Human protein: cleavage and polyadenylation specificity factor subunit 6 isoform 1
Human protein sequence: MADGVDHIDIYADVGEEFNQEAEYGGHDQIDLYDDVISPSANNGDAPEDRDYMDTLPPTVGDDVGKGAAPNVVYTYTGKRIALYIGNLTWWTTDEDLTEAVHSLGVNDILEIKFFENRANGQSKGFALVGVGSEASSKKLMDLLPKRELHGQNPVVTPCNKQFLSQFEMQSRKTTQSGQMSGEGKAGPPGGSSRAAFPQGGRGRGRFPGAVPGGDRFPGPAGPGGPPPPFPAGQTPPRPPLGPPGPPGPPGPPPPGQVLPPPLAGPPNRGDRPPPPVLFPGQPFGQPPLGPLPPGPPPPVPGYGPPPGPPPPQQGPPPPPGPFPPRPPGPLGPPLTLAPPPHLPGPPPGAPPPAPHVNPAFFPPPTNSGMPTSDSRGPPPTDPYGRPPPYDRGDYGPPGREMDTARTPLSEAEFEEIMNRNRAISSSAISRAVSDASAGDYGSAIETLVTAISLIKQSKVSADDRCKVLISSLQDCLHGIESKSYGSGSRRERSRERDHSRSREKSRRHKSRSRDRHDDYYRERSRERERHRDRDRDRDRERDREREYRHR

HIV protein: capsid
Interaction type: interacts with
Description: Truncated CPSF6-358 binds HIV-1 core complexes and N74D CA mutant impairs the interaction between CPSF6-358 and CA
HIV protein sequence: PIVQNIQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRVHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTNNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRFYKTLRAEQASQEVKNWMTETLLVQNANPDCKTILKALGPAATLEEMMTACQGVGGPGHKARVL

HIV protein: capsid
Interaction type: binds
Description: The C-terminal residues 314-322 of CPSF6-358 contribute to binding with HIV-1 CA and mutations within this region fail to restrict HIV-1
HIV protein sequence: PIVQNIQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRVHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTNNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRFYKTLRAEQASQEVKNWMTETLLVQNANPDCKTILKALGPAATLEEMMTACQGVGGPGHKARVL

HIV protein: capsid
Interaction type: binds
Description: Residues N57, M66, Q67, K70, N74, and T107 in the N-terminal domain of HIV-1 CA are important for the binding to CPSF6. Mutations on these residues lead to the loss or reduction of dependency on TNPO3 and RanBP2
HIV protein sequence: PIVQNIQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRVHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTNNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRFYKTLRAEQASQEVKNWMTETLLVQNANPDCKTILKALGPAATLEEMMTACQGVGGPGHKARVL

HIV protein: capsid
Interaction type: stabilized by
Description: Cytoplasmic CPSF6 stabilizes the HIV-1 CA core and TNPO3 is required for CPSF6 localization to the nucleus and the HIV-1 permissiveness. However, some studies indicate depletion of TNPO3 does not change the cellular distribution of CPSF6
HIV protein sequence: PIVQNIQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRVHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTNNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRFYKTLRAEQASQEVKNWMTETLLVQNANPDCKTILKALGPAATLEEMMTACQGVGGPGHKARVL

HIV protein: capsid
Interaction type: interacts with
Description: HIV-1 inhibition by TNPO3 knockdown and CPSF6-358 is CA-dependent and cytoplasmic localization of CPSF6-358 is required to inhibit HIV-1
HIV protein sequence: PIVQNIQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRVHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTNNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRFYKTLRAEQASQEVKNWMTETLLVQNANPDCKTILKALGPAATLEEMMTACQGVGGPGHKARVL

HIV protein: capsid
Interaction type: binds
Description: Endogenously expressed CPSF6 binds and stabilizes in vitro-assembled HIV-1 CA-NC complexes, but the CPSF6-FG284AA mutant loses the ability to bind and stabilize the CA-NC complexes
HIV protein sequence: PIVQNIQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRVHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTNNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRFYKTLRAEQASQEVKNWMTETLLVQNANPDCKTILKALGPAATLEEMMTACQGVGGPGHKARVL

