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Protein

Gag-Pol polyprotein

Gene

gag-pol

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

Functioni

Gag-Pol polyprotein: Mediates, with Gag polyrotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi). Gag-Pol polyprotein may regulate its own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, the polyprotein would promote translation, whereas at high concentration, the polyprotein would encapsidate genomic RNA and then shutt off translation.By similarity
Matrix protein p17: Targets the polyprotein to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. Matrix protein is part of the pre-integration complex. Implicated in the release from host cell mediated by Vpu. Binds to RNA.By similarity
Capsid protein p24: Forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry (By similarity). Host restriction factors such as TRIM5-alpha or TRIMCyp bind retroviral capsids and cause premature capsid disassembly, leading to blocks in reverse transcription. Capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species. Host PIN1 apparently facilitates the virion uncoating. On the other hand, interactions with PDZD8 or CYPA stabilize the capsid.By similarity
Nucleocapsid protein p7: Encapsulates and protects viral dimeric unspliced genomic RNA (gRNA). Binds these RNAs through its zinc fingers. Acts as a nucleic acid chaperone which is involved in rearangement of nucleic acid secondary structure during gRNA retrotranscription. Also facilitates template switch leading to recombination. As part of the polyprotein, participates in gRNA dimerization, packaging, tRNA incorporation and virion assembly.By similarity
Protease: Aspartyl protease that mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell. Also cleaves Nef and Vif, probably concomitantly with viral structural proteins on maturation of virus particles. Hydrolyzes host EIF4GI and PABP1 in order to shut off the capped cellular mRNA translation. The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response (By similarity).PROSITE-ProRule annotationBy similarity
Reverse transcriptase/ribonuclease H: 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 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.By similarity
3'-end directed exonucleolytic cleavage of viral RNA-DNA hybrid.By similarity
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

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei227 – 228Cis/trans isomerization of proline peptide bond; by human PPIA/CYPABy similarity2
Active sitei518For protease activity; shared with dimeric partnerPROSITE-ProRule annotation1
Metal bindingi702Magnesium; catalytic; for reverse transcriptase activityBy similarity1
Metal bindingi777Magnesium; catalytic; for reverse transcriptase activityBy similarity1
Metal bindingi778Magnesium; catalytic; for reverse transcriptase activityBy similarity1
Sitei993Essential for RT p66/p51 heterodimerizationBy similarity1
Sitei1006Essential for RT p66/p51 heterodimerizationBy similarity1
Metal bindingi1035Magnesium; catalytic; for RNase H activityBy similarity1
Metal bindingi1070Magnesium; catalytic; for RNase H activityBy similarity1
Metal bindingi1090Magnesium; catalytic; for RNase H activityBy similarity1
Metal bindingi1141Magnesium; catalytic; for RNase H activityBy similarity1
Metal bindingi1216Magnesium; catalytic; for integrase activityBy similarity1
Metal bindingi1268Magnesium; catalytic; for integrase activityBy similarity1
Metal bindingi1304Magnesium; catalytic; for integrase activityBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri396 – 413CCHC-type 1PROSITE-ProRule annotationAdd BLAST18
Zinc fingeri417 – 434CCHC-type 2PROSITE-ProRule annotationAdd BLAST18
Zinc fingeri1155 – 1196Integrase-typePROSITE-ProRule annotationAdd BLAST42
DNA bindingi1375 – 1422Integrase-typePROSITE-ProRule annotationAdd BLAST48

GO - Molecular functioni

GO - Biological processi

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, Lipid-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
Spacer peptide 1By similarity
Short name:
SP1
Alternative name(s):
p2
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 (EC:2.7.7.-By similarity, EC:3.1.-.-By similarity)
Short name:
IN
Gene namesi
Name:gag-pol
OrganismiHuman immunodeficiency virus type 1 group M subtype A (isolate MAL) (HIV-1)
Taxonomic identifieri11697 [NCBI]
Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeLentivirusPrimate lentivirus group
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000007696 Componenti: Genome

Subcellular locationi

Gag-Pol polyprotein :
  • Host cell membrane; Lipid-anchor
  • Host endosomehost multivesicular body

  • Note: These locations are linked to virus assembly sites. The main location is the cell membrane, but under some circumstances, late endosomal compartments can serve as productive sites for virion assembly.By similarity
Integrase :

