GBP3_HUMAN
ID GBP3_HUMAN Reviewed; 595 AA.
AC Q9H0R5; A2A317; A6NF86; B2RTW0; F8UW81; Q05D54; Q5T8L8; Q5T8L9; Q6P3V3;
AC Q9NV33;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 20-JAN-2009, sequence version 3.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Guanylate-binding protein 3;
DE EC=3.6.5.- {ECO:0000250|UniProtKB:P32455};
DE AltName: Full=GTP-binding protein 3;
DE Short=GBP-3;
DE AltName: Full=Guanine nucleotide-binding protein 3;
GN Name=GBP3;
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] (ISOFORM 2), FUNCTION, VARIANT TRP-225, AND
RP ALTERNATIVE SPLICING.
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [3]
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 [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS GLN-221
RP AND TRP-225.
RC TISSUE=Prostate;
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 [6]
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 [7]
RP SUBCELLULAR LOCATION, AND DIMERIZATION.
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).
CC -!- FUNCTION: Exhibits antiviral activity against influenza virus.
CC {ECO:0000269|PubMed:22106366}.
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:0000250|UniProtKB:P32455};
CC -!- SUBUNIT: Heterodimer with other family members, including GBP1, GBP2
CC and GBP5 (PubMed:21151871). Dimerization regulates subcellular
CC location. {ECO:0000269|PubMed:21151871}.
CC -!- INTERACTION:
CC Q9H0R5; P32455: GBP1; NbExp=3; IntAct=EBI-2798916, EBI-2869161;
CC Q9H0R5; P32456: GBP2; NbExp=3; IntAct=EBI-2798916, EBI-714388;
CC Q9H0R5; Q9H0R5: GBP3; NbExp=2; IntAct=EBI-2798916, EBI-2798916;
CC Q9H0R5; Q96PP8: GBP5; NbExp=2; IntAct=EBI-2798916, EBI-749932;
CC Q9H0R5; O95819: MAP4K4; NbExp=4; IntAct=EBI-2798916, EBI-2511133;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17266443}.
CC Cytoplasm, perinuclear region {ECO:0000269|PubMed:21151871}. Golgi
CC apparatus membrane {ECO:0000269|PubMed:21151871}. Note=Heterodimers
CC with GBP1, GBP2 and GBP5 localize in the compartment of the prenylated
CC GBPs: with GBP1 in a vesicle-like compartment, with GBP2, around the
CC nucleus and with GBP-5, at the Golgi apparatus.
CC {ECO:0000269|PubMed:21151871}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H0R5-1; Sequence=Displayed;
CC Name=2; Synonyms=GBP-3DeltaC;
CC IsoId=Q9H0R5-4; Sequence=VSP_044360, VSP_044361;
CC -!- MISCELLANEOUS: [Isoform 2]: Shows the most prominent antiviral activity
CC in epithelial cells. {ECO:0000305}.
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 -!- SEQUENCE CAUTION:
CC Sequence=AAH17992.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC Sequence=CAB66615.1; Type=Miscellaneous discrepancy; Note=Unlikely isoform. Aberrant splice sites.; Evidence={ECO:0000305};
CC Sequence=EAW73151.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; JF927951; AEI54565.1; -; mRNA.
DR EMBL; AL136680; CAB66615.1; ALT_SEQ; mRNA.
DR EMBL; AL139416; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL160008; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471097; EAW73151.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC017992; AAH17992.1; ALT_SEQ; mRNA.
DR EMBL; BC140837; AAI40838.1; -; mRNA.
DR CCDS; CCDS717.2; -. [Q9H0R5-1]
DR RefSeq; NP_001306110.1; NM_001319181.1. [Q9H0R5-4]
DR RefSeq; NP_060754.2; NM_018284.2. [Q9H0R5-1]
DR AlphaFoldDB; Q9H0R5; -.
DR SMR; Q9H0R5; -.
DR BioGRID; 108905; 9.
DR IntAct; Q9H0R5; 7.
DR MINT; Q9H0R5; -.
DR STRING; 9606.ENSP00000359512; -.
DR iPTMnet; Q9H0R5; -.
DR PhosphoSitePlus; Q9H0R5; -.
DR BioMuta; GBP3; -.
DR DMDM; 221222526; -.
DR EPD; Q9H0R5; -.
DR jPOST; Q9H0R5; -.
DR MassIVE; Q9H0R5; -.
DR MaxQB; Q9H0R5; -.
DR PaxDb; Q9H0R5; -.
DR PeptideAtlas; Q9H0R5; -.
DR PRIDE; Q9H0R5; -.
DR ProteomicsDB; 80318; -. [Q9H0R5-1]
DR Antibodypedia; 51594; 149 antibodies from 26 providers.
DR DNASU; 2635; -.
DR Ensembl; ENST00000370481.9; ENSP00000359512.4; ENSG00000117226.12. [Q9H0R5-1]
DR GeneID; 2635; -.
DR KEGG; hsa:2635; -.
DR MANE-Select; ENST00000370481.9; ENSP00000359512.4; NM_018284.3; NP_060754.2.
DR UCSC; uc001dmt.4; human. [Q9H0R5-1]
DR CTD; 2635; -.
DR DisGeNET; 2635; -.
DR GeneCards; GBP3; -.
DR HGNC; HGNC:4184; GBP3.
DR HPA; ENSG00000117226; Tissue enhanced (intestine).
DR MIM; 600413; gene.
DR neXtProt; NX_Q9H0R5; -.
