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Protein

Gag polyprotein

Gene

gag

Organism
Human immunodeficiency virus type 1 group M subtype B (isolate MN) (HIV-1)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Gag polyprotein: Mediates, with Gag-Pol polyrotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi).By similarity
Matrix protein p17: Targets the polyprotein to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus (By similarity). Matrix protein is part of the pre-integration complex. Implicated in the release from host cell mediated by Vpu. Binds to RNA (By similarity).By similarity
Capsid protein p24: Forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry (By similarity). Host restriction factors such as TRIM5-alpha or TRIMCyp bind retroviral capsids and cause premature capsid disassembly, leading to blocks in reverse transcription. Capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species. Host PIN1 apparently facilitates the virion uncoating (By similarity). On the other hand, interactions with PDZD8 or CYPA stabilize the capsid.By similarity
Nucleocapsid protein p7: Encapsulates and protects viral dimeric unspliced genomic RNA (gRNA). Binds these RNAs through its zinc fingers. Acts as a nucleic acid chaperone which is involved in rearangement of nucleic acid secondary structure during gRNA retrotranscription. Also facilitates template switch leading to recombination. As part of the polyprotein, participates in gRNA dimerization, packaging, tRNA incorporation and virion assembly.By similarity
p6-gag: Plays a role in budding of the assembled particle by interacting with the host class E VPS proteins TSG101 and PDCD6IP/AIP1.By similarity

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri393 – 410CCHC-type 1PROSITE-ProRule annotationAdd BLAST18
Zinc fingeri414 – 431CCHC-type 2PROSITE-ProRule annotationAdd BLAST18

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Host-virus interaction, Viral budding, Viral budding via the host ESCRT complexes, Virus exit from host cell

Keywords - Ligandi

Metal-binding, RNA-binding, Viral nucleoprotein, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Gag polyprotein
Alternative name(s):
Pr55Gag
Cleaved into the following 6 chains:
Matrix protein p17
Short name:
MA
Capsid protein p24
Short name:
CA
Spacer peptide 1By similarity
Short name:
SP1
Alternative name(s):
p2
Spacer peptide 2By similarity
Short name:
SP2
Alternative name(s):
p1
Gene namesi
Name:gag
OrganismiHuman immunodeficiency virus type 1 group M subtype B (isolate MN) (HIV-1)
Taxonomic identifieri11696 [NCBI]
Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeLentivirusPrimate lentivirus group
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000007697 Componenti: Genome

Subcellular locationi

Gag polyprotein :
  • Host cell membrane By similarity; Lipid-anchor By similarity
  • Host endosomehost multivesicular body By similarity

  • Note: These locations are probably linked to virus assembly sites. The main location is the cell membrane, but under some circumstances, late endosomal compartments can serve as productive sites for virion assembly.By similarity
Matrix protein p17 :
  • Virion membrane By similarity; Lipid-anchor By similarity
  • Host nucleus By similarity
  • Host cytoplasm By similarity
Capsid protein p24 :
  • Virion By similarity
Nucleocapsid protein p7 :
  • Virion By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Capsid protein, Host cell membrane, Host cytoplasm, Host endosome, Host membrane, Host nucleus, Membrane, Virion

Pathology & Biotechi

Keywords - Diseasei

AIDS

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved; by host1 Publication
ChainiPRO_00002612212 – 507Gag polyproteinAdd BLAST506
ChainiPRO_00000385472 – 135Matrix protein p17Add BLAST134
ChainiPRO_0000038548136 – 366Capsid protein p24Add BLAST231
PeptideiPRO_0000038549367 – 380Spacer peptide 1Add BLAST14
ChainiPRO_0000038550381 – 435Nucleocapsid protein p7Add BLAST55
PeptideiPRO_0000038551436 – 451Spacer peptide 2Add BLAST16
ChainiPRO_0000038552452 – 507p6-gagAdd BLAST56

