{"gene":"KLHL2","run_date":"2026-06-10T02:59:49","timeline":{"discoveries":[{"year":2013,"finding":"KLHL2 interacts with all four WNK kinase isoforms (WNK1, WNK2, WNK3, WNK4) via co-immunoprecipitation, with direct interaction confirmed by fluorescence correlation spectroscopy. Co-expression of KLHL2 and Cullin3 decreased the abundance of WNK1, WNK3, and WNK4 in HEK293T cells, and KLHL2-Cullin3 promoted WNK4 ubiquitination both in cells and in an in vitro ubiquitination assay, indicating KLHL2 functions as a substrate adaptor for a CUL3-based E3 ubiquitin ligase complex targeting WNK kinases.","method":"Co-immunoprecipitation, fluorescence correlation spectroscopy, in vitro ubiquitination assay, HEK293T overexpression","journal":"Biochemical and biophysical research communications","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro ubiquitination assay plus reciprocal Co-IP plus FCS direct binding, multiple orthogonal methods in a single focused study","pmids":["23838290"],"is_preprint":false},{"year":2015,"finding":"Wild-type CUL3 facilitates KLHL2 degradation, and a disease-mutant CUL3 (FHHt-associated) degrades KLHL2 more rapidly. KLHL2 promoted degradation of wild-type WNK4 but not disease-mutant WNK4 protein in HEK293 cells, placing KLHL2 downstream of CUL3 and upstream of WNK4 in the FHHt pathway.","method":"HEK293 cell co-expression, protein abundance measurement, genetic epistasis using disease mutants","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean cell-based epistasis with disease mutants, single lab, two complementary approaches (KLHL2 degradation by CUL3 mutant; KLHL2 effect on WNK4 mutant)","pmids":["26607111"],"is_preprint":false},{"year":2017,"finding":"KLHL2 knockout mice show significantly increased WNK4 protein levels specifically in the renal medulla (but not cortex), demonstrating that KLHL2 is a physiological regulator of medullary WNK4 degradation in vivo. KLHL2 knockout did not increase OSR1/SPAK-NCC cascade phosphorylation, distinguishing its in vivo role from that of KLHL3.","method":"KLHL2 knockout mouse generation, renal fractionation, immunoblotting for WNK4 and phosphorylated NCC/SPAK/OSR1","journal":"Biochemical and biophysical research communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean knockout mouse with defined in vivo phenotype (medullary WNK4 accumulation) and negative control (no NCC cascade activation), replicating and extending cell-based findings","pmids":["28414128"],"is_preprint":false},{"year":2020,"finding":"KLHL2 physically interacts with uridine-cytidine kinase 1 (UCK1) and mediates its polyubiquitination at lysine 81 (K81), targeting UCK1 for proteasomal degradation. The deubiquitinase USP28 antagonizes this KLHL2-mediated ubiquitination of UCK1. ATM-mediated phosphorylation of USP28 causes its dissociation from the KLHL2-UCK1 complex, leading to UCK1 destabilization; conversely, ATM-mediated phosphorylation of UCK1 (induced by 5'-AZA) enhances KLHL2-UCK1 complex formation.","method":"Mass spectrometry, co-immunoprecipitation, ubiquitination assay with K81 site mutagenesis, knockdown/overexpression in AML cell lines and murine AML model","journal":"Theranostics","confidence":"High","confidence_rationale":"Tier 1 / Strong — mass spectrometry identification, site-specific mutagenesis (K81), Co-IP, in vitro and in vivo models, multiple orthogonal methods in single study","pmids":["31938050"],"is_preprint":false},{"year":2020,"finding":"KLHL2 interacts with ARHGEF7 via its Kelch domain and promotes ARHGEF7 polyubiquitination and proteasomal degradation. Loss of the Kelch domain abolishes both ARHGEF7 binding and downstream degradation activity.","method":"Co-immunoprecipitation, ubiquitination assay, Kelch domain deletion mutant, knockdown loss-of-function in renal carcinoma cell lines","journal":"American journal of cancer research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP, domain-deletion mutagenesis, and ubiquitination assay; single lab","pmids":["33163274"],"is_preprint":false}],"current_model":"KLHL2 (Mayven) functions as a substrate-recognition adaptor for a CUL3-based E3 ubiquitin ligase complex, directly binding WNK kinases (WNK1–4), UCK1, and ARHGEF7 via its Kelch domain and mediating their polyubiquitination and proteasomal degradation; in vivo, KLHL2 specifically controls WNK4 protein levels in the renal medulla, and its own stability is regulated by CUL3 (with disease-mutant CUL3 causing enhanced KLHL2 degradation), while the deubiquitinase USP28—modulated by ATM-dependent phosphorylation—counteracts KLHL2-driven ubiquitination of UCK1."