Nomenclature Committee of the International Union of Biochemistry (NC-IUB)

Nomenclature for multienzymes

Recommendations 1989

World Wide Web version Prepared by G. P. Moss

Department of Chemistry, Queen Mary University of London,
Mile End Road, London, E1 4NS, UK

These Rules are as close as possible to the published version [see Eur. J. Biochem., 1989, 185, 485-486; and in Biochemical Nomenclature and Related Documents, 2nd edition, Portland Press, 1992, pp 107-108; and Enzyme Nomenclature. Recommendations 1992, Academic Press, 1992, pp 562-563. Copyright IUBMB; reproduced with the permission of IUBMB]. If you need to cite these rules please quote these references as their source.

NC-IUB thanks a panel whose members were J. R. Coggins (UK, convenor), H. von Döhren (FRG), P. Friedrich (Hungary), R. N. Perham (UK), P. A. Srere (USA) and G. R. Welch (USA), for drafting these recommendations.

Any comments should be sent to any member of the Committee




Multienzyme. A protein possessing more than one catalytic function contributed by distinct parts of a polypeptide chain ('domains'), or by distinct subunits, or both.

Multienzyme complex. A multienzyme with catalytic domains on more than one type of polypeptide chain.

Multienzyme polypeptide. A polypeptide chain containing at least two types of catalytic domains.

Catalytic domain. Any part of a polypeptide chain that possesses a catalytic function. It may contain more than one structural domain.


l. Catalytic functions due to distinct domains may be called 'autonomous'.

2. Multienzyme polypeptides may themselves be components of multienzyme complexes.

3. The definitions may be illustrated by giving criteria that may be used to designate a given system as multienzyme polypeptide:

a) They exclude single enzymes that can catalyse different reactions using the same catalytic centre.

b) They exclude regulatory ligand-binding domains, as the definition demands multiple catalytic functions.

c) Two or more catalytic domains must be demonstrated on a single polypeptide chain: this implies distinct domains for the different catalytic functions. Methods used for this include active-site labelling. followed by peptide mapping or gel electrophoresis in the presence of sodium dodecyl sulfate, and limited proteolysis (as most known multienzyme polypeptides contain domains joined by peptidase-sensitive linker regions).

d) Genetic methods should also be used to demonstrate that a single gene encodes several autonomous functional protein domains.


There may be contexts where symbols are required to indicate the nature of domains and the types and strengths of interactions between them. For these, the following system, which is modified from that of von Döhren [1], may be used. It should be used with caution and with a clear statement of the structural meaning intended, because there may not be clear dividing lines between the degrees of strength of association between protein subunits. Catalytic domains are given upper-case letters from early in the alphabet, A, B, C, ...; substrate-carrier domains are given upper-case letters from late in the alphabet, P, Q, R, . ..; regulatory domains are given lower-case letters from early in the alphabet, a, b, c, ...; domains of unknown function may be given lower-case letters from late in the alphabet, x, y, z, ... Domains in the same polypeptide chain are placed within the same pair of parentheses, so that (ABC) represents a multienzyme polypeptide, whereas (A)(B)(C) represents a multienzyme complex. If these letters are assigned to particular functions, then (ABC) indicates that A, B and C occur in the sequence in that order, whereas (A, B, C) is used when the order is not known.

Thus mammalian aldolase would be symbolyzed as (A)4, tryptophan synthase from Escherichia coli as (A)2(B)2, and the arom multienzyme polypeptide of Neurospora crassa as (ABCDE)2 (i.e. enzymes EC, EC EC, EC and EC

Brackets of the type {} may be used to indicate stable association, so that portraying (A)2(B)2 as {(A)2(B)2} indicates that the association is stable, whereas portraying it as {(A)(B)}2 indicates that each A chain binds one B chain tightly but that the two {(A)(B)} units are more loosely associated.


1. von Döhren, H. (1980) Trends Biochem. Sci. 5(3), VIII.

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