| 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. HE, X.M. AND CARTER, D.C.
Atomic structure and chemistry of human serum albumin.
NATURE 358 209-215 (1992).
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| 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. 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.
The 3D structure of human serum albumin has been determined by X-ray
crystallography to a resolution of 2.8A [4]. It comprises three homologous
domains that assemble to form a heart-shaped molecule [4]. Each domain is a
product of two subdomains that possess common structural motifs [4]. The
principal regions of ligand binding to human serum albumin are located in
hydrophobic cavities in subdomains IIA and IIIA, which exhibit similar
chemistry. Structurally, the serum albumins are similar, each domain
containing five or six internal disulphide bonds, as shown schematically
below:
+---+ +----+ +-----+
| | | | | |
xxCxxxxxxxxxxxxxxxxCCxxCxxxxCxxxxxCCxxxCxxxxxxxxxCxxxxxxxxxxxxxxCCxxxxCxxxx
| | | | | |
+-----------------+ +-----+ +---------------+
SERUMALBUMIN is a 7-element fingerprint that provides a signature for the
serum albumin family. The fingerprint was derived from an initial alignment
of 15 sequences: the motifs were drawn from short conserved regions spanning
the central portion of the alignment - motifs 1-3 lie in the first domain;
motifs 4-6 lie in the second domain; and motif 7 lies in the third domain.
Two iterations on OWL29.6 were required to reach convergence, at which point
a true set comprising 35 sequences was identified. Several partial matches
were also found, all of which are either fragments or serum albumin proteins
that fail to match one or more motifs.
An update on SPTR37_9f identified a true set of 27 sequences, and 1
partial match.
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