},"narrative":{"mechanistic_narrative":"KLHL2 functions as a substrate-recognition adaptor for a CUL3-based E3 ubiquitin ligase complex, using its Kelch domain to capture specific substrates and direct their polyubiquitination and proteasomal degradation [PMID:23838290, PMID:33163274]. Its best-characterized substrates are the WNK kinases: KLHL2 directly binds all four WNK isoforms and, together with CUL3, drives WNK4 ubiquitination and degradation [PMID:23838290]. In vivo, this activity is physiologically selective — KLHL2-knockout mice accumulate WNK4 specifically in the renal medulla without activating the OSR1/SPAK-NCC phosphorylation cascade, distinguishing KLHL2's role from that of the paralog KLHL3 [PMID:28414128]. KLHL2 sits downstream of CUL3 in this pathway: wild-type CUL3 promotes KLHL2 turnover, and an FHHt-associated CUL3 mutant accelerates KLHL2 degradation, while KLHL2 degrades wild-type but not disease-mutant WNK4 [PMID:26607111]. Beyond the WNK axis, KLHL2 targets additional substrates through the same adaptor mechanism: it ubiquitinates UCK1 at lysine 81 for degradation — an activity antagonized by the deubiquitinase USP28 and tuned by ATM-dependent phosphorylation of both USP28 and UCK1 [PMID:31938050] — and it binds ARHGEF7 via its Kelch domain to promote its polyubiquitination and degradation, with Kelch-domain deletion abolishing both binding and degradation [PMID:33163274].","teleology":[{"year":2013,"claim":"Established that KLHL2 is a substrate adaptor for a CUL3 E3 ligase by identifying WNK kinases as its direct binding partners and degradation substrates, defining its core molecular activity.","evidence":"Co-IP, fluorescence correlation spectroscopy, and in vitro ubiquitination in HEK293T overexpression","pmids":["23838290"],"confidence":"High","gaps":["Demonstrated in overexpression systems rather than at endogenous levels","Functional consequence of WNK degradation on downstream signaling not addressed here"]},{"year":2015,"claim":"Placed KLHL2 within the FHHt pathway by showing CUL3 controls KLHL2 stability and that KLHL2 discriminates wild-type from disease-mutant WNK4, ordering the CUL3→KLHL2→WNK4 axis.","evidence":"HEK293 co-expression epistasis using FHHt-associated CUL3 and WNK4 disease mutants","pmids":["26607111"],"confidence":"Medium","gaps":["Based on cell-based overexpression with disease mutants, not patient tissue","Mechanism by which mutant CUL3 accelerates KLHL2 degradation not resolved"]},{"year":2017,"claim":"Confirmed KLHL2 as a physiological WNK4 regulator in vivo and defined its tissue specificity, distinguishing it functionally from KLHL3.","evidence":"KLHL2 knockout mouse with renal fractionation and immunoblotting for WNK4 and NCC/SPAK/OSR1 phosphorylation","pmids":["28414128"],"confidence":"High","gaps":["Medulla-specific restriction of the phenotype not mechanistically explained","Physiological output of medullary WNK4 accumulation on renal function not characterized"]},{"year":2020,"claim":"Expanded KLHL2's substrate range beyond WNK kinases and revealed a regulatory layer, showing site-specific UCK1 ubiquitination opposed by USP28 and modulated by ATM phosphorylation.","evidence":"Mass spectrometry, Co-IP, K81 site mutagenesis, and ubiquitination assays in AML cell lines and a murine AML model","pmids":["31938050"],"confidence":"High","gaps":["How ATM-dependent phosphorylation switches USP28/UCK1 association is not structurally defined","Whether the WNK and UCK1 substrate pathways are co-regulated is unknown"]},{"year":2020,"claim":"Identified ARHGEF7 as a further KLHL2 substrate and mapped substrate engagement to the Kelch domain, generalizing the adaptor mechanism across substrates.","evidence":"Co-IP, Kelch domain-deletion mutagenesis, and ubiquitination assay in renal carcinoma cell lines","pmids":["33163274"],"confidence":"Medium","gaps":["Single lab; reciprocal in vivo confirmation absent","Downstream consequences of ARHGEF7 degradation on cell behavior not fully defined"]},{"year":null,"claim":"How KLHL2 substrate selection is governed across tissues and how its activity is integrated with upstream signaling remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural model of the Kelch domain bound to any substrate","Determinants of medulla-restricted WNK4 regulation not identified","No unified picture linking the WNK, UCK1, and