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 http://mint.bio.uniroma2.it/mint jinlong-2013-2 Progranulin Directly Binds to the CRD 2 and CRD3 of TNFR Extracellular Domains in vitro In vitro spr surface plasmon resonance Optical biosensor BIAcore(r) BIAcore(r) Optical biosensor spr predetermined predetermined participant predetermined Jian J., Zhao S., Tian Q., Gonzalez-Gugel E., Mundra J.J., Uddin S.M., Liu B., Richbourgh B., Brunetti R., Liu C.J. chuanju.liu@nyumc.org FEBS Lett. (0014-5793) 2013 Only protein-protein interactions imex curation jinlong-2013-3 Progranulin Directly Binds to the CRD 2 and CRD3 of TNFR Extracellular Domains in vitro In vitro solid phase assay solid phase assay elisa enzyme linked immunosorbent assay ELISA ELISA elisa Jian J., Zhao S., Tian Q., Gonzalez-Gugel E., Mundra J.J., Uddin S.M., Liu B., Richbourgh B., Brunetti R., Liu C.J. chuanju.liu@nyumc.org FEBS Lett. (0014-5793) 2013 Only protein-protein interactions imex curation jinlong-2013-4 Progranulin Directly Binds to the CRD 2 and CRD3 of TNFR Extracellular Domains yeast Saccharomyces cerevisiae Baker's yeast 2 hybrid two hybrid 2H 2h Gal4 transcription regeneration two-hybrid yeast two hybrid 2-hybrid classical two hybrid classical two hybrid 2H two-hybrid 2-hybrid Gal4 transcription regeneration 2h yeast two hybrid Y2H Y-2H 2 hybrid predetermined predetermined participant predetermined Jian J., Zhao S., Tian Q., Gonzalez-Gugel E., Mundra J.J., Uddin S.M., Liu B., Richbourgh B., Brunetti R., Liu C.J. chuanju.liu@nyumc.org FEBS Lett. (0014-5793) 2013 Only protein-protein interactions imex curation jinlong-2013-5 Progranulin Directly Binds to the CRD 2 and CRD3 of TNFR Extracellular Domains in vitro In vitro pull down pull down western blot western blot Immuno blot Immuno blot Jian J., Zhao S., Tian Q., Gonzalez-Gugel E., Mundra J.J., Uddin S.M., Liu B., Richbourgh B., Brunetti R., Liu C.J. chuanju.liu@nyumc.org FEBS Lett. (0014-5793) 2013 Only protein-protein interactions imex curation jinlong-2013-1 Progranulin Directly Binds to the CRD 2 and CRD3 of TNFR Extracellular Domains mouse-spleen Mus musculus spleen spleen spleen anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Jian J., Zhao S., Tian Q., Gonzalez-Gugel E., Mundra J.J., Uddin S.M., Liu B., Richbourgh B., Brunetti R., Liu C.J. chuanju.liu@nyumc.org FEBS Lett. (0014-5793) 2013 Only protein-protein interactions imex curation tnfa_human Tumor necrosis factor TNF TNFA TNFSF2 TNF-alpha Tumor necrosis factor ligand superfamily member 2 Cachectin protein protein human Homo sapiens Human MSTESMIRDVELAEEALPKKTGGPQGSRRCLFLSLFSFLIVAGATTLFCLLHFGVIGPQREEFPRDLSLISPLAQAVRSSSRTPSDKPVAHVVANPQAEGQLQWLNRRANALLANGVELRDNQLVVPSEGLYLIYSQVLFKGQGCPSTHVLLTHTISRIAVSYQTKVNLLSAIKSPCQRETPEGAEAKPWYEPIYLGGVFQLEKGDRLSAEINRPDYLDFAESGQVYFGIIAL tnr1b_human Tumor necrosis factor receptor superfamily member 1B TNFRSF1B TNFBR TNFR2 Tumor necrosis factor receptor 2 Tumor necrosis factor receptor type II p75 p80 TNF-alpha receptor protein protein human Homo sapiens Human MAPVAVWAALAVGLELWAAAHALPAQVAFTPYAPEPGSTCRLREYYDQTAQMCCSKCSPGQHAKVFCTKTSDTVCDSCEDSTYTQLWNWVPECLSCGSRCSSDQVETQACTREQNRICTCRPGWYCALSKQEGCRLCAPLRKCRPGFGVARPGTETSDVVCKPCAPGTFSNTTSSTDICRPHQICNVVAIPGNASMDAVCTSTSPTRSMAPGAVHLPQPVSTRSQHTQPTPEPSTAPSTSFLLPMGPSPPAEGSTGDFALPVGLIVGVTALGLLIIGVVNCVIMTQVKKKPLCLQREAKVPHLPADKARGTQGPEQQHLLITAPSSSSSSLESSASALDRRAPTRNQPQAPGVEASGAGEARASTGSSDSSPGGHGTQVNVTCIVNVCSSSDHSSQCSSQASSTMGDTDSSPSESPKDEQVPFSKEECAFRSQLETPETLLGSTEEKPLPLGVPDAGMKPS