KLH22_MOUSE
ID KLH22_MOUSE Reviewed; 634 AA.
AC Q99JN2; D3YW27; Q8BT13;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Kelch-like protein 22 {ECO:0000305};
GN Name=Klhl22 {ECO:0000312|MGI:MGI:1337995};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Embryo;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PROTEIN SEQUENCE OF 2-12; 45-59; 66-76; 158-184; 196-204; 240-256; 268-294;
RP 320-329; 419-434; 495-508 AND 596-603, CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryonic fibroblast;
RA Bienvenut W.V., Sandilands E., Serrels B., Brunton V.G., Frame M.C.;
RL Submitted (FEB-2008) to UniProtKB.
RN [5]
RP FUNCTION.
RX PubMed=29769719; DOI=10.1038/s41586-018-0128-9;
RA Chen J., Ou Y., Yang Y., Li W., Xu Y., Xie Y., Liu Y.;
RT "KLHL22 activates amino-acid-dependent mTORC1 signalling to promote
RT tumorigenesis and ageing.";
RL Nature 557:585-589(2018).
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 (By similarity). The BCR(KLHL22) ubiquitin
CC ligase complex is also responsible for the amino acid-stimulated 'Lys-
CC 48' polyubiquitination and proteasomal degradation of DEPDC5. Through
CC the degradation of DEPDC5, releases the GATOR1 complex-mediated
CC inhibition of the TORC1 pathway. It is therefore an amino acid-
CC dependent activator within the amino acid-sensing branch of the TORC1
CC pathway, indirectly regulating different cellular processes including
CC cell growth and autophagy (PubMed:29769719).
CC {ECO:0000250|UniProtKB:Q53GT1, ECO:0000269|PubMed:29769719}.
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}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q99JN2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q99JN2-2; Sequence=VSP_019452;
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DR EMBL; AK028197; BAC25806.1; -; mRNA.
DR EMBL; AK143514; BAE25409.1; -; mRNA.
DR EMBL; AC087802; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC005800; AAH05800.1; -; mRNA.
DR CCDS; CCDS49783.1; -. [Q99JN2-1]
DR RefSeq; NP_663454.3; NM_145479.4. [Q99JN2-1]
DR RefSeq; XP_006522103.1; XM_006522040.3.
DR RefSeq; XP_006522104.1; XM_006522041.3.
DR AlphaFoldDB; Q99JN2; -.
DR SMR; Q99JN2; -.
DR BioGRID; 230228; 6.
DR IntAct; Q99JN2; 7.
DR MINT; Q99JN2; -.
DR STRING; 10090.ENSMUSP00000114115; -.
DR iPTMnet; Q99JN2; -.
DR PhosphoSitePlus; Q99JN2; -.
DR EPD; Q99JN2; -.
DR MaxQB; Q99JN2; -.
DR PaxDb; Q99JN2; -.
DR PRIDE; Q99JN2; -.
DR ProteomicsDB; 264847; -. [Q99JN2-1]
DR ProteomicsDB; 264848; -. [Q99JN2-2]
DR Antibodypedia; 34893; 188 antibodies from 28 providers.
DR DNASU; 224023; -.
DR Ensembl; ENSMUST00000120488; ENSMUSP00000112412; ENSMUSG00000022750. [Q99JN2-1]
DR Ensembl; ENSMUST00000165790; ENSMUSP00000127227; ENSMUSG00000022750. [Q99JN2-1]
DR GeneID; 224023; -.
DR KEGG; mmu:224023; -.
DR UCSC; uc007ymc.2; mouse. [Q99JN2-1]
DR CTD; 84861; -.
DR MGI; MGI:1337995; Klhl22.
DR VEuPathDB; HostDB:ENSMUSG00000022750; -.
DR eggNOG; KOG4441; Eukaryota.
DR GeneTree; ENSGT00940000159598; -.
DR HOGENOM; CLU_004253_14_3_1; -.
DR InParanoid; Q99JN2; -.
DR OMA; ERDCWEE; -.
DR OrthoDB; 250404at2759; -.
DR PhylomeDB; Q99JN2; -.
DR Reactome; R-MMU-8951664; Neddylation.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 224023; 0 hits in 74 CRISPR screens.
DR ChiTaRS; Klhl22; mouse.
DR PRO; PR:Q99JN2; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; Q99JN2; protein.
DR Bgee; ENSMUSG00000022750; Expressed in saccule of membranous labyrinth and 246 other tissues.
DR ExpressionAtlas; Q99JN2; baseline and differential.
DR Genevisible; Q99JN2; MM.
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:0045171; C:intercellular bridge; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005764; C:lysosome; ISO:MGI.
DR GO; GO:0015630; C:microtubule cytoskeleton; ISO:MGI.
DR GO; GO:0072686; C:mitotic spindle; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005827; C:polar microtubule; ISS:UniProtKB.
DR GO; GO:0071889; F:14-3-3 protein binding; ISO:MGI.
DR GO; GO:0051301; P:cell division; ISS:UniProtKB.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; IMP:UniProtKB.
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; IMP: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; Alternative splicing; Cell cycle; Cell division; Cytoplasm;
KW Cytoskeleton; Direct protein sequencing; Kelch repeat; Lysosome; Mitosis;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Ubl conjugation pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.4"
FT CHAIN 2..634
FT /note="Kelch-like protein 22"
FT /id="PRO_0000242156"
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 495..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:0000269|Ref.4"
FT MOD_RES 463
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:D3ZZC3"
FT MOD_RES 466
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:D3ZZC3"
FT MOD_RES 475
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:D3ZZC3"
FT MOD_RES 605
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q53GT1"
FT VAR_SEQ 634
FT /note="D -> STPSHSQSLWLPFCEPWSVW (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_019452"
FT CONFLICT 22
FT /note="C -> L (in Ref. 1; BAC25806)"
FT /evidence="ECO:0000305"
FT CONFLICT 428
FT /note="Y -> C (in Ref. 1; BAC25806)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 634 AA; 71687 MW; E34C21B5919620EB CRC64;
MAEEQDFAQL CRLPTQPSHS HCVNNTYRST QHSQALLRGL LALRDSGILF DVVLVVEGKH
IEAHRILLAA SCDYFRGMFA GGLKEMEQEE VLIHGVSYNA MCQILHFIYT SELELSLSNV
QETLVAACQL QIPEIIHFCC DFLMSWVDEE NILDVYRLAD LFDLNHLTQQ LDTYILKNFV
AFSRTDKYRQ LPLEKVYSLL SSNRLEVSCE TEVYEGALLY HYSLEQVQAD QISLNEPPKL
LETVRFPLME AEVLQRLHDK LGPSPLRDTV ASALMYHRNE ILQPSLQGPQ TELRSDFQCV
VGFGGIHSTP STILSDQAKY LNPLLGEWKH FTASLAPRMS NQGIAVLNNF VYLIGGDNNV
QGFRAESRCW RYDPRHNRWF QIQSLQQEHA DLCVCVVGKY IYAVAGRDYH NDLSAVERYD
PATNSWDYVA PLKKEVYAHA GTTLQGKMYI TCGRRGEDYL KETHCYDPGS NTWHTLADGP
VRRAWHGMAA LLDKLFVIGG SNNDAGYRRD VHQVACYSCT SRQWSSVCPL PAGHGEPGIA
VLDSRIYVLG GRSHNRGSRT GYVHIYDMEK DCWEEGPQLN NSISGLAACV LTLPRSLLHE
QPRGTPNRSQ ADADFASEVM SVSDWEEFDN SSED