ARHGEF7 substrate programs"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[0,3,4]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,4]}],"localization":[],"pathway":[{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[0,3,4]}],"complexes":["CUL3 E3 ubiquitin ligase complex"],"partners":["CUL3","WNK1","WNK2","WNK3","WNK4","UCK1","USP28","ARHGEF7"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O95198","full_name":"Kelch-like protein 2","aliases":["Actin-binding protein Mayven"],"length_aa":593,"mass_kda":66.0,"function":"Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that mediates the ubiquitination of target proteins, such as NPTXR, WNK1, WNK3 and WNK4, leading most often to their proteasomal degradation (PubMed:23838290). The BCR(KLHL2) complex catalyzes ubiquitination and degradation of NPTXR (By similarity). Responsible for degradative ubiquitination of the WNK kinases WNK1, WNK3 and WNK4 (PubMed:23838290). Plays a role in the reorganization of the actin cytoskeleton (PubMed:10397770). Promotes growth of cell projections in oligodendrocyte precursors (PubMed:15715669)","subcellular_location":"Cytoplasm, cytoskeleton; Cell projection, ruffle; Cell projection; Cell projection, lamellipodium; Cytoplasm, cytosol","url":"https://www.uniprot.org/uniprotkb/O95198/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/KLHL2","classification":"Not Classified","n_dependent_lines":3,"n_total_lines":1208,"dependency_fraction":0.0024834437086092716},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/KLHL2","total_profiled":1310},"omim":[{"mim_id":"614522","title":"KELCH-LIKE 12; KLHL12","url":"https://www.omim.org/entry/614522"},{"mim_id":"611967","title":"KELCH-LIKE 8; KLHL8","url":"https://www.omim.org/entry/611967"},{"mim_id":"611201","title":"KELCH-LIKE 9; KLHL9","url":"https://www.omim.org/entry/611201"},{"mim_id":"608064","title":"KELCH-LIKE 5; KLHL5","url":"https://www.omim.org/entry/608064"},{"mim_id":"605775","title":"KELCH-LIKE 3; KLHL3","url":"https://www.omim.org/entry/605775"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Uncertain","locations":[{"location":"Nucleoplasm","reliability":"Uncertain"},{"location":"Vesicles","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"brain","ntpm":48.1}],"url":"https://www.proteinatlas.org/search/KLHL2"},"hgnc":{"alias_symbol":["MAV"],"prev_symbol":[]},"alphafold":{"accession":"O95198","domains":[{"cath_id":"3.30.710.10","chopping":"37-152","consensus_level":"high","plddt":94.5423,"start":37,"end":152},{"cath_id":"2.120.10.80","chopping":"306-589","consensus_level":"medium","plddt":97.2956,"start":306,"end":589}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O95198","model_url":"https://alphafold.ebi.ac.uk/files/AF-O95198-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O95198-F1-predicted_aligned_error_v6.png","plddt_mean":92.31},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=KLHL2","jax_strain_url":"https://www.jax.org/strain/search?query=KLHL2"},"sequence":{"accession":"O95198","fasta_url":"https://rest.uniprot.org/uniprotkb/O95198.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O95198/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O95198"}},"corpus_meta":[{"pmid":"8519812","id":"PMC_8519812","title":"Contribution 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Co-expression of KLHL2 and Cullin3 decreased the abundance of WNK1, WNK3, and WNK4 in HEK293T cells, and KLHL2-Cullin3 promoted WNK4 ubiquitination both in cells and in an in vitro ubiquitination assay, indicating KLHL2 functions as a substrate adaptor for a CUL3-based E3 ubiquitin ligase complex targeting WNK kinases.\",\n      \"method\": \"Co-immunoprecipitation, fluorescence correlation spectroscopy, in vitro ubiquitination assay, HEK293T overexpression\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro ubiquitination assay plus reciprocal Co-IP plus FCS direct binding, multiple orthogonal methods in a single focused study\",\n      \"pmids\": [\"23838290\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Wild-type CUL3 facilitates KLHL2 degradation, and a disease-mutant CUL3 (FHHt-associated) degrades KLHL2 more rapidly. KLHL2 promoted degradation of wild-type WNK4 but not disease-mutant WNK4 protein in HEK293 cells, placing KLHL2 downstream of CUL3 and upstream of WNK4 in the FHHt pathway.