Human protein: uracil-DNA glycosylase isoform UNG2
Human protein sequence: MIGQKTLYSFFSPSPARKRHAPSPEPAVQGTGVAGVPEESGDAAAIPAKKAPAGQEEPGTPPSSPLSAEQLDRIQRNKAAALLRLAARNVPVGFGESWKKHLSGEFGKPYFIKLMGFVAEERKHYTVYPPPHQVFTWTQMCDIKDVKVVILGQDPYHGPNQAHGLCFSVQRPVPPPPSLENIYKELSTDIEDFVHPGHGDLSGWAKQGVLLLNAVLTVRAHQANSHKERGWEQFTDAVVSWLNQNSNGLVFLLWGSYAQKKGSAIDRKRHHVLQTAHPSPLSVYRGFFGCRHFSKTNELLQKSGKKPIDWKEL

HIV protein: integrase
Interaction type: incorporates
Description: HIV-1 L172A/K173A mutant virus is deficient for Uracil DNA Glycosylase (UNG2) incorporation into virions and is defective for replication due to a blockage at the stage of proviral DNA integration
HIV protein sequence: FLDGIDKAQDEHEKYHSNWRAMASDFNLPPVVAKEIVASCDKCQLKGEAMHGQVDCSPGIWQLDCTHLEGKVILVAVHVASGYIEAEVIPAETGQETAYFLLKLAGRWPVKTIHTDNGSNFTGATVRAACWWAGIKQEFGIPYNPQSQGVVESMNKELKKIIGQVRDQAEHLKTAVQMAVFIHNFKRKGGIGGYSAGERIVDIIATDIQTKELQKQITKIQNFRVYYRDSRNPLWKGPAKLLWKGEGAVVIQDNSDIKVVPRRKAKIIRDYGKQMAGDDCVASRQDED

HIV protein: integrase
Interaction type: binds
Description: Uracil DNA Glycosylase (UNG2; amino acids 1-51) binds to HIV-1 integrase (amino acids 170-180) and is incorporated into HIV-1 particles by binding to the integrase domain of the HIV-1 Gag-Pol polyprotein
HIV protein sequence: FLDGIDKAQDEHEKYHSNWRAMASDFNLPPVVAKEIVASCDKCQLKGEAMHGQVDCSPGIWQLDCTHLEGKVILVAVHVASGYIEAEVIPAETGQETAYFLLKLAGRWPVKTIHTDNGSNFTGATVRAACWWAGIKQEFGIPYNPQSQGVVESMNKELKKIIGQVRDQAEHLKTAVQMAVFIHNFKRKGGIGGYSAGERIVDIIATDIQTKELQKQITKIQNFRVYYRDSRNPLWKGPAKLLWKGEGAVVIQDNSDIKVVPRRKAKIIRDYGKQMAGDDCVASRQDED

HIV protein: Vpr
Interaction type: incorporates
Description: The interaction of HIV-1 Vpr with UNG2 leads to virion incorporation of catalytically active UNG2, which is directly involved with Vpr in modulating the HIV-1 mutation rate
HIV protein sequence: MEQAPEDQGPQREPHNEWTLELLEELKNEAVRHFPRIWLHGLGQHIYETYGDTWAGVEAIIRILQQLLFIHFRIGCRHSRIGVTRQRRARNGASRS

HIV protein: Vpr
Interaction type: binds
Description: In a yeast two-hybrid assay, tryptophan in position 54 of HIV-1 Vpr is critical for maintaining the interaction of Vpr with UNG2, and the WXXF motif (residues 231-234) of UNG2 is involved in this binding to Vpr
HIV protein sequence: MEQAPEDQGPQREPHNEWTLELLEELKNEAVRHFPRIWLHGLGQHIYETYGDTWAGVEAIIRILQQLLFIHFRIGCRHSRIGVTRQRRARNGASRS

HIV protein: Vpr
Interaction type: complexes with
Description: HIV-1 Vpr induces the ubiquitination of UNG and forms a complex with UNG
HIV protein sequence: MEQAPEDQGPQREPHNEWTLELLEELKNEAVRHFPRIWLHGLGQHIYETYGDTWAGVEAIIRILQQLLFIHFRIGCRHSRIGVTRQRRARNGASRS

HIV protein: Vpr
Interaction type: downregulates
Description: HIV-1 Vpr-induced reduction in uracil DNA glycosylase (UNG) is mediated through proteasomal degradation
HIV protein sequence: MEQAPEDQGPQREPHNEWTLELLEELKNEAVRHFPRIWLHGLGQHIYETYGDTWAGVEAIIRILQQLLFIHFRIGCRHSRIGVTRQRRARNGASRS

