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Gag-Pol polyprotein



Human immunodeficiency virus type 1 group M subtype B (isolate CDC-451) (HIV-1)
Reviewed-Annotation score: -Protein inferred from homologyi


Gag-Pol polyprotein: Mediates, with Gag polyprotein, 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). Gag-Pol polyprotein may regulate its own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, the polyprotein would promote translation, whereas at high concentration, the polyprotein would encapsidate genomic RNA and then shut off translation.By similarity
Matrix protein p17: Targets the polyprotein to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. Matrix protein is part of the pre-integration complex. Implicated in the release from host cell mediated by Vpu. Binds to RNA.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. 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
Protease: Aspartyl protease that mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell. Also cleaves Nef and Vif, probably concomitantly with viral structural proteins on maturation of virus particles. Hydrolyzes host EIF4GI and PABP1 in order to shut off the capped cellular mRNA translation. The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response (By similarity).PROSITE-ProRule annotationBy similarity


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).
Resistance to inhibitors associated with mutations are observed both in viral protease and in reverse transcriptase. Most of the time, single mutations confer only a modest reduction in drug susceptibility. Combination of several mutations is usually required to develop a high-level drug resistance. These mutations are predominantly found in clade B viruses and not in other genotypes. They are listed in the clade B representative isolate HXB2 (AC P04585).

Catalytic activityi

Specific for a P1 residue that is hydrophobic, and P1' variable, but often Pro.PROSITE-ProRule annotation

Enzyme regulationi

Protease: The viral protease is inhibited by many synthetic protease inhibitors (PIs), such as amprenavir, atazanavir, indinavir, loprinavir, nelfinavir, ritonavir and saquinavir. Use of protease inhibitors in tritherapy regimens permit more ambitious therapeutic strategies.By similarity


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei221 – 222Cis/trans isomerization of proline peptide bond; by human PPIA/CYPABy similarity2
Active sitei513For protease activity; shared with dimeric partnerPROSITE-ProRule annotation1


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri390 – 407CCHC-type 1PROSITE-ProRule annotationAdd BLAST18
Zinc fingeri411 – 428CCHC-type 2PROSITE-ProRule annotationAdd BLAST18

GO - Molecular functioni

GO - Biological processi


Molecular functionAspartyl protease, Hydrolase, Protease, RNA-binding, Viral nucleoprotein
Biological processEukaryotic host gene expression shutoff by virus, Eukaryotic host translation shutoff by virus, Host gene expression shutoff by virus, Host-virus interaction, Viral release from host cell, Virion maturation
LigandLipid-binding, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Gag-Pol polyprotein
Alternative name(s):
Cleaved into the following 7 chains:
Matrix protein p17
Short name:
Capsid protein p24
Short name:
Spacer peptide 1By similarity
Short name:
Alternative name(s):
Transframe peptide
Short name:
Short name:
Alternative name(s):
Gene namesi
OrganismiHuman immunodeficiency virus type 1 group M subtype B (isolate CDC-451) (HIV-1)
Taxonomic identifieri11687 [NCBI]
Taxonomic lineageiVirusesOrterviralesRetroviridaeOrthoretrovirinaeLentivirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]

Subcellular locationi

Gag-Pol polyprotein :
  • Host cell membrane ; Lipid-anchor
  • host multivesicular body
  • Note: These locations are 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

GO - Cellular componenti

Keywords - Cellular componenti

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

Pathology & Biotechi

Keywords - Diseasei


PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved; by hostBy similarity
ChainiPRO_00002612652 – ›550Gag-Pol polyproteinAdd BLAST›549
ChainiPRO_00000423392 – 132Matrix protein p17By similarityAdd BLAST131
ChainiPRO_0000042340133 – 363Capsid protein p24By similarityAdd BLAST231
PeptideiPRO_0000042341364 – 377Spacer peptide 1By similarityAdd BLAST14
ChainiPRO_0000042342378 – 432Nucleocapsid protein p7By similarityAdd BLAST55
PeptideiPRO_0000246713433 – 440Transframe peptideSequence analysis8
ChainiPRO_0000042343441 – 488p6-polSequence analysisAdd BLAST48
ChainiPRO_0000038653489 – ›550ProteaseBy similarityAdd BLAST›62

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycine; by hostBy similarity1
Modified residuei132Phosphotyrosine; by hostBy similarity1

Post-translational modificationi

Specific enzymatic cleavages by the viral protease yield mature proteins. The protease is released by autocatalytic cleavage. The polyprotein is cleaved during and after budding, this process is termed maturation. Proteolytic cleavage of p66 RT removes the RNase H domain to yield the p51 RT subunit. Nucleocapsid protein p7 might be further cleaved after virus entry (By similarity).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


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei132 – 133Cleavage; by viral proteaseBy similarity2
Sitei363 – 364Cleavage; by viral proteaseBy similarity2
Sitei377 – 378Cleavage; by viral proteaseBy similarity2
Sitei432 – 433Cleavage; by viral proteaseSequence analysis2
Sitei440 – 441Cleavage; by viral proteaseBy similarity2
Sitei488 – 489Cleavage; by viral proteaseBy similarity2

