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Overview

Uniprot ID	Q9P2E3
Protein Name	NFX1-type zinc finger-containing protein 1
Gene Name	ZNFX1
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
142	TEQPQQAKKLGYKFL

Function

RNA-activated non-canonical E3 ubiquitin ligase required for cell survival during interferon (IFN) responses. Functions as an ATP-dependent 5'-> 3' RNA translocase that selectively recognizes long single-stranded RNA (ssRNA) molecules (>100 nt) from viral or host origin during immune activation. Upon ssRNA binding, oligomerizes to assemble a split E3 active site in trans, involving the Z-RING domain that binds and activates E2-ubiquitin conjugates, such as UBE2D2, and the RZ catalytic domain that mediates ubiquitin transfer. Catalyzes hydroxyl ubiquitination of the 2'-OH of ssRNA ribose and auto-ubiquitination, generating mainly 'Lys-48'- and 'Lys-6'-linked polyubiquitin chains (PubMed:40876457). Forms ubiquitin-coated RNA condensates and stress granules, thereby regulating RNA metabolism, limiting excessive immune signaling, and preventing IFN-induced cell death (PubMed:33872655, PubMed:40876457). Also required for immunity against some bacteria, such as mycobacteria (PubMed:33876776). Inhibits NLRP3 inflammasome activation by sequestering NLRP3 in the cytoplasm and preventing its translocation to trans-Golgi network vesicles during the resting state. Upon inflammasome activation, is cleaved by CASP1, establishing a feed-forward loop that amplifies NLRP3 inflammasome activity (PubMed:39333773)

