Global versus Local Hubs in Human Protein–Protein Interaction Network

In
this study, we have constructed tissue-specific protein–protein
interaction networks for 70 human tissues and have identified three
types of hubs based on their expression breadths: (a) tissue-specific
hubs (TSHs) (proteins that are expressed in ≤ 10 tissues and
also form hubs in ≤ 10 tissues), (b) tissue-preferred hubs
(TPHs) (proteins expressed in ≥ 60 tissues but are highly connected
in ≤ 10 tissues), and (c) housekeeping hubs (HKHs) (proteins
that are expressed in ≥ 60 tissues and also form hubs in ≥
60 tissues). Comparative analyses revealed significant differences
between TSHs and HKHs and also revealed that TPHs behave more like
HKHs. TSHs are lengthier, more disordered, and also quickly evolving
proteins as compared with HKHs. Despite having a similar number of
binding surfaces and interacting domains, TSHs are associated with
a lower degree of centrality as compared with HKHs, suggesting that
TSHs are “unsaturated” with regard to their binding
capability and are perhaps evolving with regard to their interactions.
TSHs are less abundantly expressed as compared with HKHs and are enriched
with PEST motifs, indicating their tight regulation. All of these
properties of TSHs and HKHs correlate with their distinct functional
roles; TSHs are involved in tissue-specific functional roles, viz.,
secretors, receptors, and signaling proteins, whereas HKHs are involved
in core-cellular functions such as transcription, translation, and
so on. Our study, therefore, brings forth a clear and distinct classification
of hubs simply based on their expression breadth and further assumes
significance in the light of the highly debated dichotomy of date
and party hubs, which is based on the coexpression pattern of hubs
with their partners.