ID GBP1_HUMAN Reviewed; 592 AA. AC P32455; D3DT26; Q5T8M1; DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot. DT 02-NOV-2010, sequence version 2. DT 27-MAR-2024, entry version 201. DE RecName: Full=Guanylate-binding protein 1 {ECO:0000305}; DE EC=3.6.1.- {ECO:0000269|PubMed:16511497}; DE EC=3.6.5.- {ECO:0000269|PubMed:10676968, ECO:0000269|PubMed:16511497, ECO:0000269|PubMed:32510692}; DE AltName: Full=GTP-binding protein 1 {ECO:0000303|PubMed:8830800}; DE Short=GBP-1 {ECO:0000303|PubMed:8830800}; DE Short=HuGBP-1 {ECO:0000303|PubMed:8830800}; DE Short=hGBP1 {ECO:0000303|PubMed:7512561}; DE AltName: Full=Guanine nucleotide-binding protein 1; DE AltName: Full=Interferon-induced guanylate-binding protein 1 {ECO:0000303|PubMed:1715024}; DE Flags: Precursor; GN Name=GBP1 {ECO:0000303|PubMed:7512561, ECO:0000312|HGNC:HGNC:4182}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS SER-349 AND GLY-409. RX PubMed=1715024; DOI=10.1128/mcb.11.9.4717-4725.1991; RA Cheng Y.-S.E., Patterson C.E., Staeheli P.; RT "Interferon-induced guanylate-binding proteins lack an N(T)KXD consensus RT motif and bind GMP in addition to GDP and GTP."; RL Mol. Cell. Biol. 11:4717-4725(1991). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS SER-349 AND GLY-409. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Placenta; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS SER-349 AND GLY-409. RC TISSUE=Uterus; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=7512561; DOI=10.1016/s0021-9258(19)78125-3; RA Schwemmle M., Staeheli P.; RT "The interferon-induced 67-kDa guanylate-binding protein (hGBP1) is a RT GTPase that converts GTP to GMP."; RL J. Biol. Chem. 269:11299-11305(1994). RN [8] RP ISOPRENYLATION AT CYS-589, AND METHYLATION AT CYS-589. RX PubMed=8830800; DOI=10.1002/jlb.60.3.423; RA Nantais D.E., Schwemmle M., Stickney J.T., Vestal D.J., Buss J.E.; RT "Prenylation of an interferon-gamma-induced GTP-binding protein: the human RT guanylate binding protein, huGBP1."; RL J. Leukoc. Biol. 60:423-431(1996). RN [9] RP SUBCELLULAR LOCATION. RX PubMed=15937107; DOI=10.1073/pnas.0503227102; RA Modiano N., Lu Y.E., Cresswell P.; RT "Golgi targeting of human guanylate-binding protein-1 requires nucleotide RT binding, isoprenylation, and an IFN-gamma-inducible cofactor."; RL Proc. Natl. Acad. Sci. U.S.A. 102:8680-8685(2005). RN [10] RP SUBCELLULAR LOCATION. RX PubMed=16936281; DOI=10.2353/ajpath.2006.060244; RA Naschberger E., Lubeseder-Martellato C., Meyer N., Gessner R., Kremmer E., RA Gessner A., Sturzl M.; RT "Human guanylate binding protein-1 is a secreted GTPase present in RT increased concentrations in the cerebrospinal fluid of patients with RT bacterial meningitis."; RL Am. J. Pathol. 169:1088-1099(2006). RN [11] RP SUBCELLULAR LOCATION, AND INDUCTION. RX PubMed=17266443; DOI=10.1089/jir.2007.0086; RA Tripal P., Bauer M., Naschberger E., Mortinger T., Hohenadl C., Cornali E., RA Thurau M., Sturzl M.; RT "Unique features of different members of the human guanylate-binding RT protein family."; RL J. Interferon Cytokine Res. 27:44-52(2007). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [13] RP SUBCELLULAR LOCATION, DIMERIZATION, ISOPRENYLATION, AND MUTAGENESIS OF RP LYS-51; 227-ARG-LYS-228 AND 589-CYS--SER-592. RX PubMed=21151871; DOI=10.1371/journal.pone.0014246; RA Britzen-Laurent N., Bauer M., Berton V., Fischer N., Syguda A., RA Reipschlager S., Naschberger E., Herrmann C., Sturzl M.; RT "Intracellular trafficking of guanylate-binding proteins is regulated by RT heterodimerization in a hierarchical manner."; RL PLoS ONE 5:E14246-E14246(2010). RN [14] RP FUNCTION. RX PubMed=22106366; DOI=10.1096/fj.11-189886; RA Nordmann A., Wixler L., Boergeling Y., Wixler V., Ludwig S.; RT "A new splice variant of the human guanylate-binding protein 3 mediates RT anti-influenza activity through inhibition of viral transcription and RT replication."; RL FASEB J. 26:1290-1300(2012). RN [15] RP FUNCTION, CATALYTIC ACTIVITY, ISOPRENYLATION, AND MUTAGENESIS OF ARG-48 AND RP LYS-76. RX PubMed=28645896; DOI=10.1073/pnas.1620959114; RA Shydlovskyi S., Zienert A.Y., Ince S., Dovengerds C., Hohendahl A., RA Dargazanli J.M., Blum A., Guenther S.D., Kladt N., Stuerzl M., RA Schauss A.C., Kutsch M., Roux A., Praefcke G.J.K., Herrmann C.; RT "Nucleotide-dependent farnesyl switch orchestrates polymerization and RT membrane binding of human guanylate-binding protein 1."; RL Proc. Natl. Acad. Sci. U.S.A. 