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P24740

- POL_HV1U4

UniProt

P24740 - POL_HV1U4

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Protein

Gag-Pol polyprotein

Gene

gag-pol

Organism
Human immunodeficiency virus type 1 group M subtype A (isolate U455) (HIV-1)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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).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).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).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).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. 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 annotation
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).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).By similarity

Catalytic activityi

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

Cofactori

Protein has several cofactor binding sites:
  • Mg2+By similarityNote: Binds 2 magnesium ions for reverse transcriptase polymerase activity.By similarity
  • Mg2+By similarityNote: Binds 2 magnesium ions for ribonuclease H (RNase H) activity. Substrate-binding is a precondition for magnesium binding.By similarity
  • Mg2+By similarityNote: Magnesium ions are required for integrase activity. Binds at least 1, maybe 2 magnesium ions.By similarity

Enzyme regulationi

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).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei128 – 1292Cleavage; by viral proteaseBy similarity
Sitei217 – 2182Cis/trans isomerization of proline peptide bond; by human PPIA/CYPABy similarity
Sitei359 – 3602Cleavage; by viral proteaseBy similarity
Sitei371 – 3722Cleavage; by viral proteaseBy similarity
Sitei426 – 4272Cleavage; by viral proteaseSequence Analysis
Sitei434 – 4352Cleavage; by viral proteaseBy similarity
Sitei481 – 4822Cleavage; by viral proteaseBy similarity
Active sitei506 – 5061For protease activity; shared with dimeric partnerPROSITE-ProRule annotation
Sitei580 – 5812Cleavage; by viral proteaseBy similarity
Metal bindingi690 – 6901Magnesium; catalytic; for reverse transcriptase activityBy similarity
Metal bindingi765 – 7651Magnesium; catalytic; for reverse transcriptase activityBy similarity
Metal bindingi766 – 7661Magnesium; catalytic; for reverse transcriptase activityBy similarity
Sitei981 – 9811Essential for RT p66/p51 heterodimerizationBy similarity
Sitei994 – 9941Essential for RT p66/p51 heterodimerizationBy similarity
Sitei1020 – 10212Cleavage; by viral protease; partialBy similarity
Metal bindingi1023 – 10231Magnesium; catalytic; for RNase H activityBy similarity
Metal bindingi1058 – 10581Magnesium; catalytic; for RNase H activityBy similarity
Metal bindingi1078 – 10781Magnesium; catalytic; for RNase H activityBy similarity
Metal bindingi1129 – 11291Magnesium; catalytic; for RNase H activityBy similarity
Sitei1140 – 11412Cleavage; by viral proteaseBy similarity
Metal bindingi1204 – 12041Magnesium; catalytic; for integrase activityBy similarity
Metal bindingi1256 – 12561Magnesium; catalytic; for integrase activityBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri384 – 40118CCHC-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri405 – 42218CCHC-type 2PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri1143 – 118442Integrase-typePROSITE-ProRule annotationAdd
BLAST
DNA bindingi1363 – 141048Integrase-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. aspartic-type endopeptidase activity Source: UniProtKB-KW
  2. DNA binding Source: UniProtKB-KW
  3. DNA-directed DNA polymerase activity Source: UniProtKB-KW
  4. exoribonuclease H activity Source: UniProtKB-EC
  5. RNA binding Source: UniProtKB-KW
  6. RNA-directed DNA polymerase activity Source: UniProtKB-KW
  7. RNA-DNA hybrid ribonuclease activity Source: InterPro
  8. structural molecule activity Source: InterPro
  9. zinc ion binding Source: InterPro

GO - Biological processi

  1. DNA integration Source: UniProtKB-KW
  2. DNA recombination Source: UniProtKB-KW
  3. establishment of integrated proviral latency Source: UniProtKB-KW
  4. induction by virus of host cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB-KW
  5. suppression by virus of host gene expression Source: UniProtKB-KW
  6. viral entry into host cell Source: UniProtKB-KW
  7. viral penetration into host nucleus Source: UniProtKB-KW
  8. viral release from host cell Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Aspartyl protease, DNA-directed DNA polymerase, Endonuclease, Hydrolase, Nuclease, Nucleotidyltransferase, Protease, RNA-directed DNA polymerase, Transferase

Keywords - Biological processi

Activation of host caspases by virus, DNA integration, DNA recombination, Eukaryotic host gene expression shutoff by virus, Eukaryotic host translation shutoff by virus, Host gene expression shutoff by virus, Host-virus interaction, Modulation of host cell apoptosis by virus, Viral genome integration, Viral penetration into host nucleus, Virion maturation, Virus entry into host cell, Virus exit from host cell

