KLH21_HUMAN
ID KLH21_HUMAN Reviewed; 597 AA.
AC Q9UJP4; B3KQP2; O75057; Q5SY26; Q5SY28; Q8N4I6; Q8NF10;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 18-MAR-2008, sequence version 4.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Kelch-like protein 21;
GN Name=KLHL21; Synonyms=KIAA0469;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=9455484; DOI=10.1093/dnares/4.5.345;
RA Seki N., Ohira M., Nagase T., Ishikawa K., Miyajima N., Nakajima D.,
RA Nomura N., Ohara O.;
RT "Characterization of cDNA clones in size-fractionated cDNA libraries from
RT human brain.";
RL DNA Res. 4:345-349(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Hippocampus, and Lung carcinoma;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 51-597 (ISOFORM 1).
RC TISSUE=Spleen;
RA Jikuya H., Takano J., Kikuno R., Nagase T., Ohara O.;
RT "The nucleotide sequence of a long cDNA clone isolated from human spleen.";
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP PROTEIN SEQUENCE OF 52-62; 99-122 AND 424-433 (ISOFORMS 1/2), PROTEIN
RP SEQUENCE OF 561-571 (ISOFORM 1), AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Hepatoma;
RA Bienvenut W.V., Dhillon A.S., Kolch W.;
RL Submitted (FEB-2008) to UniProtKB.
RN [8]
RP FUNCTION AS AN E3 UBIQUITIN-PROTEIN LIGASE, AND INTERACTION WITH CUL3.
RX PubMed=14528312; DOI=10.1038/ncb1056;
RA Furukawa M., He Y.J., Borchers C., Xiong Y.;
RT "Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin
RT ligases.";
RL Nat. Cell Biol. 5:1001-1007(2003).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN A BCR (BTB-CUL3-RBX1) E3
RP UBIQUITIN LIGASE COMPLEX, AND MUTAGENESIS OF 114-ASP--GLN-117.
RX PubMed=19995937; DOI=10.1083/jcb.200906117;
RA Maerki S., Olma M.H., Staubli T., Steigemann P., Gerlich D.W., Quadroni M.,
RA Sumara I., Peter M.;
RT "The Cul3-KLHL21 E3 ubiquitin ligase targets aurora B to midzone
RT microtubules in anaphase and is required for cytokinesis.";
RL J. Cell Biol. 187:791-800(2009).
CC -!- FUNCTION: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3
CC ubiquitin-protein ligase complex required for efficient chromosome
CC alignment and cytokinesis. The BCR(KLHL21) E3 ubiquitin ligase complex
CC regulates localization of the chromosomal passenger complex (CPC) from
CC chromosomes to the spindle midzone in anaphase and mediates the
CC ubiquitination of AURKB. Ubiquitination of AURKB by BCR(KLHL21) E3
CC ubiquitin ligase complex may not lead to its degradation by the
CC proteasome. {ECO:0000269|PubMed:14528312, ECO:0000269|PubMed:19995937}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Component of the BCR(KLHL21) E3 ubiquitin ligase complex, at
CC least composed of CUL3, KLHL21 and RBX1. {ECO:0000269|PubMed:19995937}.
CC -!- INTERACTION:
CC Q9UJP4; Q6P597-3: KLC3; NbExp=3; IntAct=EBI-8837113, EBI-12076930;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, spindle
CC {ECO:0000269|PubMed:19995937}. Note=Localizes to the spindle midzone
CC and targets CUL3 to this region.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9UJP4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UJP4-2; Sequence=VSP_032563, VSP_032564;
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA32314.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB007938; BAA32314.2; ALT_INIT; mRNA.
DR EMBL; AK075305; BAG52104.1; -; mRNA.
DR EMBL; AL591866; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471130; EAW71559.1; -; Genomic_DNA.
DR EMBL; BC034039; AAH34039.3; -; mRNA.
DR EMBL; BC091648; AAH91648.1; -; mRNA.
DR EMBL; AK090472; BAC03453.1; -; mRNA.
DR CCDS; CCDS30575.1; -. [Q9UJP4-1]
DR RefSeq; NP_055666.2; NM_014851.3. [Q9UJP4-1]
DR AlphaFoldDB; Q9UJP4; -.
DR SMR; Q9UJP4; -.
DR BioGRID; 115232; 149.
DR IntAct; Q9UJP4; 14.
DR MINT; Q9UJP4; -.
DR STRING; 9606.ENSP00000366886; -.
DR iPTMnet; Q9UJP4; -.
DR PhosphoSitePlus; Q9UJP4; -.
DR BioMuta; KLHL21; -.
DR DMDM; 172044863; -.
DR EPD; Q9UJP4; -.
DR jPOST; Q9UJP4; -.
DR MassIVE; Q9UJP4; -.
DR MaxQB; Q9UJP4; -.
DR PaxDb; Q9UJP4; -.
DR PeptideAtlas; Q9UJP4; -.
DR PRIDE; Q9UJP4; -.
DR ProteomicsDB; 84635; -. [Q9UJP4-1]
DR ProteomicsDB; 84636; -. [Q9UJP4-2]
DR Antibodypedia; 46561; 95 antibodies from 26 providers.
DR DNASU; 9903; -.
DR Ensembl; ENST00000377658.8; ENSP00000366886.4; ENSG00000162413.17. [Q9UJP4-1]
DR Ensembl; ENST00000377663.3; ENSP00000366891.3; ENSG00000162413.17. [Q9UJP4-2]
DR GeneID; 9903; -.
DR KEGG; hsa:9903; -.
