MINT MINT, Dpt of Biology, University of Rome Tor Vergata MINT http://mint.bio.uniroma2.it/mint url>http://mint.bio.uniroma2.it/mint/ https://mint.bio.uniroma2.it MINT-[0-9]+ https://mint.bio.uniroma2.it/index.php/results-interactions/?id=${ac} The Molecular INTeraction database (MINT) is a relational database designed to store interactions between biological molecules. http://mint.bio.uniroma2.it Aminoacylase 3 binds to and cleaves the N-terminus of the hepatitis C virus core protein. Aminoacylase 3 binds to and cleaves the N-terminus of the hepatitis C virus core protein. FEBS Lett. (0014-5793) 2012 Tsirulnikov K., Abuladze N., Vahi R., Hasnain H., Phillips M., Ryan CM., Atanasov I., Faull KF., Kurtz I., Pushkin A. ktsirulnikov@mednet.ucla.edu in vitro In vitro protease assay protease assay predetermined predetermined participant predetermined Tsirulnikov K., Abuladze N., Vahi R., Hasnain H., Phillips M., Ryan CM., Atanasov I., Faull KF., Kurtz I., Pushkin A. ktsirulnikov@mednet.ucla.edu FEBS Lett. (0014-5793) 2012 Aminoacylase 3 binds to and cleaves the N-terminus of the hepatitis C virus core protein. Aminoacylase 3 binds to and cleaves the N-terminus of the hepatitis C virus core protein. FEBS Lett. (0014-5793) 2012 Tsirulnikov K., Abuladze N., Vahi R., Hasnain H., Phillips M., Ryan CM., Atanasov I., Faull KF., Kurtz I., Pushkin A. ktsirulnikov@mednet.ucla.edu in vitro In vitro spr surface plasmon resonance Optical biosensor BIAcore(r) BIAcore(r) Optical biosensor spr predetermined predetermined participant predetermined Tsirulnikov K., Abuladze N., Vahi R., Hasnain H., Phillips M., Ryan CM., Atanasov I., Faull KF., Kurtz I., Pushkin A. ktsirulnikov@mednet.ucla.edu FEBS Lett. (0014-5793) 2012 polg_hcv1 Genome polyprotein protein protein hcv1 Hepatitis C virus genotype 1a (isolate 1) MSTNPKPQKKNKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNEGCGWAGWLLSPRGSRPSWGPTDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARALAHGVRVLEDGVNYATGNLPGCSFSIFLLALLSCLTVPASAYQVRNSTGLYHVTNDCPNSSIVYEAADAILHTPGCVPCVREGNASRCWVAMTPTVATRDGKLPATQLRRHIDLLVGSATLCSALYVGDLCGSVFLVGQLFTFSPRRHWTTQGCNCSIYPGHITGHRMAWDMMMNWSPTTALVMAQLLRIPQAILDMIAGAHWGVLAGIAYFSMVGNWAKVLVVLLLFAGVDAETHVTGGSAGHTVSGFVSLLAPGAKQNVQLINTNGSWHLNSTALNCNDSLNTGWLAGLFYHHKFNSSGCPERLASCRPLTDFDQGWGPISYANGSGPDQRPYCWHYPPKPCGIVPAKSVCGPVYCFTPSPVVVGTTDRSGAPTYSWGENDTDVFVLNNTRPPLGNWFGCTWMNSTGFTKVCGAPPCVIGGAGNNTLHCPTDCFRKHPDATYSRCGSGPWITPRCLVDYPYRLWHYPCTINYTIFKIRMYVGGVEHRLEAACNWTRGERCDLEDRDRSELSPLLLTTTQWQVLPCSFTTLPALSTGLIHLHQNIVDVQYLYGVGSSIASWAIKWEYVVLLFLLLADARVCSCLWMMLLISQAEAALENLVILNAASLAGTHGLVSFLVFFCFAWYLKGKWVPGAVYTFYGMWPLLLLLLALPQRAYALDTEVAASCGGVVLVGLMALTLSPYYKRYISWCLWWLQYFLTRVEAQLHVWIPPLNVRGGRDAVILLMCAVHPTLVFDITKLLLAVFGPLWILQASLLKVPYFVRVQGLLRFCALARKMIGGHYVQMVIIKLGALTGTYVYNHLTPLRDWAHNGLRDLAVAVEPVVFSQMETKLITWGADTAACGDIINGLPVSARRGREILLGPADGMVSKGWRLLAPITAYAQQTRGLLGCIITSLTGRDKNQVEGEVQIVSTAAQTFLATCINGVCWTVYHGAGTRTIASPKGPVIQMYTNVDQDLVGWPAPQGSRSLTPCTCGSSDLYLVTRHADVIPVRRRGDSRGSLLSPRPISYLKGSSGGPLLCPAGHAVGIFRAAVCTRGVAKAVDFIPVENLETTMRSPVFTDNSSPPVVPQSFQVAHLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGIDPNIRTGVRTITTGSPITYSTYGKFLADGGCSGGAYDIIICDECHSTDATSILGIGTVLDQAETAGARLVVLATATPPGSVTVPHPNIEEVALSTTGEIPFYGKAIPLEVIKGGRHLIFCHSKKKCDELAAKLVALGINAVAYYRGLDVSVIPTSGDVVVVATDALMTGYTGDFDSVIDCNTCVTQTVDFSLDPTFTIETITLPQDAVSRTQRRGRTGRGKPGIYRFVAPGERPSGMFDSSVLCECYDAGCAWYELTPAETTVRLRAYMNTPGLPVCQDHLEFWEGVFTGLTHIDAHFLSQTKQSGENLPYLVAYQATVCARAQAPPPSWDQMWKCLIRLKPTLHGPTPLLYRLGAVQNEITLTHPVTKYIMTCMSADLEVVTSTWVLVGGVLAALAAYCLSTGCVVIVGRVVLSGKPAIIPDREVLYREFDEMEECSQHLPYIEQGMMLAEQFKQKALGLLQTASRQAEVIAPAVQTNWQKLETFWAKHMWNFISGIQYLAGLSTLPGNPAIASLMAFTAAVTSPLTTSQTLLFNILGGWVAAQLAAPGAATAFVGAGLAGAAIGSVGLGKVLIDILAGYGAGVAGALVAFKIMSGEVPSTEDLVNLLPAILSPGALVVGVVCAAILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTAILSSLTVTQLLRRLHQWISSECTTPCSGSWLRDIWDWICEVLSDFKTWLKAKLMPQLPGIPFVSCQRGYKGVWRVDGIMHTRCHCGAEITGHVKNGTMRIVGPRTCRNMWSGTFPINAYTTGPCTPLPAPNYTFALWRVSAEEYVEIRQVGDFHYVTGMTTDNLKCPCQVPSPEFFTELDGVRLHRFAPPCKPLLREEVSFRVGLHEYPVGSQLPCEPEPDVAVLTSMLTDPSHITAEAAGRRLARGSPPSVASSSASQLSAPSLKATCTANHDSPDAELIEANLLWRQEMGGNITRVESENKVVILDSFDPLVAEEDEREISVPAEILRKSRRFAQALPVWARPDYNPPLVETWKKPDYEPPVVHGCPLPPPKSPPVPPPRKKRTVVLTESTLSTALAELATRSFGSSSTSGITGDNTTTSSEPAPSGCPPDSDAESYSSMPPLEGEPGDPDLSDGSWSTVSSEANAEDVVCCSMSYSWTGALVTPCAAEEQKLPINALSNSLLRHHNLVYSTTSRSACQRQKKVTFDRLQVLDSHYQDVLKEVKAAASKVKANLLSVEEACSLTPPHSAKSKFGYGAKDVRCHARKAVTHINSVWKDLLEDNVTPIDTTIMAKNEVFCVQPEKGGRKPARLIVFPDLGVRVCEKMALYDVVTKLPLAVMGSSYGFQYSPGQRVEFLVQAWKSKKTPMGFSYDTRCFDSTVTESDIRTEEAIYQCCDLDPQARVAIKSLTERLYVGGPLTNSRGENCGYRRCRASGVLTTSCGNTLTCYIKARAACRAAGLQDCTMLVCGDDLVVICESAGVQEDAASLRAFTEAMTRYSAPPGDPPQPEYDLELITSCSSNVSVAHDGAGKRVYYLTRDPTTPLARAAWETARHTPVNSWLGNIIMFAPTLWARMILMTHFFSVLIARDQLEQALDCEIYGACYSIEPLDLPPIIQRLHGLSAFSLHSYSPGEINRVAACLRKLGVPPLRAWRHRARSVRARLLARGGRAAICGKYLFNWAVRTKLKLTPIAAAGQLDLSGWFTAGYSGGDIYHSVSHARPRWIWFCLLLLAAGVGIYLLPNR Protease NS2-3 is a cysteine protease responsible for the autocatalytic cleavage of NS2-NS3. Seems to undergo self-inactivation following maturation NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B. NS3/NS4A complex also prevents phosphorylation of human IRF3, thus preventing the establishment of dsRNA induced antiviral state. NS3 RNA helicase binds to RNA and unwinds dsRNA in the 3' to 5' direction, and likely RNA stable secondary structure in the template strand. Cleaves and inhibits the host antiviral protein MAVS NS5B is a RNA-dependent RNA polymerase that plays an essential role in the virus replication P7 seems to be a heptameric ion channel protein (viroporin) and is inhibited by the antiviral drug amantadine. Also inhibited by long-alkyl-chain iminosugar derivatives. Essential for infectivity Core protein packages viral RNA to form a viral nucleocapsid, and promotes virion budding. Modulates viral translation initiation by interacting with HCV IRES and 40S ribosomal subunit. Also regulates many host cellular functions such as signaling pathways and apoptosis. Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by inducing human STAT1 degradation. Thought to play a role in virus-mediated cell transformation leading to hepatocellular carcinomas. Interacts with, and activates STAT3 leading to cellular transformation. May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm. Also represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation. Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses NK-kappaB activation, and activates AP-1. Could mediate apoptotic pathways through association with TNF-type receptors TNFRSF1A and LTBR, although its effect on death receptor-induced apoptosis remains controversial. Enhances TRAIL mediated apoptosis, suggesting that it might play a role in immune-mediated liver cell injury. Seric core protein is able to bind C1QR1 at the T-cell surface, resulting in down-regulation of T-lymphocytes proliferation. May transactivate human MYC, Rous sarcoma virus LTR, and SV40 promoters. May suppress the human FOS and HIV-1 LTR activity. Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage. Core protein induces up-regulation of FAS promoter activity, and thereby probably contributes to the increased triglyceride accumulation in hepatocytes (steatosis) mint NS4B induces a specific membrane alteration that serves as a scaffold for the virus replication complex. This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex homomint NS5A is a component of the replication complex involved in RNA-binding. Down-regulates viral IRES translation initiation. Mediates interferon resistance, presumably by interacting with and inhibiting human EIF2AK2/PKR. Seems to inhibit apoptosis by interacting with BIN1 and