tnr1a_human Tumor necrosis factor receptor superfamily member 1A TNFRSF1A TNFAR TNFR1 p60 Tumor necrosis factor receptor 1 Tumor necrosis factor receptor type I p55 protein protein human Homo sapiens Human MGLSTVPDLLLPLVLLELLVGIYPSGVIGLVPHLGDREKRDSVCPQGKYIHPQNNSICCTKCHKGTYLYNDCPGPGQDTDCRECESGSFTASENHLRHCLSCSKCRKEMGQVEISSCTVDRDTVCGCRKNQYRHYWSENLFQCFNCSLCLNGTVHLSCQEKQNTVCTCHAGFFLRENECVSCSNCKKSLECTKLCLPQIENVKGTEDSGTTVLLPLVIFFGLCLLSLLFIGLMYRYQRWKSKLYSIVCGKSTPEKEGELEGTTTKPLAPNPSFSPTPGFTPTLGFSPVPSSTFTSSSTYTPGDCPNFAAPRREVAPPYQGADPILATALASDPIPNPLQKWEDSAHKPQSLDTDDPATLYAVVENVPPLRWKEFVRRLGLSDHEIDRLELQNGRCLREAQYSMLATWRRRTPRREATLELLGRVLRDMDLLGCLEDIEEALCGPAALPPAPSLLR grn_human Progranulin Proepithelin GRN Acrogranin Epithelin precursor Glycoprotein of 88 Kda Granulin precursor PC cell-derived growth factor protein protein human Homo sapiens Human MWTLVSWVALTAGLVAGTRCPDGQFCPVACCLDPGGASYSCCRPLLDKWPTTLSRHLGGPCQVDAHCSAGHSCIFTVSGTSSCCPFPEAVACGDGHHCCPRGFHCSADGRSCFQRSGNNSVGAIQCPDSQFECPDFSTCCVMVDGSWGCCPMPQASCCEDRVHCCPHGAFCDLVHTRCITPTGTHPLAKKLPAQRTNRAVALSSSVMCPDARSRCPDGSTCCELPSGKYGCCPMPNATCCSDHLHCCPQDTVCDLIQSKCLSKENATTDLLTKLPAHTVGDVKCDMEVSCPDGYTCCRLQSGAWGCCPFTQAVCCEDHIHCCPAGFTCDTQKGTCEQGPHQVPWMEKAPAHLSLPDPQALKRDVPCDNVSSCPSSDTCCQLTSGEWGCCPIPEAVCCSDHQHCCPQGYTCVAEGQCQRGSEIVAGLEKMPARRASLSHPRDIGCDQHTSCPVGQTCCPSLGGSWACCQLPHAVCCEDRQHCCPAGYTCNVKARSCEKEVVSAQPATFLARSPHVGVKDVECGEGHFCHDNQTCCRDNRQGWACCPYRQGVCCADRRHCCPAGFRCAARGTKCLRREAPRWDAPLRDPALRQLL sort_human Sortilin SORT1 Neurotensin receptor 3 Glycoprotein 95 100 kDa NT receptor protein protein human Homo sapiens Human MERPWGAADGLSRWPHGLGLLLLLQLLPPSTLSQDRLDAPPPPAAPLPRWSGPIGVSWGLRAAAAGGAFPRGGRWRRSAPGEDEECGRVRDFVAKLANNTHQHVFDDLRGSVSLSWVGDSTGVILVLTTFHVPLVIMTFGQSKLYRSEDYGKNFKDITDLINNTFIRTEFGMAIGPENSGKVVLTAEVSGGSRGGRIFRSSDFAKNFVQTDLPFHPLTQMMYSPQNSDYLLALSTENGLWVSKNFGGKWEEIHKAVCLAKWGSDNTIFFTTYANGSCKADLGALELWRTSDLGKSFKTIGVKIYSFGLGGRFLFASVMADKDTTRRIHVSTDQGDTWSMAQLPSVGQEQFYSILAANDDMVFMHVDEPGDTGFGTIFTSDDRGIVYSKSLDRHLYTTTGGETDFTNVTSLRGVYITSVLSEDNSIQTMITFDQGGRWTHLRKPENSECDATAKNKNECSLHIHASYSISQKLNVPMAPLSEPNAVGIVIAHGSVGDAISVMVPDVYISDDGGYSWTKMLEGPHYYTILDSGGIIVAIEHSSRPINVIKFSTDEGQCWQTYTFTRDPIYFTGLASEPGARSMNISIWGFTESFLTSQWVSYTIDFKDILERNCEEKDYTIWLAHSTDPEDYEDGCILGYKEQFLRLRKSSVCQNGRDYVVTKQPSICLCSLEDFLCDFGYYRPENDSKCVEQPELKGHDLEFCLYGREEHLTTNGYRKIPGDKCQGGVNPVREVKDLKKKCTSNFLSPEKQNSKSNSVPIILAIVGLMLVTVVAGVLIVKKYVCGGRFLVHRYSVLQQHAEANGVDGVDALDTASHTNKSGYHDDSDEDLLE tnr1b_mouse Tumor necrosis factor receptor superfamily member 1B Tumor necrosis factor receptor 2 Tumor necrosis factor receptor type II p75 p80 TNF-alpha receptor Tnfrsf1b Tnfr2 Tnfr-2 protein protein mouse Mus musculus Mouse MAPAALWVALVFELQLWATGHTVPAQVVLTPYKPEPGYECQISQEYYDRKAQMCCAKCPPGQYVKHFCNKTSDTVCADCEASMYTQVWNQFRTCLSCSSSCTTDQVEIRACTKQQNRVCACEAGRYCALKTHSGSCRQCMRLSKCGPGFGVASSRAPNGNVLCKACAPGTFSDTTSSTDVCRPHRICSILAIPGNASTDAVCAPESPTLSAIPRTLYVSQPEPTRSQPLDQEPGPSQTPSILTSLGSTPIIEQSTKGGISLPIGLIVGVTSLGLLMLGLVNCIILVQRKKKPSCLQRDAKVPHVPDEKSQDAVGLEQQHLLTTAPSSSSSSLESSASAGDRRAPPGGHPQARVMAEAQGFQEARASSRISDSSHGSHGTHVNVTCIVNVCSSSDHSSQCSSQASATVGDPDAKPSASPKDEQVPFSQEECPSQSPCETTETLQSHEKPLPLGVPDMGMKPSQAGWFDQIAVKVA grn_mouse Progranulin Grn Proepithelin PC cell-derived growth factor Acrogranin Epithelin/granulin precursor Glycoprotein of 88 Kda protein protein mouse Mus musculus Mouse