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
Matrix - p17
Core Antigen capsid - p24
Nucleocapsid - p7
p6
p2
p1
Isoforms:
p55 - GAG Polyprotein (499 amino acids)
p160 - GAG-POL Polyprotein
Cleavage site:
Localization:
plasma membrane
cytoplasm
virion
Function:
Membrane-associated
Gag attracts two copies of viral RNA along with cellular and viral
proteins that trigger budding of virion from surface of cell (Ref# 6)
Protease cleaves the Gag precursor after virion budding (Ref. #5)
Additional
Information:
the precursor consists of a myristylated protein (p55), which is processed by protease to form Matrix protein (MA - p17),
Core Antigen capsid protein (CA - p24), Nucleo-Capsid protein (NC - p7), p6, p2 and p1 (Ref. #5)
Gag precursor protein is translated from unspliced viral mRNA
during translation, the N-terminus is Myristoylated (Ref. #4)
myristoylation triggers binding to cellular membrane
protease cleavage of p55 is the viral maturation process
Genomic Location: [TOP ]
Reference
Sequences:
HIV-1
(HXB2):
10 20 30 40 50 60 70 | | | | | | | GARASVLSGG ELDRWEKIRL RPGGKKKYKL KHIVWASREL ERFAVNPGLL ETSEGCRQIL GQLQPSLQTG 80 90 100 110 120 130 140 | | | | | | | SEELRSLYNT VATLYCVHQR IEIKDTKEAL DKIEEEQNKS KKKAQQAAAD TGHSNQVSQN YPIVQNIQGQ 150 160 170 180 190 200 210 | | | | | | | MVHQAISPRT LNAWVKVVEE KAFSPEVIPM FSALSEGATP QDLNTMLNTV GGHQAAMQML KETINEEAAE 220 230 240 250 260 270 280 | | | | | | | WDRVHPVHAG PIAPGQMREP RGSDIAGTTS TLQEQIGWMT NNPPIPVGEI YKRWIILGLN KIVRMYSPTS 290 300 310 320 330 340 350 | | | | | | | ILDIRQGPKE PFRDYVDRFY KTLRAEQASQ EVKNWMTETL LVQNANPDCK TILKALGPAA TLEEMMTACQ 360 370 380 390 400 410 420 | | | | | | | GVGGPGHKAR VLAEAMSQVT NSATIMMQRG NFRNQRKIVK CFNCGKEGHT ARNCRAPRKK GCWKCGKEGH 430 440 450 460 470 480 490 | | | | | | | QMKDCTERQA NFLGKIWPSY KGRPGNFLQS RPEPTAPPEE SFRSGVETTT PPQKQEPIDK ELYPLTSLRS 499 | 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:
N-glycosylation:
1 potential site
NKSK (108 - 111)
N-myristoylation:
9 potential sites
GAraSV (1 - 6)
GLleTS (48 - 53)
GGhqAA (191 - 196)
GSdiAG (232 - 237)
GTtsTL (237 - 242)
GNfrNQ (380 - 385)
GCwkCG (411 - 416)
GVetTT (465 - 470)
GNdpSS (493 - 498)
Amidation:
1 potential site
gGKK (23 - 26)
Protein kinase C:
8 potential sites
SkK (110 - 112)
SpR (147 - 149)
TlR (302 - 304)
TaR (400 - 402)
TeR (426 - 428)
SyK (439 - 441)
SfR (461 - 463)
SlR (487 - 489)
Casein kinase II:
9 potential sites
SggE (8 - 11)
TgsE (69 - 72)
TpqD (179 - 182)
TinE (203 - 206)
TlqE (241 - 244)
SilD (280 - 283)
TleE (341 - 344)
SrpE (450 - 453)
SgvE (464 - 467)
Tyrosine kinase:
1 potential site
RdyvDrf.Y (293 - 300)
cAMP / cGMP kinase:
none
Cell attachment motif:
none
Asp Protease motif:
none
Asp Prot Retro motif:
none
Cysteine-rich Region:
none
Tryptophan-rich Region:
none
Zinc-finger knuckle motif:
2 potential sites
(390 - 405)
(412 - 427)
Leucine Zipper motif:
none
Protein-Protein Interactions: [TOP ]
HIV protease cleaves GAG
Gag binds to Vpr for its incorporation into virion
Gag binds to Vif for its incorporation into virion
Gag binds to Protease for regulation of protease activity
Gag binds to Actin during viral particle assembly
Gag binds to Cyclophilin A during Capsid core assembly
Primary and Secondary Database Entries: [TOP ]
Identifiers:
ViralZone: HIV-1 PDB/MMDB: Search for HIV-1 & GAG
SwissProt: P04591 (HIV-1 HXB2 Gag)
EMBL: K03455; AAB50258.1 [EMBL /GenBank /DDBJ ]
PIR: UNKNOWN
HIV: K03455; GAG$HXB2
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: PF00540 - Matrix p17 / PF00607 - Nucleocapsid p24 / PF00098 - Zinc-Finger (CCHC-type)
Prints: PR00234 - HIV1MATRIX / PR00939 - Zinc-Finger (CCHC-type)
ProDom:
PD000202 (1 - 131) /
PD003398 (121 - 226) /
PD613442 (123 - 159) /
PD000209 (132 - 159)
PD460115 (132 - 188) /
PD006198 (144 - 216) /
PD579426 (160 - 195) /
PD000278 (192 - 263)
PD394824 (263 - 425) /
PD000267 (279 - 362) /
PD027136 (284 - 414) /
PD539915 (311 - 408)
PD488523 (355 - 405) /
PD506618 (363 - 413) /
PD456461 (363 - 495) /
PD000129 (363 - 412)
PD014300 (374 - 428) /
PD402044 (384 - 414) /
PD319272 (388 - 425) /
PD323937 (389 - 480)
PD617862 (390 - 424) /
PD086795 (390 - 410) /
PD594906 (390 - 456) /
PD107922 (391 - 431)
PD185557 (391 - 477) /
PD351972 (391 - 428) /
PD375076 (391 - 425) /
PD019096 (391 - 429)
PD066914 (392 - 495) /
PD008985 (412 - 460) /
PD406622 (413 - 447) /
PD149817 (448 - 485)
PD454601 (448 - 499) /
PD425744 (449 - 499) /
PD613638 (449 - 496) /
PD474283 (449 - 495)
PD612384 (449 - 499)
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
ProtoMap: P04591
PRESAGE: P04591
Database of Interacting Proteins: P04591
ModBase: P04591
Swiss-2DPAGE: 2D gel
BioAfrica Tools:
- Gag Protein Data Mining Tool provides real-time analysis of HIV-1 Gag isolates
- HIV Structure BLAST searches for similar HIV sequences that have known structures
- HIV Proteomics Resource contains protein sequence and structure analysis tools
Reviews and References: [TOP ]
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 ]