DR MANE-Select; ENST00000377658.8; ENSP00000366886.4; NM_014851.4; NP_055666.2.
DR UCSC; uc001anz.2; human. [Q9UJP4-1]
DR CTD; 9903; -.
DR DisGeNET; 9903; -.
DR GeneCards; KLHL21; -.
DR HGNC; HGNC:29041; KLHL21.
DR HPA; ENSG00000162413; Tissue enhanced (skeletal).
DR MIM; 616262; gene.
DR neXtProt; NX_Q9UJP4; -.
DR OpenTargets; ENSG00000162413; -.
DR PharmGKB; PA134989246; -.
DR VEuPathDB; HostDB:ENSG00000162413; -.
DR eggNOG; KOG4441; Eukaryota.
DR GeneTree; ENSGT00940000158631; -.
DR HOGENOM; CLU_004253_14_6_1; -.
DR InParanoid; Q9UJP4; -.
DR OMA; TWSVVGQ; -.
DR OrthoDB; 743142at2759; -.
DR PhylomeDB; Q9UJP4; -.
DR TreeFam; TF329218; -.
DR PathwayCommons; Q9UJP4; -.
DR Reactome; R-HSA-8951664; Neddylation.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q9UJP4; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 9903; 10 hits in 1115 CRISPR screens.
DR ChiTaRS; KLHL21; human.
DR GenomeRNAi; 9903; -.
DR Pharos; Q9UJP4; Tbio.
DR PRO; PR:Q9UJP4; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9UJP4; protein.
DR Bgee; ENSG00000162413; Expressed in gastrocnemius and 200 other tissues.
DR ExpressionAtlas; Q9UJP4; baseline and differential.
DR Genevisible; Q9UJP4; HS.
DR GO; GO:0031463; C:Cul3-RING ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005827; C:polar microtubule; IDA:UniProtKB.
DR GO; GO:0097602; F:cullin family protein binding; IPI:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0035853; P:chromosome passenger complex localization to spindle midzone; IMP:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0032465; P:regulation of cytokinesis; IMP: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; IPR030577; KLHL21.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR PANTHER; PTHR24412:SF255; PTHR24412:SF255; 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; 5.
DR SUPFAM; SSF117281; SSF117281; 1.
DR SUPFAM; SSF54695; SSF54695; 1.
DR PROSITE; PS50097; BTB; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell cycle; Cell division; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Kelch repeat; Mitosis; Reference proteome;
KW Repeat; Ubl conjugation pathway.
FT CHAIN 1..597
FT /note="Kelch-like protein 21"
FT /id="PRO_0000119125"
FT DOMAIN 35..103
FT /note="BTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT DOMAIN 138..239
FT /note="BACK"
FT REPEAT 287..335
FT /note="Kelch 1"
FT REPEAT 336..382
FT /note="Kelch 2"
FT REPEAT 384..422
FT /note="Kelch 3"
FT REPEAT 423..470
FT /note="Kelch 4"
FT REPEAT 472..512
FT /note="Kelch 5"
FT REPEAT 513..560
FT /note="Kelch 6"
FT REGION 570..597
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 576..597
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 502..539
FT /note="HVGGSLAVLGGKLYVSGGYDNTFELSDVVEAYDPETRA -> NFQAGQHWKH
FT RLVLILQPKCHRDECLGSTAMMGGSHLN (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9455484"
FT /id="VSP_032563"
FT VAR_SEQ 540..597
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9455484"
FT /id="VSP_032564"
FT MUTAGEN 114..117
FT /note="DLLQ->AALA: Abolishes interaction with CUL3."
FT /evidence="ECO:0000269|PubMed:19995937"
FT CONFLICT 183
FT /note="R -> C (in Ref. 6; BAC03453)"
FT /evidence="ECO:0000305"
FT CONFLICT 380
FT /note="L -> P (in Ref. 2; BAG52104)"
FT /evidence="ECO:0000305"
FT CONFLICT Q9UJP4-2:534
FT /note="G -> D (in Ref. 1; BAA32314)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 597 AA; 66617 MW; D3E682609F284645 CRC64;
MERPAPLAVL PFSDPAHALS LLRGLSQLRA ERKFLDVTLE AAGGRDFPAH RAVLAAASPY
FRAMFAGQLR ESRAERVRLH GVPPDMLQLL LDFSYTGRVA VSGDNAEPLL RAADLLQFPA
VKEACGAFLQ QQLDLANCLD MQDFAEAFSC SGLASAAQRF ILRHVGELGA EQLERLPLAR
LLRYLRDDGL CVPKEEAAYQ LALRWVRADP PRRAAHWPQL LEAVRLPFVR RFYLLAHVEA
EPLVARCPPC LRLLREARDF QAARYDRHDR GPCPRMRPRP STGLAEILVL VGGCDQDCDE
LVTVDCYNPQ TGQWRYLAEF PDHLGGGYSI VALGNDIYVT GGSDGSRLYD CVWRYNSSVN
EWAEVAPMLK AREYHSSSVL DGLLYVVAAD STERYDHTTD SWEALQPMTY PMDNCSTTAC
RGRLYAIGSL AGKETMVMQC YDPDTDLWSL VDCGQLPPWS FAPKTATLNG LMYFVRDDSA
EVDVYNPTRN EWDKIPSMNQ VHVGGSLAVL GGKLYVSGGY DNTFELSDVV EAYDPETRAW
SVVGRLPEPT FWHGSVSIFR QFMPQTFSGG RGFELDSGSD DMDPGRPRPP RDPDELH
