Reviewed, UniProtKB/Swiss-Prot P03367 (POL_HV1BR)

Names and origin

Protein names

Recommended name:
    Gag-Pol polyprotein
Alternative name(s):
    Pr160Gag-Pol
Cleaved into the following 11 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
    8- Recommended name:
            Reverse transcriptase/ribonuclease H
              EC=2.7.7.49
              EC=2.7.7.7
              EC=3.1.26.4
        Alternative name(s):
            p66 RT
    9- Recommended name:
            p51 RT
    10- Recommended name:
            p15
    11- Recommended name:
            Integrase
                Short name=IN

Gene names

Name:

gag-pol

Organism

Human immunodeficiency virus type 1 (isolate BRU/LAI group M subtype B) (HIV-1)

Taxonomic identifier

11686 [NCBI]

Taxonomic lineage

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

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	1447 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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. Reverse transcriptase/ribonuclease H (RT) is a multifunctional enzyme that converts the viral RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA(3)-Lys binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for two polypurine tracts (PPTs) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPTs that have not been removed by RNase H as primers. PPTs and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends By similarity. Integrase catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, Vpr and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allow the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV-1 integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration By similarity.
Catalytic activity	Specific for a P1 residue that is hydrophobic, and P1' variable, but often Pro. Endonucleolytic cleavage to 5'-phosphomonoester. Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).
Cofactor	Binds 2 magnesium ions for reverse transcriptase polymerase activity By similarity. Binds 2 magnesium ions for ribonuclease H (RNase H) activity. Substrate-binding is a precondition for magnesium binding By similarity. Magnesium ions for integrase activity. Binds at least 1, maybe 2 magnesium ions By similarity.
Enzyme regulation	The viral protease is inhibited by many synthetic protease inhibitors (PIs), such as amprenavir, atazanavir, indinavir, loprinavir, nelfinavir, ritonavir and saquinavir. RT can be inhibited either by nucleoside RT inhibitors (NRTIs) or by non nucleoside RT inhibitors (NNRTIs). NRTIs act as chain terminators, whereas NNRTIs inhibit DNA polymerization by binding a small hydrophobic pocket near the RT active site and inducing an allosteric change in this region. Classical NRTIs are abacavir, adefovir (PMEA), didanosine (ddI), lamivudine (3TC), stavudine (d4T), tenofovir (PMPA), zalcitabine (ddC), and zidovudine (AZT). Classical NNRTIs are atevirdine (BHAP U-87201E), delavirdine, efavirenz (DMP-266), emivirine (I-EBU), and nevirapine (BI-RG-587). The tritherapies used as a basic effective treatment of AIDS associate two NRTIs and one NNRTI. 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. The reverse transcriptase is a 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 is a homodimer and possibly can form homotetramer. Integrase interacts with human SMARCB1/INI1 and human PSIP1/LEDGF isoform 1 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. Reverse transcriptase/ribonuclease H: Virion Potential. Integrase: Virion Potential. Host nucleus Potential. Host cytoplasm Potential. Note: Nuclear at initial phase, cytoplasmic at assembly Potential.
Domain	The reverse transcriptase/ribonuclease H (RT) is structured in five subdomains: finger, palm, thumb, connection and RNase H. Within the palm subdomain, the 'primer grip' region is thought to be involved in the positioning of the primer terminus for accomodating the incoming nucleotide. The RNase H domain stabilizes the association of RT with primer-template By similarity. The tryptophan repeat motif is involved in RT p66/p51 dimerization By similarity. Integrase core domain contains the D-x(n)-D-x(35)-E motif, named for the phylogenetically conserved glutamic acid and aspartic acid residues and the invariant 35 amino acid spacing between the second and third acidic residues. Each acidic residue of the D,D(35)E motif is independently essential for the 3'-processing and strand transfer activities of purified integrase protein By similarity.
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. The reverse transcriptase is an error-prone enzyme that lacks a proof-reading function. High mutations rate is a direct consequence of this characteristic. RT also displays frequent template switching leading to high recombination rate. Recombination mostly occurs between homologous regions of the two copackaged RNA genomes. If these two RNA molecules derive from different viral strains, reverse transcription will give rise to highly recombinated proviral DNAs. 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 integrase catalytic domain. Contains 1 integrase-type DNA-binding domain. Contains 1 integrase-type zinc finger. Contains 1 peptidase A2 domain. Contains 1 reverse transcriptase domain. Contains 1 RNase H domain.

