P12499 (POL_HV1Z2) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Gag-Pol polyprotein

Alternative name(s):
Pr160Gag-Pol

Cleaved into the following 11 chains:

1. Matrix protein p17
   Short name=MA
2. Capsid protein p24
   Short name=CA
3. Spacer peptide p2
4. Nucleocapsid protein p7
   Short name=NC
5. Transframe peptide
   Short name=TF
6. p6-pol
   Short name=p6*
7. Protease
   EC=3.4.23.16
   Alternative name(s):
   PR
   Retropepsin
8. Reverse transcriptase/ribonuclease H
   EC=2.7.7.49
   EC=2.7.7.7
   EC=3.1.26.13
   Alternative name(s):
   Exoribonuclease H
   EC=3.1.13.2
   p66 RT
9. p51 RT
10. p15
11. Integrase
    Short name=IN

Gene names

Name:

gag-pol

Organism

Human immunodeficiency virus type 1 group M subtype D (isolate Z2/CDC-Z34) (HIV-1)

Taxonomic identifier

11683 [NCBI]

Taxonomic lineage

Viruses › Retro-transcribing viruses › Retroviridae › Orthoretrovirinae › Lentivirus › Primate lentivirus group › Human immunodeficiency virus 1 › HIV-1 unknown group

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	1436 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 play 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 disassembled 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 allows 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. Endohydrolysis of RNA in RNA/DNA hybrids. Three different cleavage modes: 1. sequence-specific internal cleavage of RNA. Human immunodeficiency virus type 1 and Moloney murine leukemia virus enzymes prefer to cleave the RNA strand one nucleotide away from the RNA-DNA junction. 2. RNA 5'-end directed cleavage 13-19 nucleotides from the RNA end. 3. DNA 3'-end directed cleavage 15-20 nucleotides away from the primer terminus. 3'-end directed exonucleolytic cleavage of viral RNA-DNA hybrid. 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 Integrase interacts with human KPNA3; this interaction might play a role in nuclear import of the pre-integration complex. Integrase interacts with human NUP153; this interaction might play a role in nuclear import of the pre-integration complex 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 accommodating 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,D35E 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	Activation of host caspases by virus Capsid maturation DNA integration DNA recombination Host-virus interaction Modulation of host cell apoptosis by virus Viral genome integration Viral penetration into host nucleus Virus entry into host cell
Cellular component	Host cell membrane Host cytoplasm Host membrane Host nucleus Membrane Virion
Coding sequence diversity	Ribosomal frameshifting
Disease	AIDS
Domain	Repeat Zinc-finger
Ligand	DNA-binding Magnesium Metal-binding RNA-binding Viral nucleoprotein Zinc
Molecular function	Aspartyl protease Capsid protein 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	DNA integration Inferred from electronic annotation. Source: UniProtKB-KW DNA recombination Inferred from electronic annotation. Source: UniProtKB-KW RNA-dependent DNA replication Inferred from electronic annotation. Source: InterPro establishment of integrated proviral latency Inferred from electronic annotation. Source: UniProtKB-KW induction by virus of host cysteine-type endopeptidase activity involved in apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW nucleic acid phosphodiester bond hydrolysis Inferred from electronic annotation. Source: GOC proteolysis Inferred from electronic annotation. Source: UniProtKB-KW viral entry into host cell Inferred from electronic annotation. Source: UniProtKB-KW viral penetration into host nucleus Inferred from electronic annotation. Source: UniProtKB-KW viral procapsid maturation Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	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 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: UniProtKB-KW 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 exoribonuclease H activity Inferred from electronic annotation. Source: EC ribonuclease H activity Inferred from electronic annotation. Source: InterPro structural molecule activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
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: P12499-1)

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: P12495-1)

The sequence of this isoform can be found in the external entry P12495.
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 – 1436

