Protein-Protein Interaction Analysis of Human
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Open Access Original Article Functional Interactions of IFNAR-2 Within Biological Networks Pak Armed Forces Med J 2020; 70 (1): 245-52 PROTEIN-PROTEIN INTERACTION ANALYSIS OF HUMAN INTERFERON ALPHA RECEPTOR 2 (IFNAR-2) PROTEIN USING STRING SERVER Gulshan Ara Trali, Ambreen Javed*, Alia Sadiq* Swat Medical College, Swat Pakistan, *HITEC-Institute of Medical Sciences, Taxila/National University of Medical Sciences (NUMS) Pakistan ABSTRACT Objective: To study the functional and molecular interactions of IFNAR-2 within biological networks Study Design: Computational analysis: STRING software Place and Duration of Study: Department of Biochemistry, HITEC-Institute of Medical Sciences, Taxila Cantt, Pakistan, from Dec 2017 to Jun 2018. Methodology: Protein sequence of IFNAR-2 protein was obtained from ‘National Centre for Biotechnology Information (NCBI)’ database and STRING analysis conducted by applying specific parameters including (1) Text mining (2) Experiments (3) Databases (4) Co-expression (5) Neighborhood (6) Gene fusion and (7) Co-occurrence for identifying protein-protein interactions and molecular associations. Maximum number of interactors was set at 20 and highest confidence level was set at 0.900. Results: Protein-protein interaction analysis translate that human IFNAR-2 protein has high level of interactions with a set of proteins of similar size, drawn from the genome. This set represents a partial biologically connected group of proteins. This information has a potential to set the basis for further experimental investigations in more integrated and biologically linked pathway-oriented perspective that results in more targeted outcomes. Conclusion: Functional and molecular enrichment through STRING analysis revealed that IFNAR-2 protein has strong associations and serves as a key player in antiviral response of immune system. Keywords: IFNAR-2 protein, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Protein- protein interactions, Molecular associations. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION software analysis reported that IFNAR-2 protein Interferon (IFN) receptors are assemblies of is a 515 amino acids long chain, having total 37 trans-membrane glycoproteins, belonging to the identical positions with 6.446% identity and con- helical cytokine receptor (hCR) family, which, sists of variety of secondary structures such as in response to ligand, activates the signal trans- alpha-helices (inner, outer and trans-membrane duction pathways. The IFNAR2 genes encode domain), turns and beta sheets that impart struc- multiple iso forms that contribute to the potential tural diversity, dictating the functional diversity complexity of the receptor1-3. The structure of the of this protein. In current scenario, sufficient IFNAR-2 protein binding ectodomain (IFNAR2- knowledge about functional description of EC), is the first identified helical cytokine recep- IFNAR-2 protein is not available, mainly due tor structure that provides the molecular basis to the limitations of relevant sources including for IFN binding4. Later on, three dimensional study models. Comprehensive information about structure of IFNAR-2 protein was identified by the functions and molecular associations of NMR which predicted that core of ligand binding IFNAR-2 protein is an important aspect to under- domain consists of hydrophobic aliphatic amino stand the potential role of protein in biological acids5. A previous study based upon insilico systems. Functional associations of human inter- feron alpha receptor 2 (IFNAR-2) protein based Correspondence: Dr Gulshan Ara Trali, HOD Biochemistry, Swat upon protein-protein interactions can be impor- Medical College, Saidu Shareef, Swat Pakistan Email: [email protected] tant for development of targeted drug therapy Received: 24 Feb 2019; revised received: 15 Jul 2000; accepted: 29 Jul where we need to consider these multiple 2019 245 Functional Interactions of IFNAR-2 Within Biological Networks Pak Armed Forces Med J 2020; 70 (1): 245-52 interactions of respective receptor based targeted mining (2) Experiments (3) Databases (4) Co- therapeutics6. expression (5) Neighbourhood (6) Gene fusion The database, STRING (Search Tool for the and (7) Co-occurrence. Maximum twenty pro- Retrieval of Interacting Genes/Proteins), is a fully teins (interactors) were selected and minimum pre-computed exploratory resource that contains required interaction was set at score 0.900 as the a much larger number of associations than pri- highest confidence level. Analysis of molecular mary interaction database, with varying