P32455 (GBP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Interferon-induced guanylate-binding protein 1

Alternative name(s):
GTP-binding protein 1
Short name=GBP-1
Short name=HuGBP-1
Guanine nucleotide-binding protein 1

Gene names

Name:

GBP1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	592 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Hydrolyzes GTP to GMP in two consecutive cleavage reactions. Exhibits antiviral activity against influenza virus. Promote oxidative killing and deliver antimicrobial peptides to autophagolysosomes, providing broad host protection against different pathogen classes. Ref.13
Subunit structure	Homodimerizes upon GTP-binding, dimerization is required for the second hydrolysis step from GDP to GMP. Can also heterodimerize with other members of the family. Ref.12 Ref.16
Subcellular location	Cytoplasm. Golgi apparatus membrane; Lipid-anchor; Cytoplasmic side. Secreted. Note: Secreted from endothelial cells in the cerebrospinal fluid, upon bacterial challenge and independently of interferon-gamma induction. Golgi membrane localization requires isoprenylation and the presence of another IFN-gamma-induced factor. Ref.8 Ref.9 Ref.10 Ref.12
Induction	By IFNG/IFN-gamma during macrophage activation, and by TNF-alpha and IL-1beta. Ref.10
Sequence similarities	Belongs to the GBP family.

Ontologies

Keywords
Biological process	Antiviral defense Immunity
Cellular component	Cytoplasm Golgi apparatus Membrane Secreted
Coding sequence diversity	Polymorphism
Ligand	GTP-binding Nucleotide-binding
PTM	Lipoprotein Methylation Prenylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	GTP catabolic process Inferred from electronic annotation. Source: GOC defense response to virus Inferred from electronic annotation. Source: UniProtKB-KW interferon-gamma-mediated signaling pathway Traceable author statement. Source: Reactome
Cellular_component	Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Traceable author statement. Source: Reactome extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	GTP binding Traceable author statement Ref.1. Source: ProtInc GTPase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 589

589

Interferon-induced guanylate-binding protein 1

PRO_0000190963

Propeptide

590 – 592

3

Removed in mature form

PRO_0000396777

Regions

Nucleotide binding

45 – 52

8

GTP

Nucleotide binding

67 – 69

3

GTP

Nucleotide binding

97 – 101

5

GTP

Region

1 – 311

311

GTPase domain (Globular)

Amino acid modifications

Modified residue

589

1

Cysteine methyl ester

Lipidation

589

1

S-farnesyl cysteine Ref.7

Natural variations

Natural variant

78

1

I → V.
Corresponds to variant rs1048401 [ dbSNP | Ensembl ].

VAR_033950

Natural variant

166

1

E → D.
Corresponds to variant rs17130717 [ dbSNP | Ensembl ].

VAR_033951

Natural variant

349

1

T → S. Ref.1 Ref.2 Ref.6
Corresponds to variant rs1048425 [ dbSNP | Ensembl ].

VAR_014849

Natural variant

409

1

A → G. Ref.1 Ref.2 Ref.6
Corresponds to variant rs1048443 [ dbSNP | Ensembl ].

VAR_046550

Secondary structure

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592

Helix Strand Turn

Details...

