Protein: Kelch domain-containing protein 10 (Q6PID8)
Organism: Homo sapiens (Human)
Function: Substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation. The C-degron recognized by the DesCEND pathway is usually a motif of less than ten residues and can be present in full-length proteins, truncated proteins or proteolytically cleaved forms. The CRL2(KLHDC10) complex specifically recognizes proteins with a proline-glycine (Pro-Gly) at the C-terminus, leading to their ubiquitination and degradation. Participates in the oxidative stress-induced cell death through MAP3K5 activation. Inhibits PPP5C phosphatase activity on MAP3K5. Acts as a regulator of necroptosis (By similarity).
Subcellular location: Nucleus {ECO:0000269|PubMed:23102700}. Cytoplasm {ECO:0000269|PubMed:23102700}.
Sequence: MSAAQGWDRNRRRGGGAAGAGGGGSGAGGGSGGSGGRGTGQLNRFVQLSGRPHLPGKKKIRWDPVRRRFIQSCPIIRIPNRFLRGHRPPPARSGHRCVADNTNLYVFGGYNPDYDESGGPDNEDYPLFRELWRYHFATGVWHQMGTDGYMPRELASMSLVLHGNNLLVFGGTGIPFGESNGNDVHVCNVKYKRWALLSCRGKKPSRIYGQAMAIINGSLYVFGGTTGYIYSTDLHKLDLNTREWTQLKPNNLSCDLPEERYRHEIAHDGQRIYILGGGTSWTAYSLNKIHAYNLETNAWEEIATKPHEKIGFPAARRCHSCVQIKNDVFICGGYNGEVILGDIWKLNLQTFQWVKLPATMPEPVYFHCAAVTPAGCMYIHGGVVNIHENKRTGSLFKIWLVVPSLLELAWEKLLAAFPNLANLSRTQLLHLGLTQGLIERLK
InterPro domains: - IPR006652: Kelch repeat type 1 (repeat) [271-374]
- IPR015915: Kelch-type beta-propeller (homologous_superfamily) [80-423]
- IPR052125: Kelch domain-containing protein 10 (family) [33-442]
Interaction partners: - Cullin-2
- Protein fem-1 homolog B
- Amyloid protein-binding protein 2
- Protein fem-1 homolog C
- Protein zer-1 homolog
- Kelch domain-containing protein 3
- Protein zyg-11 homolog B
- Protein fem-1 homolog A
- Kelch domain-containing protein 2
- Elongin-B
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0060090 (molecular adaptor activity), GO:0030674 (protein-macromolecule adaptor activity), GO:0003682 (chromatin binding), GO:0005515 (protein binding), GO:0140767 (enzyme-substrate adaptor activity), GO:1990756 (ubiquitin ligase-substrate adaptor activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0009987 (cellular process), GO:0065007 (biological regulation), GO:0050789 (regulation of biological process), GO:0044237 (cellular metabolic process), GO:0071704 (organic substance metabolic process), GO:0019222 (regulation of metabolic process), GO:0009056 (catabolic process), GO:0044238 (primary metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0050794 (regulation of cellular process), GO:0009894 (regulation of catabolic process), GO:0031323 (regulation of cellular metabolic process), GO:1901564 (organonitrogen compound metabolic process), GO:0019538 (protein metabolic process), GO:1901575 (organic substance catabolic process), GO:0044260 (cellular macromolecule metabolic process), GO:0043170 (macromolecule metabolic process), GO:0044248 (cellular catabolic process), GO:0009057 (macromolecule catabolic process), GO:1901565 (organonitrogen compound catabolic process), GO:0006508 (proteolysis), GO:0031329 (regulation of cellular catabolic process), GO:0044265 (cellular macromolecule catabolic process), GO:0030163 (protein catabolic process), GO:0043632 (modification-dependent macromolecule catabolic process), GO:0010498 (proteasomal protein catabolic process), GO:0051603 (proteolysis involved in protein catabolic process), GO:0019941 (modification-dependent protein catabolic process), GO:0043161 (proteasome-mediated ubiquitin-dependent protein catabolic process), GO:0006511 (ubiquitin-dependent protein catabolic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0032991 (protein-containing complex), GO:1902494 (catalytic complex), GO:0140535 (intracellular protein-containing complex), GO:1990234 (transferase complex), GO:0000151 (ubiquitin ligase complex), GO:0031461 (cullin-RING ubiquitin ligase complex), GO:0031462 (Cul2-RING ubiquitin ligase complex)