VTDB_HUMAN 14 14 -
GHALERGRDYEKDKVCKE VTDB_RABIT 14 14 -
GHALERGRDYEKDKVCNE VTDB_MOUSE 10 10 -

Motif 2 width=18
Element Seqn Id St Int Rpt
LGKEDFRSLSLILYSRKF VTDB_MOUSE 31 3 -
LGKEDFTSLSLVLYSRKF VTDB_HUMAN 35 3 -
LGKDDFRTLSLVLYSRKF VTDB_RABIT 35 3 -

Motif 3 width=21
Element Seqn Id St Int Rpt
YDNRTSALSATSCESDSPFPV VTDB_RABIT 84 31 -
YDTRTSELSVKSCESDAPFPV VTDB_MOUSE 80 31 -
YDTRTSALSAKSCESNSPFPV VTDB_HUMAN 84 31 -

Motif 4 width=15
Element Seqn Id St Int Rpt
PQEFPTYVEPANDEI VTDB_RABIT 130 25 -
PQEFPTYVEPTNDEI VTDB_HUMAN 130 25 -
PQEFPTYVEPTNDEI VTDB_MOUSE 126 25 -

Motif 5 width=20
Element Seqn Id St Int Rpt
EYSTNYGQAPLSLLVSYTKS VTDB_HUMAN 162 17 -
EYSSNYGQAPLPLLVAYTKN VTDB_MOUSE 158 17 -
EYSSNYGQAPLPILVSYTKS VTDB_RABIT 162 17 -

Motif 6 width=18
Element Seqn Id St Int Rpt
KERLQLKHLSLLTTLSNR VTDB_HUMAN 201 19 -
KERLQMKHLSLLTTMSNR VTDB_MOUSE 197 19 -
KERLQIKHLSLLTTLSNR VTDB_RABIT 201 19 -

Motif 7 width=18
Element Seqn Id St Int Rpt
ESTSEDCMASELPEHTIK VTDB_MOUSE 263 48 -
ESTSEDCMAKELPEHTVK VTDB_RABIT 267 48 -
ESASEDCMAKELPEHTVK VTDB_HUMAN 267 48 -

Motif 8 width=23
Element Seqn Id St Int Rpt
FIEKGQEMCADYSENTFTEYKKK VTDB_MOUSE 395 114 -
FIDKGQELCAGYSENTFTEYKKK VTDB_RABIT 399 114 -
FIDKGQELCADYSENTFTEYKKK VTDB_HUMAN 399 114 -

Motif 9 width=16
Element Seqn Id St Int Rpt
KHSDFASKCCSINSPP VTDB_MOUSE 440 22 -
KRSDFASNCCSINSPP VTDB_HUMAN 444 22 -
KHSDFASKCCSINSPP VTDB_RABIT 444 22 -
Final Motifs
Motif 1  width=18
Element Seqn Id St Int Rpt
GHALERGRDYEKDKVCKE VTDB_RABIT 14 14 -
GHALERGRDYEKNKVCKE VTDB_HUMAN 14 14 -
GHALERGRDYEKDKVCQE VTDB_RAT 14 14 -

Motif 2 width=18
Element Seqn Id St Int Rpt
LGKDDFRTLSLVLYSRKF VTDB_RABIT 35 3 -
LGKEDFTSLSLVLYSRKF VTDB_HUMAN 35 3 -
LGKDDFRSLSLILYSRKF VTDB_RAT 35 3 -

Motif 3 width=21
Element Seqn Id St Int Rpt
YDNRTSALSATSCESDSPFPV VTDB_RABIT 84 31 -
YDTRTSALSAKSCESNSPFPV VTDB_HUMAN 84 31 -
YDTRTSELSIKSCESDAPFPV VTDB_RAT 84 31 -

Motif 4 width=15
Element Seqn Id St Int Rpt
PQEFPTYVEPANDEI VTDB_RABIT 130 25 -
PQEFPTYVEPTNDEI VTDB_HUMAN 130 25 -
PQEFPAYVEPTNDEI VTDB_RAT 130 25 -

Motif 5 width=20
Element Seqn Id St Int Rpt
EYSSNYGQAPLPILVSYTKS VTDB_RABIT 162 17 -
EYSTNYGQAPLSLLVSYTKS VTDB_HUMAN 162 17 -
EYSSNYGQAPLPLLVGYTKS VTDB_RAT 162 17 -

Motif 6 width=18
Element Seqn Id St Int Rpt
KERLQIKHLSLLTTLSNR VTDB_RABIT 201 19 -
KERLQLKHLSLLTTLSNR VTDB_HUMAN 201 19 -
KERLQMKQLLLLTTMSNR VTDB_RAT 201 19 -

Motif 7 width=18
Element Seqn Id St Int Rpt
ESTSEDCMAKELPEHTVK VTDB_RABIT 267 48 -
ESASEDCMAKELPEHTVK VTDB_HUMAN 267 48 -
KSTSEDCMARELPEHTLK VTDB_RAT 267 48 -

Motif 8 width=23
Element Seqn Id St Int Rpt
FIDKGQELCAGYSENTFTEYKKK VTDB_RABIT 399 114 -
FIDKGQELCADYSENTFTEYKKK VTDB_HUMAN 399 114 -
FIEKGQEMCADYSENTFTEYKKK VTDB_RAT 399 114 -

Motif 9 width=16
Element Seqn Id St Int Rpt
KHSDFASKCCSINSPP VTDB_RABIT 444 22 -
KRSDFASNCCSINSPP VTDB_HUMAN 444 22 -
KHSDFASKCCSINSPP VTDB_RAT 444 22 -