Ontologies

Keywords
Biological process	Capsid maturation DNA integration DNA recombination
Cellular component	Capsid protein Cell membrane Cytoplasm Membrane Nucleus Virion
Coding sequence diversity	Ribosomal frameshifting
Disease	AIDS
Domain	Repeat Zinc-finger
Ligand	Magnesium Metal-binding RNA-binding Viral nucleoprotein Zinc
Molecular function	Aspartyl protease DNA-directed DNA polymerase Endonuclease Hydrolase Nuclease Nucleotidyltransferase Protease RNA-directed DNA polymerase Transferase
PTM	Lipoprotein Myristate Phosphoprotein
Technical term	3D-structure Multifunctional enzyme
Gene Ontology (GO)
Biological process	RNA-dependent DNA replication Inferred from electronic annotation. Source: InterPro initiation of viral infection Inferred from Experiment. Source: Reactome proteolysis Inferred from electronic annotation. Source: InterPro provirus integration Inferred from Experiment. Source: Reactome transposition Inferred from electronic annotation. Source: UniProtKB-KW 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	DNA binding Inferred from electronic annotation. Source: InterPro DNA-directed DNA polymerase activity Inferred from electronic annotation. Source: UniProtKB-KW RNA binding Inferred from electronic annotation. Source: UniProtKB-KW RNA-directed DNA polymerase activity Inferred from electronic annotation. Source: UniProtKB-KW aspartic-type endopeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW integrase activity Inferred from electronic annotation. Source: InterPro magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW ribonuclease H activity Inferred from electronic annotation. Source: EC 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: P03367-1)

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: P03348-1)

The sequence of this isoform can be found in the external entry P03348-1.
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 – 1447

1446

Gag-Pol polyprotein

PRO_0000261264

Chain

2 – 132

131

Matrix protein p17 By similarity

PRO_0000042330

Chain

133 – 363

231

Capsid protein p24 By similarity

PRO_0000042331

Peptide

364 – 377

14

Spacer peptide p2 By similarity

PRO_0000042332

Chain

378 – 432

55

Nucleocapsid protein p7 By similarity

PRO_0000042333

Peptide

433 – 440

8

Transframe peptide Potential

PRO_0000246712

Chain

441 – 500

60

p6-pol Potential

PRO_0000042334

Chain

501 – 599

99

Protease By similarity

PRO_0000038652

Chain

600 – 1159

560

Reverse transcriptase/ribonuclease H By similarity

PRO_0000042335

Chain

600 – 1039

440

p51 RT By similarity

PRO_0000042336

Chain

1040 – 1159

120

p15 By similarity

PRO_0000042337

Chain

1160 – 1447

288

Integrase By similarity

PRO_0000042338

Regions

Domain

520 – 589

70

Peptidase A2

Domain

643 – 833

191

Reverse transcriptase

Domain

1033 – 1156

124

RNase H

Domain

1213 – 1363

151

Integrase catalytic

Zinc finger

390 – 407

18

CCHC-type 1

Zinc finger

411 – 428

18

CCHC-type 2

Zinc finger

1162 – 1203

42

Integrase-type

DNA binding

1382 – 1429

48

Integrase-type

Region

826 – 834

9

RT 'primer grip' By similarity

Motif

16 – 22

7

Nuclear export signal By similarity

Motif

26 – 32

7

Nuclear localization signal By similarity

Motif

997 – 1013

17

Tryptophan repeat motif By similarity

Sites

Active site

525

1

For protease activity; shared with dimeric partner By similarity

Metal binding

709

1

Magnesium; catalytic; for reverse transcriptase activity By similarity

Metal binding

784

1

Magnesium; catalytic; for reverse transcriptase activity By similarity

Metal binding

785

1

Magnesium; catalytic; for reverse transcriptase activity By similarity

Metal binding

1042

1

Magnesium; catalytic; for RNase H activity By similarity

Metal binding

1077

1

Magnesium; catalytic; for RNase H activity By similarity

Metal binding

1097

1

Magnesium; catalytic; for RNase H activity By similarity

Metal binding

1148

1

Magnesium; catalytic; for RNase H activity By similarity

Metal binding

1223

1

Magnesium; catalytic; for integrase activity By similarity

Metal binding

1275

1

Magnesium; catalytic; for integrase activity 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