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Keywords - Diseasei

AIDS

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved; by hostBy similarity
ChainiPRO_00002612702 – 1440Gag-Pol polyproteinAdd BLAST1439
ChainiPRO_00000423852 – 138Matrix protein p17By similarityAdd BLAST137
ChainiPRO_0000042386139 – 369Capsid protein p24By similarityAdd BLAST231
PeptideiPRO_0000042387370 – 383Spacer peptide 1By similarityAdd BLAST14
ChainiPRO_0000042388384 – 438Nucleocapsid protein p7By similarityAdd BLAST55
PeptideiPRO_0000246719439 – 446Transframe peptideSequence analysis8
ChainiPRO_0000042389447 – 493p6-polSequence analysisAdd BLAST47
ChainiPRO_0000038659494 – 592ProteaseBy similarityAdd BLAST99
ChainiPRO_0000042390593 – 1152Reverse transcriptase/ribonuclease HBy similarityAdd BLAST560
ChainiPRO_0000042391593 – 1032p51 RTBy similarityAdd BLAST440
ChainiPRO_00000423921033 – 1152p15By similarityAdd BLAST120
ChainiPRO_00000423931153 – 1440IntegraseBy similarityAdd BLAST288

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycine; by hostBy similarity1
Modified residuei138Phosphotyrosine; by hostBy similarity1

Post-translational modificationi

Gag-Pol polyprotein: 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.PROSITE-ProRule annotationBy similarity
Matrix protein p17: Tyrosine phosphorylated presumably in the virion by a host kinase. Phosphorylation is apparently not a major regulator of membrane association.By similarity
Capsid protein p24: Phosphorylated possibly by host MAPK1; this phosphorylation is necessary for Pin1-mediated virion uncoating.By similarity
Nucleocapsid protein p7: Methylated by host PRMT6, impairing its function by reducing RNA annealing and the initiation of reverse transcription.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei138 – 139Cleavage; by viral proteaseBy similarity2
Sitei369 – 370Cleavage; by viral proteaseBy similarity2
Sitei383 – 384Cleavage; by viral proteaseBy similarity2
Sitei438 – 439Cleavage; by viral proteaseSequence analysis2
Sitei446 – 447Cleavage; by viral proteaseBy similarity2
Sitei493 – 494Cleavage; by viral proteaseBy similarity2
Sitei592 – 593Cleavage; by viral proteaseBy similarity2
Sitei1032 – 1033Cleavage; by viral protease; partialBy similarity2
Sitei1152 – 1153Cleavage; by viral proteaseBy similarity2

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein

Interactioni

Subunit structurei

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

Structurei

Secondary structure

11440
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi495 – 500Combined sources6
Beta strandi503 – 508Combined sources6
Beta strandi511 – 517Combined sources7
Beta strandi525 – 528Combined sources4
Beta strandi536 – 542Combined sources7
Beta strandi545 – 559Combined sources15
Beta strandi562 – 572Combined sources11
Helixi580 – 583Combined sources4
Helixi584 – 586Combined sources3
Beta strandi589 – 591Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1HHJX-ray2.50C/F901-909[»]
3IXOX-ray1.70A/B494-592[»]
ProteinModelPortaliP04588.
SMRiP04588.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP04588.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini513 – 582Peptidase A2PROSITE-ProRule annotationAdd BLAST70
Domaini636 – 826Reverse transcriptasePROSITE-ProRule annotationAdd BLAST191
Domaini1026 – 1149RNase HPROSITE-ProRule annotationAdd BLAST124
Domaini1206 – 1356Integrase catalyticPROSITE-ProRule annotationAdd BLAST151

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni7 – 31Interaction with Gp41By similarityAdd BLAST25
Regioni8 – 43Interaction with host CALM1By similarityAdd BLAST36
Regioni12 – 19Interaction with host AP3D1By similarity8
Regioni14 – 33Interaction with membrane phosphatidylinositol 4,5-bisphosphate and RNABy similarityAdd BLAST20
Regioni73 – 77Interaction with membrane phosphatidylinositol 4,5-bisphosphateBy similarity5
Regioni195 – 233Interaction with human PPIA/CYPA and NUP153By similarityAdd BLAST39
Regioni283 – 369Dimerization/Multimerization of capsid protein p24By similarityAdd BLAST87
Regioni494 – 498Dimerization of proteaseBy similarity5
Regioni542 – 548Dimerization of proteaseBy similarity7
Regioni581 – 593Dimerization of proteaseBy similarityAdd BLAST13
Regioni819 – 827RT 'primer grip'By similarity9