114:E5559-E5568(2017). RN [16] RP UBIQUITINATION (MICROBIAL INFECTION). RX PubMed=29024643; DOI=10.1016/j.chom.2017.09.007; RA Wandel M.P., Pathe C., Werner E.I., Ellison C.J., Boyle K.B., RA von der Malsburg A., Rohde J., Randow F.; RT "GBPs inhibit motility of Shigella flexneri but are targeted for RT degradation by the bacterial ubiquitin ligase IpaH9.8."; RL Cell Host Microbe 22:507-518(2017). RN [17] RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF 584-ARG--ARG-586. RX PubMed=29233899; DOI=10.1128/mbio.01979-17; RA Piro A.S., Hernandez D., Luoma S., Feeley E.M., Finethy R., Yirga A., RA Frickel E.M., Lesser C.F., Coers J.; RT "Detection of cytosolic Shigella flexneri via a C-terminal triple-arginine RT motif of GBP1 inhibits actin-based motility."; RL MBio 8:0-0(2017). RN [18] RP UBIQUITINATION AT LYS-207; LYS-209; LYS-210; LYS-382; LYS-562; LYS-567; RP LYS-573 AND LYS-587 (MICROBIAL INFECTION), FUNCTION, ISOPRENYLATION AT RP CYS-589, AND MUTAGENESIS OF ARG-48; ASP-184; LYS-207; LYS-209; LYS-210; RP LYS-382; LYS-562; LYS-567; LYS-573; LYS-587 AND CYS-589. RX PubMed=29144452; DOI=10.1038/nature24467; RA Li P., Jiang W., Yu Q., Liu W., Zhou P., Li J., Xu J., Xu B., Wang F., RA Shao F.; RT "Ubiquitination and degradation of GBPs by a Shigella effector to suppress RT host defence."; RL Nature 551:378-383(2017). RN [19] RP FUNCTION, SUBCELLULAR LOCATION, ISOPRENYLATION AT CYS-589, AND MUTAGENESIS RP OF LYS-51; 227-ARG-LYS-228 AND CYS-589. RX PubMed=31268602; DOI=10.15252/embj.2018100926; RA Fisch D., Bando H., Clough B., Hornung V., Yamamoto M., Shenoy A.R., RA Frickel E.M.; RT "Human GBP1 is a microbe-specific gatekeeper of macrophage apoptosis and RT pyroptosis."; RL EMBO J. 38:e100926-e100926(2019). RN [20] RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, SUBCELLULAR LOCATION, ISOPRENYLATION RP AT CYS-589, AND MUTAGENESIS OF ARG-48; LYS-51; HIS-74 AND 584-ARG--ARG-586. RX PubMed=32510692; DOI=10.15252/embj.2020104926; RA Kutsch M., Sistemich L., Lesser C.F., Goldberg M.B., Herrmann C., Coers J.; RT "Direct binding of polymeric GBP1 to LPS disrupts bacterial cell envelope RT functions."; RL EMBO J. 39:e104926-e104926(2020). RN [21] RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, SUBCELLULAR LOCATION, AND RP MUTAGENESIS OF 61-LYS--LYS-63; 87-LYS-LYS-88; 207-LYS--LYS-210 AND RP 244-ARG--LYS-246. RX PubMed=32581219; DOI=10.1038/s41467-020-16889-z; RA Santos J.C., Boucher D., Schneider L.K., Demarco B., Dilucca M., RA Shkarina K., Heilig R., Chen K.W., Lim R.Y.H., Broz P.; RT "Human GBP1 binds LPS to initiate assembly of a caspase-4 activating RT platform on cytosolic bacteria."; RL Nat. Commun. 11:3276-3276(2020). RN [22] RP UBIQUITINATION (MICROBIAL INFECTION). RX PubMed=37014865; DOI=10.1073/pnas.2218469120; RA Goers L., Kim K., Stedman T.C., Canning P.J., Mou X., Ernst N.H., Coers J., RA Lesser C.F.; RT "Shigella IpaH9.8 limits GBP1-dependent LPS release from intracytosolic RT bacteria to suppress caspase-4 activation."; RL Proc. Natl. Acad. Sci. U.S.A. 120:e2218469120-e2218469120(2023). RN [23] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS), AND GTP-BINDING. RX PubMed=10676968; DOI=10.1038/35000617; RA Prakash B., Praefcke G.J.K., Renault L., Wittinghofer A., Herrmann C.; RT "Structure of human guanylate-binding protein 1 representing a unique class RT of GTP-binding proteins."; RL Nature 403:567-571(2000). RN [24] RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEX WITH GTP ANALOG, AND RP GTP-BINDING. RX PubMed=10970849; DOI=10.1093/emboj/19.17.4555; RA Prakash B., Renault L., Praefcke G.J., Herrmann C., Wittinghofer A.; RT "Triphosphate structure of guanylate-binding protein 1 and implications for RT nucleotide binding and GTPase mechanism."; RL EMBO J. 19:4555-4564(2000). RN [25] {ECO:0007744|PDB:2B8W, ECO:0007744|PDB:2B92, ECO:0007744|PDB:2BC9, ECO:0007744|PDB:2D4H} RP X-RAY CRYSTALLOGRAPHY (2.22 ANGSTROMS) OF 1-317 IN COMPLEX WITH GDP AND RP GMP, FUNCTION, CATALYTIC ACTIVITY, AND SUBUNIT. RX PubMed=16511497; DOI=10.1038/nature04510; RA Ghosh A., Praefcke G.J., Renault L., Wittinghofer A., Herrmann C.; RT "How guanylate-binding proteins achieve assembly-stimulated processive RT cleavage of GTP to GMP."; RL Nature 440:101-104(2006). RN [26] {ECO:0007744|PDB:6K1Z, ECO:0007744|PDB:6K2D} RP X-RAY CRYSTALLOGRAPHY (2.31 ANGSTROMS) IN COMPLEX WITH S.FLEXNERI IPAH9.8, RP AND UBIQUITINATION (MICROBIAL INFECTION). RX PubMed=31216343; DOI=10.1371/journal.ppat.1007876; RA Ji C., Du S., Li P., Zhu Q., Yang X., Long C., Yu J., Shao F., Xiao J.; RT "Structural mechanism for guanylate-binding proteins (GBPs) targeting by RT the Shigella E3 ligase IpaH9.8."; RL PLoS Pathog. 