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Protein

Guanylate-binding protein 5

Gene

GBP5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

As an activator of NLRP3 inflammasome assembly, plays a role in innate immunity and inflammation. Promotes selective NLRP3 inflammasome assembly in response to microbial and soluble, but not crystalline, agents (PubMed:22461501). Hydrolyzes GTP, but in contrast to other family members, does not produce GMP (PubMed:20180847).2 Publications

Catalytic activityi

GTP + H2O = GDP + phosphate.2 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi45 – 528GTPBy similarity
Nucleotide bindingi67 – 693GTPBy similarity
Nucleotide bindingi97 – 1015GTPBy similarity

GO - Molecular functioni

  • GTPase activity Source: InterPro
  • GTP binding Source: UniProtKB-KW
  • identical protein binding Source: IntAct

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Antimicrobial, Hydrolase

Keywords - Biological processi

Immunity, Inflammatory response

Keywords - Ligandi

GTP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-877300. Interferon gamma signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Guanylate-binding protein 5 (EC:3.6.5.-2 Publications)
Alternative name(s):
GBP-TA antigen
GTP-binding protein 5
Short name:
GBP-5
Guanine nucleotide-binding protein 5
Gene namesi
Name:GBP5
ORF Names:UNQ2427/PRO4987
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:19895. GBP5.

Subcellular locationi

GO - Cellular componenti

  • cytoplasmic vesicle Source: Ensembl
  • Golgi membrane Source: UniProtKB-SubCell
  • membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi51 – 522KS → AA: Loss of GTPase activity. No effect on tetramerization. 1 Publication
Mutagenesisi583 – 5864Missing : Loss of isoprenylation and of localization at the Golgi apparatus. 1 Publication

Organism-specific databases

PharmGKBiPA134862968.

Polymorphism and mutation databases

BioMutaiGBP5.
DMDMi37999757.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 583583Guanylate-binding protein 5PRO_0000190969Add
BLAST
Propeptidei584 – 5863Removed in mature formSequence analysisPRO_0000370785

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei583 – 5831Cysteine methyl esterSequence analysis
Lipidationi583 – 5831S-geranylgeranyl cysteine1 Publication

Post-translational modificationi

Isoprenylation is required for proper subcellular location.1 Publication

Keywords - PTMi

Lipoprotein, Methylation, Prenylation

Proteomic databases

EPDiQ96PP8.
MaxQBiQ96PP8.
PaxDbiQ96PP8.
PRIDEiQ96PP8.

PTM databases

iPTMnetiQ96PP8.
PhosphoSiteiQ96PP8.

Expressioni

Tissue specificityi

Expressed in peripheral blood monocytes (at protein level).1 Publication

Inductioni

By IFNG in endothelial cells and in LPS-primed macrophages.2 Publications

Gene expression databases

BgeeiQ96PP8.
CleanExiHS_GBP5.
ExpressionAtlasiQ96PP8. baseline and differential.
GenevisibleiQ96PP8. HS.

Organism-specific databases

HPAiHPA028656.

Interactioni

Subunit structurei

Homodimer (PubMed:21151871). Heterodimer with other family members, including GBP1, GBP2, GBP3 and GBP4 (PubMed:21151871). Dimerization is nucleotide-dependent; isoform 1 and isoform 2 form dimers when GTP-bound. GDP-bound isoform 2 is monomeric, while isoform 1 remains dimeric (PubMed:20180847). Dimerization regulates subcellular location. May also form tetramers (dimer of dimers) in the presence of GTP (PubMed:20180847). Interacts with NLRP3, possibly in its tetrameric form, and promotes PYCARD/ASC polymerization (PubMed:22461501).3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself5EBI-749932,EBI-749932

GO - Molecular functioni

  • identical protein binding Source: IntAct

Protein-protein interaction databases

BioGridi125431. 9 interactions.
MINTiMINT-4920446.
STRINGi9606.ENSP00000340396.

Structurei

3D structure databases

ProteinModelPortaliQ96PP8.
SMRiQ96PP8. Positions 2-574.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini35 – 276242GB1/RHD3-type GAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 309309GTPase domain (Globular)By similarityAdd
BLAST
Regioni1 – 306306NLRP3-binding1 PublicationAdd
BLAST
Regioni529 – 58658Required for tetramerization, but not for dimerization1 PublicationAdd
BLAST

