KLH22_RAT
ID KLH22_RAT Reviewed; 634 AA.
AC D3ZZC3; D4A9W5;
DT 10-AUG-2010, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 1.
DT 03-AUG-2022, entry version 70.
DE RecName: Full=Kelch-like protein 22 {ECO:0000305};
GN Name=Klhl22 {ECO:0000312|RGD:1306288};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-463; TYR-466 AND THR-475, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT regulation of aquaporin-2 phosphorylation at two sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
CC -!- FUNCTION: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3
CC ubiquitin ligase complex required for chromosome alignment and
CC localization of PLK1 at kinetochores. The BCR(KLHL22) ubiquitin ligase
CC complex mediates monoubiquitination of PLK1, leading to PLK1
CC dissociation from phosphoreceptor proteins and subsequent removal from
CC kinetochores, allowing silencing of the spindle assembly checkpoint
CC (SAC) and chromosome segregation. Monoubiquitination of PLK1 does not
CC lead to PLK1 degradation. The BCR(KLHL22) ubiquitin ligase complex is
CC also responsible for the amino acid-stimulated 'Lys-48'
CC polyubiquitination and proteasomal degradation of DEPDC5. Through the
CC degradation of DEPDC5, releases the GATOR1 complex-mediated inhibition
CC of the TORC1 pathway. It is therefore an amino acid-dependent activator
CC within the amino acid-sensing branch of the TORC1 pathway, indirectly
CC regulating different cellular processes including cell growth and
CC autophagy. {ECO:0000250|UniProtKB:Q53GT1}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q53GT1}.
CC -!- SUBUNIT: Component of the BCR(KLHL22) E3 ubiquitin ligase complex, at
CC least composed of CUL3, KLHL22 and RBX1. Interacts with PLK1. Interacts
CC with DEPDC5 (via DEP domain); the interaction depends on amino acid
CC availability. Interacts with YWHAE; required for the nuclear
CC localization of KLHL22 upon amino acid starvation.
CC {ECO:0000250|UniProtKB:Q53GT1}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q53GT1}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000250|UniProtKB:Q53GT1}.
CC Cytoplasm, cytoskeleton, spindle {ECO:0000250|UniProtKB:Q53GT1}.
CC Nucleus {ECO:0000250|UniProtKB:Q53GT1}. Lysosome
CC {ECO:0000250|UniProtKB:Q53GT1}. Note=Mainly cytoplasmic in prophase and
CC prometaphase. Associates with the mitotic spindle as the cells reach
CC chromosome bi-orientation. Localizes to the centrosomes shortly before
CC cells enter anaphase After anaphase onset, predominantly associates
CC with the polar microtubules connecting the 2 opposing centrosomes and
CC gradually diffuses into the cytoplasm during telophase. Localizes to
CC the nucleus upon amino acid starvation. Relocalizes to the cytosol and
CC associates with lysosomes when amino acids are available.
CC {ECO:0000250|UniProtKB:Q53GT1}.
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DR EMBL; CH473999; EDL77904.1; -; Genomic_DNA.
DR RefSeq; NP_001100549.1; NM_001107079.1.
DR RefSeq; XP_006248763.1; XM_006248701.3.
DR AlphaFoldDB; D3ZZC3; -.
DR SMR; D3ZZC3; -.
DR BioGRID; 257676; 1.
DR STRING; 10116.ENSRNOP00000063573; -.
DR iPTMnet; D3ZZC3; -.
DR PhosphoSitePlus; D3ZZC3; -.
DR jPOST; D3ZZC3; -.
DR PaxDb; D3ZZC3; -.
DR PeptideAtlas; D3ZZC3; -.
DR PRIDE; D3ZZC3; -.
DR GeneID; 303792; -.
DR KEGG; rno:303792; -.
DR CTD; 84861; -.
DR RGD; 1306288; Klhl22.
DR VEuPathDB; HostDB:ENSRNOG00000001878; -.
DR eggNOG; KOG4441; Eukaryota.
DR HOGENOM; CLU_004253_14_3_1; -.
DR InParanoid; D3ZZC3; -.
DR PhylomeDB; D3ZZC3; -.
DR Reactome; R-RNO-8951664; Neddylation.
DR Reactome; R-RNO-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR PRO; PR:D3ZZC3; -.
DR Proteomes; UP000002494; Chromosome 11.
DR Proteomes; UP000234681; Chromosome 11.
DR Bgee; ENSRNOG00000001878; Expressed in skeletal muscle tissue and 19 other tissues.
DR ExpressionAtlas; D3ZZC3; baseline and differential.
