GBP6_HUMAN
ID GBP6_HUMAN Reviewed; 633 AA.
AC Q6ZN66; A2RRM3; Q6ZN86; Q7Z3F0;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Guanylate-binding protein 6;
DE EC=3.6.5.- {ECO:0000250|UniProtKB:P32455};
DE AltName: Full=GTP-binding protein 6;
DE Short=GBP-6;
DE AltName: Full=Guanine nucleotide-binding protein 6;
GN Name=GBP6;
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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANTS
RP PHE-344; VAL-355 AND VAL-520.
RC TISSUE=Esophageal carcinoma, and Trachea;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS SER-331;
RP PHE-344; VAL-355 AND VAL-520.
RC TISSUE=Retina;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
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 MRNA] (ISOFORM 1), AND VARIANTS SER-331;
RP PHE-344; VAL-355 AND VAL-520.
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).
CC -!- FUNCTION: Hydrolyzes GTP to GMP in 2 consecutive cleavage reactions (By
CC similarity). Confers protection to several pathogens, including the
CC bacterial pathogens Listeria monocytogenes and Mycobacterium bovis BCG
CC as well as the protozoan pathogen Toxoplasma gondii (By similarity).
CC {ECO:0000250|UniProtKB:A0A0G2JDV3, ECO:0000250|UniProtKB:P32455}.
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 -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle
CC {ECO:0000250|UniProtKB:A0A0G2JDV3}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6ZN66-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6ZN66-2; Sequence=VSP_030155;
CC -!- SIMILARITY: Belongs to the TRAFAC class dynamin-like GTPase
CC superfamily. GB1/RHD3 GTPase family. GB1 subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU01052}.
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DR EMBL; AK131329; BAD18489.1; -; mRNA.
DR EMBL; AK131356; BAD18509.1; -; mRNA.
DR EMBL; BX537949; CAD97917.1; -; mRNA.
DR EMBL; AL691464; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC131713; AAI31714.1; -; mRNA.
DR CCDS; CCDS723.1; -. [Q6ZN66-1]
DR RefSeq; NP_940862.2; NM_198460.2. [Q6ZN66-1]
DR RefSeq; XP_011539137.1; XM_011540835.2. [Q6ZN66-1]
DR AlphaFoldDB; Q6ZN66; -.
DR SMR; Q6ZN66; -.
DR BioGRID; 127864; 19.
DR IntAct; Q6ZN66; 9.
DR STRING; 9606.ENSP00000359485; -.
DR iPTMnet; Q6ZN66; -.
DR PhosphoSitePlus; Q6ZN66; -.
DR BioMuta; GBP6; -.
DR DMDM; 74749570; -.
DR EPD; Q6ZN66; -.
DR jPOST; Q6ZN66; -.
DR MassIVE; Q6ZN66; -.
DR MaxQB; Q6ZN66; -.
DR PaxDb; Q6ZN66; -.
DR PeptideAtlas; Q6ZN66; -.
DR PRIDE; Q6ZN66; -.
DR ProteomicsDB; 67986; -. [Q6ZN66-1]
DR ProteomicsDB; 67987; -. [Q6ZN66-2]
DR Antibodypedia; 33619; 91 antibodies from 25 providers.
DR DNASU; 163351; -.
DR Ensembl; ENST00000370456.5; ENSP00000359485.5; ENSG00000183347.15. [Q6ZN66-1]
DR GeneID; 163351; -.
DR KEGG; hsa:163351; -.
DR MANE-Select; ENST00000370456.5; ENSP00000359485.5; NM_198460.3; NP_940862.2.
DR UCSC; uc001dnf.3; human. [Q6ZN66-1]
DR CTD; 163351; -.
DR DisGeNET; 163351; -.
DR GeneCards; GBP6; -.
DR HGNC; HGNC:25395; GBP6.
DR HPA; ENSG00000183347; Tissue enriched (esophagus).
DR MIM; 612467; gene.
DR neXtProt; NX_Q6ZN66; -.
DR OpenTargets; ENSG00000183347; -.
DR PharmGKB; PA134964409; -.
DR VEuPathDB; HostDB:ENSG00000183347; -.
DR eggNOG; KOG2037; Eukaryota.
DR GeneTree; ENSGT00940000154265; -.
DR HOGENOM; CLU_018608_2_1_1; -.