FKBP8. The hyperphosphorylated form of NS5A is an inhibitor of viral replication E1 and E2 glycoproteins form a heterodimer that is involved in virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane. E1/E2 heterodimer binds to human LDLR, CD81 and SCARB1/SR-BI receptors, but this binding is not sufficient for infection, some additional liver specific cofactors may be needed. The fusion function may possibly be carried by E1. E2 inhibits human EIF2AK2/PKR activation, preventing the establishment of an antiviral state. E2 is a viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses. These interactions allow capture of circulating HCV particles by these cells and subsequent transmission to permissive cells. DCs act as sentinels in various tissues where they entrap pathogens and convey them to local lymphoid tissue or lymph node for establishment of immunity. Capture of circulating HCV particles by these SIGN+ cells may facilitate virus infection of proximal hepatocytes and lymphocyte subpopulations and may be essential for the establishment of persistent infection 65F8C9447FCE5AF9 acy3_mouse N-acyl-aromatic-L-amino acid amidohydrolase (carboxylate-forming) Acy3 Aspa2 Aminoacylase-3 Aminoacylase III Acylase III Hepatitis C virus core-binding protein 1 Aspartoacylase-2 protein protein mouse Mus musculus Mouse MSSLPGSREPLLRVAVTGGTHGNEMCGVYLARYWLQNPGELQRPSFSAMPVLANPAATAACCRYLDRDLNRSCTLTFLGSTATPDDPYEVKRARELNQLLGPKGTGQAFDFTLDLHNTTANTGVCLISESNISFNLHLCHYLQRQNPGMPCRLFLYEPAGTETFSVESISKNGICLEMGPQPQGVLRADLFSRMRALVASILDFIELFNQGMDLPAFEMDIYRNLGSVDFPRTADGDLAGTVHPQLQDHDFEPLRPGEPIFKLFSGEDVLYEGDSIVYPVFINEAAYYEKHVAFLKSEKIRVTVPALLRLTPRSTQTP DIP protein Q91XE4 original sequence version: 75 mint homomint 8332731E7E9B30D2 acy3-polg 2 HCVCP 3 peptide synthesis peptide synthesis predetermined predetermined participant predetermined unspecified role unspecified role prey prey purified purified binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain p21 p21 polyprotein frag polyprotein fragment polyprotein frag certain certain sequence position certain certain certain sequence position certain AA3 4 predetermined predetermined participant predetermined predetermined predetermined participant predetermined unspecified role unspecified role bait bait purified purified tag tag tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined direct interaction direct interaction t1 homomint domino mint acy3-polg-1 2 AA3 4 predetermined predetermined participant predetermined predetermined predetermined participant predetermined unspecified role unspecified role bait bait purified purified tag tag tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined HCVCP 3 peptide synthesis peptide synthesis predetermined predetermined participant predetermined unspecified role unspecified role prey prey purified purified binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain acetylated residue ac1res monoacetylated residue Acetyl Acetylation (N terminus, N epsilon of Lysine, O of Serine) (Ac) Acetylation Ac1Res certain certain sequence position certain certain certain sequence position certain prerequisite-ptm p21 p21 polyprotein frag polyprotein fragment polyprotein frag certain certain sequence position certain certain certain sequence position certain direct interaction direct interaction t1 homomint domino mint acy3-polg-2 2 AA3 4 predetermined predetermined participant predetermined predetermined predetermined participant predetermined unspecified role unspecified role bait bait purified purified tag tag tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined HCVCP 3 peptide synthesis peptide synthesis predetermined predetermined participant predetermined unspecified role unspecified role prey prey purified purified binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain p21 