HIV protein: Vpr
Interaction type: binds
Description: Expression of exogenous HIV-1 Vpr inhibits class switch recombination (CSR) by competing with some endogenous factors for the WXXF site (residues 222-225) of uracil-DNA glycosylase
HIV protein sequence: MEQAPEDQGPQREPHNEWTLELLEELKNEAVRHFPRIWLHGLGQHIYETYGDTWAGVEAIIRILQQLLFIHFRIGCRHSRIGVTRQRRARNGASRS

HIV protein: Vpr
Interaction type: downregulates
Description: Downregulation of UNG2 by Vpr is related to a transcriptional regulation and is independent of Vpr binding, Vpr-induced G2 arrest, and the proteasome degradation
HIV protein sequence: MEQAPEDQGPQREPHNEWTLELLEELKNEAVRHFPRIWLHGLGQHIYETYGDTWAGVEAIIRILQQLLFIHFRIGCRHSRIGVTRQRRARNGASRS

HIV protein: Vpr
Interaction type: induces ubiquitination of
Description: DCAF1 interacts with DDB1 as well as the Vpr-UNG2 complex, which leads to polyubiquitination of UNG2 via Vpr
HIV protein sequence: MEQAPEDQGPQREPHNEWTLELLEELKNEAVRHFPRIWLHGLGQHIYETYGDTWAGVEAIIRILQQLLFIHFRIGCRHSRIGVTRQRRARNGASRS

HIV protein: Vpr
Interaction type: interacts with
Description: W54R/S79A Vpr mutant impairs interaction with UNG2, but is still able to recruit DCAF1
HIV protein sequence: MEQAPEDQGPQREPHNEWTLELLEELKNEAVRHFPRIWLHGLGQHIYETYGDTWAGVEAIIRILQQLLFIHFRIGCRHSRIGVTRQRRARNGASRS

HIV protein: Vpr
Interaction type: activates
Description: HIV-1-Vpr induced upregulation of NKG2D ligands in HIV-infected T cells by activating UNG2-dependent repair of uridine-containing DNA
HIV protein sequence: MEQAPEDQGPQREPHNEWTLELLEELKNEAVRHFPRIWLHGLGQHIYETYGDTWAGVEAIIRILQQLLFIHFRIGCRHSRIGVTRQRRARNGASRS

HIV protein: Vpr
Interaction type: induces phosphorylation of
Description: High levels of HIV-1 Vpr expression leads to the accumulation of phosphorylated UNG2 and the redistribution of UNG2 into the cell nucleus
HIV protein sequence: MEQAPEDQGPQREPHNEWTLELLEELKNEAVRHFPRIWLHGLGQHIYETYGDTWAGVEAIIRILQQLLFIHFRIGCRHSRIGVTRQRRARNGASRS

HIV protein: Vpr
Interaction type: binds
Description: HIV-1 Vpr binding to UNG2 results in a rapid reduced level of UNG2 protein and a significant loss of uracil-DNA glycosylate activity
HIV protein sequence: MEQAPEDQGPQREPHNEWTLELLEELKNEAVRHFPRIWLHGLGQHIYETYGDTWAGVEAIIRILQQLLFIHFRIGCRHSRIGVTRQRRARNGASRS

HIV protein: Vpr
Interaction type: degrades
Description: HIV-1 Vpr-mediated degradation of UNG2 is dependent on CUL4A neddylation
HIV protein sequence: MEQAPEDQGPQREPHNEWTLELLEELKNEAVRHFPRIWLHGLGQHIYETYGDTWAGVEAIIRILQQLLFIHFRIGCRHSRIGVTRQRRARNGASRS

HIV protein: Vpr
Interaction type: degrades
Description: HIV-1 Vpr-mediated UNG2 degradation and constitutive UNG2 turnover are dependent on DCAF1 or DDB1 but not on CUL4a or CUL4B in the cullin4 (CUL4)-containing ubiquitin ligase complex in HEK293T cells
HIV protein sequence: MEQAPEDQGPQREPHNEWTLELLEELKNEAVRHFPRIWLHGLGQHIYETYGDTWAGVEAIIRILQQLLFIHFRIGCRHSRIGVTRQRRARNGASRS

HIV protein: Vpr
Interaction type: degrades
Description: The coexpression of UNG2 with a dominant negative CUL4 molecule prevents UNG2 degradation from the presence of HIV-1 Vpr
HIV protein sequence: MEQAPEDQGPQREPHNEWTLELLEELKNEAVRHFPRIWLHGLGQHIYETYGDTWAGVEAIIRILQQLLFIHFRIGCRHSRIGVTRQRRARNGASRS

HIV protein: Vpr
Interaction type: complexes with
Description: HIV-1 Vpr complexes with DCAF1, DDB1, CUL4A, CUL4B, and UNG2 proteins in the cullin4 (CUL4)-containing ubiquitin ligase complex in HEK293T cells
HIV protein sequence: MEQAPEDQGPQREPHNEWTLELLEELKNEAVRHFPRIWLHGLGQHIYETYGDTWAGVEAIIRILQQLLFIHFRIGCRHSRIGVTRQRRARNGASRS