Keywords - Ligandi

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

Names & Taxonomyi

Protein namesi
Recommended name:
Gag-Pol polyprotein
Alternative name(s):
Pr160Gag-Pol
Cleaved into the following 11 chains:
Matrix protein p17
Short name:
MA
Capsid protein p24
Short name:
CA
Transframe peptide
Short name:
TF
p6-pol
Short name:
p6*
Alternative name(s):
PR
Retropepsin
Alternative name(s):
Exoribonuclease H (EC:3.1.13.2)
p66 RT
Integrase
Short name:
IN
Gene namesi
Name:gag-pol
OrganismiHuman immunodeficiency virus type 1 group M subtype A (isolate U455) (HIV-1)
Taxonomic identifieri11703 [NCBI]
Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeLentivirusPrimate lentivirus group
Virus hostiHomo sapiens (Human) [TaxID: 9606]

Subcellular locationi

Chain Matrix protein p17 : Virion Curated. Host nucleus By similarity. Host cytoplasm By similarity. Host cell membrane Curated; Lipid-anchor Curated
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).By similarity
Chain Integrase : Virion Curated. Host nucleus Curated. Host cytoplasm Curated
Note: Nuclear at initial phase, cytoplasmic at assembly.Curated

GO - Cellular componenti

  1. host cell cytoplasm Source: UniProtKB-KW
  2. host cell nucleus Source: UniProtKB-KW
  3. host cell plasma membrane Source: UniProtKB-KW
  4. intracellular Source: GOC
  5. membrane Source: UniProtKB-KW
  6. viral nucleocapsid Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Keywords - Diseasei

AIDS

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed; by hostBy similarity
Chaini2 – 14281427Gag-Pol polyproteinPRO_0000261282Add
BLAST
Chaini2 – 128127Matrix protein p17By similarityPRO_0000042430Add
BLAST
Chaini129 – 359231Capsid protein p24By similarityPRO_0000042431Add
BLAST
Peptidei360 – 37112Spacer peptide p2By similarityPRO_0000042432Add
BLAST
Chaini372 – 42655Nucleocapsid protein p7By similarityPRO_0000042433Add
BLAST
Peptidei427 – 4348Transframe peptideSequence AnalysisPRO_0000246732
Chaini435 – 48147p6-polSequence AnalysisPRO_0000042434Add
BLAST
Chaini482 – 58099ProteaseBy similarityPRO_0000038664Add
BLAST
Chaini581 – 1140560Reverse transcriptase/ribonuclease HBy similarityPRO_0000042435Add
BLAST
Chaini581 – 1020440p51 RTBy similarityPRO_0000042436Add
BLAST
Chaini1021 – 1140120p15By similarityPRO_0000042437Add
BLAST
Chaini1141 – 1428288IntegraseBy similarityPRO_0000042438Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycine; by hostBy similarity
Modified residuei128 – 1281Phosphotyrosine; by hostBy similarity

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).PROSITE-ProRule annotation
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).By similarity

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein

Interactioni

Subunit structurei

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).By similarity

Structurei

Secondary structure

1
1428
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi407 – 42014Combined sources
Beta strandi486 – 4883Combined sources
Beta strandi491 – 4966Combined sources
Beta strandi499 – 5057Combined sources
Beta strandi510 – 5167Combined sources
Beta strandi524 – 5307Combined sources
Beta strandi533 – 54715Combined sources
Beta strandi550 – 55910Combined sources
Helixi568 – 5714Combined sources
Helixi572 – 5743Combined sources
Beta strandi577 – 5793Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1E27X-ray2.20C1168-1176[»]
1NCPNMR-C405-422[»]
3LZSX-ray1.95A/B482-580[»]
3LZUX-ray1.76A/B482-580[»]
ProteinModelPortaliP24740.
SMRiP24740. Positions 2-426, 482-1137, 1141-1410.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP24740.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini501 – 57070Peptidase A2PROSITE-ProRule annotationAdd
BLAST
Domaini624 – 814191Reverse transcriptasePROSITE-ProRule annotationAdd
BLAST
Domaini1014 – 1137124RNase HPROSITE-ProRule annotationAdd
BLAST
Domaini1194 – 1344151Integrase catalyticPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni807 – 8159RT 'primer grip'By similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi16 – 227Nuclear export signalBy similarity
Motifi26 – 327Nuclear localization signalBy similarity
Motifi978 – 99417Tryptophan repeat motifBy similarityAdd
BLAST

Domaini

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).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).By similarity

Sequence similaritiesi

Contains 2 CCHC-type zinc fingers.PROSITE-ProRule annotation
Contains 1 integrase catalytic domain.PROSITE-ProRule annotation
Contains 1 integrase-type DNA-binding domain.PROSITE-ProRule annotation
Contains 1 integrase-type zinc finger.PROSITE-ProRule annotation
Contains 1 peptidase A2 domain.PROSITE-ProRule annotation
Contains 1 reverse transcriptase domain.PROSITE-ProRule annotation
Contains 1 RNase H domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri384 – 40118CCHC-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri405 – 42218CCHC-type 2PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri1143 – 118442Integrase-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Repeat, Zinc-finger