MWVLMSWLAFAAGLVAGTQCPDGQFCPVACCLDQGGANYSCCNPLLDTWPRITSHHLDGSCQTHGHCPAGYSCLLTVSGTSSCCPFSKGVSCGDGYHCCPQGFHCSADGKSCFQMSDNPLGAVQCPGSQFECPDSATCCIMVDGSWGCCPMPQASCCEDRVHCCPHGASCDLVHTRCVSPTGTHTLLKKFPAQKTNRAVSLPFSVVCPDAKTQCPDDSTCCELPTGKYGCCPMPNAICCSDHLHCCPQDTVCDLIQSKCLSKNYTTDLLTKLPGYPVKEVKCDMEVSCPEGYTCCRLNTGAWGCCPFAKAVCCEDHIHCCPAGFQCHTEKGTCEMGILQVPWMKKVIAPLRLPDPQILKSDTPCDDFTRCPTNNTCCKLNSGDWGCCPIPEAVCCSDNQHCCPQGFTCLAQGYCQKGDTMVAGLEKIPARQTTPLQIGDIGCDQHTSCPVGQTCCPSLKGSWACCQLPHAVCCEDRQHCCPAGYTCNVKARTCEKDVDFIQPPVLLTLGPKVGNVECGEGHFCHDNQTCCKDSAGVWACCPYLKGVCCRDGRHCCPGGFHCSARGTKCLRKKIPRWDMFLRDPVPRPLL tnf-tnfrsf1b 1438351 n/a TNF alpha 1438356 unspecified role unspecified role bait bait n/a TNFR2 1438357 unspecified role unspecified role prey prey direct interaction direct interaction false false false 1438351 1438351 1438351 t1 f2a f2c As shown in Fig. 2A and C, TNFα binds to TNFR on COOH1 and COOHV chips in SensiQ methods. When tested on the COOH1 chip, the same chip used in our previous study [26], PGRN from Adipogen shows high binding affinity to both TNFR1 and TNFR2 (Fig. 2D). Consistent with our previous study [26], PGRN shows selectively higher binding affinity to TNFR2 than to TNFR1. However, when switched to COOHV chip, PGRN fails to bind to TFNR (Fig. 2B). These data were repeated in three individual experiments. Furthermore PGRN fails to bind to TNFR1 and TNFR2 in CM5 chips in Biacore, which is the same chip used in Chen’s study [29]. As summarized in Table 1, the successful demonstration of the binding of PGRN to TNFR1 and TNFR2 in surface plasmon resonance is highly dependent upon the chips used. tnf-tnfrsf1a-6 1438351 n/a TNFR1 1438358 unspecified role unspecified role prey prey n/a TNF alpha 1438356 unspecified role unspecified role bait bait direct interaction direct interaction false false false 1438351 1438351 1438351 t1 f2a f2c As shown in Fig. 2A and C, TNFα binds to TNFR on COOH1 and COOHV chips in SensiQ methods. When tested on the COOH1 chip, the same chip used in our previous study [26], PGRN from Adipogen shows high binding affinity to both TNFR1 and TNFR2 (Fig. 2D). Consistent with our previous study [26], PGRN shows selectively higher binding affinity to TNFR2 than to TNFR1. However, when switched to COOHV chip, PGRN fails to bind to TFNR (Fig. 2B). These data were repeated in three individual experiments. Furthermore PGRN fails to bind to TNFR1 and TNFR2 in CM5 chips in Biacore, which is the same chip used in Chen’s study [29]. As summarized in Table 1, the successful demonstration of the binding of PGRN to TNFR1 and TNFR2 in surface plasmon resonance is highly dependent upon the chips used. grn-tnfrsf1a 1438351 n/a PGRN 1438359 unspecified role unspecified role bait bait n/a TNFR1 1438358 unspecified role unspecified role prey prey direct interaction direct interaction false false false 1438351 t1 f2d grn-tnfrsf1b 1438351 n/a PGRN 1438359 unspecified role unspecified role bait bait n/a 1438357 unspecified role unspecified role unspecified role unspecified role direct interaction direct interaction false false false 1438351 t1 f2d grn-tnfrsf1b-2 1438352 n/a TNFR2 1438357 unspecified role unspecified role prey prey n/a PGRN 1438359 unspecified role unspecified role bait bait direct interaction direct interaction false false false f3b To test this hypothesis, PGRN was pretreated with 10mM DTT, which is known to disturb the formation of disulfide bonds in PGRN and in turn affects its folding, and then the binding of PGRN to TNFR2 and Sortilin were measured using solid phase binding. DTT treatment