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 Progranulin Directly Binds to the CRD 2 and CRD3 of TNFR Extracellular Domains Progranulin Directly Binds to the CRD 2 and CRD3 of TNFR Extracellular Domains FEBS Lett. (0014-5793) 2013 imex curation 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 14-Oct-2013: Contacted by IntAct-Help. Only protein-protein interactions 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 Accepted 2013-SEP-13 by LPERFETTO 14-Oct-2013: Contacted by IntAct-Help. FEBS Lett. (0014-5793) 2013 Only protein-protein interactions imex curation Progranulin Directly Binds to the CRD 2 and CRD3 of TNFR Extracellular Domains Progranulin Directly Binds to the CRD 2 and CRD3 of TNFR Extracellular Domains FEBS Lett. (0014-5793) 2013 imex curation 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 14-Oct-2013: Contacted by IntAct-Help. Only protein-protein interactions 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 Accepted 2013-SEP-13 by LPERFETTO 14-Oct-2013: Contacted by IntAct-Help. FEBS Lett. (0014-5793) 2013 Only protein-protein interactions imex curation Progranulin Directly Binds to the CRD 2 and CRD3 of TNFR Extracellular Domains Progranulin Directly Binds to the CRD 2 and CRD3 of TNFR Extracellular Domains FEBS Lett. (0014-5793) 2013 imex curation 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 14-Oct-2013: Contacted by IntAct-Help. Only protein-protein interactions 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 Accepted 2013-SEP-13 by LPERFETTO 14-Oct-2013: Contacted by IntAct-Help. FEBS Lett. (0014-5793) 2013 Only protein-protein interactions imex curation Progranulin Directly Binds to the CRD 2 and CRD3 of TNFR Extracellular Domains Progranulin Directly Binds to the CRD 2 and CRD3 of TNFR Extracellular Domains FEBS Lett. (0014-5793) 2013 imex curation 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 14-Oct-2013: Contacted by IntAct-Help. Only protein-protein interactions 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 Accepted 2013-SEP-13 by LPERFETTO 14-Oct-2013: Contacted by IntAct-Help. FEBS Lett. (0014-5793) 2013 Only protein-protein interactions imex curation Progranulin Directly Binds to the CRD 2 and CRD3 of TNFR Extracellular Domains Progranulin Directly Binds to the CRD 2 and CRD3 of TNFR Extracellular Domains FEBS Lett. (0014-5793) 2013 imex curation 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 14-Oct-2013: Contacted by IntAct-Help. Only protein-protein interactions 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 Accepted 2013-SEP-13 by LPERFETTO 14-Oct-2013: Contacted by IntAct-Help. FEBS Lett. (0014-5793) 2013 Only protein-protein interactions imex curation 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 603D0AE1CD69ACBF 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 DIP protein P28799 original sequence version: 144 4E5947F1B4EDE619 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 DIP protein P25119 original sequence version: 125 462EAE398C4D6563 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 1DE8229C413CB787 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 DIP protein P19438 original sequence version: 135 DIP protein P19438 original sequence version: 150 DIP protein P19438 original sequence version: 177 4CEFBA96D03B8225 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 DIP protein P01375 original sequence version: 198 DIP protein P01375 original sequence version: 151 DIP protein P01375 original sequence version: 156 DIP protein P01375 original sequence version: 186 DIP protein P01375 original sequence version: 201 DIP protein P01375 original sequence version: 174 DIP protein P01375 original sequence version: 211 3DF90F96C9031FFE sort_human Sortilin SORT1 Neurotensin receptor 3 Glycoprotein 95 100 kDa NT receptor protein protein human Homo