\",\n      \"method\": \"HEK293 cell co-expression, protein abundance measurement, genetic epistasis using disease mutants\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean cell-based epistasis with disease mutants, single lab, two complementary approaches (KLHL2 degradation by CUL3 mutant; KLHL2 effect on WNK4 mutant)\",\n      \"pmids\": [\"26607111\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"KLHL2 knockout mice show significantly increased WNK4 protein levels specifically in the renal medulla (but not cortex), demonstrating that KLHL2 is a physiological regulator of medullary WNK4 degradation in vivo. KLHL2 knockout did not increase OSR1/SPAK-NCC cascade phosphorylation, distinguishing its in vivo role from that of KLHL3.\",\n      \"method\": \"KLHL2 knockout mouse generation, renal fractionation, immunoblotting for WNK4 and phosphorylated NCC/SPAK/OSR1\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean knockout mouse with defined in vivo phenotype (medullary WNK4 accumulation) and negative control (no NCC cascade activation), replicating and extending cell-based findings\",\n      \"pmids\": [\"28414128\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"KLHL2 physically interacts with uridine-cytidine kinase 1 (UCK1) and mediates its polyubiquitination at lysine 81 (K81), targeting UCK1 for proteasomal degradation. The deubiquitinase USP28 antagonizes this KLHL2-mediated ubiquitination of UCK1. ATM-mediated phosphorylation of USP28 causes its dissociation from the KLHL2-UCK1 complex, leading to UCK1 destabilization; conversely, ATM-mediated phosphorylation of UCK1 (induced by 5'-AZA) enhances KLHL2-UCK1 complex formation.\",\n      \"method\": \"Mass spectrometry, co-immunoprecipitation, ubiquitination assay with K81 site mutagenesis, knockdown/overexpression in AML cell lines and murine AML model\",\n      \"journal\": \"Theranostics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — mass spectrometry identification, site-specific mutagenesis (K81), Co-IP, in vitro and in vivo models, multiple orthogonal methods in single study\",\n      \"pmids\": [\"31938050\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"KLHL2 interacts with ARHGEF7 via its Kelch domain and promotes ARHGEF7 polyubiquitination and proteasomal degradation. Loss of the Kelch domain abolishes both ARHGEF7 binding and downstream degradation activity.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assay, Kelch domain deletion mutant, knockdown loss-of-function in renal carcinoma cell lines\",\n      \"journal\": \"American journal of cancer research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP, domain-deletion mutagenesis, and ubiquitination assay; single lab\",\n      \"pmids\": [\"33163274\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"KLHL2 (Mayven) functions as a substrate-recognition adaptor for a CUL3-based E3 ubiquitin ligase complex, directly binding WNK kinases (WNK1–4), UCK1, and ARHGEF7 via its Kelch domain and mediating their polyubiquitination and proteasomal degradation; in vivo, KLHL2 specifically controls WNK4 protein levels in the renal medulla, and its own stability is regulated by CUL3 (with disease-mutant CUL3 causing enhanced KLHL2 degradation), while the deubiquitinase USP28—modulated by ATM-dependent phosphorylation—counteracts KLHL2-driven ubiquitination of UCK1.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"KLHL2 functions as a substrate-recognition adaptor for a CUL3-based E3 ubiquitin ligase complex, using its Kelch domain to capture specific substrates and direct their polyubiquitination and proteasomal degradation [#0, #4]. Its best-characterized substrates are the WNK kinases: KLHL2 directly binds all four WNK isoforms and, together with CUL3, drives WNK4 ubiquitination and degradation [#0]. In vivo, this activity is physiologically selective — KLHL2-knockout mice accumulate WNK4 specifically in the renal medulla without activating the OSR1/SPAK-NCC phosphorylation cascade, distinguishing KLHL2's role from that of the paralog KLHL3 [#2]. KLHL2 sits downstream of CUL3 in this pathway: wild-type CUL3 promotes KLHL2 turnover, and an FHHt-associated CUL3 mutant accelerates KLHL2 degradation, while KLHL2 degrades wild-type but not disease-mutant WNK4 [#1]. Beyond the WNK axis, KLHL2 targets additional substrates through the same adaptor mechanism: it ubiquitinates UCK1 at lysine 81 for degradation — an activity antagonized by the deubiquitinase USP28 and tuned by ATM-dependent phosphorylation of both USP28 and UCK1 [#3] — and it binds ARHGEF7 via its Kelch domain to promote its polyubiquitination and degradation, with Kelch-domain deletion abolishing both binding and degradation [#4].