DR Genevisible; D3ZZC3; RN.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0031463; C:Cul3-RING ubiquitin ligase complex; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR GO; GO:0072686; C:mitotic spindle; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005827; C:polar microtubule; ISS:UniProtKB.
DR GO; GO:0071889; F:14-3-3 protein binding; ISO:RGD.
DR GO; GO:0051301; P:cell division; ISS:UniProtKB.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; ISO:RGD.
DR GO; GO:0071233; P:cellular response to leucine; ISS:UniProtKB.
DR GO; GO:0000070; P:mitotic sister chromatid segregation; ISS:UniProtKB.
DR GO; GO:0007094; P:mitotic spindle assembly checkpoint signaling; ISS:UniProtKB.
DR GO; GO:0010507; P:negative regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0030307; P:positive regulation of cell growth; ISS:UniProtKB.
DR GO; GO:1904263; P:positive regulation of TORC1 signaling; ISS:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0006513; P:protein monoubiquitination; ISS:UniProtKB.
DR Gene3D; 2.120.10.80; -; 1.
DR Gene3D; 3.30.710.10; -; 1.
DR InterPro; IPR011705; BACK.
DR InterPro; IPR017096; BTB-kelch_protein.
DR InterPro; IPR000210; BTB/POZ_dom.
DR InterPro; IPR015915; Kelch-typ_b-propeller.
DR InterPro; IPR006652; Kelch_1.
DR InterPro; IPR030575; KLHL22.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR PANTHER; PTHR45632:SF5; PTHR45632:SF5; 1.
DR Pfam; PF07707; BACK; 1.
DR Pfam; PF00651; BTB; 1.
DR Pfam; PF01344; Kelch_1; 2.
DR PIRSF; PIRSF037037; Kelch-like_protein_gigaxonin; 1.
DR SMART; SM00875; BACK; 1.
DR SMART; SM00225; BTB; 1.
DR SMART; SM00612; Kelch; 6.
DR SUPFAM; SSF117281; SSF117281; 1.
DR SUPFAM; SSF54695; SSF54695; 1.
DR PROSITE; PS50097; BTB; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cell cycle; Cell division; Cytoplasm; Cytoskeleton;
KW Kelch repeat; Lysosome; Mitosis; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Ubl conjugation pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q53GT1"
FT CHAIN 2..634
FT /note="Kelch-like protein 22"
FT /id="PRO_0000396635"
FT DOMAIN 50..117
FT /note="BTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT REPEAT 299..349
FT /note="Kelch 1"
FT REPEAT 350..399
FT /note="Kelch 2"
FT REPEAT 400..446
FT /note="Kelch 3"
FT REPEAT 448..493
FT /note="Kelch 4"
FT REPEAT 494..544
FT /note="Kelch 5"
FT REPEAT 545..593
FT /note="Kelch 6"
FT REGION 600..634
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 602..616
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q53GT1"
FT MOD_RES 463
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 466
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 475
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 605
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q53GT1"
SQ SEQUENCE 634 AA; 71774 MW; 4A2CFEDE40A4E8B3 CRC64;
MAEEQDFAQL CKLSTQPSHS HCVNNTYRST QHSQALLRGL LALRDSGILF DVVLVVEGRH
IEAHRILLAA SCDYFRGMFA GGLKEMEQEE VLIHGVSYNA MCQILHFIYT SELELSLSNV
QETLVAACQL QIPEIIHFCC DFLMSWVDEE NILDVYRLAE LFDLNRLTQQ LDTYILKNFV
AFSRTDKYRQ LPLEKVYSLL SSNRLEVSCE TEVYEGALLY HYSMEQVQAD QISLHEPPKL
LETVRFPLME AEVLQRLHDK LGPSPLRDTV ASALMYHRNE SLQPSLQGPH TELRSDFQCV
VGFGGIHSTP STILSDQAKY LNPLLGEWKH FTASLAPRMS NQGIAVLNNF VYLIGGDNNV
QGFRAESRCW RYDPRHNRWF QIQSLQQEHA DLCVCVVGKY IYAVAGRDYH NNLSAVERYD
PATNSWEYVA PLKKEVYAHA GTTLQGKMYI TCGRRGEDYL KETHCYDPGS NTWHTLADGP
VRRAWHGMAA LLDKLFVIGG SNNDAGYRRD VHQVACYSCT SRQWSSVCPL PAGHGEPGIA
VLDNRIYVLG GRSHNRGSRT GYVHIYDMEK DCWEEGPQLN NSISGLAACV LTLPRSLLHE
QPRGTPNRSQ ADADFASEVM SVSDWEEFDN SSED
