Human protein: tyrosine-protein kinase HCK isoform a
Human protein sequence: MGGRSSCEDPGCPRDEERAPRMGCMKSKFLQVGGNTFSKTETSASPHCPVYVPDPTSTIKPGPNSHNSNTPGIREAGSEDIIVVALYDYEAIHHEDLSFQKGDQMVVLEESGEWWKARSLATRKEGYIPSNYVARVDSLETEEWFFKGISRKDAERQLLAPGNMLGSFMIRDSETTKGSYSLSVRDYDPRQGDTVKHYKIRTLDNGGFYISPRSTFSTLQELVDHYKKGNDGLCQKLSVPCMSSKPQKPWEKDAWEIPRESLKLEKKLGAGQFGEVWMATYNKHTKVAVKTMKPGSMSVEAFLAEANVMKTLQHDKLVKLHAVVTKEPIYIITEFMAKGSLLDFLKSDEGSKQPLPKLIDFSAQIAEGMAFIEQRNYIHRDLRAANILVSASLVCKIADFGLARVIEDNEYTAREGAKFPIKWTAPEAINFGSFTIKSDVWSFGILLMEIVTYGRIPYPGMSNPEVIRALERGYRMPRPENCPEELYNIMMRCWKNRPEERPTFEYIQSVLDDFYTATESQYQQQP

HIV protein: Vif
Interaction type: inhibits
Description: Vif binds specifically to the Src homology 3 domain of Hck, represses the kinase activity of Hck, and suppresses negative effects of Hck on HIV-1 replication
HIV protein sequence: MENRWQVMIVWQVDRMRIRTWKSLVKHHMYVSGKARGWFYRHHYESPHPRISSEVHIPLGDARLVITTYWGLHTGERDWHLGQGVSIEWRKKRYSTQVDPELADQLIHLYYFDCFSDSAIRKALLGHIVSPRCEYQAGHNKVGSLQYLALAALITPKKIKPPLPSVTKLTEDRWNKPQKTKGHRGSHTMNGH

HIV protein: Vif
Interaction type: interacts with
Description: The interaction of Hck with HIV-1 Vif affects Vif oligomerization in living cells
HIV protein sequence: MENRWQVMIVWQVDRMRIRTWKSLVKHHMYVSGKARGWFYRHHYESPHPRISSEVHIPLGDARLVITTYWGLHTGERDWHLGQGVSIEWRKKRYSTQVDPELADQLIHLYYFDCFSDSAIRKALLGHIVSPRCEYQAGHNKVGSLQYLALAALITPKKIKPPLPSVTKLTEDRWNKPQKTKGHRGSHTMNGH

HIV protein: Envelope surface glycoprotein gp120
Interaction type: downregulates
Description: HIV-1 gp120 downregulates the expression of HCK proto-oncogene, Src family tyrosine kinase (HCK) in human B cells
HIV protein sequence: SATEKLWVTVYYGVPVWKEATTTLFCASDAKAYDTEVHNVWATHACVPTDPNPQEVVLVNVTENFNMWKNDMVEQMHEDIISLWDQSLKPCVKLTPLCVSLKCTDLKNDTNTNSSSGRMIMEKGEIKNCSFNISTSIRGKVQKEYAFFYKLDIIPIDNDTTSYKLTSCNTSVITQACPKVSFEPIPIHYCAPAGFAILKCNNKTFNGTGPCTNVSTVQCTHGIRPVVSTQLLLNGSLAEEEVVIRSVNFTDNAKTIIVQLNTSVEINCTRPNNNTRKRIRIQRGPGRAFVTIGKIGNMRQAHCNISRAKWNNTLKQIASKLREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWSTEGSNNTEGSDTITLPCRIKQIINMWQKVGKAMYAPPISGQIRCSSNITGLLLTRDGGNSNNESEIFRPGGGDMRDNWRSELYKYKVVKIEPLGVAPTKAKRRVVQREKR

HIV protein: Nef
Interaction type: binds
Description: The interaction of SIV Nef with human Hck is not mediated via conserved proline-rich motifs, which are known to mediate HIV-1 Nef binding to the Hck SH3 domain; instead, SIV Nef binds the Hck SH2 domain
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: requires
Description: Induction of AP-1 by HIV-1 Nef is a specific feature of human and murine macrophage cell lines that requires signal transduction events involving Hck and MAPK
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: binds
Description: HIV-1 Nef increases the amount of intracellular stored Ca2+ in myelomonocytic cells through binding to Hck
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: activates
Description: HIV-1 Nef activates endogenous Hck in the granulocyte-macrophage colony-stimulating factor-dependent human myeloid cell line, TF-1, resulting in TF-1 cytokine-independence and Stat 3 activation
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: binds
Description: Peptides derived from the Hck SH3 domain with high affinity binding to HIV-1 Nef inhibit SH3-dependent Nef functions, such as association with PAK2 and induction of NFAT
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: interacts with
Description: A dominant-negative mutant protein derived from Hck, (composed of the N-terminal region, SH2, and SH3 domains) interacts with HIV-1 Nef and inhibits Nef-induced downregulation of MHC class I
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: interacts with
Description: Mutation of the PXXP motif in HIV-1 Nef abolishes the interaction of Nef with Hck in transgenic mice, resulting in the delayed development of an AIDS-like disease in the mice
