Fatty acid synthase (FASN) is one of the most dramatic examples of multiple enzymatic activities encoded in a single polypeptide. Some of its domains have been found in separate mitochondrial proteins. Fatty acid oxidation also provides examples of proteins with separate and fused domains encoding different activities.
In some cases, domains with very different functions are found in a single protein. One interesting case is YARS, the cytoplasmic tyrosyl-tRNA synthetase. In addition to its familiar function in translation, it contains a domain also found in a protein that is a cytokine precursor.
Protein kinase domains are found in proteins that vary greatly in structure. An extreme example is the kinase domain in TTN (titin; also several other isoforms; see Muscle), the largest human protein. Although such domains are generally easy to locate by sequence similarity, largely unrelated sequences may have similar types of activities, as is observed with the RIO kinases.
One of the most interesting and complex examples of duplications involves the ubiquitin genes. This family includes genes encoding proteins with exact duplications of the ubiquitin protein sequence, fusions to other genes that encode identical protein sequences in their ubiquitin domains, and additional family members with related domains.
The ATP-binding cassette family includes half transporters that require dimerization for function and larger proteins that contain an internal duplicated region.
Duplicated regions are seen in many other types of proteins. One interesting case is the terminal duplication in pleckstrin (see Inositol Pathways). MUC16 (see Mucins) contains a large tandem array of a sequence not found in other proteins. The sequence of EML5 (see Tubulin and Microtubules) is essentially a triplication of another family member.
The human genome contains multiple calmodulin genes that encode identical proteins. In addition to calmodulin, many other proteins have calmodulin-related domains. These domains are found in different parts of proteins (see Calmodulin and Calcium).
An interesting case is the sterol-binding regions in proteins with diverse functions (see Cholesterol Biosynthesis). Related sequences are present in an enzyme, a chaperone, a cholesterol trafficking protein, and others.
Some protein domains are associated with modifications to specific residues of the proteins. One example is the vitamin-K-dependent modification of glutamates in coagulation factors and related proteins.
Although a protein domain may be generally associated with a family of proteins with related functions, it also may be found in proteins with very different functions. One such example is the hemopexin-related proteins.
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See also the additional reading for this chapter.