500 – 501

2

Cleavage; by viral protease By similarity

Site

599 – 600

2

Cleavage; by viral protease By similarity

Site

1000

1

Essential for RT p66/p51 heterodimerization By similarity

Site

1013

1

Essential for RT p66/p51 heterodimerization By similarity

Site

1039 – 1040

2

Cleavage; by viral protease; partial By similarity

Site

1159 – 1160

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

Secondary structure

1

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1447

Helix Strand Turn

Details...

Beta strand

505 – 507

3

Beta strand

510 – 515

6

Beta strand

518 – 524

7

Beta strand

543 – 549

7

Beta strand

552 – 566

15

Beta strand

569 – 578

10

Helix

587 – 590

4

Helix

591 – 593

3

Beta strand

596 – 598

3

Helix

627 – 642

16

Beta strand

645 – 648

4

Beta strand

659 – 662

4

Beta strand

671 – 674

4

Helix

677 – 687

11

Turn

688 – 690

3

Helix

698 – 701

4

Beta strand

702 – 709

8

Helix

711 – 715

5

Beta strand

716 – 718

3

Helix

723 – 725

3

Beta strand

729 – 731

3

Helix

734 – 736

3

Beta strand

741 – 745

5

Helix

755 – 773

19

Beta strand

778 – 782

5

Beta strand

785 – 790

6

Helix

794 – 811

18

Beta strand

831 – 833

3

Helix

835 – 837

3

Turn

847 – 850

4

Helix

853 – 869

17

Helix

876 – 881

6

Helix

896 – 908

13

Beta strand

920 – 922

3

Beta strand

925 – 930

6

Beta strand

932 – 943

12

Beta strand

946 – 951

6

Helix

963 – 981

19

Beta strand

987 – 992

6

Helix

994 – 1004

11

Beta strand

1013 – 1015

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform Gag-Pol polyprotein [UniParc]. Last modified January 23, 2007. Version 3. Checksum: B41D8D00F0940740	FASTA	1,447	163,279
	10 20 30 40 50 60 MGARASVLSG GELDRWEKIR LRPGGKKKYK LKHIVWASRE LERFAVNPGL LETSEGCRQI 70 80 90 100 110 120 LGQLQPSLQT GSEELRSLYN TVATLYCVHQ RIEIKDTKEA LDKIEEEQNK SKKKAQQAAA 130 140 150 160 170 180 DTGHSSQVSQ NYPIVQNIQG QMVHQAISPR TLNAWVKVVE EKAFSPEVIP MFSALSEGAT 190 200 210 220 230 240 PQDLNTMLNT VGGHQAAMQM LKETINEEAA EWDRVHPVHA GPIAPGQMRE PRGSDIAGTT 250 260 270 280 290 300 STLQEQIGWM TNNPPIPVGE IYKRWIILGL NKIVRMYSPT SILDIRQGPK EPFRDYVDRF 310 320 330 340 350 360 YKTLRAEQAS QEVKNWMTET LLVQNANPDC KTILKALGPA ATLEEMMTAC QGVGGPGHKA 370 380 390 400 410 420 RVLAEAMSQV TNSATIMMQR GNFRNQRKIV KCFNCGKEGH IARNCRAPRK KGCWKCGKEG 430 440 450 460 470 480 HQMKDCTERQ ANFLREDLAF LQGKAREFSS EQTRANSPTI SSEQTRANSP TRRELQVWGR 490 500 510 520 530 540 DNNSLSEAGA DRQGTVSFNF PQITLWQRPL VTIKIGGQLK EALLDTGADD TVLEEMSLPG 550 560 570 580 590 600 RWKPKMIGGI GGFIKVRQYD QILIEICGHK AIGTVLVGPT PVNIIGRNLL TQIGCTLNFP 610 620 630 640 650 660 ISPIETVPVK LKPGMDGPKV KQWPLTEEKI KALVEICTEM EKEGKISKIG PENPYNTPVF 670 680 690 700 710 720 AIKKKDSTKW RKLVDFRELN KRTQDFWEVQ LGIPHPAGLK KKKSVTVLDV GDAYFSVPLD 730 740 750 760 770 780 EDFRKYTAFT IPSINNETPG IRYQYNVLPQ GWKGSPAIFQ SSMTKILEPF RKQNPDIVIY 790 800 810 820 830 840 QYMDDLYVGS DLEIGQHRTK IEELRQHLLR WGLTTPDKKH QKEPPFLWMG YELHPDKWTV 850 860 870 880 890 900 QPIVLPEKDS WTVNDIQKLV GKLNWASQIY PGIKVRQLCK LLRGTKALTE VIPLTEEAEL 910 920 930 940 950 960 ELAENREILK EPVHGVYYDP SKDLIAEIQK QGQGQWTYQI YQEPFKNLKT GKYARTRGAH 970 980 990 1000 1010 1020 TNDVKQLTEA VQKITTESIV IWGKTPKFKL PIQKETWETW WTEYWQATWI PEWEFVNTPP 1030 1040 1050 1060 1070 1080 LVKLWYQLEK EPIVGAETFY VDGAASRETK LGKAGYVTNR GRQKVVTLTD TTNQKTELQA 1090 1100 1110 1120 1130 1140 IHLALQDSGL EVNIVTDSQY ALGIIQAQPD KSESELVNQI IEQLIKKEKV YLAWVPAHKG 1150 1160 1170 1180 1190 1200 IGGNEQVDKL VSAGIRKVLF LDGIDKAQDE HEKYHSNWRA MASDFNLPPV VAKEIVASCD 1210 1220 1230 1240 1250 1260 KCQLKGEAMH GQVDCSPGIW QLDCTHLEGK VILVAVHVAS GYIEAEVIPA ETGQETAYFL 1270 1280 1290 1300 1310 1320 LKLAGRWPVK TIHTDNGSNF TSTTVKAACW WAGIKQEFGI PYNPQSQGVV ESMNKELKKI 1330 1340 1350 1360 1370 1380 IGQVRDQAEH LKTAVQMAVF IHNFKRKGGI GGYSAGERIV DIIATDIQTK ELQKQITKIQ 1390 1400 1410 1420 1430 1440 NFRVYYRDSR DPLWKGPAKL LWKGEGAVVI QDNSDIKVVP RRKAKIIRDY GKQMAGDDCV ASRQDED
	Isoform Gag polyprotein. See P03348.	FASTA	–	–