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi16 – 22Nuclear export signalBy similarity7
Motifi26 – 32Nuclear localization signalBy similarity7
Motifi990 – 1006Tryptophan repeat motifBy similarityAdd BLAST17

Domaini

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
Reverse transcriptase/ribonuclease H: The tryptophan repeat motif is involved in RT p66/p51 dimerization (By similarity).By similarity
Integrase: The 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

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)DescriptionActionsGraphical viewLength
Zinc fingeri396 – 413CCHC-type 1PROSITE-ProRule annotationAdd BLAST18
Zinc fingeri417 – 434CCHC-type 2PROSITE-ProRule annotationAdd BLAST18
Zinc fingeri1155 – 1196Integrase-typePROSITE-ProRule annotationAdd BLAST42

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_HIV/RSV.
IPR001995. Peptidase_A2_cat.
IPR021109. Peptidase_aspartic_dom.
IPR018061. Retropepsins.
IPR008916. Retrov_capsid_C.
IPR008919. Retrov_capsid_N.
IPR010999. Retrovr_matrix.
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. AlignAdd to basket

Note: Translation results in the formation of the Gag polyprotein most of the time. Ribosomal frameshifting at the gag-pol genes boundary occurs at low frequency and produces the Gag-Pol polyprotein. This strategy of translation probably allows the virus to modulate the quantity of each viral protein. Maintenance of a correct Gag to Gag-Pol ratio is essential for RNA dimerization and viral infectivity.
Isoform Gag-Pol polyprotein (identifier: P04588-1) [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.