confi- interactions comprised the same parameters dence scores. It basically provides three types of except text mining source. STRING consortium protein-protein interactions/associations eviden- 2017 consists of SIB (Swiss Institute of Bioinfor- ced under one common framework with an inte- matics), CPR-NNF (Centre for Protein Research) grated approach. This approach offers various and EMBL (European Molecular Biology Labora- advantages such as (1) comparative analysis tory) databases8. based upon single and stable set of proteins (2) RESULTS more coverage for the protein of interest, based The fasta protein sequence of human upon known and predicted information that com- IFNAR-2 protein used in this study is given plements its relevant associations (3) independent below: evidence based scoring providing confidence Uni Prot KB / Swiss-Prot: P48551.1 >sp| about the role and importance of specific protein P48551.1 | INAR2_HUMAN Rec Name: Full = (4) association mapping and transformation onto Interferon alpha / beta receptor 2; Short = IFN-R- other kingdom systems setting the basis for 2; Short = IFN-alpha binding protein; Short = evolutionary studies7. By far, this is best tool to IFN-alpha/beta receptor 2; Alt Name: Full = provide a quick initial over-view of the functional Interferon alpha binding protein; Alt Name: Full partners of a query protein, especially for pro- = Type I interferon receptor 2; Flags: Precursor teins that are still poorly characterized such as human IFNAR-2 protein. Hence, the present MLLSQNAFIFRSLNLVLMVYISLVFGISYDS study was conducted to determine some inter- PDYTDESCTFKISLRNFRSILSWELKNHSIVPTH action or association features of human IFNAR-2 YTLLYTIMSKPEDLKVVKNCANTTRSFCDLTDE protein with other proteins by employing the WRSTHEAYVTVLEGFSGNTTLFSCSHNFWLAI STRING server tool. DMSFEPPEFEIVGFTNHINVMVKFPSIVEEELQF DLSLVIEEQSEGIVKKHKPEIKGNMSGNFTYIID METHODOLOGY KLIPNTNYCVSVYLEHSDEQAVIKSPLKCTLLP The present study was conducted from PGQESESAESAKIGGIITVFLIALVLTSTIVTLKWI December 2017 till June 2018, after approval from GYICLRNSLPKVLNFHNFLAWPFPNLPPLEAM Institutional Review Board (IBR), at Department DMVEVIYINRKKKVWDYNYDDESDSDTEAAP of Biochemistry, HITEC - Institute of Medical RTSGGGYTMHGLTVRPLGQASATSTESQLIDPE Sciences, Taxila Cantt, Pakistan. In this study SEEEPDLPEVDVELPTMPKDSPQQLELLSGPCE STRING version 10.0, has been employed to find RRKSPLQDPFPEEDYSSTEGSGGRITFNVDLNSV multiple protein interactions of human IFNAR-2 FLRVLDDEDSDDLEAPLMLSSHLEEMVDPEDP protein with other proteins by using coding DNVQSNHLLASGEGTQPTFPSPSSEGLWSEDA sequence, NCBI Accession: P48551.1. Analysis PSDQSDTSESDVDLGDGYIMR was conducted by applying specific parameters. Protein-protein interactions of human Initially, network edges were analysed based IFNAR-2 protein were studied by STRING upon evidence. Following this, selective interac- platform. We used fasta protein sequence of tions were evaluated on the basis of experimental human IFNAR-2 protein (query protein) in source. Protein-protein analysis consisted of STRING software with a total number of 20 active interaction parameters including (1) Text proteins to study a network of associations 246 Functional Interactions of IFNAR-2 Within Biological Networks Pak Armed Forces Med J 2020; 70 (1): 245-52 around the query protein. Enrichment was tested Network nodes represented proteins, produced statistically and validated. The average local by a single, coding gene locus. Small size of node Figure-1: Predicted protein - protein associations of human IFNAR-2 protein. clustering coefficient was 0.928 for total 21 nodes indicated the protein of unknown 3D structure, (one query and set of proteins) and 165 edges. whereas large size of node represented the 247 Functional Interactions of IFNAR-2 Within Biological Networks Pak Armed Forces Med J 2020; 70 (1): 245-52 known or predicted 3D protein structures. Figure IFNAR-2 protein interacts with many other 1 consisted of only large nodes, which showed proteins including groups of interferon (IFNA2, that our analysis only included proteins of IFNA4, IFNA5, IFNA6, IFNA8, IFNA10, IFNA14, known 3D structures. Red coloured node repre- IFNA16, IFNA21, IFNA17, IFNB1, IFNW1, IFNG sented the human IFNAR-2 protein (query pro- and IRF9), interferon receptor 1 (IFNAR1) (alpha, tein) and the first shell of interactions with other beta and omega) and signalling pathway proteins proteins, whereas white nodes symbolized the (STAT1, STAT 2, JAK1, TYK2 and GNB2L1) (fig- second shell of interactions. The edges high- 1). These associations showed that human Table: Functional enrichment for human IFNAR-2 protein interaction. Biological Process (GO) Pathway ID Pathway description Count in gene set