1435

Gag-Pol polyprotein

PRO_0000261288

Chain

2 – 133

132

Matrix protein p17 By similarity

PRO_0000042312

Chain

134 – 364

231

Capsid protein p24 By similarity

PRO_0000042313

Peptide

365 – 378

14

Spacer peptide p2 By similarity

PRO_0000042314

Chain

379 – 434

56

Nucleocapsid protein p7 By similarity

PRO_0000042315

Peptide

435 – 442

8

Transframe peptide Potential

PRO_0000246738

Chain

443 – 489

47

p6-pol Potential

PRO_0000042316

Chain

490 – 588

99

Protease By similarity

PRO_0000038650

Chain

589 – 1148

560

Reverse transcriptase/ribonuclease H By similarity

PRO_0000042317

Chain

589 – 1028

440

p51 RT By similarity

PRO_0000042318

Chain

1029 – 1148

120

p15 By similarity

PRO_0000042319

Chain

1149 – 1436

288

Integrase By similarity

PRO_0000042320

Regions

Domain

509 – 578

70

Peptidase A2

Domain

632 – 822

191

Reverse transcriptase

Domain

1022 – 1145

124

RNase H

Domain

1202 – 1352

151

Integrase catalytic

Zinc finger

392 – 409

18

CCHC-type 1

Zinc finger

413 – 430

18

CCHC-type 2

Zinc finger

1151 – 1192

42

Integrase-type

DNA binding

1371 – 1418

48

Integrase-type

Region

815 – 823

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

986 – 1002

17

Tryptophan repeat motif By similarity

Sites

Active site

514

1

For protease activity; shared with dimeric partner By similarity

Metal binding

698

1

Magnesium; catalytic; for reverse transcriptase activity By similarity

Metal binding

773

1

Magnesium; catalytic; for reverse transcriptase activity By similarity

Metal binding

774

1

Magnesium; catalytic; for reverse transcriptase activity By similarity

Metal binding

1031

1

Magnesium; catalytic; for RNase H activity By similarity

Metal binding

1066

1

Magnesium; catalytic; for RNase H activity By similarity

Metal binding

1086

1

Magnesium; catalytic; for RNase H activity By similarity

Metal binding

1137

1

Magnesium; catalytic; for RNase H activity By similarity

Metal binding

1212

1

Magnesium; catalytic; for integrase activity By similarity

Metal binding

1264

1

Magnesium; catalytic; for integrase activity By similarity

Site

133 – 134

2

Cleavage; by viral protease By similarity

Site

222 – 223

2

Cis/trans isomerization of proline peptide bond; by human PPIA/CYPA By similarity

Site

364 – 365

2

Cleavage; by viral protease By similarity

Site

378 – 379

2

Cleavage; by viral protease By similarity

Site

434 – 435

2

Cleavage; by viral protease Potential

Site

442 – 443

2

Cleavage; by viral protease By similarity

Site

489 – 490

2

Cleavage; by viral protease By similarity

Site

588 – 589

2

Cleavage; by viral protease By similarity

Site

989

1

Essential for RT p66/p51 heterodimerization By similarity

Site

1002

1

Essential for RT p66/p51 heterodimerization By similarity

Site

1028 – 1029

2

Cleavage; by viral protease; partial By similarity

Site

1148 – 1149

2

Cleavage; by viral protease By similarity

Amino acid modifications

Modified residue

133

1

Phosphotyrosine; by host By similarity

Lipidation

2

1

N-myristoyl glycine; by host By similarity

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

1436

Helix Strand Turn

Details...