References

[1]	"Nucleotide sequence of the AIDS virus, LAV." Wain-Hobson S., Sonigo P., Danos O., Cole S., Alizon M. Cell 40:9-17(1985) [PubMed: 2981635] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"Genetic variability of the AIDS virus: nucleotide sequence analysis of two isolates from African patients." Alizon M., Wain-Hobson S., Montagnier L., Sonigo P. Cell 46:63-74(1986) [PubMed: 2424612] [Abstract] Cited for: SEQUENCE REVISION TO 455-467.
[3]	"Cleavage of recombinant and cell derived human immunodeficiency virus 1 (HIV-1) Nef protein by HIV-1 protease." Gaedigk-Nitschko K., Schoen A., Wachinger G., Erfle V., Kohleisen B. FEBS Lett. 357:275-278(1995) [PubMed: 7835426] [Abstract] Cited for: CLEAVAGE OF NEF BY VIRAL PROTEASE.
[4]	"Intravirion processing of the human immunodeficiency virus type 1 Vif protein by the viral protease may be correlated with Vif function." Khan M.A., Akari H., Kao S., Aberham C., Davis D., Buckler-White A., Strebel K. J. Virol. 76:9112-9123(2002) [PubMed: 12186895] [Abstract] Cited for: CLEAVAGE OF VIF BY VIRAL PROTEASE.
[5]	"Proteolytic processing and particle maturation." Vogt V.M. Curr. Top. Microbiol. Immunol. 214:95-131(1996) [PubMed: 8791726] [Abstract] Cited for: REVIEW.
[6]	"Structural biology of HIV." Turner B.G., Summers M.F. J. Mol. Biol. 285:1-32(1999) [PubMed: 9878383] [Abstract] Cited for: REVIEW.
[7]	"Mechanisms of retroviral recombination." Negroni M., Buc H. Annu. Rev. Genet. 35:275-302(2001) [PubMed: 11700285] [Abstract] Cited for: REVIEW.
[8]	"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.
[9]	"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.
[10]	"The three-dimensional structure of the aspartyl protease from the HIV-1 isolate BRU." Spinelli S., Liu Q.Z., Alzari P.M., Hirel P.H., Poljak R.J. Biochimie 73:1391-1396(1991) [PubMed: 1799632] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 501-599.
[11]	"Structure of HIV-1 reverse transcriptase/DNA complex at 7 A resolution showing active site locations." Arnold E., Jacobo-Molina A., Nanni R.G., Williams R.L., Lu X., Ding J., Clark A.D. Jr., Zhang A., Ferris A.L., Clark P., Hizi A., Hughes S.H. Nature 357:85-89(1992) [PubMed: 1374166] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 600-1026.
[12]	"Crystal structure at 1.9-A resolution of human immunodeficiency virus (HIV) II protease complexed with L-735,524, an orally bioavailable inhibitor of the HIV proteases." Chen Z., Li Y., Chen E., Hall D.L., Darke P.L., Culberson C., Shafer J.A., Kuo L.C. J. Biol. Chem. 269:26344-26348(1994) [PubMed: 7929352] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 501-599 IN COMPLEX WITH THE INHIBITOR L-736,524.
[13]	"Structure-based design of HIV protease inhibitors: sulfonamide-containing 5,6-dihydro-4-hydroxy-2-pyrones as non-peptidic inhibitors." Thaisrivongs S., Skulnick H.I., Turner S.R., Strohbach J.W., Tommasi R.A., Johnson P.D., Aristoff P.A., Judge T.M., Gammill R.B., Morris J.K., Romines K.R., Chrusciel R.A., Hinshaw R.R., Chong K.-T., Tarpley W.G., Poppe S.M., Slade D.E., Lynn J.C. , Horng M.-M., Tomich P.K., Seest E.P., Dolak L.A., Howe W.J., Howard G.M., Schwende F.J., Toth L.N., Padbury G.E., Wilson G.J., Shiou L., Zipp G.L., Wilkinson K.F., Rush B.D., Ruwart M.J., Koeplinger K.A., Zhao Z., Cole S., Zaya R.M., Kakuk T.J., Janakiraman M.N., Watenpaugh K.D. J. Med. Chem. 39:4349-4353(1996) [PubMed: 8893827] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 501-599.
[14]	"Inhibition and catalytic mechanism of HIV-1 aspartic protease." Silva A.M., Cachau R.E., Sham H.L., Erickson J.W. J. Mol. Biol. 255:321-346(1996) [PubMed: 8551523] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 501-599 IN COMPLEX WITH THE DIFLUOROKETONE CONTAINING INHIBITOR A79285.
[15]	"Crystallographic analysis of human immunodeficiency virus 1 protease with an analog of the conserved CA-p2 substrate -- interactions with frequently occurring glutamic acid residue at P2' position of substrates." Weber I.T., Wu J., Adomat J.M., Harrison R.W., Kimmel A.R., Wondrak E.M., Louis J.M. Eur. J. Biochem. 249:523-530(1997) [PubMed: 9370363] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 501-599.
[16]	"Structural basis for specificity of retroviral proteases." Wu J., Adomat J.M., Ridky T.W., Louis J.M., Leis J., Harrison R.W., Weber I.T. Biochemistry 37:4518-4526(1998) [PubMed: 9521772] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 501-599.
[17]	"X-ray structure and conformational dynamics of the HIV-1 protease in complex with the inhibitor SDZ283-910: agreement of time-resolved spectroscopy and molecular dynamics simulations." Ringhofer S., Kallen J., Dutzler R., Billich A., Visser A.J., Scholz D., Steinhauser O., Schreiber H., Auer M., Kungl A.J. J. Mol. Biol. 286:1147-1159(1999) [PubMed: 10047488] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 501-599 IN COMPLEX WITH INHIBITOR SDZ283-910.
[18]	"A distinct binding mode of a hydroxyethylamine isostere inhibitor of HIV-1 protease." Dohnalek J., Hasek J., Duskova J., Petrokova H., Hradilek M., Soucek M., Konvalinka J., Brynda J., Sedlacek J., Fabry M. Acta Crystallogr. D 57:472-476(2001) [PubMed: 11223536] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 501-599 IN COMPLEX WITH A PEPTIDOMIMETIC INHIBITOR.
[19]	"Hydroxyethylamine isostere of an HIV-1 protease inhibitor prefers its amine to the hydroxy group in binding to catalytic aspartates. A synchrotron study of HIV-1 protease in complex with a peptidomimetic inhibitor." Dohnalek J., Hasek J., Duskova J., Petrokova H., Hradilek M., Soucek M., Konvalinka J., Brynda J., Sedlacek J., Fabry M. J. Med. Chem. 45:1432-1438(2002) [PubMed: 11906284] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.83 ANGSTROMS) OF 501-599.
[20]	"An ethylenamine inhibitor binds tightly to both wild type and mutant HIV-1 proteases. Structure and energy study." Skalova T., Hasek J., Dohnalek J., Petrokova H., Buchtelova E., Duskova J., Soucek M., Majer P., Uhlikova T., Konvalinka J. J. Med. Chem. 46:1636-1644(2003) [PubMed: 12699382] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 501-599 IN COMPLEX WITH AN ETHYLENAMINE PEPTIDOMIMETIC INHIBITOR.
[21]	"Role of hydroxyl group and R/S configuration of isostere in binding properties of HIV-1 protease inhibitors." Petrokova H., Duskova J., Dohnalek J., Skalova T., Vondrackova-Buchtelova E., Soucek M., Konvalinka J., Brynda J., Fabry M., Sedlacek J., Hasek J. Eur. J. Biochem. 271:4451-4461(2004) [PubMed: 15560786] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 501-599 IN COMPLEX WITH AN ETHYLENEAMINE INHIBITOR.
[22]	"A structural and thermodynamic escape mechanism from a drug resistant mutation of the HIV-1 protease." Vega S., Kang L.W., Velazquez-Campoy A., Kiso Y., Amzel L.M., Freire E. Proteins 55:594-602(2004) [PubMed: 15103623] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 501-599 IN COMPLEX WITH THE INHIBITOR KNI-577.
[23]	"A phenylnorstatine inhibitor binding to HIV-1 protease: geometry, protonation, and subsite-pocket interactions analyzed at atomic resolution." Brynda J., Rezacova P., Fabry M., Horejsi M., Stouracova R., Sedlacek J., Soucek M., Hradilek M., Lepsik M., Konvalinka J. J. Med. Chem. 47:2030-2036(2004) [PubMed: 15056001] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.03 ANGSTROMS) OF 501-599 IN COMPLEX WITH A PEPTIDOMIMETIC INHIBITOR.
[24]	"High resolution crystal structures of HIV-1 protease with a potent non-peptide inhibitor (UIC-94017) active against multi-drug-resistant clinical strains." Tie Y., Boross P.I., Wang Y.-F., Gaddis L., Hussain A.K., Leshchenko S., Ghosh A.K., Louis J.M., Harrison R.W., Weber I.T. J. Mol. Biol. 338:341-352(2004) [PubMed: 15066436] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.1 ANGSTROMS) OF 501-599 IN COMPLEX WITH THE INHIBITOR UIC-94017.
[25]	"Crystal structures of HIV protease V82A and L90M mutants reveal changes in the indinavir-binding site." Mahalingam B., Wang Y.-F., Boross P.I., Tozser J., Louis J.M., Harrison R.W., Weber I.T. Eur. J. Biochem. 271:1516-1524(2004) [PubMed: 15066177] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) OF 501-599.
[26]	"Comparing the accumulation of active- and nonactive-site mutations in the HIV-1 protease." Clemente J.C., Moose R.E., Hemrajani R., Whitford L.R., Govindasamy L., Reutzel R., McKenna R., Agbandje-McKenna M., Goodenow M.M., Dunn B.M. Biochemistry 43:12141-12151(2004) [PubMed: 15379553] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 501-599.
[27]	"Inhibitor binding at the protein interface in crystals of a HIV-1 protease complex." Brynda J., Rezacova P., Fabry M., Horejsi M., Stouracova R., Soucek M., Hradilek M., Konvalinka J., Sedlacek J. Acta Crystallogr. D 60:1943-1948(2004) [PubMed: 15502300] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 501-599 IN COMPLEX WITH A PEPTIDOMIMETIC INHIBITOR.