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: activates
Description: SH3-dependent activation of Hck by HIV-1 Nef binding or by SH2-kinase linker mutation does not modulate tail tyrosine phosphorylation in vivo
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: activates
Description: HIV-1 Nef alleles (HIV-1 SF2, LAI and Consensus) bind and activate Hck, while HIV-1 ELI Nef fails to bind to the Hck SH3 domain in vitro and does not cooperate with Hck in fibroblast transformation
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: activates
Description: Molecular modeling has identified three residues in the core region of Nef from HIV-1 SF2 (Ala83, His116, and Tyr120) that are required for Hck recruitment and activation
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: activates
Description: In Rat-2 fibroblasts co-expressing Hck and a Nef fusion protein with the hormone-binding domain of estrogen receptor (Nef-ER), 4-hydroxytamoxifen treatment induces Nef-ER oligomerization, leading to Hck kinase activation and cellular transformation
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: Inhibits
Description: HIV-1 Nef-induced aberrant molecular formation between Hck and M-CSF receptor inhibits M-CSF bioactivities in monocytes/macrophages
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: complexes with
Description: In promonocytic cells, Nef/Hck complex recruits the ZAP-70 homolog Syk to downregulate MHC-I
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: complexes with
Description: Nef/Hck complex recruits and phosphorylates the tyrosine kinase ZAP-70, which binds class I PI3K to trigger MHC-I downregulation in primary CD4+ T cells
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: binds
Description: PACS-1S278A mutant blocks the association of Nef with Hck on the cell membrane, while wild-type PACS-1 has no effect
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: binds
Description: The HIV-1 Nef EEEE(65) targeting motif enables the Nef PXXP(75) motif to bind and activate a trans-Golgi network-localized tyrosine kinase Hck
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: binds
Description: HIV-1 Nef binds Hck and induces skewed Golgi-localization of Hck, which leads to Fms maturation arrest
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: activates
Description: HIV-1 Nef-induced activation of p61Hck is required for the formation of multinucleated giant cells (MGCs), which is dependent on lysosomal proteins including vacuolar adenosine triphosphatase and proteases participated in Nef-induced MGCs
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: activates
Description: HIV-1 Nef causes the FMS N-glycosylation defect and induces relocalization of the GM130 by activating the p56Hck/MEK/ERK/GRASP65 phosphorylation cascade in the Golgi
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: binds
Description: Small molecule compounds, which inhibit the SH3 domain of HIV-1 Nef binding to Hck, significantly reduce Nef-mediated viral infectivity enhancement
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: activates
Description: The primary M-group HIV-1 Nef proteins (from A, B, C, F, G, H, J, and K subtypes) strongly activate HCK in cells
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: binds
Description: The HIV-1 Nef highly conserved valine-glycine-phenylalanine amino acid triplet (VGF) motif is required for the physical interaction of the adjacent proline-rich motif with Hck
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: binds
Description: The binding of HIV-1 Nef to the SH3 domain of Hck is required for Nef/activated PAK2 complex formation. A new locus GFP/F (G67, F68, P69 and F90) of Nef is involved in the Nef/activated PAK2 complex formation
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: binds