completely abolished the binding of PGRN to TNFR2 (Fig. 3A). In marked contrast, the binding of PGRN to Sortilin was significantly enhanced by DTT treatment (Fig. 3B). grn-sort1 1438352 n/a PGRN 1438359 unspecified role unspecified role bait bait n/a Sortilin 1438360 unspecified role unspecified role prey prey direct interaction direct interaction false false false f3c To test this hypothesis, PGRN was pretreated with 10mM DTT, which is known to disturb the formation of disulfide bonds in PGRN and in turn affects its folding, and then the binding of PGRN to TNFR2 and Sortilin were measured using solid phase binding. DTT treatment completely abolished the binding of PGRN to TNFR2 (Fig. 3A). In marked contrast, the binding of PGRN to Sortilin was significantly enhanced by DTT treatment (Fig. 3B). tnfrsf1a-grn-3 1438352 n/a TNFR2 1438357 unspecified role unspecified role bait bait binding region binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain false n/a PGRN 1438359 unspecified role unspecified role prey prey direct interaction direct interaction false false false f5c grn-tnfrsf1a-2 1438352 n/a TNFR1 1438358 unspecified role unspecified role bait bait binding region binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain false n/a PGRN 1438359 unspecified role unspecified role prey prey direct interaction direct interaction false false false f5b tnfrsf1a-grn 1438353 n/a PGRN 1438359 unspecified role unspecified role prey prey tag fusion protein fusion protein undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false n/a TNFR1 1438358 unspecified role unspecified role bait bait binding region binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain false tag fusion protein fusion protein undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false physical association physical association false false false f4a tnfrsf1a-grn-1 1438353 n/a TNFR2 1438357 unspecified role unspecified role bait bait binding region binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain false tag fusion protein fusion protein undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false n/a PGRN 1438359 unspecified role unspecified role prey prey tag fusion protein fusion protein undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false physical association physical association false false false f4a grn-tnfrsf1a-1 1438354 n/a PGRN 1438359 unspecified role unspecified role prey prey n/a TNFR1 1438358 unspecified role unspecified role bait bait tag gst tag glutathione s tranferase tag glutathione S-tranferase tag glutathione S-tranferase tag gst tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false binding region binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain false direct interaction direct interaction false false false f5a tnfrsf1a-grn-2 1438354 n/a PGRN 1438359 unspecified role unspecified role prey prey n/a TNFR2 1438357 unspecified role unspecified role bait bait tag gst tag glutathione s tranferase tag glutathione S-tranferase tag glutathione S-tranferase tag gst tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false binding region binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain false direct interaction direct interaction false false false f5a tnfrsf1b-grn 1438355 n/a TNFR2 1438361 unspecified role unspecified role bait bait n/a PGRN 1438362 unspecified role unspecified role prey prey physical association physical association false false false f1a