Reviewed, UniProtKB/Swiss-Prot P05960 (POL_HV1C4)

Names and origin

Protein names

Recommended name:
    Gag-Pol polyprotein
Alternative name(s):
    Pr160Gag-Pol
Cleaved into the following 7 chains:
    1- Recommended name:
            Matrix protein p17
                Short name=MA
    2- Recommended name:
            Capsid protein p24
                Short name=CA
    3- Recommended name:
            Spacer peptide p2
    4- Recommended name:
            Nucleocapsid protein p7
                Short name=NC
    5- Recommended name:
            Transframe peptide
                Short name=TF
    6- Recommended name:
            p6-pol
                Short name=p6*
    7- Recommended name:
            Protease
              EC=3.4.23.16
        Alternative name(s):
            Retropepsin
            PR

Gene names

Name:

gag-pol

Organism

Human immunodeficiency virus type 1 (isolate CDC-451 group M subtype B) (HIV-1)

Taxonomic identifier

11687 [NCBI]

Taxonomic lineage

Viruses › Retro-transcribing viruses › Retroviridae › Orthoretrovirinae › Lentivirus › Primate lentivirus group

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	550 AA.
Sequence status	Fragment.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Inferred from homology.

General annotation (Comments)

Function	Gag-Pol polyprotein and Gag polyprotein may regulate their own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, Gag-Pol and Gag would promote translation, whereas at high concentration, the polyproteins encapsidate genomic RNA and then shutt off translation By similarity. Matrix protein p17 has two main functions: in infected cell, it targets Gag and Gag-pol polyproteins to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. The second function is to plays a role in nuclear localization of the viral genome at the very start of cell infection. Matrix protein is the part of the pre-integration complex. It binds in the cytoplasm the human BAF protein which prevent autointegration of the viral genome, and might be included in virions at the ration of zero to 3 BAF dimer per virion. The myristoylation signal and the NLS thus exert conflicting influences its subcellular localization. The key regulation of these motifs might be phosphorylation of a portion of MA molecules on the C-terminal tyrosine at the time of virus maturation, by virion-associated cellular tyrosine kinase. Implicated in the release from host cell mediated by Vpu 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 dissassembled soon after virion entry. Interaction with human PPIA/CYPA protects the virus from restriction by human TRIM5-alpha and from an unknown antiviral activity in human cells. This capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species By similarity. Nucleocapsid protein p7 encapsulates and protects viral dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc fingers. Facilitates rearangement of nucleic acid secondary structure during retrotranscription of genomic RNA. This capability is referred to as nucleic acid chaperone activity By similarity. The aspartyl protease 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 By similarity.
Catalytic activity	Specific for a P1 residue that is hydrophobic, and P1' variable, but often Pro.
Enzyme regulation	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.
Subunit structure	Pre-integration complex interacts with human HMGA1. Matrix protein p17 is a trimer. Interacts with gp120 and human BAF. Capsid is a homodimer. Interacts with human PPIA/CYPA. The protease is a homodimer, whose active site consists of two apposed aspartic acid residues By similarity.
Subcellular location	Matrix protein p17: Virion Potential. Host nucleus By similarity. Host cytoplasm By similarity. Host cell membrane; Lipid-anchor Potential. Note: Following virus entry, the nuclear localization signal (NLS) of the matrix protein participates with Vpr to the nuclear localization of the viral genome. During virus production, the nuclear export activity of the matrix protein counteracts the NLS to maintain the Gag and Gag-Pol polyproteins in the cytoplasm, thereby directing unspliced RNA to the plasma membrane By similarity. Capsid protein p24: Virion Potential. Nucleocapsid protein p7: Virion Potential.
Post-translational modification	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. Capsid protein p24 is phosphorylated By similarity. Matrix protein p17 is tyrosine phosphorylated presumably in the virion by a host kinase. This modification targets the matrix protein to the nucleus By similarity.
Miscellaneous	Capsid protein p24 is able to bind macaque TRIM5-alpha or owl monkey TRIMCyp, preventing reverse transcription of the viral genome and succesfull infection of macaque or owl monkey by HIV-1 By 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).
Sequence similarities	Contains 2 CCHC-type zinc fingers. Contains 1 peptidase A2 domain.

Ontologies

Keywords
Biological process	Capsid maturation
Cellular component	Capsid protein Cell membrane Cytoplasm Membrane Nucleus Virion
Coding sequence diversity	Ribosomal frameshifting
Disease	AIDS
Domain	Repeat Zinc-finger
Ligand	Metal-binding RNA-binding Viral nucleoprotein Zinc
Molecular function	Aspartyl protease Hydrolase Protease
PTM	Lipoprotein Myristate Phosphoprotein
Gene Ontology (GO)
Biological process	initiation of viral infection Inferred from Experiment. Source: Reactome proteolysis Inferred from electronic annotation. Source: InterPro provirus integration Inferred from Experiment. Source: Reactome viral procapsid maturation Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Inferred from Experiment. Source: Reactome host cell cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell host cell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell host cell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW viral capsid Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	RNA binding Inferred from electronic annotation. Source: UniProtKB-KW aspartic-type endopeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW structural molecule activity Inferred from electronic annotation. Source: UniProtKB-KW zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by ribosomal frameshifting. [Align] [Select]

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)

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.

Note: Produced by -1 ribosomal frameshifting.

Isoform Gag polyprotein (identifier: P05887-1)

The sequence of this isoform can be found in the external entry P05887-1.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

Note: Produced by conventional translation.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed; by host By similarity
	Chain	2 – ›550	›549	Gag-Pol polyprotein		PRO_0000261265
	Chain	2 – 132	131	Matrix protein p17 By similarity		PRO_0000042339
	Chain	133 – 363	231	Capsid protein p24 By similarity		PRO_0000042340
	Peptide	364 – 377	14	Spacer peptide p2 By similarity		PRO_0000042341
	Chain	378 – 432	55	Nucleocapsid protein p7 By similarity		PRO_0000042342
	Peptide	433 – 440	8	Transframe peptide Potential		PRO_0000246713
	Chain	441 – 488	48	p6-pol Potential		PRO_0000042343
	Chain	489 – ›550	›62	Protease By similarity		PRO_0000038653
Regions
	Domain	508 – ›550	›43	Peptidase A2
	Zinc finger	390 – 407	18	CCHC-type 1
	Zinc finger	411 – 428	18	CCHC-type 2
	Motif	16 – 22	7	Nuclear export signal By similarity
	Motif	26 – 32	7	Nuclear localization signal By similarity
Sites
	Active site	513	1	For protease activity; shared with dimeric partner By similarity
	Site	132 – 133	2	Cleavage; by viral protease By similarity
	Site	221 – 222	2	Cis/trans isomerization of proline peptide bond; by human PPIA/CYPA By similarity
	Site	363 – 364	2	Cleavage; by viral protease By similarity
	Site	377 – 378	2	Cleavage; by viral protease By similarity
	Site	432 – 433	2	Cleavage; by viral protease Potential
	Site	440 – 441	2	Cleavage; by viral protease By similarity
	Site	488 – 489	2	Cleavage; by viral protease By similarity
Amino acid modifications
	Modified residue	132	1	Phosphotyrosine; by host By similarity
	Lipidation	2	1	N-myristoyl glycine; by host By similarity
Experimental info
	Non-terminal residue	550	1

Sequences

	Sequence		Length	Mass (Da)
	Isoform Gag-Pol polyprotein [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 5A1D58D84EA7A824	FASTA	550	61,404
	10 20 30 40 50 60 MGARASVLSG GELDRWEKIR LRPGGKKQYR LKHIVWASRK LERFAVNPGL LETSKGCRQI 70 80 90 100 110 120 LGQLQPSLQT GSEELRSLYN TVATLYCVHQ RIEVRDTKEA LDKIEEEQNK SKKKAQQAAA 130 140 150 160 170 180 DTGNSSQVSQ NYPIVQNLQG QMVHQAISPR TLNAWVKVIE EKAFSPEVIP MFAALSEGAT 190 200 210 220 230 240 PQDLNTMLNT VGGHQAAMQM LKETINEEAA EWDRLHPVHA GPIAPGQMRE PRGSDIAGTT 250 260 270 280 290 300 STLQEQIGWM TNNPPTPVGE IYKRWIILGL NKIVRMYSPI SILDIRQGPK EPFRDYVDRF 310 320 330 340 350 360 YKTLRAEQAS QEVKNWMTET LLVQNANPDC KTILKALGPA ATLEEMMTAC QGVGGPGHKA 370 380 390 400 410 420 RVLAEAMSQV TNSATIMMQR GNFRRQGKTV KCFNCGKEGH IARNCKAPRK KGCWKCGREG 430 440 450 460 470 480 HQMKDCTERQ ANFLREDLAF PQGKAREFSS EQTRANSPTR GELQVWGRDN NSLSEAGAER 490 500 510 520 530 540 QGTVSFSFPQ ITLWQRPIVT IKIGGQLKEA LLDTGADDTV LEEINLPGRW KPKMIGGIGG 550 FIKVRQYDEV
	Isoform Gag polyprotein. See P05887.	FASTA	–	–

References

[1]	"Molecular cloning and primary nucleotide sequence analysis of a distinct human immunodeficiency virus isolate reveal significant divergence in its genomic sequences." Desai S.M., Kalyanaraman V.S., Casey J.M., Srinivasan A., Andersen P.R., Devare S.G. Proc. Natl. Acad. Sci. U.S.A. 83:8380-8384(1986) [PubMed: 3490666] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"Proteolytic processing and particle maturation." Vogt V.M. Curr. Top. Microbiol. Immunol. 214:95-131(1996) [PubMed: 8791726] [Abstract] Cited for: REVIEW.
[3]	"Structural biology of HIV." Turner B.G., Summers M.F. J. Mol. Biol. 285:1-32(1999) [PubMed: 9878383] [Abstract] Cited for: REVIEW.
[4]	"Mechanisms of retroviral recombination." Negroni M., Buc H. Annu. Rev. Genet. 35:275-302(2001) [PubMed: 11700285] [Abstract] Cited for: REVIEW.
[5]	"Retroviral proteases." Dunn B.M., Goodenow M.M., Gustchina A., Wlodawer A. Genome Biol. 3:REVIEWS3006.1-REVIEWS3006.7(2002) [PubMed: 11983066] [Abstract] Cited for: REVIEW.
[6]	"Role of HIV-1 Gag domains in viral assembly." Scarlata S., Carter C. Biochim. Biophys. Acta 1614:62-72(2003) [PubMed: 12873766] [Abstract] Cited for: REVIEW.

Web resources

HIV drug resistance mutations

hivdb

HIV drug resistance database

BioAfrica: HIV bioinformatics in Africa

Cross-references

Sequence databases
EMBLGenBankDDBJ	M13136 Genomic RNA. No translation available.
3D structure databases
SMR	P05960. Positions 2-283, 143-351, 484-550.
ModBase	Search...
Enzyme and pathway databases
Reactome	REACT_6185. HIV Infection.
Family and domain databases
InterPro	IPR000721. Gag_p24. IPR000071. Lentvrl_matrix_N. IPR018061. Pept_A2A_retrovirus_sg. IPR001995. Peptidase_A2_cat. IPR001969. Peptidase_aspartic_AS. IPR009007. Peptidase_aspartic_catalytic. IPR008916. Retrov_capsid_C. IPR008919. Retrov_capsid_N. IPR013084. Znf_CCH_retrovir. IPR001878. Znf_CCHC. [Graphical view]
Gene3D	G3DSA:2.40.70.10. Pept_Aspartc_cat. 1 hit. G3DSA:1.10.1200.30. Retrov_capsid_C. 1 hit. G3DSA:1.10.375.10. Retrov_capsid_N. 1 hit. G3DSA:4.10.60.10. Znf_CCH_retrovir. 1 hit.
Pfam	PF00540. Gag_p17. 1 hit. PF00607. Gag_p24. 1 hit. PF00077. RVP. 1 hit. PF00098. zf-CCHC. 2 hits. [Graphical view]
PRINTS	PR00234. HIV1MATRIX.
SMART	SM00343. ZnF_C2HC. 2 hits. [Graphical view]
PROSITE	PS50175. ASP_PROT_RETROV. 1 hit. PS00141. ASP_PROTEASE. 1 hit. PS50158. ZF_CCHC. 2 hits. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

POL_HV1C4

Accession

Primary (citable) accession number: P05960

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1988
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 99 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Virus (Virus annotation project)