Web resources

HIV drug resistance mutations

hivdb

HIV drug resistance database

BioAfrica: HIV bioinformatics in Africa

Cross-references

Sequence databases

EMBLGenBankDDBJ

K02013 Genomic RNA. No translation available.

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A8G	X-ray	2.50	A/B	501-599	[»]
1A8K	X-ray	2.00	A/B/D/E	501-599	[»]
1A94	X-ray	2.00	A/B/D/E	501-599	[»]
1AAQ	X-ray	2.50	A/B	501-599	[»]
1D4S	X-ray	2.50	A/B	501-599	[»]
1D4Y	X-ray	1.97	A/B	501-599	[»]
1DAZ	X-ray	1.55	C/D	501-599	[»]
1DIF	X-ray	1.70	A/B	501-599	[»]
1FQX	X-ray	3.10	A/B	501-599	[»]
1HHP	X-ray	2.70	A	501-599	[»]
1HNI	X-ray	2.80	B	600-1026	[»]
1HPO	X-ray	2.50	A/B	501-599	[»]
1HPX	X-ray	2.00	A/B	501-599	[»]
1HSG	X-ray	2.00	A/B	501-599	[»]
1HVL	X-ray	1.80	A/B	501-599	[»]
1IIQ	X-ray	1.83	A/B	501-599	[»]
1IZI	X-ray	2.15	A/B	501-599	[»]
1LZQ	X-ray	2.20	A/B	501-599	[»]
1M0B	X-ray	2.45	A/B	501-599	[»]
1MRW	X-ray	2.00	A/B	501-599	[»]
1MRX	X-ray	2.00	A/B	501-599	[»]
1MSM	X-ray	2.00	A/B	501-599	[»]
1MSN	X-ray	2.00	A/B	501-599	[»]
1NH0	X-ray	1.03	A/B	501-599	[»]
1RL8	X-ray	2.00	A/B	501-599	[»]
1SDT	X-ray	1.30	A/B	501-599	[»]
1SDU	X-ray	1.25	A/B	501-599	[»]
1SDV	X-ray	1.40	A/B	501-599	[»]
1SGU	X-ray	1.90	A/B	501-599	[»]
1SH9	X-ray	2.50	A/B	501-599	[»]
1SP5	X-ray	1.80	A/B	501-599	[»]
			I	559-563	[»]
1U8G	X-ray	2.20	A/B	501-599	[»]
1UPJ	X-ray	2.22	A	501-599	[»]
1XL2	X-ray	1.50	A/B	501-599	[»]
1XL5	X-ray	1.73	A/B	501-599	[»]
1Z8C	X-ray	2.20	A/B	501-599	[»]
1ZBG	X-ray	2.00	A/B	501-599	[»]
1ZJ7	X-ray	1.93	A	501-599	[»]
1ZLF	X-ray	2.30	A/B	501-599	[»]
1ZPK	X-ray	1.65	A/B	501-599	[»]
1ZSF	X-ray	1.98	B	501-599	[»]
1ZSR	X-ray	2.06	B	501-599	[»]
1ZTZ	X-ray	2.15	A/B	501-599	[»]