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein

Proteomic databases



Subunit structurei

Matrix protein p17: Homotrimer; further assembles as hexamers of trimers (By similarity). Matrix protein p17: Interacts with gp41 (via C-terminus) (By similarity). Matrix protein p17: interacts with host CALM1; this interaction induces a conformational change in the Matrix protein, triggering exposure of the myristate group (By similarity). Matrix protein p17: interacts with host AP3D1; this interaction allows the polyprotein trafficking to multivesicular bodies during virus assembly (By similarity). Matrix protein p17: Part of the pre-integration complex (PIC) which is composed of viral genome, matrix protein, Vpr and integrase (By similarity). Capsid protein p24: Homodimer; the homodimer further multimerizes as homohexamers or homopentamers. Capsid protein p24: Interacts with human PPIA/CYPA (By similarity); This interaction stabilizes the capsid. Capsid protein p24: Interacts with human NUP153 (By similarity). Capsid protein p24: Interacts with host PDZD8; this interaction stabilizes the capsid (By similarity). Capsid protein p24: Interacts with monkey TRIM5; this interaction destabilizes the capsid (By similarity).Protease: Homodimer, whose active site consists of two apposed aspartic acid residues. Reverse transcriptase/ribonuclease H: Heterodimer of p66 RT and p51 RT (RT p66/p51). Heterodimerization of RT is essential for DNA polymerase activity. Despite the sequence identities, p66 RT and p51 RT have distinct folding. Integrase: Homodimer; possibly can form homotetramer. Integrase: Part of the pre-integration complex (PIC) which is composed of viral genome, matrix protein, Vpr and integrase. Integrase: Interacts with human SMARCB1/INI1 and human PSIP1/LEDGF isoform 1. Integrase: Interacts with human KPNA3; this interaction might play a role in nuclear import of the pre-integration complex (By similarity). Integrase: Interacts with human NUP153; this interaction might play a role in nuclear import of the pre-integration complex (By similarity).By similarity


3D structure databases


Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini508 – ›550Peptidase A2PROSITE-ProRule annotationAdd BLAST›43


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
Regioni189 – 227Interaction with human PPIA/CYPA and NUP153By similarityAdd BLAST39
Regioni277 – 363Dimerization/Multimerization of capsid protein p24By similarityAdd BLAST87
Regioni489 – 493Dimerization of proteaseBy similarity5
Regioni537 – 543Dimerization of proteaseBy similarity7


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi16 – 22Nuclear export signalBy similarity7
Motifi26 – 32Nuclear localization signalBy similarity7

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri390 – 407CCHC-type 1PROSITE-ProRule annotationAdd BLAST18
Zinc fingeri411 – 428CCHC-type 2PROSITE-ProRule annotationAdd BLAST18

Keywords - Domaini

Repeat, Zinc-finger

Family and domain databases

Gene3Di1.10.1200.30, 1 hit, 1 hit
1.10.375.10, 1 hit, 1 hit
InterProiView protein in InterPro
IPR001969 Aspartic_peptidase_AS
IPR000721 Gag_p24
IPR000071 Lentvrl_matrix_N
IPR012344 Matrix_HIV/RSV_N
IPR001995 Peptidase_A2_cat
IPR021109 Peptidase_aspartic_dom_sf
IPR018061 Retropepsins
IPR008916 Retrov_capsid_C
IPR008919 Retrov_capsid_N
IPR010999 Retrovr_matrix
IPR001878 Znf_CCHC
IPR036875 Znf_CCHC_sf
PfamiView protein in Pfam
PF00540 Gag_p17, 1 hit
PF00607 Gag_p24, 1 hit
PF00077 RVP, 1 hit
PF00098 zf-CCHC, 2 hits
SMARTiView protein in SMART
SM00343 ZnF_C2HC, 2 hits
SUPFAMiSSF47836 SSF47836, 1 hit
SSF47943 SSF47943, 1 hit
SSF50630 SSF50630, 1 hit
SSF57756 SSF57756, 1 hit
PROSITEiView protein in PROSITE
PS50175 ASP_PROT_RETROV, 1 hit
PS00141 ASP_PROTEASE, 1 hit
PS50158 ZF_CCHC, 2 hits

Sequences (2)i

Sequence statusi: Fragment.

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-Pol polyprotein (identifier: P05960-1) [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.

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Note: Produced by -1 ribosomal frameshifting.
Mass (Da):61,404
Last modified:January 23, 2007 - v3
Isoform Gag polyprotein (identifier: P05887-1) [UniParc]FASTAAdd to basket
The sequence of this isoform can be found in the external entry P05887.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Note: Produced by conventional translation.
Mass (Da):55,928

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Non-terminal residuei5501

Sequence databases

Select the link destinations:
Links Updated
M13136 Genomic RNA No translation available.

Keywords - Coding sequence diversityi

Ribosomal frameshifting

Similar proteinsi

Entry informationi

Entry nameiPOL_HV1C4
AccessioniPrimary (citable) accession number: P05960
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: January 23, 2007
Last modified: June 20, 2018
This is version 154 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

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