Family and domain databases

Gene3Di1.10.10.200. 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.
3.30.420.10. 2 hits.
4.10.60.10. 1 hit.
InterProiIPR001969. Aspartic_peptidase_AS.
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_dom.
IPR008916. Retrov_capsid_C.
IPR008919. Retrov_capsid_N.
IPR010999. Retrovr_matrix_N.
IPR012337. RNaseH-like_dom.
IPR002156. RNaseH_domain.
IPR000477. RT_dom.
IPR010659. RVT_connect.
IPR010661. RVT_thumb.
IPR001878. Znf_CCHC.
[Graphical view]
PfamiPF00540. 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]
PRINTSiPR00234. HIV1MATRIX.
SMARTiSM00343. ZnF_C2HC. 2 hits.
[Graphical view]
SUPFAMiSSF46919. SSF46919. 1 hit.
SSF47353. SSF47353. 1 hit.
SSF47836. SSF47836. 1 hit.
SSF47943. SSF47943. 1 hit.
SSF50122. SSF50122. 1 hit.
SSF50630. SSF50630. 1 hit.
SSF53098. SSF53098. 2 hits.
SSF57756. SSF57756. 1 hit.
PROSITEiPS50175. 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]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by ribosomal frameshifting. Align

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: P24740-1) [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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        10         20         30         40         50
MGARASVLSG KKLDSWEKIR LRPGGNKKYR LKHLVWASRE LEKFTLNPGL
60 70 80 90 100
LETAEGCQQI LGQLQPALQT GTEELRSLYN TVAVLYCVHQ RIDVKDTKEA
110 120 130 140 150
LNKIEEMQNK NKQRTQQAAA NTGSSQNYPI VQNAQGQPVH QALSPRTLNA
160 170 180 190 200
WVKVVEDKAF SPEVIPMFSA LSEGATPQDL NMMLNVVGGH QAAMQMLKDT
210 220 230 240 250
INEEAAEWDR LHPVHAGPIP PGQMREPRGS DIAGTTSTVQ EQIGWMTGNP
260 270 280 290 300
PIPVGDIYRR WIILGLNKIV RMYSPVSILD IRQGPKEPFR DYVDRFFKTL
310 320 330 340 350
RAEQATQDVK NWMTETLLVQ NANPDCKSIL RALGPGATLE EMMTACQGVG
360 370 380 390 400
GPGHKARVLA EAMSQVQQTS IMMQRGNFRG PRRIKCFNCG KEGHLAKNCR
410 420 430 440 450
APRKKGCWKC GKEGHQMKDC TERQANFLRE NLAFQQGEAR EFSSEQTRAN
460 470 480 490 500
SPTSRNLWDG GKDDLPCETG AERQGTDSFS FPQITLWQRP LVTVKIGGQL
510 520 530 540 550
IEALLDTGAD DTVLEDINLP GKWKPKIIGG IGGFIKVRQY DQILIEICGK
560 570 580 590 600
KTIGTVLVGP TPVNIIGRNM LTQIGCTLNF PISPIETVPV KLKPEMDGPK
610 620 630 640 650
VKQWPLTEEK IKALTEICNE MEKEGKISKI GPENPYNTPV FAIKKKDSTK
660 670 680 690 700
WRKLVDFREL NKRTQDFWEV QLGIPHTAGL KKKKSVTVLD VGDAYFSVPL
710 720 730 740 750
DESFRKYTAF TIPSINNETP GVRYQYNVLP QGWKGSPSIF QSSMTKILEP
760 770 780 790 800
FRSQHPDIVI YQYMDDLYVG SDLEIGQHRA KIEELRAHLL SWGFITPDKK
810 820 830 840 850
HQKEPPFLWM GYELHPDKWT VQPIQLPEKD SWTVNDIQKL VGKLNWASQI
860 870 880 890 900
YAGIKVKQLC KLLRGAKALT DIVTLTEEAE LELAENREIL KDPVHGVYYD
910 920 930 940 950
PSKDLVAEIQ KQGQDQWTYQ IYQEPFKNLK TGKYARKRSA HTNDVKQLTE
960 970 980 990 1000
VVQKVSTESI VIWGKIPKFR LPIQKETWEA WWMEYWQATW IPEWEFVNTP
1010 1020 1030 1040 1050
PLVKLWYQLE KDPIAGAETF YVDGAANRET KLGKAGYVTD RGRQKVVSLT
1060 1070 1080 1090 1100
ETTNQKTELH AIHLALQDSG SEVNIVTDSQ YALGIIQAQP DRSESEIVNQ
1110 1120 1130 1140 1150
IIEKLIEKEK VYLSWVPAHK GIGGNEQVDK LVSSGIRKVL FLDGIDKAQE
1160 1170 1180 1190 1200
DHEKYHCNWR AMASDFNLPP VVAKEIVASC NKCQLKGEAM HGQVDCSPGI
1210 1220 1230 1240 1250
WQLDCTHLEG KVILVAVHVA SGYIEAEVIP AETGQETAYF ILKLAGRWPV
1260 1270 1280 1290 1300
KVIHTDNGSN FTSAAVKAVC WWANIQQEFG IPYNPQSQGV VESMNKELKK
1310 1320 1330 1340 1350
IIGQVREQAE HLKTAVQMAV FIHNFKRKGG IGGYSAGERI IDIIATDIQT
1360 1370 1380 1390 1400
KELQKQISKI QNFRVYYRDS RDPIWKGPAK LLWKGEGAVV IQDNSDIKVV
1410 1420
PRRKAKIIRD YGKQMAGDDC MAGRQDED