Beta strand

491 – 493

3

Beta strand

494 – 496

3

Beta strand

499 – 504

6

Beta strand

507 – 513

7

Beta strand

521 – 523

3

Beta strand

532 – 538

7

Beta strand

541 – 555

15

Beta strand

558 – 566

9

Beta strand

570 – 574

5

Helix

576 – 579

4

Helix

580 – 582

3

Beta strand

585 – 587

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform Gag-Pol polyprotein [UniParc]. Last modified January 23, 2007. Version 3. Checksum: D44EFD3E809AA3F3	FASTA	1,436	161,899
	10 20 30 40 50 60 MGARASVLSG GKLDAWEKIR LRPGGKKKYR LKHLVWASRE LERFALNPGL LETSDGCKQI 70 80 90 100 110 120 IGQLQPAIRT GSEELRSLFN TVATLYCVHE RIEVKDTKEA LEKMEEEQNK SKNKKAQQAA 130 140 150 160 170 180 ADAGNNSQVS QNYPIVQNLQ GQMVHQAISP RTLNAWVKVI EEKAFSPEVI PMFSALSEGA 190 200 210 220 230 240 TPQDLNTMLN TVGGHQAAMQ MLKETINEEA AEWDRLHPVH AGPIAPGQMR EPRGSDIAGT 250 260 270 280 290 300 TSTLQEQIAW MTSNPPIPVG EIYKRWIILG LNKIVRMYSP VSILDIRQGP KEPFRDYVDR 310 320 330 340 350 360 FYKTLRAEQA SQEVKGWMTE TLLVQNANPD CKTILKALGP QATLEEMMTA CQGVGGPSHK 370 380 390 400 410 420 ARVLAEAMSQ ATNSAAAVMM QRGNFKGPRK TIKCFNCGKE GHIAKNCRAP RRKGCWKCGK 430 440 450 460 470 480 EGHQLKDCTE RQANFLREDL AFPQGKAGEL SSEQTRANSP TSRELRVWGR DNPLSETGAE 490 500 510 520 530 540 RQGTVSFNCP QITLWQRPLV TIKIGGQLKE ALLDTGADDT VLEEMNLPGK WKPKMIGGIG 550 560 570 580 590 600 GFIKVRQYDQ ILIEICGHKA IGTVLVGPTP VNIIGRNLLT QIGCTLNFPI SPIETVPVKL 610 620 630 640 650 660 KPGMDGPKVK QWPLTEEKIK ALTEICTEME KEGKISRVGP ENPYNTPIFA IKKKDSTKWR 670 680 690 700 710 720 KLVDFRELNK RTQDFWEVQL GIPHPAGLKK KKSVTVLDVG DAYFSVPLDK DFRKYTAFTI 730 740 750 760 770 780 PSINNETPGI RYQYNVLPQG WKGSPAIFQS SMTKILEPFR KQNPEIVIYQ YMDDLYVGSD 790 800 810 820 830 840 LEIGQHRTKI EELREHLLRW GFTTPDKKHQ KEPPFLWMGY ELHPDKWTVQ SIKLPEKESW 850 860 870 880 890 900 TVNDIQKLVG KLNWASQIYP GIKVRQLCKL LRGTKALTEV IPLTEEAELE LAENREILKE 910 920 930 940 950 960 PVHGVYYDPS KDLIAEIQKQ GHGQWTYQIY QEPFKNLKTG KYARMRGAHT NDVKQLAEVV 970 980 990 1000 1010 1020 QKISTESIVI WGKTPKFRLP IQKETWETWW VEYWQATWIP EWEFVNTPPL VKLWYQLEKE 1030 1040 1050 1060 1070 1080 PIIGAETFYV DGAANRETKL GKAGYVTDRG RQKVVPFTDT TNQKTELQAI NLALQDSGLE 1090 1100 1110 1120 1130 1140 VNIVTDSQYA LGIIQAQPDK SESELVSQII EQLIKKEKVY LAWVPAHKGI GGNEQVDKLV 1150 1160 1170 1180 1190 1200 SQGIRKVLFL DGIDKAQEEH EKYHNNWRAM ASDFNLPPVV AKEIVASCDK CQLKGEAMHG 1210 1220 1230 1240 1250 1260 QVDCSPGIWQ LDCTHLEGKV ILVAVHVASG YIEAEVIPAE TGQETAYFIL KLAGRWPVKI 1270 1280 1290 1300 1310 1320 VHTDNGSNFT SAAVKAACWW AGIKQEFGIP YNPQSQGVVE SMNKELKKII GQVRDQAEHL 1330 1340 1350 1360 1370 1380 KTAVQMAVFI HNFKRKGGIG GYSAGERIID IIATDIQTKE LQKQITKIQN FRVYYRDSRD 1390 1400 1410 1420 1430 PIWKGPAKLL WKGEGAVVIQ DNSDIKVVPR RKVKIIRDYG KQMAGDDCVA SRQDED
	Isoform Gag polyprotein [UniParc]. See P12495.		–	–

References

[1]	Theodore T., Buckler-White A.J. Submitted (JUL-1989) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"Proteolytic processing and particle maturation." Vogt V.M. Curr. Top. Microbiol. Immunol. 214:95-131(1996) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[3]	"Structural biology of HIV." Turner B.G., Summers M.F. J. Mol. Biol. 285:1-32(1999) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[4]	"Mechanisms of retroviral recombination." Negroni M., Buc H. Annu. Rev. Genet. 35:275-302(2001) [PubMed] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: REVIEW.
[7]	"ABT-538 is a potent inhibitor of human immunodeficiency virus protease and has high oral bioavailability in humans." Kempf D.J., Marsh K.C., Denissen J.F., McDonald E., Vasavanonda S., Flentge C.A., Green B.E., Fino L., Park C.H., Kong X.-P., Wideburg N.E., Saldivar A., Ruiz L., Kati W.M., Sham H.L., Robins T., Stewart K.D., Hsu A. , Plattner J.J., Leonard J.M., Norbeck D.W. Proc. Natl. Acad. Sci. U.S.A. 92:2484-2488(1995) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 490-588 IN COMPLEX WITH THE INHIBITOR A-84539.
[8]	"A novel, picomolar inhibitor of human immunodeficiency virus type 1 protease." Sham H.L., Zhao C., Stewart K.D., Betebenner D.A., Lin S., Park C.H., Kong X.-P., Rosenbrook W. Jr., Herrin T., Madigan D., Vasavanonda S., Lyons N., Molla A., Saldivar A., Marsh K.C., McDonald E., Wideburg N.E., Denissen J.F. , Robins T., Kempf D.J., Plattner J.J., Norbeck D.W. J. Med. Chem. 39:392-397(1996) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 490-588.
+	Additional computationally mapped references.