15:e1007876-e1007876(2019). RN [27] {ECO:0007744|PDB:6LOJ} RP X-RAY CRYSTALLOGRAPHY (3.72 ANGSTROMS) IN COMPLEX WITH S.FLEXNERI IPAH9.8, RP AND UBIQUITINATION (MICROBIAL INFECTION). RX PubMed=33303953; DOI=10.1038/s42003-020-01492-1; RA Ye Y., Xiong Y., Huang H.; RT "Substrate-binding destabilizes the hydrophobic cluster to relieve the RT autoinhibition of bacterial ubiquitin ligase IpaH9.8."; RL Commun. Biol. 3:752-752(2020). RN [28] {ECO:0007744|PDB:8Q4L} RP STRUCTURE BY ELECTRON MICROSCOPY (5.12 ANGSTROMS) OF 7-583 IN COMPLEX WITH RP SFN, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SFN, PHOSPHORYLATION RP AT SER-156 AND THR-590, AND MUTAGENESIS OF ARG-151; 153-ARG--PRO-158; RP ARG-153; LYS-155; SER-156; SER-157; TYR-427 AND THR-590. RX PubMed=37797010; DOI=10.1126/science.adg2253; RA Fisch D., Pfleiderer M.M., Anastasakou E., Mackie G.M., Wendt F., Liu X., RA Clough B., Lara-Reyna S., Encheva V., Snijders A.P., Bando H., Yamamoto M., RA Beggs A.D., Mercer J., Shenoy A.R., Wollscheid B., Maslowski K.M., RA Galej W.P., Frickel E.M.; RT "PIM1 controls GBP1 activity to limit self-damage and to guard against RT pathogen infection."; RL Science 382:eadg2253-eadg2253(2023). CC -!- FUNCTION: Interferon (IFN)-inducible GTPase that plays important roles CC in innate immunity against a diverse range of bacterial, viral and CC protozoan pathogens (PubMed:16511497, PubMed:22106366, PubMed:29144452, CC PubMed:31268602, PubMed:7512561, PubMed:37797010, PubMed:32510692, CC PubMed:32581219). Hydrolyzes GTP to GMP in two consecutive cleavage CC reactions: GTP is first hydrolyzed to GDP and then to GMP in a CC processive manner (PubMed:16511497, PubMed:32510692, PubMed:7512561). CC Following infection, recruited to the pathogen-containing vacuoles or CC vacuole-escaped bacteria and promotes both inflammasome assembly and CC autophagy (PubMed:29144452, PubMed:31268602). Acts as a positive CC regulator of inflammasome assembly by facilitating the detection of CC inflammasome ligands from pathogens (PubMed:31268602, PubMed:32510692, CC PubMed:32581219). Involved in the lysis of pathogen-containing CC vacuoles, releasing pathogens into the cytosol (By similarity). CC Following pathogen release in the cytosol, forms a protein coat in a CC GTPase-dependent manner that encapsulates pathogens and promotes the CC detection of ligands by pattern recognition receptors (PubMed:32510692, CC PubMed:32581219). Plays a key role in inflammasome assembly in response CC to infection by Gram-negative bacteria: following pathogen release in CC the cytosol, forms a protein coat that encapsulates Gram-negative CC bacteria and directly binds to lipopolysaccharide (LPS), disrupting the CC O-antigen barrier and unmasking lipid A that is that detected by the CC non-canonical inflammasome effector CASP4/CASP11 (PubMed:32510692, CC PubMed:32581219). Also promotes recruitment of proteins that mediate CC bacterial cytolysis, leading to release double-stranded DNA (dsDNA) CC that activates the AIM2 inflammasome (PubMed:31268602). Involved in CC autophagy by regulating bacteriolytic peptide generation via its CC interaction with ubiquitin-binding protein SQSTM1, which delivers CC monoubiquitinated proteins to autolysosomes for the generation of CC bacteriolytic peptides (By similarity). Confers protection to several CC pathogens, including the bacterial pathogens L.monocytogenes and CC M.bovis BCG as well as the protozoan pathogen T.gondii CC (PubMed:31268602). Exhibits antiviral activity against influenza virus CC (PubMed:22106366). {ECO:0000250|UniProtKB:Q01514, CC ECO:0000269|PubMed:16511497, ECO:0000269|PubMed:22106366, CC ECO:0000269|PubMed:29144452, ECO:0000269|PubMed:31268602, CC ECO:0000269|PubMed:32510692, ECO:0000269|PubMed:32581219, CC ECO:0000269|PubMed:37797010, ECO:0000269|PubMed:7512561}. CC -!- CATALYTIC ACTIVITY: CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; CC Evidence={ECO:0000269|PubMed:10676968, ECO:0000269|PubMed:16511497, CC ECO:0000269|PubMed:28645896, ECO:0000269|PubMed:32510692}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670; CC Evidence={ECO:0000269|PubMed:10676968, ECO:0000269|PubMed:16511497, CC ECO:0000269|PubMed:28645896, ECO:0000269|PubMed:32510692, CC ECO:0000269|PubMed:32581219}; CC -!