sapiens Human MERPWGAADGLSRWPHGLGLLLLLQLLPPSTLSQDRLDAPPPPAAPLPRWSGPIGVSWGLRAAAAGGAFPRGGRWRRSAPGEDEECGRVRDFVAKLANNTHQHVFDDLRGSVSLSWVGDSTGVILVLTTFHVPLVIMTFGQSKLYRSEDYGKNFKDITDLINNTFIRTEFGMAIGPENSGKVVLTAEVSGGSRGGRIFRSSDFAKNFVQTDLPFHPLTQMMYSPQNSDYLLALSTENGLWVSKNFGGKWEEIHKAVCLAKWGSDNTIFFTTYANGSCKADLGALELWRTSDLGKSFKTIGVKIYSFGLGGRFLFASVMADKDTTRRIHVSTDQGDTWSMAQLPSVGQEQFYSILAANDDMVFMHVDEPGDTGFGTIFTSDDRGIVYSKSLDRHLYTTTGGETDFTNVTSLRGVYITSVLSEDNSIQTMITFDQGGRWTHLRKPENSECDATAKNKNECSLHIHASYSISQKLNVPMAPLSEPNAVGIVIAHGSVGDAISVMVPDVYISDDGGYSWTKMLEGPHYYTILDSGGIIVAIEHSSRPINVIKFSTDEGQCWQTYTFTRDPIYFTGLASEPGARSMNISIWGFTESFLTSQWVSYTIDFKDILERNCEEKDYTIWLAHSTDPEDYEDGCILGYKEQFLRLRKSSVCQNGRDYVVTKQPSICLCSLEDFLCDFGYYRPENDSKCVEQPELKGHDLEFCLYGREEHLTTNGYRKIPGDKCQGGVNPVREVKDLKKKCTSNFLSPEKQNSKSNSVPIILAIVGLMLVTVVAGVLIVKKYVCGGRFLVHRYSVLQQHAEANGVDGVDALDTASHTNKSGYHDDSDEDLLE DIP protein Q99523 original sequence version: 97 DIP protein Q99523-1 original sequence version: 127 91F96A3035A4B43A tnfrsf1b-grn 4 TNFR2 8 unspecified role unspecified role bait bait PGRN 9 unspecified role unspecified role prey prey physical association physical association f1a tnf-tnfrsf1b 2 TNF alpha 11 unspecified role unspecified role bait bait TNFR2 6 unspecified role unspecified role prey prey direct interaction direct interaction 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 2 TNFR1 10 unspecified role unspecified role prey prey TNF alpha 11 unspecified role unspecified role bait bait direct interaction direct interaction 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 2 PGRN 7 unspecified role unspecified role bait bait TNFR1 10 unspecified role unspecified role prey prey direct interaction direct interaction t1 f2d grn-tnfrsf1b 2 PGRN 7 unspecified role unspecified role bait bait 6 unspecified role unspecified role unspecified role unspecified role direct interaction direct interaction t1 f2d grn-tnfrsf1b-2 3 TNFR2 6 unspecified role unspecified role prey prey PGRN 7 unspecified role unspecified role bait bait direct interaction direct interaction 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 3 PGRN 7 unspecified role unspecified role bait bait Sortilin 12 unspecified role unspecified role prey prey direct interaction direct interaction 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 1 PGRN 7 unspecified role unspecified role prey prey tag fusion protein fusion protein undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined TNFR1 10 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 tag fusion protein fusion protein undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined physical association physical association f4a tnfrsf1a-grn-1 1 TNFR2 6 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 tag fusion protein fusion protein undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined PGRN 7 unspecified role unspecified role prey prey tag fusion protein fusion protein undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined physical association physical association f4a grn-tnfrsf1a-1 5 PGRN 7 unspecified role unspecified role prey prey TNFR1 10 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 binding region binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain direct interaction direct interaction f5a tnfrsf1a-grn-2 5 PGRN 7 unspecified role unspecified role prey prey TNFR2 6 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 binding region binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain direct interaction direct interaction f5a tnfrsf1a-grn-3 3 TNFR2 6 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 PGRN 7 unspecified role unspecified role prey prey direct interaction direct interaction f5c grn-tnfrsf1a-2 3 TNFR1 10 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 PGRN 7 unspecified role unspecified role prey prey direct interaction direct interaction f5b