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycine; by host1 Publication1
Modified residuei151Phosphoserine; by host MAPK1By similarity1
Modified residuei390Asymmetric dimethylarginine; in Nucleocapsid protein p7; by host PRMT6By similarity1
Modified residuei412Asymmetric dimethylarginine; in Nucleocapsid protein p7; by host PRMT6By similarity1

Post-translational modificationi

Gag-Pol polyprotein: Specific enzymatic cleavages by the viral protease yield mature proteins.By similarity
Matrix protein p17: Tyrosine phosphorylated presumably in the virion by a host kinase. Phosphorylation is apparently not a major regulator of membrane association.By similarity
Capsid protein p24: Phosphorylated possibly by host MAPK1; this phosphorylation is necessary for Pin1-mediated virion uncoating.By similarity
Nucleocapsid protein p7: Methylated by host PRMT6, impairing its function by reducing RNA annealing and the initiation of reverse transcription.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei135 – 136Cleavage; by viral proteaseBy similarity2
Sitei366 – 367Cleavage; by viral proteaseBy similarity2
Sitei380 – 381Cleavage; by viral proteaseBy similarity2
Sitei435 – 436Cleavage; by viral proteaseBy similarity2
Sitei451 – 452Cleavage; by viral proteaseBy similarity2

Keywords - PTMi

Lipoprotein, Methylation, Myristate, Phosphoprotein

Interactioni

Subunit structurei

Gag polyprotein: Homotrimer; further assembles as hexamers of trimers. Oligomerization possibly creates a central hole into which the cytoplasmic tail of the gp41 envelope protein may be inserted.Gag polyprotein: Interacts with host TRIM22; this interaction seems to disrupt proper trafficking of Gag polyprotein and may interfere with budding. Gag polyprotein: Interacts with host PDZD8. Matrix protein p17: Homotrimer; further assembles as hexamers of trimers. Matrix protein p17: Interacts with gp41 (via C-terminus). Matrix protein p17: Interacts with host CALM1; this interaction induces a conformational change in the Matrix protein, triggering exposure of the myristate group. Matrix protein p17: Interacts with host AP3D1; this interaction allows the polyprotein trafficking to multivesicular bodies during virus assembly. Matrix protein p17: Part of the pre-integration complex (PIC) which is composed of viral genome, matrix protein, Vpr and integrase. Capsid protein p24: Homodimer; the homodimer further multimerizes as homohexamers or homopentamers. Capsid protein p24: Interacts with human PPIA/CYPA. Capsid protein p24: Interacts with human NUP153. Capsid protein p24: Interacts with host PDZD8; this interaction stabilizes the capsid. Capsid protein p24: Interacts with monkey TRIM5; this interaction destabilizes the capsid. p6-gag interacts with Vpr; this interaction allows Vpr incorporation into the virion. p6-gag interacts with host TSG101. p6-gag interacts with host PDCD6IP/AIP1 (By similarity).By similarity

Protein-protein interaction databases

IntActiP05888. 4 interactors.
MINTiMINT-7014121.

Chemistry databases

BindingDBiP05888.

Structurei

Secondary structure

1507
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni396 – 3983
Beta strandi401 – 4033
Helixi405 – 4073
Turni417 – 4193
Beta strandi422 – 4243
Helixi426 – 4283

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AAFNMR-A381-435[»]
ProteinModelPortaliP05888.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP05888.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni7 – 31Interaction with Gp41By similarityAdd BLAST25
Regioni8 – 43Interaction with host CALM1By similarityAdd BLAST36
Regioni12 – 19Interaction with host AP3D1By similarity8
Regioni14 – 33Interaction with membrane phosphatidylinositol 4,5-bisphosphate and RNABy similarityAdd BLAST20
Regioni73 – 77Interaction with membrane phosphatidylinositol 4,5-bisphosphateBy similarity5
Regioni192 – 230Interaction with host PPIA/CYPA and NUP153By similarityAdd BLAST39
Regioni220 – 228PPIA/CYPA-binding loopBy similarity9
Regioni280 – 366Dimerization/Multimerization of capsid protein p24By similarityAdd BLAST87