DR InParanoid; Q6ZN66; -.
DR OMA; IRHFFPT; -.
DR OrthoDB; 1027269at2759; -.
DR PhylomeDB; Q6ZN66; -.
DR TreeFam; TF331602; -.
DR PathwayCommons; Q6ZN66; -.
DR Reactome; R-HSA-877300; Interferon gamma signaling.
DR SignaLink; Q6ZN66; -.
DR BioGRID-ORCS; 163351; 10 hits in 1066 CRISPR screens.
DR GenomeRNAi; 163351; -.
DR Pharos; Q6ZN66; Tbio.
DR PRO; PR:Q6ZN66; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q6ZN66; protein.
DR Bgee; ENSG00000183347; Expressed in gingival epithelium and 82 other tissues.
DR GO; GO:0031410; C:cytoplasmic vesicle; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IBA:GO_Central.
DR GO; GO:0003924; F:GTPase activity; IBA:GO_Central.
DR GO; GO:0071346; P:cellular response to interferon-gamma; ISS:CAFA.
DR GO; GO:0042742; P:defense response to bacterium; ISS:CAFA.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IBA:GO_Central.
DR GO; GO:0042832; P:defense response to protozoan; IBA:GO_Central.
DR GO; GO:0006955; P:immune response; ISS:CAFA.
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 2: Evidence at transcript level;
KW Alternative splicing; Antimicrobial; Cytoplasmic vesicle; GTP-binding;
KW Hydrolase; Immunity; Nucleotide-binding; Reference proteome.
FT CHAIN 1..633
FT /note="Guanylate-binding protein 6"
FT /id="PRO_0000313811"
FT DOMAIN 35..277
FT /note="GB1/RHD3-type G"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01052"
FT REGION 1..310
FT /note="GTPase domain (Globular)"
FT /evidence="ECO:0000250|UniProtKB:P32455"
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 1..337
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_030155"
FT VARIANT 278
FT /note="T -> I (in dbSNP:rs4582772)"
FT /id="VAR_037750"
FT VARIANT 331
FT /note="A -> S (in dbSNP:rs4658359)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17974005"
FT /id="VAR_037751"
FT VARIANT 344
FT /note="L -> F (in dbSNP:rs4658360)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17974005"
FT /id="VAR_037752"
FT VARIANT 355
FT /note="M -> V (in dbSNP:rs4658146)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17974005"
FT /id="VAR_037753"
FT VARIANT 520
FT /note="D -> V (in dbSNP:rs959460)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17974005"
FT /id="VAR_037754"
FT CONFLICT 13
FT /note="L -> Q (in Ref. 2; CAD97917)"
FT /evidence="ECO:0000305"
FT CONFLICT 313
FT /note="N -> D (in Ref. 2; CAD97917)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 633 AA; 72427 MW; D3487659300D5678 CRC64;
MESGPKMLAP VCLVENNNEQ LLVNQQAIQI LEKISQPVVV VAIVGLYRTG KSYLMNHLAG
QNHGFPLGST VQSETKGIWM WCVPHPSKPN HTLVLLDTEG LGDVEKGDPK NDSWIFALAV
LLCSTFVYNS MSTINHQALE QLHYVTELTE LIKAKSSPRP DGVEDSTEFV SFFPDFLWTV
RDFTLELKLN GHPITEDEYL ENALKLIQGN NPRVQTSNFP RECIRRFFPK RKCFVFDRPT
NDKDLLANIE KVSEKQLDPK FQEQTNIFCS YIFTHARTKT LREGITVTGN RLGTLAVTYV
EAINSGAVPC LENAVITLAQ RENSAAVQRA ADYYSQQMAQ RVKLPTDTLQ ELLDMHAACE
REAIAIFMEH SFKDENQEFQ KKFMETTMNK KGDFLLQNEE SSVQYCQAKL NELSKGLMES
ISAGSFSVPG GHKLYMETKE RIEQDYWQVP RKGVKAKEVF QRFLESQMVI EESILQSDKA
LTDREKAVAV DRAKKEAAEK EQELLKQKLQ EQQQQMEAQD KSRKENIAQL KEKLQMEREH
LLREQIMMLE HTQKVQNDWL HEGFKKKYEE MNAEISQFKR MIDTTKNDDT PWIARTLDNL
ADELTAILSA PAKLIGHGVK GVSSLFKKHK LPF