HIV protein: Vpr
Interaction type: induces ubiquitination of
Description: Ubiquitination levels of UNG2 is upregulated in the presence of HIV-1 Vpr in the proviral backbone compared to the levels for control
HIV protein sequence: MEQAPEDQGPQREPHNEWTLELLEELKNEAVRHFPRIWLHGLGQHIYETYGDTWAGVEAIIRILQQLLFIHFRIGCRHSRIGVTRQRRARNGASRS

HIV protein: Vpr
Interaction type: downregulates
Description: HIV-1 Vpr downregulates the gene expression of UNG2 and amino-acid residues A30/V31 are critical for the Vpr-mediated downregulation of UNG2
HIV protein sequence: MEQAPEDQGPQREPHNEWTLELLEELKNEAVRHFPRIWLHGLGQHIYETYGDTWAGVEAIIRILQQLLFIHFRIGCRHSRIGVTRQRRARNGASRS

HIV protein: Vpr
Interaction type: binds
Description: HIV-1 Vpr binds UNG2 and forms a trimolecular complex containing Vpr, UNG2 and RPA2
HIV protein sequence: MEQAPEDQGPQREPHNEWTLELLEELKNEAVRHFPRIWLHGLGQHIYETYGDTWAGVEAIIRILQQLLFIHFRIGCRHSRIGVTRQRRARNGASRS

HIV protein: Vpr
Interaction type: depletes
Description: HIV-1 Vpr depletes UNG (UNG2) in HIV-1 infected cells
HIV protein sequence: MEQAPEDQGPQREPHNEWTLELLEELKNEAVRHFPRIWLHGLGQHIYETYGDTWAGVEAIIRILQQLLFIHFRIGCRHSRIGVTRQRRARNGASRS

HIV protein: Vpr
Interaction type: targets
Description: HIV-1 and SIVcpz Vpr targets UNG (UNG2)
HIV protein sequence: MEQAPEDQGPQREPHNEWTLELLEELKNEAVRHFPRIWLHGLGQHIYETYGDTWAGVEAIIRILQQLLFIHFRIGCRHSRIGVTRQRRARNGASRS

HIV protein: Vpr
Interaction type: inhibits
Description: HIV-1 Vpr inhibits UNG (UNG2) activity when complexed with DDB1-DCAF1 by interfering with substrate (DNA) binding
HIV protein sequence: MEQAPEDQGPQREPHNEWTLELLEELKNEAVRHFPRIWLHGLGQHIYETYGDTWAGVEAIIRILQQLLFIHFRIGCRHSRIGVTRQRRARNGASRS

HIV protein: Vpr
Interaction type: mimics DNA binding to
Description: HIV-1 Vpr mimics DNA binding to UNG; UNG bind site for Vpr is identical to UNG-DNA; UNG uses Leu272 to insert into DNA minor groove whilst in the DDB1-DCAF1-Vpr-UNG complex , Leu272 inserts into Vpr cleft and Vpr insert loop mimics DNA phosphate backbone.
HIV protein sequence: MEQAPEDQGPQREPHNEWTLELLEELKNEAVRHFPRIWLHGLGQHIYETYGDTWAGVEAIIRILQQLLFIHFRIGCRHSRIGVTRQRRARNGASRS

HIV protein: Vpr
Interaction type: binds
Description: HIV-1 Vpr (amino acids 15-77) binds to the uracil DNA glycosylase DNA repair enzyme (amino acids 222-225) and thereby modulates the HIV-1 mutation rate
HIV protein sequence: MEQAPEDQGPQREPHNEWTLELLEELKNEAVRHFPRIWLHGLGQHIYETYGDTWAGVEAIIRILQQLLFIHFRIGCRHSRIGVTRQRRARNGASRS

HIV protein: Vpr
Interaction type: incorporates
Description: One report indicates incorporation of uracil DNA glycosylase (UNG) into HIV-1 virions is mediated by binding of HIV-1 Vpr to UNG, however another indicates virion incorporation of UNG is independent of Vpr and is mediated by the HIV-1 Integrase protein
HIV protein sequence: MEQAPEDQGPQREPHNEWTLELLEELKNEAVRHFPRIWLHGLGQHIYETYGDTWAGVEAIIRILQQLLFIHFRIGCRHSRIGVTRQRRARNGASRS

HIV protein: Tat
Interaction type: inhibited by
Description: The antiviral activity of UNG2 requires the integrity of its catalytic domain (residues 153 and 154). Depletion of endogenous UMG2 promotes Tat-mediated LTR transcription
HIV protein sequence: MEPVDPRLEPWKHPGSQPKTACTNCYCKKCCFHCQVCFITKALGISYGRKKRRQRRRAHQNSQTHQASLSKQPTSQPRGDPTGPKE