Note: Produced by -1 ribosomal frameshifting.

Length:1,428
Mass (Da):161,103
Last modified:January 23, 2007 - v3
Checksum:iE98527B81D866C0C
GO
Isoform Gag polyprotein (identifier: P24736-1) [UniParc]FASTAAdd to Basket

The sequence of this isoform can be found in the external entry P24736.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

Note: Produced by conventional translation.

Length:493
Mass (Da):54,922
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M62320 Genomic DNA. Translation: AAA75019.1. Sequence problems.

Keywords - Coding sequence diversityi

Ribosomal frameshifting

Cross-referencesi

Web resourcesi

HIV drug resistance mutations
hivdb

HIV drug resistance database

BioAfrica: HIV bioinformatics in Africa

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M62320 Genomic DNA. Translation: AAA75019.1 . Sequence problems.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1E27 X-ray 2.20 C 1168-1176 [» ]
1NCP NMR - C 405-422 [» ]
3LZS X-ray 1.95 A/B 482-580 [» ]
3LZU X-ray 1.76 A/B 482-580 [» ]
ProteinModelPortali P24740.
SMRi P24740. Positions 2-426, 482-1137, 1141-1410.
ModBasei Search...
MobiDBi Search...

Protocols and materials databases

Structural Biology Knowledgebase Search...

Miscellaneous databases

EvolutionaryTracei P24740.

Family and domain databases

Gene3Di 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.
3.30.420.10. 2 hits.
4.10.60.10. 1 hit.
InterProi IPR001969. Aspartic_peptidase_AS.
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_dom.
IPR008916. Retrov_capsid_C.
IPR008919. Retrov_capsid_N.
IPR010999. Retrovr_matrix_N.
IPR012337. RNaseH-like_dom.
IPR002156. RNaseH_domain.
IPR000477. RT_dom.
IPR010659. RVT_connect.
IPR010661. RVT_thumb.
IPR001878. Znf_CCHC.
[Graphical view ]
Pfami 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 ]
PRINTSi PR00234. HIV1MATRIX.
SMARTi SM00343. ZnF_C2HC. 2 hits.
[Graphical view ]
SUPFAMi SSF46919. SSF46919. 1 hit.
SSF47353. SSF47353. 1 hit.
SSF47836. SSF47836. 1 hit.
SSF47943. SSF47943. 1 hit.
SSF50122. SSF50122. 1 hit.
SSF50630. SSF50630. 1 hit.
SSF53098. SSF53098. 2 hits.
SSF57756. SSF57756. 1 hit.
PROSITEi 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 ]
ProtoNeti Search...

Publicationsi

  1. "Nucleotide sequence of a Ugandan HIV-1 provirus reveals genetic diversity from other HIV-1 isolates."
    Oram J.D., Downing R.G., Roff M., Clegg J.C.S., Serwadda D., Carswell J.W.
    AIDS Res. Hum. Retroviruses 6:1073-1078(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  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. 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. 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. "Structural characterization of a 39-residue synthetic peptide containing the two zinc binding domains from the HIV-1 p7 nucleocapsid protein by CD and NMR spectroscopy."
    Omichinski J.G., Clore G.M., Sakaguchi K., Appella E., Gronenborn A.M.
    FEBS Lett. 292:25-30(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 405-422.

Entry informationi

Entry nameiPOL_HV1U4
AccessioniPrimary (citable) accession number: P24740
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: January 23, 2007
Last modified: November 26, 2014
This is version 151 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

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).

Keywords - Technical termi

3D-structure, Multifunctional enzyme

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3