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG2037. Eukaryota.
ENOG410XR6Z. LUCA.
GeneTreeiENSGT00550000074475.
HOGENOMiHOG000266974.
HOVERGENiHBG001979.
InParanoidiQ96PP8.
OMAiFPVKKCF.
OrthoDBiEOG7BW0J3.
PhylomeDBiQ96PP8.
TreeFamiTF331602.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR030386. G_GB1_RHD3_dom.
IPR003191. Guanylate-bd_C.
IPR015894. Guanylate-bd_N.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF02263. GBP. 1 hit.
PF02841. GBP_C. 1 hit.
[Graphical view]
SUPFAMiSSF48340. SSF48340. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEiPS51715. G_GB1_RHD3. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q96PP8-1) [UniParc]FASTAAdd to basket

Also known as: GBP-5a/b

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MALEIHMSDP MCLIENFNEQ LKVNQEALEI LSAITQPVVV VAIVGLYRTG
60 70 80 90 100
KSYLMNKLAG KNKGFSVAST VQSHTKGIWI WCVPHPNWPN HTLVLLDTEG
110 120 130 140 150
LGDVEKADNK NDIQIFALAL LLSSTFVYNT VNKIDQGAID LLHNVTELTD
160 170 180 190 200
LLKARNSPDL DRVEDPADSA SFFPDLVWTL RDFCLGLEID GQLVTPDEYL
210 220 230 240 250
ENSLRPKQGS DQRVQNFNLP RLCIQKFFPK KKCFIFDLPA HQKKLAQLET
260 270 280 290 300
LPDDELEPEF VQQVTEFCSY IFSHSMTKTL PGGIMVNGSR LKNLVLTYVN
310 320 330 340 350
AISSGDLPCI ENAVLALAQR ENSAAVQKAI AHYDQQMGQK VQLPMETLQE
360 370 380 390 400
LLDLHRTSER EAIEVFMKNS FKDVDQSFQK ELETLLDAKQ NDICKRNLEA
410 420 430 440 450
SSDYCSALLK DIFGPLEEAV KQGIYSKPGG HNLFIQKTEE LKAKYYREPR
460 470 480 490 500
KGIQAEEVLQ KYLKSKESVS HAILQTDQAL TETEKKKKEA QVKAEAEKAE
510 520 530 540 550
AQRLAAIQRQ NEQMMQERER LHQEQVRQME IAKQNWLAEQ QKMQEQQMQE
560 570 580
QAAQLSTTFQ AQNRSLLSEL QHAQRTVNND DPCVLL
Length:586
Mass (Da):66,617
Last modified:December 1, 2001 - v1
Checksum:i95DDC02F0FB705D0
GO
Isoform 2 (identifier: Q96PP8-2) [UniParc]FASTAAdd to basket

Also known as: GBP-5ta

The sequence of this isoform differs from the canonical sequence as follows:
     489-489: E → K
     490-586: Missing.

Note: Antigenic tumor-specific truncated splice form.
Show »
Length:489
Mass (Da):55,247
Checksum:iB493C3586DFFDA1D
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti4 – 41E → Q.
Corresponds to variant rs17130763 [ dbSNP | Ensembl ].
VAR_053104
Natural varianti35 – 351T → M.
Corresponds to variant rs3806339 [ dbSNP | Ensembl ].
VAR_033956

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei489 – 4891E → K in isoform 2. 1 PublicationVSP_044362
Alternative sequencei490 – 58697Missing in isoform 2. 1 PublicationVSP_044363Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF288815 mRNA. Translation: AAL02055.1.
AF328727 mRNA. Translation: AAO40731.1.
AF430642 mRNA. Translation: AAN39035.1.
AF430643 mRNA. Translation: AAN39036.1.
AY358953 mRNA. Translation: AAQ89312.1.
AK315064 mRNA. Translation: BAG37538.1.
CH471097 Genomic DNA. Translation: EAW73141.1.
BC031639 mRNA. Translation: AAH31639.1.
CCDSiCCDS722.1. [Q96PP8-1]
RefSeqiNP_001127958.1. NM_001134486.2. [Q96PP8-1]
NP_443174.1. NM_052942.3. [Q96PP8-1]
UniGeneiHs.513726.

Genome annotation databases

EnsembliENST00000370459; ENSP00000359488; ENSG00000154451. [Q96PP8-1]
GeneIDi115362.
KEGGihsa:115362.
UCSCiuc057iek.1. human. [Q96PP8-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF288815 mRNA. Translation: AAL02055.1.
AF328727 mRNA. Translation: AAO40731.1.
AF430642 mRNA. Translation: AAN39035.1.
AF430643 mRNA. Translation: AAN39036.1.
AY358953 mRNA. Translation: AAQ89312.1.
AK315064 mRNA. Translation: BAG37538.1.
CH471097 Genomic DNA. Translation: EAW73141.1.
BC031639 mRNA. Translation: AAH31639.1.
CCDSiCCDS722.1. [Q96PP8-1]
RefSeqiNP_001127958.1. NM_001134486.2. [Q96PP8-1]
NP_443174.1. NM_052942.3. [Q96PP8-1]
UniGeneiHs.513726.