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi16 – 22Nuclear export signalBy similarity7
Motifi26 – 32Nuclear localization signalBy similarity7
Motifi458 – 461PTAP/PSAP motif4
Motifi490 – 499LYPX(n)L motif10

Domaini

Late-budding domains (L domains) are short sequence motifs essential for viral particle budding. They recruit proteins of the host ESCRT machinery (Endosomal Sorting Complex Required for Transport) or ESCRT-associated proteins. p6-gag contains two L domains: a PTAP/PSAP motif, which interacts with the UEV domain of TSG101 and a LYPX(n)L motif which interacts with PDCD6IP/AIP1.By similarity

Sequence similaritiesi

Contains 2 CCHC-type zinc fingers.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri393 – 410CCHC-type 1PROSITE-ProRule annotationAdd BLAST18
Zinc fingeri414 – 431CCHC-type 2PROSITE-ProRule annotationAdd BLAST18

Keywords - Domaini

Repeat, Zinc-finger

Family and domain databases

Gene3Di1.10.1200.30. 1 hit.
1.10.150.90. 1 hit.
1.10.375.10. 1 hit.
4.10.60.10. 1 hit.
InterProiIPR000721. Gag_p24.
IPR014817. Gag_p6.
IPR000071. Lentvrl_matrix_N.
IPR012344. Matrix_HIV/RSV.
IPR008916. Retrov_capsid_C.
IPR008919. Retrov_capsid_N.
IPR010999. Retrovr_matrix.
IPR001878. Znf_CCHC.
[Graphical view]
PfamiPF00540. Gag_p17. 1 hit.
PF00607. Gag_p24. 1 hit.
PF08705. Gag_p6. 1 hit.
PF00098. zf-CCHC. 2 hits.
[Graphical view]
PRINTSiPR00234. HIV1MATRIX.
SMARTiSM00343. ZnF_C2HC. 2 hits.
[Graphical view]
SUPFAMiSSF47353. SSF47353. 1 hit.
SSF47836. SSF47836. 1 hit.
SSF47943. SSF47943. 1 hit.
SSF57756. SSF57756. 1 hit.
PROSITEiPS50158. ZF_CCHC. 2 hits.
[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 ribosomal frameshifting. AlignAdd to basket

Note: Translation results in the formation of the Gag polyprotein most of the time. Ribosomal frameshifting at the gag-pol genes boundary occurs at low frequency and produces the Gag-Pol polyprotein. This strategy of translation probably allows the virus to modulate the quantity of each viral protein. Maintenance of a correct Gag to Gag-Pol ratio is essential for RNA dimerization and viral infectivity.
Isoform Gag polyprotein (identifier: P05888-1) [UniParc]FASTAAdd to basket

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
MGARASVLSG GELDRWEKIR LRPGGKKKYK LKHVVWASRE LERFAINPGL
60 70 80 90 100
LETSEGCRQI LGQLQPSLQT GSEERKSLYN TVATLYCVHQ KIKIKDTKEA
110 120 130 140 150
LEKIEEEQNK SKKKAQQAAA DTGNRGNSSQ VSQNYPIVQN IQGQMVHQAI
160 170 180 190 200
SPRTLNAWVK VVEEKAFSPE VIPMFSALSE GATPQDLNTM LNTVGGHQAA
210 220 230 240 250
MQMLKETINE EAAEWDRLHP AHAGPIAPGQ MREPRGSDIA GTTSTLQEQI
260 270 280 290 300
GWMTNNPPIP VGEIYKRWII LGLNKIVRMY SPSSILDIRQ GPKEPFRDYV
310 320 330 340 350
DRFYKTLRAE QASQEVKNWM TETLLVQNAN PDCKTILKAL GPAATLEEMM
360 370 380 390 400
TACQGVGGPG HKARVLAEAM SQVTNSATIM MQRGNFRNQR KIIKCFNCGK
410 420 430 440 450
EGHIAKNCRA PRKRGCWKCG KEGHQMKDCT ERQANFLGKI WPSCKGRPGN
460 470 480 490 500
FPQSRTEPTA PPEESFRFGE ETTTPYQKQE KKQETIDKDL YPLASLKSLF