p21 polyprotein frag polyprotein fragment polyprotein frag certain certain sequence position certain certain certain sequence position certain direct interaction direct interaction t1 homomint domino mint acy3-polg-3 2 AA3 4 predetermined predetermined participant predetermined predetermined predetermined participant predetermined unspecified role unspecified role bait bait purified purified tag tag tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined HCVCP 3 peptide synthesis peptide synthesis predetermined predetermined participant predetermined unspecified role unspecified role prey prey purified purified p21 p21 polyprotein frag polyprotein fragment polyprotein frag certain certain sequence position certain certain certain sequence position certain acetylated residue ac1res monoacetylated residue Acetyl Acetylation (N terminus, N epsilon of Lysine, O of Serine) (Ac) Acetylation Ac1Res certain certain sequence position certain certain certain sequence position certain prerequisite-ptm binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain direct interaction direct interaction t1 homomint domino mint acy3-polg-4 2 AA3 4 predetermined predetermined participant predetermined predetermined predetermined participant predetermined unspecified role unspecified role bait bait purified purified tag tag tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined HCVCP 3 peptide synthesis peptide synthesis predetermined predetermined participant predetermined unspecified role unspecified role prey prey purified purified binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain p21 p21 polyprotein frag polyprotein fragment polyprotein frag certain certain sequence position certain certain certain sequence position certain direct interaction direct interaction t1 homomint domino mint acy3-polg-5 1 AA3 4 predetermined predetermined participant predetermined predetermined predetermined participant predetermined enzyme enzyme neutral component neutral component purified purified tag tag tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined HCVCP 3 ms participant Identification by mass spectrometry ms participant predetermined predetermined participant predetermined enzyme target enzyme target substrate substrate neutral component neutral component purified purified binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain p21 p21 polyprotein frag polyprotein fragment polyprotein frag certain certain sequence position certain certain certain sequence position certain cleavage cleavage reaction cleavage homomint domino mint Three peptides (STLPKP, STLPKPQ and STLPKPQR) were detected after incubation of both N-acetylated and non-acetylated short HCVCP peptide (STLPKPQRKT). No C-terminal peptides were detected. The results suggested that AA3 has endopeptidase activity towards the HCVCP peptides. This is in agreement with the structural similarity of the active site of AA3 and carboxypeptidase A [20]. Surprisingly, both Ac-HCVCPlong and HCVCP-long were not hydrolyzed by AA3 f3a f3b f3c f3d acy3-acy3 1 AA3 4 predetermined predetermined participant predetermined predetermined predetermined participant predetermined enzyme enzyme neutral component neutral component purified purified tag tag tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined AA3 4 ms participant Identification by mass spectrometry ms participant predetermined predetermined participant predetermined enzyme target enzyme target substrate substrate neutral component neutral component purified purified binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain cleavage cleavage reaction cleavage homomint mint f3e f3f Both the N-acetylated and non-acetylated AA3 peptide (SSLPGSREPL) were hydrolyzed between Gly5 and Ser6 and both moieties (SSLPG and SREPL) were present (Fig. 3E-H)