DR OpenTargets; ENSG00000117226; -.
DR PharmGKB; PA28598; -.
DR VEuPathDB; HostDB:ENSG00000117226; -.
DR eggNOG; KOG2037; Eukaryota.
DR GeneTree; ENSGT00940000164799; -.
DR HOGENOM; CLU_018608_2_2_1; -.
DR InParanoid; Q9H0R5; -.
DR OMA; ELTKHVC; -.
DR OrthoDB; 1027269at2759; -.
DR PhylomeDB; Q9H0R5; -.
DR TreeFam; TF331602; -.
DR PathwayCommons; Q9H0R5; -.
DR Reactome; R-HSA-877300; Interferon gamma signaling.
DR SignaLink; Q9H0R5; -.
DR BioGRID-ORCS; 2635; 12 hits in 1071 CRISPR screens.
DR ChiTaRS; GBP3; human.
DR GenomeRNAi; 2635; -.
DR Pharos; Q9H0R5; Tbio.
DR PRO; PR:Q9H0R5; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9H0R5; protein.
DR Bgee; ENSG00000117226; Expressed in ileal mucosa and 183 other tissues.
DR ExpressionAtlas; Q9H0R5; baseline and differential.
DR Genevisible; Q9H0R5; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005525; F:GTP binding; IBA:GO_Central.
DR GO; GO:0003924; F:GTPase activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0071346; P:cellular response to interferon-gamma; IBA:GO_Central.
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:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR CDD; cd16269; GBP_C; 1.
DR Gene3D; 3.40.50.300; -; 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 Pfam; PF02263; GBP; 1.
DR Pfam; PF02841; GBP_C; 1.
DR SUPFAM; SSF48340; SSF48340; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS51715; G_GB1_RHD3; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Antiviral defense; Coiled coil; Cytoplasm;
KW Golgi apparatus; GTP-binding; Hydrolase; Immunity; Membrane;
KW Nucleotide-binding; Reference proteome.
FT CHAIN 1..595
FT /note="Guanylate-binding protein 3"
FT /id="PRO_0000261159"
FT DOMAIN 35..276
FT /note="GB1/RHD3-type G"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01052"
FT REGION 1..309
FT /note="GTPase domain (Globular)"
FT /evidence="ECO:0000250|UniProtKB:P32455"
FT COILED 482..595
FT /evidence="ECO:0000255"
FT BINDING 45..52
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P32455"
FT BINDING 67..69
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P32455"
FT BINDING 97..101
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P32455"
FT VAR_SEQ 357..383
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:22106366"
FT /id="VSP_044360"
FT VAR_SEQ 554..595
FT /note="EQARVLKERCQGESTQLQNEIQKLQKTLKKKTKRYMSHKLKI -> VSKCIT
FT LWFVFLFSLCSS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:22106366"
FT /id="VSP_044361"
FT VARIANT 221
FT /note="R -> Q (in dbSNP:rs4656078)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_054136"
FT VARIANT 225
FT /note="R -> W (in dbSNP:rs4656077)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:22106366"
FT /id="VAR_054137"
FT VARIANT 347
FT /note="T -> S (in dbSNP:rs3188433)"
FT /id="VAR_054138"
FT VARIANT 469
FT /note="V -> M (in dbSNP:rs10493821)"
FT /id="VAR_029082"
FT VARIANT 491
FT /note="C -> R (in dbSNP:rs17433780)"
FT /id="VAR_029083"
FT VARIANT 558
FT /note="V -> A (in dbSNP:rs11808228)"
FT /id="VAR_029084"
FT CONFLICT 271
FT /note="I -> T (in Ref. 5; AAH17992)"
FT /evidence="ECO:0000305"
FT CONFLICT 290
FT /note="R -> C (in Ref. 1; CAB66615 and 4; AAI40838)"
FT /evidence="ECO:0000305"
FT CONFLICT 334
FT /note="D -> G (in Ref. 5; AAH17992)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 595 AA; 68114 MW; 410A9BED9ABD2DDF CRC64;
MAPEIHMTGP MCLIENTNGE LVANPEALKI LSAITQPVVV VAIVGLYRTG KSYLMNKLAG
KNKGFSLGST VKSHTKGIWM WCVPHPKKPE HTLVLLDTEG LGDVKKGDNQ NDSWIFTLAV
LLSSTLVYNS MGTINQQAMD QLYYVTELTH RIRSKSSPDE NENEDSADFV SFFPDFVWTL
RDFSLDLEAD GQPLTPDEYL EYSLKLTQGT SQKDKNFNLP RLCIRKFFPK KKCFVFDLPI
HRRKLAQLEK LQDEELDPEF VQQVADFCSY IFSNSKTKTL SGGIKVNGPR LESLVLTYIN
AISRGDLPCM ENAVLALAQI ENSAAVQKAI AHYDQQMGQK VQLPAETLQE LLDLHRVSER
EATEVYMKNS FKDVDHLFQK KLAAQLDKKR DDFCKQNQEA SSDRCSALLQ VIFSPLEEEV
KAGIYSKPGG YCLFIQKLQD LEKKYYEEPR KGIQAEEILQ TYLKSKESVT DAILQTDQIL
TEKEKEIEVE CVKAESAQAS AKMVEEMQIK YQQMMEEKEK SYQEHVKQLT EKMERERAQL
LEEQEKTLTS KLQEQARVLK ERCQGESTQL QNEIQKLQKT LKKKTKRYMS HKLKI