2A1E	X-ray	1.30	A/B	501-599	[»]
2AZ8	X-ray	2.00	A	501-599	[»]
2AZ9	X-ray	2.50	A	501-599	[»]
2AZB	X-ray	2.03	A	501-599	[»]
2AZC	X-ray	2.01	A/B	501-599	[»]
2B7Z	X-ray	2.20	A/B	500-598	[»]
2FDE	X-ray	2.70	A/B	501-599	[»]
2FND	model	-	P	501-599	[»]
2HB2	X-ray	2.30	A	501-598	[»]
2HB4	X-ray	2.15	A	501-598	[»]
2HC0	X-ray	1.30	A/B	501-598	[»]
2IEN	X-ray	1.30	A/B	501-599	[»]
2O4K	X-ray	1.60	A/B	501-599	[»]
2O4L	X-ray	1.33	A/B	501-599	[»]
2O4N	X-ray	2.00	A/B	501-598	[»]
2O4P	X-ray	1.80	A/B	501-599	[»]
2O4S	X-ray	1.54	A/B	501-599	[»]
2P3B	X-ray	2.10	A/B	501-599	[»]
2PK5	X-ray	1.90	A/B	501-599	[»]
2PK6	X-ray	1.45	A/B	501-599	[»]
2PQZ	X-ray	1.55	A/B	501-599	[»]
2PWC	X-ray	1.78	A/B	501-599	[»]
2PWR	X-ray	1.50	A/B	501-599	[»]
2PYM	X-ray	1.90	A/B	501-599	[»]
2PYN	X-ray	1.85	A/B	501-599	[»]
2Q63	X-ray	2.20	A/B	501-599	[»]
2Q64	X-ray	2.50	A/B	501-599	[»]
2QAK	X-ray	2.20	A/B	501-599	[»]
2QCI	X-ray	1.20	A/B	501-599	[»]
2QD6	X-ray	1.28	A/B	501-599	[»]
2QD7	X-ray	1.11	A/B	501-599	[»]
2QD8	X-ray	1.35	A/B	501-599	[»]
2QHC	X-ray	2.80	A/B	501-599	[»]
2QNN	X-ray	1.48	A/B	501-599	[»]
2QNP	X-ray	1.41	A/B	501-599	[»]
2QNQ	X-ray	2.30	A/B	501-599	[»]
2R43	X-ray	1.58	A/B	501-599	[»]
2UPJ	X-ray	3.00	A/B	501-599	[»]
2Z4O	X-ray	1.60	A/B	501-599	[»]
2ZGA	X-ray	1.65	A	501-599	[»]
2ZYE	Other	1.90	A/B	501-599	[»]
3BC4	X-ray	1.82	A	501-599	[»]
3BGB	X-ray	1.90	A/B	501-599	[»]
3BGC	X-ray	1.80	A/B	501-599	[»]
3BHE	X-ray	1.75	A/B	501-599	[»]
3BVA	X-ray	1.05	A/B	501-599	[»]
3BVB	X-ray	1.30	A/B	501-599	[»]
3CKT	X-ray	1.65	A/B	501-599	[»]
3DJK	X-ray	1.00	A/B	501-599	[»]
3DK1	X-ray	1.07	A/B	501-599	[»]
3FX5	X-ray	0.93	A/B	501-599	[»]
7UPJ	X-ray	2.00	A/B	501-599	[»]

