PROSITE documentation PDOC00499
Avidin-like domain signature and profile


Avidin [1] is a minor constituent of egg white in several groups of oviparous vertebrates. Avidin, which was discovered in the 1920's, takes its name from the avidity with which it binds biotin. These two molecules bind so strongly that it is highly difficult to separate them. Streptavidin is a protein produced by Streptomyces avidinii which also binds biotin and whose sequence is evolutionary related to that of avidin.

Avidin and streptavidin both form homotetrameric complexes of non-covalently associated chains. Each chain forms a very strong and specific non-covalent complex with one molecule of biotin.

The dimeric avidin sub-family includes several members, all originating from different bacterial sources: rhizavidin from Rhizobium etli, shwanavidin from Shewanella denitrificans, hoefavidin from Hoeflea phototrophica DFL-43, afifavidin from Afifella pfennigii and wilavidin from a member of the class γproteobacteria. Members of the sub-family exhibit a dimeric (1-4 dimer) rather than a tetrameric structure. These proteins are characterized by the lack of the critical Trp of the tetrameric avidins but retain compensatory elements that result in remarkably high affinities toward biotin, comparable to those of the tetrameric forms. Members of the dimeric sub-family are also characterized by a conserved disulfide bridge in the vicinity of the biotin-binding site that was shown to be essential for the high affinity toward biotin [2,3,4,5].

Fibropellins I and III [6] are proteins that form the apical lamina of the sea urchin embryo, a component of the extracellular matrix. These two proteins have a modular structure composed of a CUB domain (see <PDOC00908>), followed by a variable number of EGF repeats (see <PDOC00021>) and a C-terminal avidin-like domain. The fibropellin avidin-like domain forms a homotetramer incapable of binding biotin [7].

The three-dimensional structures of streptavidin [8,9], avidin [10] and dimeric bacterial avidin [2,3,4,5] have been determined and revealed them to share a common fold: an eight stranded anti-parallel β-barrel with a repeated +1 topology enclosing an internal ligand binding site (see <PDB:1AVD>).

As a signature sequence for the avidin-like domain we selected a conserved motif located in its C-terminal section. We also developed a profile that covers the entire avidin-like domain.


It is suggested, on the basis of similarities of structure, function, and sequence, that this family forms an overall superfamily, called the calycins, with the lipocalin <PDOC00187> and the cytosolic fatty-acid binding proteins <PDOC00188> families [11,12].

Expert(s) to contact by email:

Flower D.R.

Last update:

June 2023 / Text revised.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

AVIDIN_2, PS51326; Avidin-like domain profile  (MATRIX)

AVIDIN_1, PS00577; Avidin-like domain signature  (PATTERN)


1AuthorsGreen N.M.
TitleAvidin and streptavidin.
SourceMethods Enzymol. 184:51-67(1990).
PubMed ID2388586

2AuthorsAvraham O. Meir A. Fish A. Bayer E.A. Livnah O.
TitleHoefavidin: A dimeric bacterial avidin with a C-terminal binding tail.
SourceJ. Struct. Biol. 191:139-148(2015).
PubMed ID26126731

3AuthorsAvraham O. Bayer E.A. Livnah O.
TitleCrystal structure of afifavidin reveals common features of molecular assemblage in the bacterial dimeric avidins.
SourceFEBS. J. 285:4617-4630(2018).
PubMed ID30369031

4AuthorsAvraham O. Bayer E.A. Livnah O.
TitleWilavidin - a novel member of the avidin family that forms unique biotin-binding hexamers.
SourceFEBS. J. 289:1700-1714(2022).
PubMed ID34726340

5AuthorsBana J. Warwar J. Bayer E.A. Livnah O.
TitleSelf-assembly of a dimeric avidin into unique higher-order oligomers.
SourceFEBS. J. 0:0-0(2023).
PubMed ID36853192

6AuthorsBisgrove B.W. Raff R.A.
TitleThe SpEGF III gene encodes a member of the fibropellins: EGF repeat-containing proteins that form the apical lamina of the sea urchin embryo.
SourceDev. Biol. 157:526-538(1993).
PubMed ID8500658

7AuthorsYanai I. Yu Y. Zhu X. Cantor C.R. Weng Z.
TitleAn avidin-like domain that does not bind biotin is adopted for oligomerization by the extracellular mosaic protein fibropellin.
SourceProtein. Sci. 14:417-423(2005).
PubMed ID15659374

8AuthorsHendrickson W.A. Pahler A. Smith J.L. Satow Y. Merritt E.A. Phizackerley R.P.
TitleCrystal structure of core streptavidin determined from multiwavelength anomalous diffraction of synchrotron radiation.
SourceProc. Natl. Acad. Sci. U.S.A. 86:2190-2194(1989).
PubMed ID2928324

9AuthorsPugliese L. Coda A. Malcovati M. Bolognesi M.
TitleThree-dimensional structure of the tetragonal crystal form of egg-white avidin in its functional complex with biotin at 2.7 A resolution.
SourceJ. Mol. Biol. 231:698-710(1993).
PubMed ID8515446

10AuthorsHunt L.T. Barker W.C.
TitleAvidin-like domain in an epidermal growth factor homolog from a sea urchin.
SourceFASEB J. 3:1760-1764(1989).
PubMed ID2784773

11AuthorsFlower D.R.
TitleStructural relationship of streptavidin to the calycin protein superfamily.
SourceFEBS Lett. 333:99-102(1993).
PubMed ID8224179

12AuthorsHolm L. Sander C.
TitleSearching protein structure databases has come of age.
SourceProteins 19:165-173(1994).
PubMed ID7937731

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