\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"Established that KLHL2 is a substrate adaptor for a CUL3 E3 ligase by identifying WNK kinases as its direct binding partners and degradation substrates, defining its core molecular activity.\",\n      \"evidence\": \"Co-IP, fluorescence correlation spectroscopy, and in vitro ubiquitination in HEK293T overexpression\",\n      \"pmids\": [\n        \"23838290\"\n      ],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Demonstrated in overexpression systems rather than at endogenous levels\",\n        \"Functional consequence of WNK degradation on downstream signaling not addressed here\"\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Placed KLHL2 within the FHHt pathway by showing CUL3 controls KLHL2 stability and that KLHL2 discriminates wild-type from disease-mutant WNK4, ordering the CUL3→KLHL2→WNK4 axis.\",\n      \"evidence\": \"HEK293 co-expression epistasis using FHHt-associated CUL3 and WNK4 disease mutants\",\n      \"pmids\": [\n        \"26607111\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Based on cell-based overexpression with disease mutants, not patient tissue\",\n        \"Mechanism by which mutant CUL3 accelerates KLHL2 degradation not resolved\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Confirmed KLHL2 as a physiological WNK4 regulator in vivo and defined its tissue specificity, distinguishing it functionally from KLHL3.\",\n      \"evidence\": \"KLHL2 knockout mouse with renal fractionation and immunoblotting for WNK4 and NCC/SPAK/OSR1 phosphorylation\",\n      \"pmids\": [\n        \"28414128\"\n      ],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Medulla-specific restriction of the phenotype not mechanistically explained\",\n        \"Physiological output of medullary WNK4 accumulation on renal function not characterized\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Expanded KLHL2's substrate range beyond WNK kinases and revealed a regulatory layer, showing site-specific UCK1 ubiquitination opposed by USP28 and modulated by ATM phosphorylation.\",\n      \"evidence\": \"Mass spectrometry, Co-IP, K81 site mutagenesis, and ubiquitination assays in AML cell lines and a murine AML model\",\n      \"pmids\": [\n        \"31938050\"\n      ],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"How ATM-dependent phosphorylation switches USP28/UCK1 association is not structurally defined\",\n        \"Whether the WNK and UCK1 substrate pathways are co-regulated is unknown\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Identified ARHGEF7 as a further KLHL2 substrate and mapped substrate engagement to the Kelch domain, generalizing the adaptor mechanism across substrates.\",\n      \"evidence\": \"Co-IP, Kelch domain-deletion mutagenesis, and ubiquitination assay in renal carcinoma cell lines\",\n      \"pmids\": [\n        \"33163274\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single lab; reciprocal in vivo confirmation absent\",\n        \"Downstream consequences of ARHGEF7 degradation on cell behavior not fully defined\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How KLHL2 substrate selection is governed across tissues and how its activity is integrated with upstream signaling remains unresolved.\",\n      \"evidence\": null,\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structural model of the Kelch domain bound to any substrate\",\n        \"Determinants of medulla-restricted WNK4 regulation not identified\",\n        \"No unified picture linking the WNK, UCK1, and ARHGEF7 substrate programs\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\n        \"term_id\": \"GO:0140096\",\n        \"supporting_discovery_ids\": [\n          0,\n          3,\n          4\n        ]\n      },\n      {\n        \"term_id\": \"GO:0060090\",\n        \"supporting_discovery_ids\": [\n          0,\n          4\n        ]\n      }\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\n        \"term_id\": \"R-HSA-392499\",\n        \"supporting_discovery_ids\": [\n          0,\n          3,\n          4\n        ]\n      }\n    ],\n    \"complexes\": [\n      \"CUL3 E3 ubiquitin ligase complex\"\n    ],\n    \"partners\": [\n      \"CUL3\",\n      \"WNK1\",\n      \"WNK2\",\n      \"WNK3\",\n      \"WNK4\",\n      \"UCK1\",\n      \"USP28\",\n      \"ARHGEF7\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}