- CATALYTIC ACTIVITY: CC Reaction=GDP + H2O = GMP + H(+) + phosphate; Xref=Rhea:RHEA:22156, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:58115, ChEBI:CHEBI:58189; CC Evidence={ECO:0000269|PubMed:16511497, ECO:0000269|PubMed:28645896, CC ECO:0000269|PubMed:32510692, ECO:0000269|PubMed:32581219}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22157; CC Evidence={ECO:0000269|PubMed:16511497, ECO:0000269|PubMed:28645896, CC ECO:0000269|PubMed:32510692}; CC -!- SUBUNIT: Homodimer; homodimerization occurs upon GTP-binding and is CC required for the second hydrolysis step from GDP to GMP CC (PubMed:10970849, PubMed:16511497). Undergoes conformational changes CC and oligomerization upon GTP-binding and hydrolysis (PubMed:28645896, CC PubMed:32510692, PubMed:32581219). Heterodimer with other family CC members, including GBP2, GBP3, GBP4 and GBP5 (PubMed:10970849, CC PubMed:16511497, PubMed:32581219). Dimerization regulates subcellular CC location to membranous structures (PubMed:21151871). Interacts with CC SQSTM1 (By similarity). Interacts (when phosphorylated) with 14-3-3 CC protein sigma (SFN); leading to GBP1 retention in the cytosol and CC inactivation (PubMed:37797010). {ECO:0000250|UniProtKB:Q01514, CC ECO:0000269|PubMed:10970849, ECO:0000269|PubMed:16511497, CC ECO:0000269|PubMed:21151871, ECO:0000269|PubMed:28645896, CC ECO:0000269|PubMed:32510692, ECO:0000269|PubMed:32581219, CC ECO:0000269|PubMed:37797010}. CC -!- INTERACTION: CC P32455; P32455: GBP1; NbExp=15; IntAct=EBI-2869161, EBI-2869161; CC P32455; P32456: GBP2; NbExp=9; IntAct=EBI-2869161, EBI-714388; CC P32455; Q9H0R5: GBP3; NbExp=3; IntAct=EBI-2869161, EBI-2798916; CC P32455; Q96PP9: GBP4; NbExp=2; IntAct=EBI-2869161, EBI-20840650; CC P32455; Q96PP8: GBP5; NbExp=9; IntAct=EBI-2869161, EBI-749932; CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle membrane CC {ECO:0000269|PubMed:29144452, ECO:0000269|PubMed:29233899, CC ECO:0000269|PubMed:31268602}; Lipid-anchor CC {ECO:0000269|PubMed:21151871}; Cytoplasmic side CC {ECO:0000269|PubMed:21151871}. Golgi apparatus membrane CC {ECO:0000269|PubMed:15937107}; Lipid-anchor CC {ECO:0000269|PubMed:21151871}; Cytoplasmic side CC {ECO:0000269|PubMed:21151871}. Cell membrane CC {ECO:0000269|PubMed:21151871}; Lipid-anchor CC {ECO:0000269|PubMed:21151871}; Cytoplasmic side CC {ECO:0000269|PubMed:21151871}. Cytoplasm, cytosol CC {ECO:0000269|PubMed:21151871, ECO:0000269|PubMed:37797010}. Secreted CC {ECO:0000269|PubMed:16936281}. Note=Localizes to pathogen-containing CC vacuoles or to the cell surface of bacteria that escaped vacuoles CC (PubMed:29144452, PubMed:31268602, PubMed:32510692, PubMed:32581219). CC Secreted from endothelial cells in the cerebrospinal fluid, upon CC bacterial challenge and independently of IFNG induction CC (PubMed:16936281). Golgi membrane localization requires isoprenylation CC and the presence of another IFNG-induced factor (PubMed:15937107). CC Sequestered in the cytosol following phosphorylation by PIM1 and CC subsequent interaction with 14-3-3 protein sigma (SFN) CC (PubMed:37797010). {ECO:0000269|PubMed:15937107, CC ECO:0000269|PubMed:16936281, ECO:0000269|PubMed:29144452, CC ECO:0000269|PubMed:31268602, ECO:0000269|PubMed:32510692, CC ECO:0000269|PubMed:32581219, ECO:0000269|PubMed:37797010}. CC -!- INDUCTION: By IFNG during macrophage activation, and by TNF and IL1B. CC {ECO:0000269|PubMed:17266443}. CC -!- PTM: Isoprenylation is required for proper subcellular location. CC {ECO:0000269|PubMed:21151871, ECO:0000269|PubMed:28645896, CC ECO:0000269|PubMed:31268602, ECO:0000269|PubMed:32510692}. CC -!- PTM: Phosphorylated at Ser-156 by PIM1 in absence of infection, CC inhibits GBP1: phosphorylation promotes interaction with 14-3-3 protein CC sigma (SFN), leading to GBP1 retention in the cytosol CC (PubMed:37797010). Dephosphorylated in response to infection, CC liberating GBP1 (PubMed:37797010). {ECO:0000269|PubMed:37797010}. CC -!- PTM: (Microbial infection) Ubiquitinated by S.flexneri IpaH9.8, leading CC to its degradation by the proteasome, thereby preventing its ability to CC promote host defense against bacterial infection. CC {ECO:0000269|PubMed:29024643, ECO:0000269|PubMed:29144452, CC ECO:0000269|PubMed:31216343, ECO:0000269|PubMed:33303953, CC ECO:0000269|PubMed:37014865}. CC -!- SIMILARITY: Belongs to the TRAFAC class dynamin-like GTPase CC superfamily. GB1/RHD3 GTPase family. GB1 subfamily. CC {ECO:0000255|PROSITE-ProRule:PRU01052}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/50147/GBP1"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M55542; AAA35871.1; -; mRNA. DR EMBL; BT006847; AAP35493.1; -; mRNA. DR EMBL; AK291783; BAF84472.1; -; mRNA. DR EMBL; AL160008; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471097; EAW73148.1; -; Genomic_DNA. DR EMBL; CH471097; EAW73150.1; -; Genomic_DNA. DR EMBL; BC002666; AAH02666.1; -; mRNA. DR CCDS; CCDS718.1; -. DR PIR; A41268; A41268. DR RefSeq; NP_002044.2; NM_002053.2. DR PDB; 1DG3; X-ray; 1.80 A; A=1-592. DR PDB; 1F5N; X-ray; 1.70 A; A=1-592. DR PDB; 2B8W; X-ray; 2.22 A; A/B=1-317. DR PDB; 2B92; X-ray; 3.20 A; A/B=1-317. DR PDB; 2BC9; X-ray; 2.80 A; A=1-317. DR PDB; 2D4H; X-ray; 2.90 A; A/B=1-317. DR PDB; 6K1Z; X-ray; 2.31 A; A=1-592. DR PDB; 6K2D; X-ray; 3.60 A; A=1-479. DR PDB; 6LOJ; X-ray; 3.72 A; B=1-592. DR PDB; 8Q4L; EM; 5.12 A; A=7-583. DR PDBsum; 1DG3; -. DR PDBsum; 1F5N; -. DR PDBsum; 2B8W; -. DR PDBsum; 2B92; -. DR PDBsum; 2BC9; -. DR PDBsum; 2D4H; -. DR PDBsum; 6K1Z; -. DR PDBsum; 6K2D; -. DR PDBsum; 6LOJ; -. DR PDBsum; 8Q4L; -. DR AlphaFoldDB; P32455; -. DR EMDB; EMD-18149; -. DR SASBDB; P32455; -. DR SMR; P32455; -. DR BioGRID; 108903; 41. DR DIP; DIP-60423N; -. DR IntAct; P32455; 13. DR MINT; P32455; -. DR STRING; 9606.ENSP00000359504; -. DR iPTMnet; P32455; -. DR MetOSite; P32455; -. DR PhosphoSitePlus; P32455; -. DR SwissPalm; P32455; -. DR BioMuta; GBP1; -. DR DMDM; 311033383; -. DR EPD; P32455; -. DR jPOST; P32455; -. DR MassIVE; P32455; -. DR MaxQB; P32455; -. DR PaxDb; 9606-ENSP00000359504; -. DR PeptideAtlas; P32455; -. DR ProteomicsDB; 54877; -. DR Pumba; P32455; -. DR Antibodypedia; 4224; 353 antibodies from 34 providers. DR DNASU; 2633; -. DR Ensembl; ENST00000370473.5; ENSP00000359504.4; ENSG00000117228.11. DR GeneID; 2633; -. DR KEGG; hsa:2633; -. DR MANE-Select; ENST00000370473.5; ENSP00000359504.4; NM_002053.3; NP_002044.2. DR UCSC; uc001dmx.3; human. DR AGR; HGNC:4182; -. DR CTD; 2633; -. DR DisGeNET; 2633; -. DR GeneCards; GBP1; -. DR HGNC; HGNC:4182; GBP1. DR HPA; ENSG00000117228; Tissue enhanced (liver). DR MIM; 600411; gene. DR neXtProt; NX_P32455; -. DR OpenTargets; ENSG00000117228; -. DR PharmGKB; PA28596; -. DR VEuPathDB; HostDB:ENSG00000117228; -. DR eggNOG; KOG2037; Eukaryota. DR GeneTree; ENSGT00940000156840; -. DR HOGENOM; CLU_018608_2_2_1; -. DR InParanoid; P32455; -. DR OMA; MQNEIRN; -. DR OrthoDB; 5309032at2759; -. DR PhylomeDB; P32455; -. DR TreeFam; TF331602; -. DR PathwayCommons; P32455; -. DR Reactome; R-HSA-877300; Interferon gamma signaling. DR SignaLink; P32455; -. DR BioGRID-ORCS; 2633; 22 hits in 1144 CRISPR screens. DR ChiTaRS; GBP1; human. DR EvolutionaryTrace; P32455; -. DR GeneWiki; GBP1; -. DR GenomeRNAi; 2633; -. DR Pharos; P32455; Tbio. DR PRO; PR:P32455; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; P32455; Protein. DR Bgee; ENSG00000117228; Expressed in pericardium and 196 other cell types or tissues. DR GO; GO:0015629; C:actin cytoskeleton; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProt. DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0106139; C:symbiont cell surface; IDA:UniProtKB. DR GO; GO:0012506; C:vesicle membrane; IDA:UniProtKB. DR GO; GO:0003779; F:actin binding; IDA:UniProtKB. DR GO; GO:0019955; F:cytokine binding; IPI:UniProtKB. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0003925; F:G protein activity; IDA:UniProtKB. DR GO; GO:0019003; F:GDP binding; IDA:CAFA. DR GO; GO:0004382; F:GDP phosphatase activity; IDA:UniProtKB. DR GO; GO:0005525; F:GTP binding; IDA:UniProtKB. DR GO; GO:0003924; F:GTPase activity; IDA:UniProtKB. DR GO; GO:0051879; F:Hsp90 protein binding; IPI:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0001530; F:lipopolysaccharide binding; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0030507; F:spectrin binding; IPI:UniProtKB. DR GO; GO:0071347; P:cellular response to interleukin-1; IEP:UniProtKB. DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:UniProtKB. DR GO; GO:0071346; P:cellular response to type II interferon; IDA:UniProtKB. DR GO; GO:0051715; P:cytolysis in another organism; IDA:UniProtKB. DR GO; GO:0042742; P:defense response to bacterium; IDA:UniProtKB. DR GO; GO:0042832; P:defense response to protozoan; IDA:UniProtKB. DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW. DR GO; GO:0045087; P:innate immune response; IDA:UniProtKB. DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IMP:UniProtKB. DR GO; GO:0032703; P:negative regulation of interleukin-2 production; IMP:UniProtKB. DR GO; GO:1903077; P:negative regulation of protein localization to plasma membrane; IMP:UniProtKB. DR GO; GO:1900025; P:negative regulation of substrate adhesion-dependent cell spreading; IMP:UniProtKB. DR GO; GO:0050860; P:negative regulation of T cell receptor signaling pathway; IMP:UniProtKB. DR GO; GO:0160075; P:non-canonical inflammasome complex assembly; IDA:UniProtKB. DR GO; GO:0140639; P:positive regulation of pyroptosis; IDA:UniProtKB. DR GO; GO:0072665; P:protein localization to vacuole; IDA:UniProtKB. DR GO; GO:0050848; P:regulation of calcium-mediated signaling; IMP:UniProtKB. DR GO; GO:1903076; P:regulation of protein localization to plasma membrane; IGI:UniProtKB. DR CDD; cd01851; GBP; 1. DR CDD; cd16269; GBP_C; 1. DR Gene3D; 1.20.1000.10; Guanylate-binding protein, C-terminal domain; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR InterPro; IPR030386; G_GB1_RHD3_dom. DR InterPro; IPR037684; GBP_C. DR InterPro; IPR003191; Guanylate-bd/ATL_C. DR InterPro; IPR036543; Guanylate-bd_C_sf. DR InterPro; IPR015894; Guanylate-bd_N. DR InterPro; IPR027417; P-loop_NTPase. DR PANTHER; PTHR10751; GUANYLATE BINDING PROTEIN; 1. DR PANTHER; PTHR10751:SF113; GUANYLATE-BINDING PROTEIN 1; 1. DR Pfam; PF02263; GBP; 1. DR Pfam; PF02841; GBP_C; 1. DR SUPFAM; SSF48340; Interferon-induced guanylate-binding protein 1 (GBP1), C-terminal domain; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS51715; G_GB1_RHD3; 1. DR Genevisible; P32455; HS. PE 1: Evidence at protein level; KW 3D-structure; Antiviral defense; Cell membrane; Cytoplasm; KW Cytoplasmic vesicle; Golgi apparatus; GTP-binding; Hydrolase; Immunity; KW Innate immunity; Isopeptide bond; Lipoprotein; Membrane; Methylation; KW Nucleotide-binding; Phosphoprotein; Prenylation; Reference proteome; KW Secreted; Ubl conjugation. FT CHAIN 1..589 FT /note="Guanylate-binding protein 1" FT /id="PRO_0000190963" FT PROPEP 590..592 FT /note="Removed in mature form" FT /evidence="ECO:0000305|PubMed:8830800" FT /id="PRO_0000396777" FT DOMAIN 35..278 FT /note="GB1/RHD3-type G" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01052" FT REGION 1..311 FT /note="GTPase domain (Globular)" FT /evidence="ECO:0000305|PubMed:10676968" FT BINDING 45..52 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000269|PubMed:10676968, FT ECO:0000269|PubMed:10970849, ECO:0000269|PubMed:16511497, FT ECO:0007744|PDB:1F5N, ECO:0007744|PDB:2B8W, FT ECO:0007744|PDB:2B92, ECO:0007744|PDB:2D4H" FT BINDING 67..69 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000269|PubMed:10676968, FT ECO:0000269|PubMed:10970849, ECO:0000269|PubMed:16511497, FT ECO:0007744|PDB:1F5N, ECO:0007744|PDB:2B8W, FT ECO:0007744|PDB:2B92, ECO:0007744|PDB:2D4H" FT BINDING 97..101 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000269|PubMed:10676968, FT ECO:0000269|PubMed:10970849, ECO:0007744|PDB:1F5N" FT MOD_RES 156 FT /note="Phosphoserine; by PIM1" FT /evidence="ECO:0000269|PubMed:37797010" FT MOD_RES 589 FT /note="Cysteine methyl ester" FT /evidence="ECO:0000305|PubMed:8830800" FT MOD_RES 590 FT /note="Phosphothreonine; by PIM1" FT /evidence="ECO:0000269|PubMed:37797010" FT LIPID 589 FT /note="S-farnesyl cysteine" FT /evidence="ECO:0000269|PubMed:29144452, FT ECO:0000269|PubMed:31268602, ECO:0000269|PubMed:32510692, FT ECO:0000269|PubMed:8830800" FT CROSSLNK 207 FT /note="(Microbial infection) Glycyl lysine isopeptide (Lys- FT Gly) (interchain with G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:29144452" FT CROSSLNK 209 FT /note="(Microbial infection) Glycyl lysine isopeptide (Lys- FT Gly) (interchain with G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:29144452" FT CROSSLNK 210 FT /note="(Microbial infection) Glycyl lysine isopeptide (Lys- FT Gly) (interchain with G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:29144452" FT CROSSLNK 382 FT /note="(Microbial infection) Glycyl lysine isopeptide (Lys- FT Gly) (interchain with G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:29144452" FT CROSSLNK 562 FT /note="(Microbial infection) Glycyl lysine isopeptide (Lys- FT Gly) (interchain with G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:29144452" FT CROSSLNK 567 FT /note="(Microbial infection) Glycyl lysine isopeptide (Lys- FT Gly) (interchain with G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:29144452" FT CROSSLNK 573 FT /note="(Microbial infection) Glycyl lysine isopeptide (Lys- FT Gly) (interchain with G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:29144452" FT CROSSLNK 587 FT /note="(Microbial infection) Glycyl lysine isopeptide (Lys- FT Gly) (interchain with G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:29144452" FT VARIANT 78 FT /note="I -> V (in dbSNP:rs1048401)" FT /id="VAR_033950" FT VARIANT 166 FT /note="E -> D (in dbSNP:rs17130717)" FT /id="VAR_033951" FT VARIANT 349 FT /note="T -> S (in dbSNP:rs1048425)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:1715024, ECO:0000269|Ref.2" FT /id="VAR_014849" FT VARIANT 409 FT /note="A -> G (in dbSNP:rs1048443)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:1715024, ECO:0000269|Ref.2" FT /id="VAR_046550" FT MUTAGEN 48 FT /note="R->A: Abolished GTPase activity." FT /evidence="ECO:0000269|PubMed:28645896, FT ECO:0000269|PubMed:29144452, ECO:0000269|PubMed:32510692" FT MUTAGEN 51 FT /note="K->A: Loss of GTPase activity. Constitutively FT monomeric. Expressed throughout the cytoplasm, loss of FT vesicular accumulation. Impaired ability to promote FT pyroptosis in response to T.gondii infection." FT /evidence="ECO:0000269|PubMed:31268602, FT ECO:0000269|PubMed:32510692, ECO:0000305|PubMed:21151871" FT MUTAGEN 61..63 FT /note="KKK->AAA: Impaired homooligomarization and FT localization to bacterial surface." FT /evidence="ECO:0000269|PubMed:32581219" FT MUTAGEN 74 FT /note="H->A: Abolished GDP hydrolysis." FT /evidence="ECO:0000269|PubMed:32510692" FT MUTAGEN 76 FT /note="K->A: Abolished GDPase activity." FT /evidence="ECO:0000269|PubMed:28645896" FT MUTAGEN 87..88 FT /note="KK->AA: Does not affect localization to bacterial FT surface." FT /evidence="ECO:0000269|PubMed:32581219" FT MUTAGEN 151 FT /note="R->A: Reduced phosphorylation by PIM1." FT /evidence="ECO:0000269|PubMed:37797010" FT MUTAGEN 153..158 FT /note="RSKSSP->ASKSSA: Abolished phosphorylation by PIM1 FT and interaction with 14-3-3 protein sigma (SFN)." FT /evidence="ECO:0000269|PubMed:37797010" FT MUTAGEN 153 FT /note="R->A: Abolished phosphorylation by PIM1." FT /evidence="ECO:0000269|PubMed:37797010" FT MUTAGEN 155 FT /note="K->A: Abolished phosphorylation by PIM1." FT /evidence="ECO:0000269|PubMed:37797010" FT MUTAGEN 156 FT /note="S->A: Reduced phosphorylation by PIM1, leading to FT hyperactivation and Golgi fragmentation." FT /evidence="ECO:0000269|PubMed:37797010" FT MUTAGEN 157 FT /note="S->A: No effect." FT /evidence="ECO:0000269|PubMed:37797010" FT MUTAGEN 184 FT /note="D->N: Strongly decreased nucleotide-binding." FT /evidence="ECO:0000269|PubMed:29144452" FT MUTAGEN 207..210 FT /note="KLKK->ALAA: Does not affect localization to FT bacterial surface." FT /evidence="ECO:0000269|PubMed:32581219" FT MUTAGEN 207 FT /note="K->R: In 8KR mutant; abolished ubiquitination by S. FT flexneri IpaH9.8 when associated with R-209, R-210, R-382, FT R-562, R-567, R-573 and R-587." FT /evidence="ECO:0000269|PubMed:29144452" FT MUTAGEN 209 FT /note="K->R: In 8KR mutant; abolished ubiquitination by S. FT flexneri IpaH9.8 when associated with R-207, R-210, R-382, FT R-562, R-567, R-573 and R-587." FT /evidence="ECO:0000269|PubMed:29144452" FT MUTAGEN 210 FT /note="K->R: In 8KR mutant; abolished ubiquitination by S. FT flexneri IpaH9.8 when associated with R-207, R-209, R-382, FT R-562, R-567, R-573 and R-587." FT /evidence="ECO:0000269|PubMed:29144452" FT MUTAGEN 227..228 FT /note="RK->EE: Constitutively dimeric. Localizes at FT vesicle-like structures at the plasma membrane." FT /evidence="ECO:0000269|PubMed:21151871, FT ECO:0000269|PubMed:31268602" FT MUTAGEN 244..246 FT /note="RRK->AAA: Does not affect localization to bacterial FT surface." FT /evidence="ECO:0000269|PubMed:32581219" FT MUTAGEN 382 FT /note="K->R: In 8KR mutant; abolished ubiquitination by S. FT flexneri IpaH9.8 when associated with R-207, R-209, R-210, FT R-562, R-567, R-573 and R-587." FT /evidence="ECO:0000269|PubMed:29144452" FT MUTAGEN 427 FT /note="Y->F: No effect." FT /evidence="ECO:0000269|PubMed:37797010" FT MUTAGEN 562 FT /note="K->R: In 8KR mutant; abolished ubiquitination by S. FT flexneri IpaH9.8 when associated with R-207, R-209, R-210, FT R-382, R-567, R-573 and R-587." FT /evidence="ECO:0000269|PubMed:29144452" FT MUTAGEN 567 FT /note="K->R: In 8KR mutant; abolished ubiquitination by S. FT