GBP4_HUMAN
ID GBP4_HUMAN Reviewed; 640 AA.
AC Q96PP9; B2R630; Q05D63; Q6NSL0; Q86T99;
DT 24-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Guanylate-binding protein 4;
DE EC=3.6.5.- {ECO:0000250|UniProtKB:P32455};
DE AltName: Full=GTP-binding protein 4;
DE Short=GBP-4;
DE AltName: Full=Guanine nucleotide-binding protein 4;
GN Name=GBP4;
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].
RA Avdalovic A., Fu H., Tsurushita N.;
RT "Human GBP-4 and -5: new members of the IFN-gamma-inducible guanylate
RT binding protein family.";
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Spinal cord;
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 MRNA].
RC TISSUE=Spleen;
RX PubMed=12693554; DOI=10.1093/dnares/10.1.49;
RA Jikuya H., Takano J., Kikuno R., Hirosawa M., Nagase T., Nomura N.,
RA Ohara O.;
RT "Characterization of long cDNA clones from human adult spleen. II. The
RT complete sequences of 81 cDNA clones.";
RL DNA Res. 10:49-57(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta, and Testis;
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: Binds GTP, GDP and GMP. Hydrolyzes GTP very efficiently; GDP
CC rather than GMP is the major reaction product. Plays a role in
CC erythroid differentiation (By similarity). {ECO:0000250}.
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 Q96PP9; P32455: GBP1; NbExp=2; IntAct=EBI-20840650, EBI-2869161;
CC Q96PP9; P32456: GBP2; NbExp=2; IntAct=EBI-20840650, EBI-714388;
CC Q96PP9; Q96PP9: GBP4; NbExp=2; IntAct=EBI-20840650, EBI-20840650;
CC Q96PP9; Q96PP8: GBP5; NbExp=2; IntAct=EBI-20840650, EBI-749932;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17266443}. Nucleus
CC {ECO:0000269|PubMed:17266443}. Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:21151871}. Golgi apparatus membrane
CC {ECO:0000269|PubMed:21151871}. Note=Heterodimers with GBP1, GBP2 and
CC GBP5 localize in the compartment of the prenylated GBPs: with GBP1 in a
CC vesicle-like compartment, with GBP2, around the nucleus and with GBP-5,
CC at the Golgi apparatus. {ECO:0000269|PubMed:21151871}.
CC -!- INDUCTION: By IFNG during macrophage activation.
CC {ECO:0000269|PubMed:17266443}.
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=BAC85144.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF288814; AAL02054.1; -; mRNA.
DR EMBL; AL832576; CAD89936.1; -; mRNA.
DR EMBL; AK131094; BAC85144.1; ALT_INIT; mRNA.
DR EMBL; AK312417; BAG35327.1; -; mRNA.
DR EMBL; BC017889; AAH17889.1; -; mRNA.
DR EMBL; BC070055; AAH70055.1; -; mRNA.
DR CCDS; CCDS721.1; -.
DR RefSeq; NP_443173.2; NM_052941.4.
DR AlphaFoldDB; Q96PP9; -.
DR SMR; Q96PP9; -.
DR BioGRID; 125430; 5.
DR IntAct; Q96PP9; 4.
DR STRING; 9606.ENSP00000359490; -.
DR iPTMnet; Q96PP9; -.
DR PhosphoSitePlus; Q96PP9; -.
DR BioMuta; GBP4; -.
DR DMDM; 116242487; -.
DR EPD; Q96PP9; -.
DR jPOST; Q96PP9; -.
DR MassIVE; Q96PP9; -.
DR MaxQB; Q96PP9; -.
DR PaxDb; Q96PP9; -.
DR PeptideAtlas; Q96PP9; -.
DR PRIDE; Q96PP9; -.
DR ProteomicsDB; 77726; -.
DR Antibodypedia; 33614; 215 antibodies from 28 providers.
DR DNASU; 115361; -.
DR Ensembl; ENST00000355754.7; ENSP00000359490.5; ENSG00000162654.9.
DR GeneID; 115361; -.
DR KEGG; hsa:115361; -.
DR MANE-Select; ENST00000355754.7; ENSP00000359490.5; NM_052941.5; NP_443173.2.
DR UCSC; uc001dnb.4; human.
DR CTD; 115361; -.
DR DisGeNET; 115361; -.
DR GeneCards; GBP4; -.
DR HGNC; HGNC:20480; GBP4.
DR HPA; ENSG00000162654; Low tissue specificity.
DR MIM; 612466; gene.
DR neXtProt; NX_Q96PP9; -.
DR OpenTargets; ENSG00000162654; -.
DR PharmGKB; PA134959399; -.
DR VEuPathDB; HostDB:ENSG00000162654; -.
DR eggNOG; KOG2037; Eukaryota.
DR GeneTree; ENSGT00940000164661; -.
DR HOGENOM; CLU_018608_2_1_1; -.
DR InParanoid; Q96PP9; -.
DR OMA; MQSDNFC; -.
DR OrthoDB; 1027269at2759; -.
DR PhylomeDB; Q96PP9; -.
DR TreeFam; TF331602; -.
DR PathwayCommons; Q96PP9; -.
DR Reactome; R-HSA-877300; Interferon gamma signaling.
DR SignaLink; Q96PP9; -.
