%X As a result of the genome sequencing and structural genomics initiatives, we have a wealth of protein sequence and structural data. However, only about 1% of these proteins have experimental functional annotations. As a result, computational approaches that can predict protein functions are essential in bridging this widening annotation gap. This article reviews the current approaches of protein function prediction using structure and sequence based classification of protein domain family resources with a special focus on functional families in the CATH-Gene3D resource. %L discovery1471540 %O Copyright © 2015 Elsevier B.V. This manuscript is made available under a Creative Commons Attribution Non-commercial Non-derivative 4.0 International license (CC BY-NC-ND 4.0). This license allows you to share, copy, distribute and transmit the work for personal and non-commercial use providing author and publisher attribution is clearly stated. Further details about CC BY licenses are available at http://creativecommons.org/ licenses/by/4.0. Access may be initially restricted by the publisher. %J Methods %A S Das %A CA Orengo %V 93 %P 24-34 %K Moonlighting protein, Protein classification, Protein family, Protein function annotation, Protein function prediction %T Protein function annotation using protein domain family resources %D 2016