flexneri IpaH9.8 when associated with R-207, R-209, R-210, FT R-382, R-562, R-573 and R-587." FT /evidence="ECO:0000269|PubMed:29144452" FT MUTAGEN 573 FT /note="K->R: In 8KR mutant; abolished ubiquitination by S. FT flexneri IpaH9.8 when associated with R-207, R-209, R-210, FT R-382, R-562, R-567 and R-587." FT /evidence="ECO:0000269|PubMed:29144452" FT MUTAGEN 584..586 FT /note="RRR->AAA: Abolished localization to FT pathogen-containing vacuoles. Abolished binding to FT bacterial surface." FT /evidence="ECO:0000269|PubMed:29233899, FT ECO:0000269|PubMed:32510692" FT MUTAGEN 584..586 FT /note="Missing: Abolished localization to FT pathogen-containing vacuoles." FT /evidence="ECO:0000269|PubMed:29233899" FT MUTAGEN 587 FT /note="K->R: In 8KR mutant; abolished ubiquitination by S. FT flexneri IpaH9.8 when associated with R-207, R-209, R-210, FT R-382, R-562, R-567 and R-573." FT /evidence="ECO:0000269|PubMed:29144452" FT MUTAGEN 589..592 FT /note="Missing: Loss of association with membranes." FT /evidence="ECO:0000269|PubMed:21151871" FT MUTAGEN 589 FT /note="C->S: Abolished farnesylation and recruitment to the FT pathogen-containing vacuoles or vacuole-escaped bacteria. FT Impaired ability to promote pyroptosis in response to FT T.gondii infection." FT /evidence="ECO:0000269|PubMed:29144452, FT ECO:0000269|PubMed:31268602" FT MUTAGEN 590 FT /note="T->A: Does not affect interaction with 14-3-3 FT protein sigma (SFN)." FT /evidence="ECO:0000269|PubMed:37797010" FT STRAND 11..17 FT /evidence="ECO:0007829|PDB:1F5N" FT STRAND 20..23 FT /evidence="ECO:0007829|PDB:1F5N" FT HELIX 25..32 FT /evidence="ECO:0007829|PDB:1F5N" FT STRAND 36..46 FT /evidence="ECO:0007829|PDB:1F5N" FT HELIX 47..49 FT /evidence="ECO:0007829|PDB:1DG3" FT HELIX 51..58 FT /evidence="ECO:0007829|PDB:1F5N" FT STRAND 62..65 FT /evidence="ECO:0007829|PDB:2B8W" FT STRAND 70..72 FT /evidence="ECO:0007829|PDB:1F5N" FT STRAND 77..84 FT /evidence="ECO:0007829|PDB:1F5N" FT STRAND 86..88 FT /evidence="ECO:0007829|PDB:1F5N" FT STRAND 92..98 FT /evidence="ECO:0007829|PDB:1F5N" FT TURN 101..103 FT /evidence="ECO:0007829|PDB:1DG3" FT HELIX 104..106 FT /evidence="ECO:0007829|PDB:1F5N" FT HELIX 112..122 FT /evidence="ECO:0007829|PDB:1F5N" FT STRAND 124..132 FT /evidence="ECO:0007829|PDB:1F5N" FT HELIX 136..140 FT /evidence="ECO:0007829|PDB:1F5N" FT HELIX 143..146 FT /evidence="ECO:0007829|PDB:1F5N" FT HELIX 148..151 FT /evidence="ECO:0007829|PDB:1F5N" FT STRAND 156..158 FT /evidence="ECO:0007829|PDB:2D4H" FT HELIX 167..170 FT /evidence="ECO:0007829|PDB:1F5N" FT HELIX 171..174 FT /evidence="ECO:0007829|PDB:1F5N" FT STRAND 177..183 FT /evidence="ECO:0007829|PDB:1F5N" FT STRAND 192..194 FT /evidence="ECO:0007829|PDB:1F5N" FT HELIX 198..205 FT /evidence="ECO:0007829|PDB:1F5N" FT HELIX 214..229 FT /evidence="ECO:0007829|PDB:1F5N" FT STRAND 233..237 FT /evidence="ECO:0007829|PDB:1F5N" FT HELIX 244..252 FT /evidence="ECO:0007829|PDB:1F5N" FT HELIX 255..257 FT /evidence="ECO:0007829|PDB:1F5N" FT HELIX 260..276 FT /evidence="ECO:0007829|PDB:1F5N" FT TURN 283..285 FT /evidence="ECO:0007829|PDB:1F5N" FT HELIX 290..306 FT /evidence="ECO:0007829|PDB:1F5N" FT HELIX 312..342 FT /evidence="ECO:0007829|PDB:1F5N" FT HELIX 350..371 FT /evidence="ECO:0007829|PDB:1F5N" FT HELIX 376..378 FT /evidence="ECO:0007829|PDB:1F5N" FT HELIX 379..423 FT /evidence="ECO:0007829|PDB:1F5N" FT TURN 424..427 FT /evidence="ECO:0007829|PDB:1F5N" FT HELIX 432..449 FT /evidence="ECO:0007829|PDB:1F5N" FT HELIX 457..467 FT /evidence="ECO:0007829|PDB:1F5N" FT HELIX 469..478 FT /evidence="ECO:0007829|PDB:1F5N" FT STRAND 480..482 FT /evidence="ECO:0007829|PDB:1F5N" FT HELIX 484..563 FT /evidence="ECO:0007829|PDB:1F5N" FT HELIX 566..582 FT /evidence="ECO:0007829|PDB:1F5N" SQ SEQUENCE 592 AA; 67931 MW; 3A06741218360732 CRC64; MASEIHMTGP MCLIENTNGR LMANPEALKI LSAITQPMVV VAIVGLYRTG KSYLMNKLAG KKKGFSLGST VQSHTKGIWM WCVPHPKKPG HILVLLDTEG LGDVEKGDNQ NDSWIFALAV LLSSTFVYNS IGTINQQAMD QLYYVTELTH RIRSKSSPDE NENEVEDSAD FVSFFPDFVW TLRDFSLDLE ADGQPLTPDE YLTYSLKLKK GTSQKDETFN LPRLCIRKFF PKKKCFVFDR PVHRRKLAQL EKLQDEELDP EFVQQVADFC SYIFSNSKTK TLSGGIQVNG PRLESLVLTY VNAISSGDLP CMENAVLALA QIENSAAVQK AIAHYEQQMG QKVQLPTETL QELLDLHRDS EREAIEVFIR SSFKDVDHLF QKELAAQLEK KRDDFCKQNQ EASSDRCSAL LQVIFSPLEE EVKAGIYSKP GGYRLFVQKL QDLKKKYYEE PRKGIQAEEI LQTYLKSKES MTDAILQTDQ TLTEKEKEIE VERVKAESAQ ASAKMLQEMQ RKNEQMMEQK ERSYQEHLKQ LTEKMENDRV QLLKEQERTL ALKLQEQEQL LKEGFQKESR IMKNEIQDLQ TKMRRRKACT IS //