KLHDC2
entrez
23588
canonical
uniprot
Q9Y2U9
canonical
ensembl
ENSG00000165516
resolver
ensp
ENSP00000298307
resolver
ensp
ENSP00000786945
resolver
genesymbol
KLHDC2
resolver
genesymbol_syn
HCA33
resolver
hgnc
HGNC:20231
resolver
uniprot
B3KPF9
resolver
uniprot
Q6IAF0
resolver
uniprot
Q86TY9
resolver
uniprot_entry
KLDC2_HUMAN
resolver
uniprot_sec
B3KPF9
resolver
uniprot_sec
Q6IAF0
resolver
uniprot_sec
Q86TY9
resolver
amino_acid_sequence
MADGNEDLRADDLPGPAFESYESMELACPAERSGHVAVSDGRHMFVWGGYKSNQVRGLYDFYLPREELWIYNMETGRWKKINTEGDVPPSMSGSCAVCVDRVLYLFGGHHSRGNTNKFYMLDSRSTDRVLQWERIDCQGIPPSSKDKLGVWVYKNKLIFFGGYGYLPEDKVLGTFEFDETSFWNSSHPRGWNDHVHILDTETFTWSQPITTGKAPSPRAAHACATVGNRGFVFGGRYRDARMNDLHYLNLDTWEWNELIPQGICPVGRSWHSLTPVSSDHLFLFGGFTTDKQPLSDAWTYCISKNEWIQFNHPYTEKPRLWHTACASDEGEVIVFGGCANNLLVHHRAAHSNEILIFSVQPKSLVRLSLEAVICFKEMLANSWNCLPKHLLHSVNQRFGSNNTSGS
uniprot
proteins
function
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 (PubMed:29775578, PubMed:29779948, PubMed:30526872, PubMed:36805027, PubMed:38177675). 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 (PubMed:29775578, PubMed:29779948, PubMed:30526872). The CRL2(KLHDC2) complex specifically recognizes proteins with a diglycine (Gly-Gly) at the C-terminus, leading to their ubiquitination and degradation (PubMed:29775578, PubMed:29779948, PubMed:30526872, PubMed:36805027, PubMed:38177675). The CRL2(KLHDC2) complex mediates ubiquitination and degradation of truncated SELENOK and SELENOS selenoproteins produced by failed UGA/Sec decoding, which end with a diglycine (PubMed:26138980, PubMed:30526872, PubMed:36805027). The CRL2(KLHDC2) complex also recognizes proteolytically cleaved proteins ending with Gly-Gly, such as the N-terminal fragment of USP1, leading to their degradation (PubMed:29775578, PubMed:30526872, PubMed:36805027, PubMed:38177675). May also act as an indirect repressor of CREB3-mediated transcription by interfering with CREB3-DNA-binding (PubMed:11384994). {ECO:0000269|PubMed:11384994, ECO:0000269|PubMed:26138980, ECO:0000269|PubMed:29775578, ECO:0000269|PubMed:29779948, ECO:0000269|PubMed:30526872, ECO:0000269|PubMed:36805027, ECO:0000269|PubMed:38177675}.
uniprot
proteins
mass_dalton
46099
uniprot
proteins
mutagenesis
MUTAGEN 147; /note="K->A: Strongly impaired ability to recognize truncated SELENOK or cleaved USP1 with a diglycine (Gly-Gly) at the C-terminus."; /evidence="ECO:0000269|PubMed:30526872"; MUTAGEN 177; /note="F->A: Impairs oligomerization of KLHDC2-ELOB-ELOC complex; when associated with A-182 and A-183. Impairs oligomerization of KLHDC2-ELOB-ELOC complex; when associated with K-182 and A-183."; /evidence="ECO:0000269|PubMed:36805027"; MUTAGEN 182; /note="F->A: Impairs oligomerization of KLHDC2-ELOB-ELOC complex; when associated with A-177 and A-183."; /evidence="ECO:0000269|PubMed:36805027"; MUTAGEN 182; /note="F->K: Impairs oligomerization of KLHDC2-ELOB-ELOC complex; when associated with A-177 and A-183."; /evidence="ECO:0000269|PubMed:36805027"; MUTAGEN 183; /note="W->A: Impairs oligomerization of KLHDC2-ELOB-ELOC complex; when associated with A-177 and A-182. Impairs oligomerization of KLHDC2-ELOB-ELOC complex; when associated with A-177 and K-182."; /evidence="ECO:0000269|PubMed:36805027"; MUTAGEN 189; /note="R->A: Does not affect ability to recognize truncated SELENOK or cleaved USP1 with a diglycine (Gly-Gly) at the C-terminus."; /evidence="ECO:0000269|PubMed:30526872"; MUTAGEN 236; /note="R->A: Does not affect ability to recognize truncated SELENOK with a diglycine (Gly-Gly) at the C-terminus. Abolished ability to recognize cleaved USP1 with a diglycine (Gly-Gly) at the C-terminus."; /evidence="ECO:0000269|PubMed:30526872"; MUTAGEN 236; /note="R->E: Abolished ability to recognize truncated SELENOK with a diglycine (Gly-Gly) at the C-terminus."; /evidence="ECO:0000269|PubMed:30526872"; MUTAGEN 241; /note="R->A,L,E: Abolished ability to recognize truncated SELENOK or cleaved USP1 with a diglycine (Gly-Gly) at the C-terminus."; /evidence="ECO:0000269|PubMed:30526872"; MUTAGEN 241; /note="R->K: Does not affect ability to recognize truncated SELENOK with a diglycine (Gly-Gly) at the C-terminus. Abolished ability to recognize cleaved USP1 with a diglycine (Gly-Gly) at the C-terminus."; /evidence="ECO:0000269|PubMed:30526872"; MUTAGEN 269; /note="S->A: Does not affect ability to recognize truncated SELENOK with a diglycine (Gly-Gly) at the C-terminus."; /evidence="ECO:0000269|PubMed:30526872"; MUTAGEN 269; /note="S->E,L: Abolished ability to recognize truncated SELENOK with a diglycine (Gly-Gly) at the C-terminus."; /evidence="ECO:0000269|PubMed:30526872"; MUTAGEN 269; /note="S->E: Abolishes oligomerization of KLHDC2-ELOB-ELOC complex."; /evidence="ECO:0000269|PubMed:36805027"; MUTAGEN 373; /note="I->R: Impairs oligomerization of KLHDC2-ELOB-ELOC complex."; /evidence="ECO:0000269|PubMed:36805027"; MUTAGEN 401..406; /note="Missing: Abolishes oligomerization of KLHDC2-ELOB-ELOC complex."; /evidence="ECO:0000269|PubMed:36805027"; MUTAGEN 405..406; /note="GS->KK: Abolishes oligomerization of KLHDC2-ELOB-ELOC complex."; /evidence="ECO:0000269|PubMed:36805027"; MUTAGEN 406; /note="S->G: Promotes oligomerization of KLHDC2-ELOB-ELOC complex. Abolishes the activity of CRL2(KLHDC2) complex to ubiquitinate SELENOK."; /evidence="ECO:0000269|PubMed:36805027
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:29775578, ECO:0000269|PubMed:29779948, ECO:0000269|PubMed:30526872, ECO:0000269|PubMed:36805027, ECO:0000269|PubMed:38177675}.
uniprot
proteins
post_translational_modification
PTM: Autoubiquitinated by the CRL2(KLHDC2) E3 ligase complex. {ECO:0000269|PubMed:36805027}.
uniprot
proteins
pubmed
11384994
uniprot
proteins
pubmed
12097419
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16964437
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
26138980
uniprot
proteins
pubmed
29775578
uniprot
proteins
pubmed
29779948
uniprot
proteins
pubmed
30526872
uniprot
proteins
pubmed
36805027
uniprot
proteins
pubmed
38177675
uniprot
proteins
sequence_length
406
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11384994, ECO:0000269|PubMed:16964437}.
uniprot
proteins