GAG - Group-specific Antigen protein

HIV GAG encodes the structural capsid proteins. The proteins are produced as a GAG precursor polyprotein, which is processed by viral protease.





Key web links:
ViralZone: HIV-1, HIV replication cycle, HIV resource
UniProt: P04591 (HIV-1 HXB2 Gag)
Chime Tutorial:  not available
HIV-1/Human Protein Interaction DB: HIV-1 Gag
Los Alamos HIV structure DB: not available
EMBL: K03455 [EMBL/GenBank/DDBJ]


Isoforms:

  • p55 - GAG Polyprotein (499 amino acids)
  • p160 - GAG-POL Polyprotein


Cleavage sites:


Function:

  • Membrane-associated Gag attracts two copies of viral RNA along with cellular and viral proteins that trigger budding of the virion from surface of cell .
  • Along with Gag-pol, Gag mediates the events essential to virion assembly; including plasma membrane binding, mediating the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA by interacting with Psi, the RNA packaging sequence .
  • Involved in virion ESCRT-dependent budding .
  • Has a role in Vpr incorporation into virions .

Localization:

  • Plasma membrane
  • Cytoplasm
  • Virion
  • Late endosomes/Multivesicular bodies

Additional Information:


Gag Function & Host-Virus Protein Interactions:[TOP]




Interactions highlighted in the image:


  • Interacts with the cellular ESCRT system for budding.
  • Plasma membrane lipid raft-rich domains.

Potential interactions (not in the image):



Genomic Location & Protein Sequence: [TOP]

HIV-1 (HXB2):

          10         20         30         40         50         60         70         80         90        100
| | | | | | | | | |
GARASVLSGG ELDRWEKIRL RPGGKKKYKL KHIVWASREL ERFAVNPGLL ETSEGCRQIL GQLQPSLQTG SEELRSLYNT VATLYCVHQR IEIKDTKEAL
110 120 130 140 150 160 170 180 190 200
| | | | | | | | | |
DKIEEEQNKS KKKAQQAAAD TGHSNQVSQN YPIVQNIQGQ MVHQAISPRT LNAWVKVVEE KAFSPEVIPM FSALSEGATP QDLNTMLNTV GGHQAAMQML
210 220 230 240 250 260 270 280 290 300
| | | | | | | | | |
KETINEEAAE WDRVHPVHAG PIAPGQMREP RGSDIAGTTS TLQEQIGWMT NNPPIPVGEI YKRWIILGLN KIVRMYSPTS ILDIRQGPKE PFRDYVDRFY
310 320 330 340 350 360 370 380 390 400
| | | | | | | | | |
KTLRAEQASQ EVKNWMTETL LVQNANPDCK TILKALGPAA TLEEMMTACQ GVGGPGHKAR VLAEAMSQVT NSATIMMQRG NFRNQRKIVK CFNCGKEGHT
410 420 430 440 450 460 470 480 490 499
| | | | | | | | | |
ARNCRAPRKK GCWKCGKEGH QMKDCTERQA NFLGKIWPSY KGRPGNFLQS RPEPTAPPEE SFRSGVETTT PPQKQEPIDK ELYPLTSLRS LFGNDPSSQ
[download in fasta format]

Length: 499 amino acids
Molecular Weight: 55798 Da
Theoretical pI: 9.18


Protein Domains/Folds/Motifs: [TOP]

p17 - Matrix protein - 131 amino acids (residues 1 - 131)
p24 - Core Antigen capsid protein - 231 amino acids (residues 132 - 362)
p7 - Nucleo-Capsid protein - 55 amino acids (residues 377 - 431)
p6 - 52 amino acids (residues 448 - 499)
p2 - 14 amino acids (residues 363 - 376)
p1 - 16 amino acids (residues 432 - 447)


Secondary Structure prediction:

Coiled-coil Regions - ncoils:


Low Complexity Regions - seg:


Antigenic Sites - EMBOSS:




Predicted Motifs: Printer-friendly version

N-glycosylation:
N-myristoylation:
Amidation:
Protein kinase C:
Casein kinase II:
Tyrosine kinase:
cAMP / cGMP kinase:
Cell attachment motif:
Asp Protease motif:
Asp Prot Retro motif:
Cysteine-rich Region:
Tryptophan-rich Region:
Zinc-finger knuckle motif:
Leucine Zipper motif:

Primary and Secondary Database Entries: [TOP]

Identifiers:



ViralZone: HIV-1, HIV replication cycle, HIV resource
PDB/MMDB: Search for HIV-1 & GAG

UniProt: P04591 (HIV-1 HXB2 Gag)
EMBL: K03455; AAB50258.1 [EMBL/GenBank/DDBJ]

InterPro: IPR000071 - Retroviral Matrix p17 family / IPR000721 - Retroviral Nuceocapsid p24 family
IPR001878 - Zinc-finger (CCHC-type) Domain / IPR008916 - Retroviral Core Antigen C-terminal Domain
IPR008919 - Retroviral Core Antigen N-terminal Core Domain
Pfam: P04591 - Gag / PF00540 - Matrix p17 / PF00607 - Nucleocapsid p24 / PF00098 - Zinc-Finger (CCHC-type)
Prints: PR00234 - HIV1MATRIX / PR00939 - Zinc-Finger (CCHC-type)
SCOP: SSF47943 - Retroviral Core Antigen N-terminus / SSF47836 - Retroviral matrix protein
SSF47756 - Retroviral zinc finger-like domains / SSF47353 - Retroviral Core Antigen C-terminus
BLOCKS: P04591
Prosite: P04591
ProtoNet: P04591
Database of Interacting Proteins: P04591
ModBase: P04591
HIV-1/Human Protein Interaction DB: HIV-1 Gag
HIV-1 Sequence Database Los Alamos HIV Sequence Database



Reviews and References: [TOP]

Cite the resource by citing the following paper:
Doherty R et al. BioAfrica's HIV-1 Proteomics Resource: Combining protein data with bioinformatics tools. Retrovirology (2005), 9;2(1):18.