SMR

P03367. Positions 2-283, 143-351, 600-1142, 1160-1371, 1216-1429.

ModBase

Search...

Enzyme and pathway databases

Reactome

REACT_6185. HIV Infection.

Family and domain databases

InterPro

IPR000477. DNA_pol_RVTase.
IPR000721. Gag_p24.
IPR001037. Integrase_C_retrovir.
IPR001584. Integrase_cat-core.
IPR017856. Integrase_Zn-bd_dom-like_N.
IPR003308. Integrase_Zn-bd_dom_N.
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.
IPR002156. RNase_H.
IPR010659. RVT_connect.
IPR010661. RVT_thumb.
IPR013084. Znf_CCH_retrovir.
IPR001878. Znf_CCHC.
[Graphical view]

Gene3D

G3DSA:2.30.30.10. Integrase_C. 1 hit.
G3DSA:1.10.10.200. Intgrase_N_Zn_bd. 1 hit.
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.
PF00552. Integrase. 1 hit.
PF02022. Integrase_Zn. 1 hit.
PF00075. RnaseH. 1 hit.
PF00665. rve. 1 hit.
PF00077. RVP. 1 hit.
PF00078. RVT_1. 1 hit.
PF06815. RVT_connect. 1 hit.
PF06817. RVT_thumb. 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.
PS50994. INTEGRASE. 1 hit.
PS51027. INTEGRASE_DBD. 1 hit.
PS50879. RNASE_H. 1 hit.
PS50878. RT_POL. 1 hit.
PS50158. ZF_CCHC. 2 hits.
PS50876. ZF_INTEGRASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

POL_HV1BR

Accession

Primary (citable) accession number: P03367

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	January 23, 2007
Last modified:	July 7, 2009
This is version 121 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Virus (Virus annotation project)