3D structure databases

ProteinModelPortaliQ96PP8.
SMRiQ96PP8. Positions 2-574.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi125431. 9 interactions.
MINTiMINT-4920446.
STRINGi9606.ENSP00000340396.

PTM databases

iPTMnetiQ96PP8.
PhosphoSiteiQ96PP8.

Polymorphism and mutation databases

BioMutaiGBP5.
DMDMi37999757.

Proteomic databases

EPDiQ96PP8.
MaxQBiQ96PP8.
PaxDbiQ96PP8.
PRIDEiQ96PP8.

Protocols and materials databases

DNASUi115362.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000370459; ENSP00000359488; ENSG00000154451. [Q96PP8-1]
GeneIDi115362.
KEGGihsa:115362.
UCSCiuc057iek.1. human. [Q96PP8-1]

Organism-specific databases

CTDi115362.
GeneCardsiGBP5.
HGNCiHGNC:19895. GBP5.
HPAiHPA028656.
MIMi611467. gene.
neXtProtiNX_Q96PP8.
PharmGKBiPA134862968.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2037. Eukaryota.
ENOG410XR6Z. LUCA.
GeneTreeiENSGT00550000074475.
HOGENOMiHOG000266974.
HOVERGENiHBG001979.
InParanoidiQ96PP8.
OMAiFPVKKCF.
OrthoDBiEOG7BW0J3.
PhylomeDBiQ96PP8.
TreeFamiTF331602.

Enzyme and pathway databases

ReactomeiR-HSA-877300. Interferon gamma signaling.

Miscellaneous databases

GenomeRNAii115362.
PROiQ96PP8.
SOURCEiSearch...

Gene expression databases

BgeeiQ96PP8.
CleanExiHS_GBP5.
ExpressionAtlasiQ96PP8. baseline and differential.
GenevisibleiQ96PP8. HS.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR030386. G_GB1_RHD3_dom.
IPR003191. Guanylate-bd_C.
IPR015894. Guanylate-bd_N.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF02263. GBP. 1 hit.
PF02841. GBP_C. 1 hit.
[Graphical view]
SUPFAMiSSF48340. SSF48340. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEiPS51715. G_GB1_RHD3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Human GBP-4 and -5: new members of the IFN-gamma-inducible guanylate binding protein family."
    Avdalovic A., Fu H., Tsurushita N.
    Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  2. "GBP-5 splicing variants: New guanylate-binding proteins with tumor-associated expression and antigenicity."
    Fellenberg F., Hartmann T.B., Dummer R., Usener D., Schadendorf D., Eichmuller S.
    J. Invest. Dermatol. 122:1510-1517(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
    Tissue: Lymphoma.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  4. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Brain.
  7. "Unique features of different members of the human guanylate-binding protein family."
    Tripal P., Bauer M., Naschberger E., Mortinger T., Hohenadl C., Cornali E., Thurau M., Sturzl M.
    J. Interferon Cytokine Res. 27:44-52(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, INDUCTION BY IFNG.
  8. "Biochemical properties of the human guanylate binding protein 5 and a tumor-specific truncated splice variant."
    Wehner M., Herrmann C.
    FEBS J. 277:1597-1605(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, DIMERIZATION.
  9. "Intracellular trafficking of guanylate-binding proteins is regulated by heterodimerization in a hierarchical manner."
    Britzen-Laurent N., Bauer M., Berton V., Fischer N., Syguda A., Reipschlager S., Naschberger E., Herrmann C., Sturzl M.
    PLoS ONE 5:E14246-E14246(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, ISOPRENYLATION, MUTAGENESIS OF 583-CYS--LEU-586, DIMERIZATION.
  10. "GBP5 promotes NLRP3 inflammasome assembly and immunity in mammals."
    Shenoy A.R., Wellington D.A., Kumar P., Kassa H., Booth C.J., Cresswell P., MacMicking J.D.
    Science 336:481-485(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH NLRP3, OLIGOMERIZATION, MUTAGENESIS OF 51-LYS-SER-52, INDUCTION BY IFNG.

Entry informationi

Entry nameiGBP5_HUMAN
AccessioniPrimary (citable) accession number: Q96PP8
Secondary accession number(s): B2RCE1, Q86TM5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 24, 2003
Last sequence update: December 1, 2001
Last modified: June 8, 2016
This is version 128 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.