1 - HIV Sequence Compendium 2000
Kuiken CL, Foley B, Hahn B, Korber B, Marx PA, McCutchan F, Mellors JW, Mullins JI, Sodroski J, Wolinksy S.
Theoretical Biol. & Biophys. Group, Los Alamos Nat Lab, LA-UR 01-3860 [Read it online: Compendium]
2 - Retroviruses
Coffin JM, Hughes SH, Varmus HE.
CD-ROM ed. (2002) Cold Spring Harbor Laboratory Press [Read it online: NCBI Bookshelf]
3 - Molecular Characteristics of HIV-1 Subtype C Viruses from KwaZulu-Natal, South Africa:
Implications for Vaccine and Antiretroviral Control Strategies.
Gordon M, De Oliveira T, Bishop K, Coovadia HM, Madurai L, Engelbrecht S, Janse van Rensburg E, Mosam A, Smith A, Cassol S.
Journal of Virology 77(4): 2587-2599 (2003) [pubmed: 12551997]
4 - Myristoylation-dependent replication and assembly of human immunodeficiency virus 1.
Bryant M, Ratner L.
Proc Natl Acad Sci USA 87: 523-527 (1990) [pubmed: 2405382]
5 - Role of capsid precursor processing and myristoylation in morphogenesis and infectivity of
human immunodeficiency virus type 1.
Gottlinger HG, Sodroski JG, Haseltine WA.
Proc Natl Acad Sci USA 86: 5781-5785 (1989) [pubmed: 2788277]
6 - The structural biology of HIV assembly.
Ganser-Pornillos BK, Yeager M, Sundquist WI.
Curr Opin Struct Biol. 18(2):203-17 (2008) [pubmed: 18406133]
7 - HIV-1 assembly, budding, and maturation.
Sundquist WI, Kräusslich HG.
Cold Spring Harb Perspect Med. 2(7):a006924 (2012) [pubmed: 22762019]
8 - Wrapping up the bad news: HIV assembly and release.
Meng B, Lever AM.
Retrovirology 10:5 (2013) [pubmed: 23305486]
9 - The phosphorylation of HIV-1 Gag by atypical protein kinase C facilitates viral infectivity by promoting Vpr incorporation into virions.
Kudoh A, Takahama S, Sawasaki T, Ode H, Yokoyama M, Okayama A, Ishikawa A, Miyakawa K, Matsunaga S, Kimura H, Sugiura W, Sato H, Hirano H, Ohno S, Yamamoto N, Ryo A.
Retrovirology 11:9 (2014) [pubmed: 24447338]
10 - Association of RNA helicase a with human immunodeficiency virus type 1 particles.
Roy BB, Hu J, Guo X, Russell RS, Guo F, Kleiman L, Liang C.
J Biol Chem. 281(18):12625-35 (2006) [pubmed: 16527808]
11 - The host protein Staufen1 interacts with the Pr55Gag zinc fingers and regulates HIV-1 assembly via its N-terminus.
Chatel-Chaix L, Boulay K, Mouland AJ, Desgroseillers L.
Retrovirology 5:41 (2008) [pubmed: 18498651]
12 - ESCRT-II's involvement in HIV-1 genomic RNA trafficking and assembly.
Ghoujal B, Milev MP, Ajamian L, Abel K, Mouland AJ.
Biol Cell 104(12):706-21 (2012) [pubmed: 22978549]
13 - Basic residues in the nucleocapsid domain of Gag are required for interaction of HIV-1 gag with ABCE1 (HP68), a cellular protein important for HIV-1 capsid assembly.
Lingappa JR, Dooher JE, Newman MA, Kiser PK, Klein KC.
J Biol Chem. 281(7):3773-84 (2006) [pubmed: 16275648]
14 - Crystal structure of human cyclophilin A bound to the amino-terminal domain of HIV-1 capsid.
Gamble TR, Vajdos FF, Yoo S, Worthylake DK, Houseweart M, Sundquist WI, Hill CP.
Cell 87(7):1285-94 (1996) [pubmed: 8980234]
15 - Life of psi: how full-length HIV-1 RNAs become packaged genomes in the viral particles.
Kuzembayeva M, Dilley K, Sardo L, Hu WS.
Virology 454-455:362-70 (2014) [pubmed: 24530126]



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Page last updated by Megan Druce, Paula Sommer and Tulio de Oliveira (UKZN/Africa Centre) & Philippe Le Mercier, Chantal Hulo and Patrick Masson (SIB/ViralZone).