HIV protein: capsid
Interaction type: binds
Description: HIV-1 CA mutants N74D and P90A fail to bind to CPSF6 and cyclophilins (Nup358 and CypA), respectively, and trigger innate sensors, leading to nuclear translocation of NFkappaB and IRF3, production of type 1 IFN and induction of an antiviral state
HIV protein sequence: PIVQNIQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRVHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTNNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRFYKTLRAEQASQEVKNWMTETLLVQNANPDCKTILKALGPAATLEEMMTACQGVGGPGHKARVL

HIV protein: capsid
Interaction type: binds
Description: HIV-1 CA T107I and N74D substitutions can rescue the CA mutant RKLM by reducing the binding to CPSF6, while the CA S41A substitution resuces RKLM from CPSF6 inhibition without significantly changing the extent of CPSF6 binding
HIV protein sequence: PIVQNIQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRVHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTNNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRFYKTLRAEQASQEVKNWMTETLLVQNANPDCKTILKALGPAATLEEMMTACQGVGGPGHKARVL

HIV protein: capsid
Interaction type: associates with
Description: The HIV-1 CA mutant T54A infection is inhibited by CPSF6, but the A106T substitution in CA reduces the association of CPSF6 with CA to resuce the mutant T54A
HIV protein sequence: PIVQNIQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRVHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTNNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRFYKTLRAEQASQEVKNWMTETLLVQNANPDCKTILKALGPAATLEEMMTACQGVGGPGHKARVL

HIV protein: capsid
Interaction type: binds
Description: Five substitutions Q67H, K70R, H87P, T107N, and L111I in HIV-1 CA resistant to PF74 reduce the binding of the host protein CPSF6 to assembled CA complexes in vitro and permit infection of cells expressing the inhibitory protein CPSF6-358
HIV protein sequence: PIVQNIQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRVHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTNNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRFYKTLRAEQASQEVKNWMTETLLVQNANPDCKTILKALGPAATLEEMMTACQGVGGPGHKARVL

HIV protein: capsid
Interaction type: binds
Description: Crystal structure analysis demonstrates that helixes 3, 4, 8, and 9 in HIV-1 CA are involved in its binding to the CPSF6 peptide (residues 313-327)
HIV protein sequence: PIVQNIQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRVHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTNNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRFYKTLRAEQASQEVKNWMTETLLVQNANPDCKTILKALGPAATLEEMMTACQGVGGPGHKARVL

HIV protein: capsid
Interaction type: binds
Description: CPSF6 binds to the CA hexamer more tightly than the isolated CA NTD or unassembled CA, and the binding of CPSF6 to the hexamer involves energetically significant contacts with both the NTD and CTD in CA
HIV protein sequence: PIVQNIQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRVHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTNNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRFYKTLRAEQASQEVKNWMTETLLVQNANPDCKTILKALGPAATLEEMMTACQGVGGPGHKARVL

HIV protein: capsid
Interaction type: binds
Description: HIV-1 CA binds CPSF6; this interaction is inhibited by the inhibitor BI-2
HIV protein sequence: PIVQNIQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRVHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTNNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRFYKTLRAEQASQEVKNWMTETLLVQNANPDCKTILKALGPAATLEEMMTACQGVGGPGHKARVL

HIV protein: capsid
Interaction type: binds
Description: CPSF6 (313-327) F321N mutant impairs to bind to HIV-1 CA monomers and hexamers, and is inactive in the functional Epic assay
HIV protein sequence: PIVQNIQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRVHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTNNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRFYKTLRAEQASQEVKNWMTETLLVQNANPDCKTILKALGPAATLEEMMTACQGVGGPGHKARVL