Beta strand

11 – 17

7

Beta strand

20 – 23

4

Helix

25 – 32

8

Beta strand

36 – 46

11

Helix

47 – 49

3

Helix

51 – 58

8

Beta strand

62 – 65

4

Beta strand

70 – 72

3

Beta strand

77 – 84

8

Beta strand

86 – 88

3

Beta strand

92 – 98

7

Turn

101 – 103

3

Helix

104 – 106

3

Helix

112 – 122

11

Beta strand

124 – 132

9

Helix

136 – 140

5

Helix

143 – 146

4

Helix

148 – 151

4

Beta strand

156 – 158

3

Helix

167 – 170

4

Helix

171 – 174

4

Beta strand

177 – 183

7

Beta strand

192 – 194

3

Helix

198 – 205

8

Helix

214 – 229

16

Beta strand

233 – 237

5

Helix

244 – 252

9

Helix

255 – 257

3

Helix

260 – 276

17

Turn

283 – 285

3

Helix

290 – 306

17

Helix

312 – 342

31

Helix

350 – 371

22

Helix

376 – 378

3

Helix

379 – 423

45

Turn

424 – 427

4

Helix

432 – 449

18

Helix

457 – 467

11

Helix

469 – 478

10

Beta strand

480 – 482

3

Helix

484 – 563

80

Helix

566 – 582

17

Sequences

	Sequence		Length	Mass (Da)
	P32455 [UniParc]. Last modified November 2, 2010. Version 2. Checksum: 3A06741218360732	FASTA	592	67,931
	10 20 30 40 50 60 MASEIHMTGP MCLIENTNGR LMANPEALKI LSAITQPMVV VAIVGLYRTG KSYLMNKLAG 70 80 90 100 110 120 KKKGFSLGST VQSHTKGIWM WCVPHPKKPG HILVLLDTEG LGDVEKGDNQ NDSWIFALAV 130 140 150 160 170 180 LLSSTFVYNS IGTINQQAMD QLYYVTELTH RIRSKSSPDE NENEVEDSAD FVSFFPDFVW 190 200 210 220 230 240 TLRDFSLDLE ADGQPLTPDE YLTYSLKLKK GTSQKDETFN LPRLCIRKFF PKKKCFVFDR 250 260 270 280 290 300 PVHRRKLAQL EKLQDEELDP EFVQQVADFC SYIFSNSKTK TLSGGIQVNG PRLESLVLTY 310 320 330 340 350 360 VNAISSGDLP CMENAVLALA QIENSAAVQK AIAHYEQQMG QKVQLPTETL QELLDLHRDS 370 380 390 400 410 420 EREAIEVFIR SSFKDVDHLF QKELAAQLEK KRDDFCKQNQ EASSDRCSAL LQVIFSPLEE 430 440 450 460 470 480 EVKAGIYSKP GGYRLFVQKL QDLKKKYYEE PRKGIQAEEI LQTYLKSKES MTDAILQTDQ 490 500 510 520 530 540 TLTEKEKEIE VERVKAESAQ ASAKMLQEMQ RKNEQMMEQK ERSYQEHLKQ LTEKMENDRV 550 560 570 580 590 QLLKEQERTL ALKLQEQEQL LKEGFQKESR IMKNEIQDLQ TKMRRRKACT IS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Interferon-induced guanylate-binding proteins lack an N(T)KXD consensus motif and bind GMP in addition to GDP and GTP." Cheng Y.-S.E., Patterson C.E., Staeheli P. Mol. Cell. Biol. 11:4717-4725(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS SER-349 AND GLY-409.
[2]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS SER-349 AND GLY-409.
[3]	"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]. Tissue: Placenta.
[4]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases 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], VARIANTS SER-349 AND GLY-409. Tissue: Uterus.
[7]	"Prenylation of an interferon-gamma-induced GTP-binding protein: the human guanylate binding protein, huGBP1." Nantais D.E., Schwemmle M., Stickney J.T., Vestal D.J., Buss J.E. J. Leukoc. Biol. 60:423-431(1996) [PubMed] [Europe PMC] [Abstract] Cited for: ISOPRENYLATION AT CYS-589.
[8]	"Golgi targeting of human guanylate-binding protein-1 requires nucleotide binding, isoprenylation, and an IFN-gamma-inducible cofactor." Modiano N., Lu Y.E., Cresswell P. Proc. Natl. Acad. Sci. U.S.A. 102:8680-8685(2005) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[9]	"Human guanylate binding protein-1 is a secreted GTPase present in increased concentrations in the cerebrospinal fluid of patients with bacterial meningitis." Naschberger E., Lubeseder-Martellato C., Meyer N., Gessner R., Kremmer E., Gessner A., Sturzl M. Am. J. Pathol. 169:1088-1099(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[10]	"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.
[11]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell.
[12]	"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, SUBUNIT.
[13]	"A new splice variant of the human guanylate-binding protein 3 mediates anti-influenza activity through inhibition of viral transcription and replication." Nordmann A., Wixler L., Boergeling Y., Wixler V., Ludwig S. FASEB J. 26:1290-1300(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[14]	"Structure of human guanylate-binding protein 1 representing a unique class of GTP-binding proteins." Prakash B., Praefcke G.J.K., Renault L., Wittinghofer A., Herrmann C. Nature 403:567-571(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
[15]	"Triphosphate structure of guanylate-binding protein 1 and implications for nucleotide binding and GTPase mechanism." Prakash B., Renault L., Praefcke G.J., Herrmann C., Wittinghofer A. EMBO J. 19:4555-4564(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEX WITH GTP ANALOG.
[16]	"How guanylate-binding proteins achieve assembly-stimulated processive cleavage of GTP to GMP." Ghosh A., Praefcke G.J., Renault L., Wittinghofer A., Herrmann C. Nature 440:101-104(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.22 ANGSTROMS) OF 1-317, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M55542 mRNA. Translation: AAA35871.1.
BT006847 mRNA. Translation: AAP35493.1.
AK291783 mRNA. Translation: BAF84472.1.
AL160008 Genomic DNA. Translation: CAI22972.1.
CH471097 Genomic DNA. Translation: EAW73148.1.
CH471097 Genomic DNA. Translation: EAW73150.1.
BC002666 mRNA. Translation: AAH02666.1.