DR BioGRID-ORCS; 115361; 9 hits in 1074 CRISPR screens.
DR ChiTaRS; GBP4; human.
DR GenomeRNAi; 115361; -.
DR Pharos; Q96PP9; Tbio.
DR PRO; PR:Q96PP9; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q96PP9; protein.
DR Bgee; ENSG00000162654; Expressed in leukocyte and 146 other tissues.
DR Genevisible; Q96PP9; HS.
DR GO; GO:0031410; C:cytoplasmic vesicle; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
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; IEP:UniProtKB.
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 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 Coiled coil; Cytoplasm; Golgi apparatus; GTP-binding; Hydrolase; Membrane;
KW Nucleotide-binding; Nucleus; Reference proteome.
FT CHAIN 1..640
FT /note="Guanylate-binding protein 4"
FT /id="PRO_0000190968"
FT DOMAIN 50..292
FT /note="GB1/RHD3-type G"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01052"
FT REGION 1..325
FT /note="GTPase domain (Globular)"
FT /evidence="ECO:0000250|UniProtKB:P32455"
FT COILED 499..612
FT /evidence="ECO:0000255"
FT BINDING 60..67
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P32455"
FT BINDING 82..84
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P32455"
FT BINDING 112..116
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P32455"
FT VARIANT 125
FT /note="K -> E (in dbSNP:rs17130745)"
FT /id="VAR_028283"
FT VARIANT 379
FT /note="I -> V (in dbSNP:rs1831240)"
FT /id="VAR_028284"
FT VARIANT 541
FT /note="Y -> N (in dbSNP:rs655260)"
FT /id="VAR_028285"
FT VARIANT 542
FT /note="M -> I (in dbSNP:rs1142886)"
FT /id="VAR_033952"
FT VARIANT 545
FT /note="M -> I (in dbSNP:rs1142889)"
FT /id="VAR_033953"
FT VARIANT 545
FT /note="M -> L (in dbSNP:rs1142888)"
FT /id="VAR_033954"
FT VARIANT 546
FT /note="E -> K (in dbSNP:rs1142890)"
FT /id="VAR_033955"
FT VARIANT 549
FT /note="L -> M (in dbSNP:rs608339)"
FT /id="VAR_028286"
FT VARIANT 551
FT /note="E -> G (in dbSNP:rs561042)"
FT /id="VAR_028288"
FT VARIANT 551
FT /note="E -> K (in dbSNP:rs561037)"
FT /id="VAR_028287"
FT CONFLICT 298
FT /note="E -> K (in Ref. 5; AAH70055)"
FT /evidence="ECO:0000305"
FT CONFLICT 402..410
FT /note="IEKKKGDFV -> KKKKKKKKK (in Ref. 5; AAH17889)"
FT /evidence="ECO:0000305"
FT CONFLICT 416
FT /note="A -> P (in Ref. 4; BAG35327)"
FT /evidence="ECO:0000305"
FT CONFLICT 502
FT /note="A -> S (in Ref. 5; AAH70055)"
FT /evidence="ECO:0000305"
FT CONFLICT 541..542
FT /note="YM -> NI (in Ref. 1; AAL02054 and 3; BAC85144)"
FT /evidence="ECO:0000305"
FT CONFLICT 545..546
FT /note="ME -> LK (in Ref. 1; AAL02054 and 3; BAC85144)"
FT /evidence="ECO:0000305"
FT CONFLICT 549..551
FT /note="LEE -> MER (in Ref. 1; AAL02054 and 3; BAC85144)"
FT /evidence="ECO:0000305"
FT CONFLICT 582
FT /note="K -> R (in Ref. 4; BAG35327)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 640 AA; 73165 MW; 06ABFF47E615DAFC CRC64;
MGERTLHAAV PTPGYPESES IMMAPICLVE NQEEQLTVNS KALEILDKIS QPVVVVAIVG
LYRTGKSYLM NRLAGKRNGF PLGSTVQSET KGIWMWCVPH LSKPNHTLVL LDTEGLGDVE
KSNPKNDSWI FALAVLLSSS FVYNSVSTIN HQALEQLHYV TELAELIRAK SCPRPDEAED
SSEFASFFPD FIWTVRDFTL ELKLDGNPIT EDEYLENALK LIPGKNPKIQ NSNMPRECIR
HFFRKRKCFV FDRPTNDKQY LNHMDEVPEE NLERHFLMQS DNFCSYIFTH AKTKTLREGI
IVTGKRLGTL VVTYVDAINS GAVPCLENAV TALAQLENPA AVQRAADHYS QQMAQQLRLP
TDTLQELLDV HAACEREAIA VFMEHSFKDE NHEFQKKLVD TIEKKKGDFV LQNEEASAKY
CQAELKRLSE HLTESILRGI FSVPGGHNLY LEEKKQVEWD YKLVPRKGVK ANEVLQNFLQ
SQVVVEESIL QSDKALTAGE KAIAAERAMK EAAEKEQELL REKQKEQQQM MEAQERSFQE
YMAQMEKKLE EERENLLREH ERLLKHKLKV QEEMLKEEFQ KKSEQLNKEI NQLKEKIEST
KNEQLRLLKI LDMASNIMIV TLPGASKLLG VGTKYLGSRI