Web resources

HIV drug resistance mutations

hivdb

HIV drug resistance database

BioAfrica: HIV bioinformatics in Africa

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M22639 Genomic RNA. Translation: AAA45366.1. Sequence problems.

PIR

S54378.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1E28	X-ray	3.00	C	716-723	[»]
1HXW	X-ray	1.80	A/B	490-588	[»]
1PRO	X-ray	1.80	A/B	490-588	[»]
1Q94	X-ray	2.40	C/F	746-754	[»]
1VIJ	X-ray	2.40	A/B	490-588	[»]
1VIK	X-ray	2.40	A/B	490-588	[»]
2WKZ	X-ray	1.70	A/B	490-588	[»]
2WL0	X-ray	1.90	A/B	490-588	[»]
2XYE	X-ray	2.00	A/B	490-588	[»]
2XYF	X-ray	1.80	A/B	490-588	[»]
3KF0	X-ray	1.80	A/B	490-588	[»]
3KFN	X-ray	1.77	A/B	490-588	[»]
3KFP	X-ray	1.77	A	490-588	[»]
3KFR	X-ray	1.30	A/B	490-588	[»]
3KFS	X-ray	1.80	A/B	490-588	[»]
3W39	X-ray	3.10	C/F	716-723	[»]
4DQB	X-ray	1.50	A/B	490-588	[»]
4DQC	X-ray	1.94	A/B	490-588	[»]
4DQE	X-ray	1.30	A/B	490-588	[»]
4DQF	X-ray	1.90	A/B	490-588	[»]
4DQG	X-ray	2.79	A/B	490-588	[»]
4DQH	X-ray	1.79	A/B	490-588	[»]
4E43	X-ray	1.54	A/B	490-588	[»]

ProteinModelPortal

P12499.

SMR

P12499. Positions 2-434, 490-1131, 1149-1418.

ModBase

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Protocols and materials databases

StructuralBiologyKnowledgebase

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Enzyme and pathway databases

Reactome

REACT_116125. Disease.

Family and domain databases

Gene3D

1.10.10.200. 1 hit.
1.10.1200.30. 1 hit.
1.10.150.90. 1 hit.
1.10.375.10. 1 hit.
2.30.30.10. 1 hit.
2.40.70.10. 1 hit.
4.10.60.10. 1 hit.

InterPro

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.
IPR012344. Matrix_N_HIV/RSV.
IPR018061. Pept_A2A_retrovirus_sg.
IPR001995. Peptidase_A2_cat.
IPR021109. Peptidase_aspartic.
IPR001969. Peptidase_aspartic_AS.
IPR008916. Retrov_capsid_C.
IPR008919. Retrov_capsid_N.
IPR010999. Retrovr_matrix_N.
IPR012337. RNaseH-like_dom.
IPR002156. RNaseH_domain.
IPR000477. RVT.
IPR010659. RVT_connect.
IPR010661. RVT_thumb.
IPR001878. Znf_CCHC.
[Graphical view]

Pfam

PF00540. Gag_p17. 1 hit.
PF00607. Gag_p24. 1 hit.
PF00552. IN_DBD_C. 1 hit.
PF02022. Integrase_Zn. 1 hit.
PF00075. RNase_H. 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]

SUPFAM

SSF50122. Integrase_C. 1 hit.
SSF46919. Integrase_Zn_N. 1 hit.
SSF50630. Pept_Aspartic. 1 hit.
SSF47353. Retrov_capsid_C. 1 hit.
SSF47943. Retrov_capsid_N. 1 hit.
SSF47836. Retrovir_matrix. 1 hit.
SSF53098. RNaseH_fold. 2 hits.
SSF57756. SSF57756. 1 hit.

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

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Other

EvolutionaryTrace

P12499.

Entry information

Entry name

POL_HV1Z2

Accession

Primary (citable) accession number: P12499

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	January 23, 2007
Last modified:	May 29, 2013
This is version 153 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program