Description: Mutations P72G, V74I, P75G, and R77K in the PXXPXR motif of HIV-1 Nef abolish the binding between Nef and Hck
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: complexes with
Description: The Nef/hnRNPK/PKC-delta/Hck protein complex activates Pak2 activity but inhibits Pak1 activity, which induces paxillin phosphorylation on Ser272/274 and regulates paxillin/TACE association and secretion
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: complexes with
Description: The Nef/hnRNPK/PKC-delta/Hck protein complex increases paxillin phosphorylation at position Y118 and activates and secrets TACE through Erk1/2 activation
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: induces accumulation of
Description: The first 18 amino acids (SH4 domain) of Hck, including the myristoylation site (G2), are required for the HIV-1 Nef-induced accumulation of Hck at the recycling endosomes and the trans-Golgi network
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: induces accumulation of
Description: HIV-1 Nef induces accumulation of Hck at the recycling endosomes and the trans-Golgi network by blocking the anterograde transport of Hck to the plasma membrane
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: associates with
Description: HIV-1 Nef associates with Hck in HIV-1 virions derived from 293T cells and primary monocyte-derived macrophages
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: associates with
Description: Diaminoquinoxaline benzenesulfonamide (DQBS) treatment reduces the amount of both HCK and the p85 regulatory subunit of PI3K associated with HIV-1 Nef and completely blocks Nef-dependent activation of ZAP-70
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: stabilized by
Description: HCK SH2 kinase linker residues Pro250 and Pro253 make stable hydrophobic contacts with SH3 domain residues Tyr90, Trp118, and Tyr136 to stabilize the HIV-1 Nef dimer interface
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: complexes with
Description: The Nef-HCK complex involves the Nef PXXPXR motif intercalating with the HCK SH3 surface residues Tyr-90, Tyr-92, Trp-118, Pro-133, and Tyr-136
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: interacts with
Description: HIV-1-mediated effects on podosomes and migration involve Nef-HCK interaction, and HCK-mediated phosphorylation of WASP at podosomes
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: activates
Description: HIV-1 Nef activates HCK via HCK SH3 domain displacement NOT via dephosphorylation or release from the SH2 domain
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: binds
Description: HIV-1 Nef binds HCK without affecting SH2-tail interaction and impacts local dynamics near the HCK active site; these changes are reversed in the presence of a selective inhibitor of the Nef-HCK complex
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: binds
Description: The PXXP motif (65-82) and C-terminal proline residues 147 and 150 of HIV-1 Nef interacts with the SH3 domain of Hck; the single amino acid residue 96 in the Hck SH3 domain determines its high affinity in binding to Nef
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: binds
Description: Structure analyses reveal that an RT loop region (residues 90-108) in the Hck SH3 domain binds to the PXXP motif (residues 69-78) of HIV-1 Nef; proline residues substituted by alanine in the PXXP motif abolish its binding to Hck
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: activates
Description: The Interaction of HIV-1 Nef with the SH3 domain of Hck regulates the effects of Nef on Hck tyrosine kinase activation
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: binds
Description: Hck binds to HIV-1 subtype B and E Nef proteins with equal affinity, but has weaker binding to HIV-2 subtype A Nef and no binding to HIV-2 subtype B Nef
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC