KLHL6
entrez
89857
canonical
uniprot
Q8WZ60
canonical
ensembl
ENSG00000172578
resolver
ensp
ENSP00000341342
resolver
enst
ENST00000341319
resolver
genesymbol
KLHL6
resolver
hgnc
HGNC:18653
resolver
uniprot
B2RB31
resolver
uniprot
D3DNS8
resolver
uniprot
Q8N5I1
resolver
uniprot
Q8N892
resolver
uniprot_entry
KLHL6_HUMAN
resolver
uniprot_sec
B2RB31
resolver
uniprot_sec
D3DNS8
resolver
uniprot_sec
Q8N5I1
resolver
uniprot_sec
Q8N892
resolver
amino_acid_sequence
MLMAGQRGAWTMGDVVEKSLEGPLAPSTDEPSQKTGDLVEILNGEKVKFDDAGLSLILQNGLETLRMENALTDVILCVDIQEFSCHRVVLAAASNYFRAMFCNDLKEKYEKRIIIKGVDAETMHTLLDYTYTSKALITKQNVQRVLEAANLFQFLRMVDACASFLTEALNPENCVGILRLADTHSLDSLKKQVQSYIIQNFVQILNSEEFLDLPVDTLHHILKSDDLYVTEEAQVFETVMSWVRHKPSERLCLLPYVLENVRLPLLDPWYFVETVEADPLIRQCPEVFPLLQEARMYHLSGNEIISERTKPRMHEFQSEVFMIIGGCTKDERFVAEVTCLDPLRRSRLEVAKLPLTEHELESENKKWVEFACVTLKNEVYISGGKETQHDVWKYNSSINKWIQIEYLNIGRWRHKMVVLGGKVYVIGGFDGLQRINNVETYDPFHNCWSEAAPLLVHVSSFAATSHKKKLYVIGGGPNGKLATDKTQCYDPSTNKWSLKAAMPVEAKCINAVSFRDRIYVVGGAMRALYAYSPLEDSWCLVTQLSHERASCGIAPCNNRLYITGGRDEKNEVIATVLCWDPEAQKLTEECVLPRGVSHHGSVTIRKSYTHIRRIVPGAVSV
uniprot
proteins
function
FUNCTION: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a multifunctional regulator of B-cell receptor (BCR) signaling, germinal center formation, and T-cell function. Functions by mediating polyubiquitination of target proteins, leading to their proteasomal degradation. In B-cells, plays an essential role in BCR signaling and germinal center B-cell maturation. Targets the BCR signaling subunits CD79A and CD79B for ubiquitin-mediated degradation, thereby controlling surface BCR homeostasis (PubMed:38630892). Mediates polyubiquitination and degradation of the mRNA decay factor roquin-2/RC3H2, which in turn allows accumulation of TNFAIP3, a negative regulator of NF-kappa-B signaling, thereby providing feedback inhibition of BCR-induced NF-kappa-B activation (PubMed:29695787). In T-cells, acts as a dual negative regulator of T-cell exhaustion and mitochondrial dysfunction. Promotes 'Lys-48'-linked polyubiquitination and proteasomal degradation of the transcription factor TOX, thereby attenuating the transition of progenitor exhausted T-cells towards terminal exhaustion (PubMed:41535474). Also targets the mitochondrial phosphatase PGAM5 for degradation, thereby preventing excessive PGAM5-mediated dephosphorylation and activation of DRP1, which would otherwise drive pathological mitochondrial fission (PubMed:41535474). Through these mechanisms, maintains mitochondrial fitness in T-cells during chronic antigen stimulation. {ECO:0000269|PubMed:29695787, ECO:0000269|PubMed:38630892, ECO:0000269|PubMed:41535474}.
uniprot
proteins
mass_dalton
70359
uniprot
proteins
mutagenesis
MUTAGEN 65; /note="L->P: Complete loss of interaction with CUL3."; /evidence="ECO:0000269|PubMed:38630892"; MUTAGEN 72; /note="T->R: Complete loss of interaction with CUL3."; /evidence="ECO:0000269|PubMed:29695787
uniprot
proteins
pubmed
12617994
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16641997
uniprot
proteins
pubmed
29695787
uniprot
proteins
pubmed
38630892
uniprot
proteins
pubmed
41535474
uniprot
proteins
sequence_length
621
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:38630892}.
uniprot
proteins