GNDPLSQ
Note: Produced by conventional translation.
Length:507
Mass (Da):56,761
Last modified:January 23, 2007 - v3
Checksum:iAC6F207EC41C4726
GO
Isoform Gag-Pol polyprotein (identifier: P05961-1) [UniParc]FASTAAdd to basket
The sequence of this isoform can be found in the external entry P05961.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Note: Produced by -1 ribosomal frameshifting.
Length:1,441
Mass (Da):162,328
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti18K → N in AAA44853 (PubMed:3369091).Curated1
Sequence conflicti142Q → E in AAA44853 (PubMed:3369091).Curated1
Sequence conflicti221A → V in AAA44853 (PubMed:3369091).Curated1
Sequence conflicti227A → T in AAA44853 (PubMed:3369091).Curated1
Sequence conflicti319 – 320WM → RT in AAA44853 (PubMed:3369091).Curated2
Sequence conflicti448 – 449PG → R in AAA44853 (PubMed:3369091).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti35V → I.1
Natural varianti46I → V.1
Natural varianti75R → L.1
Natural varianti75R → N.1
Natural varianti75R → S.1
Natural varianti93K → E.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M17449 Genomic RNA. Translation: AAA44853.1.
PIRiA38068.

Keywords - Coding sequence diversityi

Ribosomal frameshifting

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M17449 Genomic RNA. Translation: AAA44853.1.
PIRiA38068.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AAFNMR-A381-435[»]
ProteinModelPortaliP05888.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP05888. 4 interactors.
MINTiMINT-7014121.

Chemistry databases

BindingDBiP05888.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Miscellaneous databases

EvolutionaryTraceiP05888.

Family and domain databases

Gene3Di1.10.1200.30. 1 hit.
1.10.150.90. 1 hit.
1.10.375.10. 1 hit.
4.10.60.10. 1 hit.
InterProiIPR000721. Gag_p24.
IPR014817. Gag_p6.
IPR000071. Lentvrl_matrix_N.
IPR012344. Matrix_HIV/RSV.
IPR008916. Retrov_capsid_C.
IPR008919. Retrov_capsid_N.
IPR010999. Retrovr_matrix.
IPR001878. Znf_CCHC.
[Graphical view]
PfamiPF00540. Gag_p17. 1 hit.
PF00607. Gag_p24. 1 hit.
PF08705. Gag_p6. 1 hit.
PF00098. zf-CCHC. 2 hits.
[Graphical view]
PRINTSiPR00234. HIV1MATRIX.
SMARTiSM00343. ZnF_C2HC. 2 hits.
[Graphical view]
SUPFAMiSSF47353. SSF47353. 1 hit.
SSF47836. SSF47836. 1 hit.
SSF47943. SSF47943. 1 hit.
SSF57756. SSF57756. 1 hit.
PROSITEiPS50158. ZF_CCHC. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiGAG_HV1MN
AccessioniPrimary (citable) accession number: P05888
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 145 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Miscellaneous

The MN isolate was taken from a pediatric AIDS patient in 1984.
HIV-1 lineages are divided in three main groups, M (for Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast majority of strains found worldwide belong to the group M. Group O seems to be endemic to and largely confined to Cameroon and neighboring countries in West Central Africa, where these viruses represent a small minority of HIV-1 strains. The group N is represented by a limited number of isolates from Cameroonian persons. The group M is further subdivided in 9 clades or subtypes (A to D, F to H, J and K).

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. 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.