Protein Sequence

10 MEERRPHLDA 20 RPRNSHTNHR 30 GPVDGELPPR 40 ARNQANNPPA 50 NALRGGASHP 60 GRHPRANNHP 70 AAYWQREERF 80 RAMGRNPHQG 90 RRNQEGHASD 100 EARDQRHDQE 110 NDTRWRNGNQ 120 DCRNRRPPWS 130 NDNFQQWRTP 140 HQKPTEQPQQ 150 AKKLGYKFLE 160 SLLQKDPSEV 170 VITLATSLGL 180 KELLSHSSMK 190 SNFLELICQV 200 LRKACSSKMD 210 RQSVLHVLGI 220 LKNSKFLKVC 230 LPAYVVGMIT 240 EPIPDIRNQY 250 PEHISNIISL 260 LQDLVSVFPA 270 SSVQETSMLV 280 SLLPTSLNAL 290 RASGVDIEEE 300 TEKNLEKVQT 310 IIEHLQEKRR 320 EGTLRVDTYT 330 LVQPEAEDHV 340 ESYRTMPIYP 350 TYNEVHLDER 360 PFLRPNIISG 370 KYDSTAIYLD 380 THFRLLREDF 390 VRPLREGILE 400 LLQSFEDQGL 410 RKRKFDDIRI 420 YFDTRIITPM 430 CSSSGIVYKV 440 QFDTKPLKFV 450 RWQNSKRLLY 460 GSLVCMSKDN 470 FETFLFATVS 480 NREQEDLCRG 490 IVQLCFNEQS 500 QQLLAEVQPS 510 DSFLMVETTA 520 YFEAYRHVLE 530 GLQEVQEEDV 540 PFQRNIVECN 550 SHVKEPRYLL 560 MGGRYDFTPL 570 IENPSATGEF 580 LRNVEGLRHP 590 RINVLDPGQW 600 PSKEALKLDD 610 SQMEALQFAL 620 TRELAIIQGP 630 PGTGKTYVGL 640 KIVQALLTNE 650 SVWQISLQKF 660 PILVVCYTNH 670 ALDQFLEGIY 680 NCQKTSIVRV 690 GGRSNSEILK 700 QFTLRELRNK 710 REFRRNLPMH 720 LRRAYMSIMT 730 QMKESEQELH 740 EGAKTLECTM 750 RGVLREQYLQ 760 KYISPQHWES 770 LMNGPVQDSE 780 WICFQHWKHS 790 MMLEWLGLGV 800 GSFTQSVSPA 810 GPENTAQAEG 820 DEEEEGEEES 830 SLIEIAEEAD 840 LIQADRVIEE 850 EEVVRPQRRK 860 KEESGADQEL 870 AKMLLAMRLD 880 HCGTGTAAGQ 890 EQATGEWQTQ 900 RNQKKKMKKR 910 VKDELRKLNT 920 MTAAEANEIE 930 DVWQLDLSSR 940 WQLYRLWLQL 950 YQADTRRKIL 960 SYERQYRTSA 970 ERMAELRLQE 980 DLHILKDAQV 990 VGMTTTGAAK 1000 YRQILQKVEP 1010 RIVIVEEAAE 1020 VLEAHTIATL 1030 SKACQHLILI 1040 GDHQQLRPSA 1050 NVYDLAKNFN 1060 LEVSLFERLV 1070 KVNIPFVRLN 1080 YQHRMCPEIA 1090 RLLTPHIYQD 1100 LENHPSVLKY 1110 EKIKGVSSNL 1120 FFVEHNFPEQ 1130 EIQEGKSHQN 1140 QHEAHFVVEL 1150 CKYFLCQEYL 1160 PSQITILTTY 1170 TGQLFCLRKL 1180 MPAKTFAGVR 1190 VHVVDKYQGE 1200 ENDIILLSLV 1210 RSNQEGKVGF 1220 LQISNRICVA 1230 LSRAKKGMYC 1240 IGNMQMLAKV 1250 PLWSKIIHTL 1260 RENNQIGPML 1270 RLCCQNHPET 1280 HTLVSKASDF 1290 QKVPEGGCSL 1300 PCEFRLGCGH 1310 VCTRACHPYD 1320 SSHKEFQCMK 1330 PCQKVICQEG 1340 HRCPLVCFQE 1350 CQPCQVKVPK 1360 TIPRCGHEQM 1370 VPCSVPESDF 1380 CCQEPCSKSL 1390 RCGHRCSHPC 1400 GEDCVQLCSE 1410 MVTIKLKCGH 1420 SQPVKCGHVE 1430 GLLYGGLLVK 1440 CTTKCGTILD 1450 CGHPCPGSCH 1460 SCFEGRFHER 1470 CQQPCKRLLI 1480 CSHKCQEPCI 1490 GECPPCQRTC 1500 QNRCVHSQCK 1510 KKCGELCSPC 1520 VEPCVWRCQH 1530 YQCTKLCSEP 1540 CNRPPCYVPC 1550 TKLLVCGHPC 1560 IGLCGEPCPK 1570 KCRICHMDEV 1580 TQIFFGFEDE 1590 PDARFVQLED 1600 CSHIFEVQAL 1610 DRYMNEQKDD 1620 EVAIRLKVCP 1630 ICQVPIRKNL 1640 RYGTSIKQRL 1650 EEIEIIKEKI 1660 QGSAGEIATS 1670 QERLKALLER 1680 KSLLHQLLPE 1690 DFLMLKEKLA 1700 QKNLSVKDLG 1710 LVENYISFYD 1720 HLASLWDSLK 1730 KMHVLEEKRV 1740 RTRLEQVHEW 1750 LAKKRLSFTS 1760 QELSDLRSEI 1770 QRLTYLVNLL 1780 TRYKIAEKKV 1790 KDSIAVEVYS 1800 VQNILEKTCK 1810 FTQEDEQLVQ 1820 EKMEALKATL 1830 PCSGLGISEE 1840 ERVQIVSAIG 1850 YPRGHWFKCR 1860 NGHIYVIGDC 1870 GGAMERGTCP 1880 DCKEVIGGTN 1890 HTLERSNQLA 1900 SEMDGAQHAA 1910 WSDTANNLMN FEEIQGMM

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0010494	cytoplasmic stress granule
Cellular Component	GO:0005741	mitochondrial outer membrane
Cellular Component	GO:0031380	nuclear RNA-directed RNA polymerase complex
Molecular Function	GO:0004386	helicase activity
Molecular Function	GO:0003723	RNA binding
Molecular Function	GO:0008270	zinc ion binding
Biological Process	GO:0002218	activation of innate immune response
Biological Process	GO:0042742	defense response to bacterium
Biological Process	GO:0051607	defense response to virus
Biological Process	GO:0045087	innate immune response
Biological Process	GO:0045071	negative regulation of viral genome replication
Biological Process	GO:0031048	regulatory ncRNA-mediated heterochromatin formation

Reference

PMID: N/A