IPI

IPI00028564.

PIR

A41268.

RefSeq

NP_002044.2. NM_002053.2.

UniGene

Hs.62661.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1DG3	X-ray	1.80	A	1-592	[»]
1F5N	X-ray	1.70	A	1-592	[»]
2B8W	X-ray	2.22	A/B	1-317	[»]
2B92	X-ray	3.20	A/B	1-317	[»]
2BC9	X-ray	2.80	A	1-317	[»]
2D4H	X-ray	2.90	A/B	1-317	[»]

DisProt

DP00313.

ProteinModelPortal

P32455.

SMR

P32455. Positions 7-583.

ModBase

Search...

Protein-protein interaction databases

IntAct

P32455. 1 interaction.

STRING

9606.ENSP00000359504.

PTM databases

PhosphoSite

P32455.

Polymorphism databases

DMDM

311033383.

Proteomic databases

PaxDb

P32455.

PRIDE

P32455.

Protocols and materials databases

DNASU

2633.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000370473; ENSP00000359504; ENSG00000117228.

GeneID

2633.

KEGG

hsa:2633.

UCSC

uc001dmx.2. human.

Organism-specific databases

CTD

2633.

GeneCards

GC01M089517.

H-InvDB

HIX0018119.
HIX0200036.

HGNC

HGNC:4182. GBP1.

HPA

CAB015450.

MIM

600411. gene.

neXtProt

NX_P32455.

PharmGKB

PA28596.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG288755.

HOGENOM

HOG000266974.

HOVERGEN

HBG001979.

InParanoid

P32455.

OMA

GFQKESR.

OrthoDB

EOG42BX87.

PhylomeDB

P32455.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P32455.

Bgee

P32455.

CleanEx

HS_GBP1.

Genevestigator

P32455.

GermOnline

ENSG00000117228. Homo sapiens.

Family and domain databases

InterPro

IPR003191. Guanylate-bd_C.
IPR015894. Guanylate-bd_N.
[Graphical view]

Pfam

PF02263. GBP. 1 hit.
PF02841. GBP_C. 1 hit.
[Graphical view]

SUPFAM

SSF48340. GBP. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

P32455.

GenomeRNAi

2633.

NextBio

10380.

SOURCE

Search...

Entry information

Entry name

GBP1_HUMAN

Accession

Primary (citable) accession number: P32455
Secondary accession number(s): D3DT26, Q5T8M1

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1993
Last sequence update:	November 2, 2010
Last modified:	April 3, 2013
This is version 120 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.