HIV protein: capsid
Interaction type: binds
Description: HIV-1 CA binds CPSF6; HIV-1 CA mutations S41A, Q67H, V165I and V172I in combination abrogate this interaction
HIV protein sequence: PIVQNIQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRVHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTNNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRFYKTLRAEQASQEVKNWMTETLLVQNANPDCKTILKALGPAATLEEMMTACQGVGGPGHKARVL

HIV protein: capsid
Interaction type: binds
Description: HIV-1 CA binds CPSF6 to enhance HIV-1 nuclear entry
HIV protein sequence: PIVQNIQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRVHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTNNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRFYKTLRAEQASQEVKNWMTETLLVQNANPDCKTILKALGPAATLEEMMTACQGVGGPGHKARVL

HIV protein: capsid
Interaction type: binds
Description: HIV-1 CA binds to CPSF6, which is abrogated by mutation A77V in CA and confers a significant viral fitness advantage
HIV protein sequence: PIVQNIQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRVHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTNNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRFYKTLRAEQASQEVKNWMTETLLVQNANPDCKTILKALGPAATLEEMMTACQGVGGPGHKARVL

HIV protein: capsid
Interaction type: requires
Description: HIV-1 CA relocalizes RANBP2 (NUP358) into the cytoplasm of infected cells, which requires CPSF6 and KIF5B
HIV protein sequence: PIVQNIQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRVHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTNNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRFYKTLRAEQASQEVKNWMTETLLVQNANPDCKTILKALGPAATLEEMMTACQGVGGPGHKARVL

HIV protein: nucleocapsid
Interaction type: binds
Description: Endogenously expressed CPSF6 binds and stabilizes in vitro-assembled HIV-1 CA-NC complexes, but the CPSF6-FG284AA mutant loses the ability to bind and stabilize the CA-NC complexes
HIV protein sequence: MQRGNFRNQRKIVKCFNCGKEGHTARNCRAPRKKGCWKCGKEGHQMKDCTERQAN

HIV protein: reverse transcriptase
Interaction type: inhibited by
Description: Mutational analyses reveal that the residues encoded by exon 6, but not the C-terminal 54 residues in hCPSF6-375, is responsible for inhibition of HIV-1 RT-mediated viral cDNA synthesis
HIV protein sequence: PISPIETVPVKLKPGMDGPKVKQWPLTEEKIKALVEICTEMEKEGKISKIGPENPYNTPVFAIKKKDSTKWRKLVDFRELNKRTQDFWEVQLGIPHPAGLKKKKSVTVLDVGDAYFSVPLDEDFRKYTAFTIPSINNETPGIRYQYNVLPQGWKGSPAIFQSSMTKILEPFRKQNPDIVIYQYMDDLYVGSDLEIGQHRTKIEELRQHLLRWGLTTPDKKHQKEPPFLWMGYELHPDKWTVQPIVLPEKDSWTVNDIQKLVGKLNWASQIYPGIKVRQLCKLLRGTKALTEVIPLTEEAELELAENREILKEPVHGVYYDPSKDLIAEIQKQGQGQWTYQIYQEPFKNLKTGKYARMRGAHTNDVKQLTEAVQKITTESIVIWGKTPKFKLPIQKETWETWWTEYWQATWIPEWEFVNTPPLVKLWYQLEKEPIVGAETFYVDGAANRETKLGKAGYVTNRGRQKVVTLTDTTNQKTELQAIYLALQDSGLEVNIVTDSQYALGIIQAQPDQSESELVNQIIEQLIKKEKVYLAWVPAHKGIGGNEQVDKLVSAGIRKVL

HIV protein: Rev
Interaction type: interacts with
Description: HIV-1 Rev interacting protein, cleavage and polyadenylation specific factor 6, (CPSF6), is identified by the in-vitro binding experiments involving cytosolic or nuclear extracts from HeLa cells.  The interaction of Rev with CPSF6 is increased by RRE
HIV protein sequence: MAGRSGDSDEELIRTVRLIKLLYQSNPPPNPEGTRQARRNRRRRWRERQRQIHSISERILGTYLGRSAEPVPLQLPPLERLTLDCNEDCGTSGTQGVGSPQILVESPTVLESGTKE