« Hide

        10         20         30         40         50
MGARASVLSG GKLDAWEKIR LRPGGKKKYR LKHLVWASRE LERFALNPGL
60 70 80 90 100
LETGEGCQQI MEQLQSTLKT GSEEIKSLYN TVATLYCVHQ RIDVKDTKEA
110 120 130 140 150
LDKIEEIQNK SRQKTQQAAA AQQAAAATKN SSSVSQNYPI VQNAQGQMIH
160 170 180 190 200
QAISPRTLNA WVKVIEEKAF SPEVIPMFSA LSEGATPQDL NMMLNIVGGH
210 220 230 240 250
QAAMQMLKDT INEEAADWDR VHPVHAGPIP PGQMREPRGS DIAGTTSTLQ
260 270 280 290 300
EQIGWMTSNP PIPVGDIYKR WIILGLNKIV RMYSPVSILD IRQGPKEPFR
310 320 330 340 350
DYVDRFFKTL RAEQATQEVK NWMTETLLVQ NANPDCKTIL KALGPGATLE
360 370 380 390 400
EMMTACQGVG GPSHKARVLA EAMSQATNST AAIMMQRGNF KGQKRIKCFN
410 420 430 440 450
CGKEGHLARN CRAPRKKGCW KCGKEGHQMK DCTERQANFL RENLAFPQGK
460 470 480 490 500
AREFPSEQTR ANSPTSRELR VWGGDKTLSE TGAERQGIVS FSFPQITLWQ
510 520 530 540 550
RPVVTVRVGG QLKEALLDTG ADDTVLEEIN LPGKWKPKMI GGIGGFIKVR
560 570 580 590 600
QYDQILIEIC GKKAIGTILV GPTPVNIIGR NMLTQIGCTL NFPISPIETV
610 620 630 640 650
PVKLKPGMDG PRVKQWPLTE EKIKALTEIC KDMEKEGKIL KIGPENPYNT
660 670 680 690 700
PVFAIKKKDS TKWRKLVNFR ELNKRTQDFW EVQLGIPHPA GLKKKKSVTV
710 720 730 740 750
LDVGDAYFSV PLDEDFRKYT AFTIPSINNE TPGIRYQYNV LPQGWKGSPA
760 770 780 790 800
IFQSSMTKIL EPFRTKNPEI VIYQYMDDLY VGSDLEIGQH RTKIEELREH
810 820 830 840 850
LLKWGFTTPD KKHQKEPPFL WMGYELHPDK WTVQPIQLPD KESWTVNDIQ
860 870 880 890 900
KLVGKLNWAS QIYPGIKVKQ LCKLLRGAKA LTDIVPLTAE AELELAENRE
910 920 930 940 950
ILKEPVHGVY YDPSKDLIAE IQKQGQGQWT YQIYQEQYKN LKTGKYARIK
960 970 980 990 1000
SAHTNDVKQL TEAVQKIAQE SIVIWGKTPK FRLPIQKETW EAWWTEYWQA
1010 1020 1030 1040 1050
TWIPEWEFVN TPPLVKLWYQ LETEPIVGAE TFYVDGAANR ETKKGKAGYV
1060 1070 1080 1090 1100
TDRGRQKVVS LTETTNQKTE LQAIHLALQD SGSEVNIVTD SQYALGIIQA
1110 1120 1130 1140 1150
QPDKSESEIV NQIIEQLIQK DKVYLSWVPA HKGIGGNEQV DKLVSSGIRK
1160 1170 1180 1190 1200
VLFLDGIDKA QEEHEKYHSN WRAMASDFNL PPIVAKEIVA SCDKCQLKGE
1210 1220 1230 1240 1250
AMHGQVDCSP GIWQLDCTHL EGKIIIVAVH VASGYIEAEV IPAETGQETA
1260 1270 1280 1290 1300
YFILKLAGRW PVKVVHTDNG SNFTSAAVKA ACWWANIKQE FGIPYNPQSQ
1310 1320 1330 1340 1350
GVVESMNKEL KKIIGQVREQ AEHLKTAVQM AVFIHNFKRK GGIGGYSAGE
1360 1370 1380 1390 1400
RIIDMIATDI QTKELQKQIT KIQNFRVYYR DNRDPIWKGP AKLLWKGEGA
1410 1420 1430 1440
VVIQDNSDIK VVPRRKAKII RDYGKQMAGD DCVAGGQDED
Note: Produced by -1 ribosomal frameshifting.
Length:1,440
Mass (Da):162,122
Last modified:January 23, 2007 - v3
Checksum:iD212FABD311A9AB8
GO
Isoform Gag polyprotein (identifier: P04594-1) [UniParc]FASTAAdd to basket
The sequence of this isoform can be found in the external entry P04594.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Note: Produced by conventional translation.
Length:505
Mass (Da):56,132
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X04415 Genomic RNA. Translation: CAA28012.1. Sequence problems.
PIRiT01668.

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
X04415 Genomic RNA. Translation: CAA28012.1. Sequence problems.
PIRiT01668.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1HHJX-ray2.50C/F901-909[»]
3IXOX-ray1.70A/B494-592[»]
ProteinModelPortaliP04588.
SMRiP04588.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Miscellaneous databases

EvolutionaryTraceiP04588.

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_HIV/RSV.
IPR001995. Peptidase_A2_cat.
IPR021109. Peptidase_aspartic_dom.
IPR018061. Retropepsins.
IPR008916. Retrov_capsid_C.
IPR008919. Retrov_capsid_N.
IPR010999. Retrovr_matrix.
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]
ProtoNetiSearch...

Entry informationi

Entry nameiPOL_HV1MA
AccessioniPrimary (citable) accession number: P04588
Secondary accession number(s): Q79582
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 177 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Miscellaneous

Reverse transcriptase/ribonuclease H: 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.By similarity
HIV-1 lineages are divided in three main groups, M (for Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast majority of strains found worldwide belong to the group M. Group O seems to be endemic to and largely confined to Cameroon and neighboring countries in West Central Africa, where these viruses represent a small minority of HIV-1 strains. The group N is represented by a limited number of isolates from Cameroonian persons. The group M is further subdivided in 9 clades or subtypes (A to D, F to H, J and K).
Resistance to inhibitors associated with mutations are observed both in viral protease and in reverse transcriptase. Most of the time, single mutations confer only a modest reduction in drug susceptibility. Combination of several mutations is usually required to develop a high-level drug resistance. These mutations are predominantly found in clade B viruses and not in other genotypes. They are listed in the clade B representative isolate HXB2 (AC P04585).

Keywords - Technical termi

3D-structure, Complete proteome, Multifunctional enzyme, Reference proteome

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.