KLH15_MOUSE
ID KLH15_MOUSE Reviewed; 604 AA.
AC A2AAX3; Q3TEP6; Q8K1Y4;
DT 18-JAN-2017, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 1.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Kelch-like protein 15;
GN Name=Klhl15;
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 2 AND 3).
RC STRAIN=C57BL/6J; TISSUE=Embryonic head, and Thymus;
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 GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC STRAIN=FVB/N; TISSUE=Brain, and Mammary cancer;
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).
CC -!- FUNCTION: Substrate-specific adapter for CUL3 E3 ubiquitin-protein
CC ligase complex. Acts as an adapter for CUL3 to target the
CC serine/threonine-protein phosphatase 2A (PP2A) subunit PPP2R5B for
CC ubiquitination and subsequent proteasomal degradation, thus promoting
CC exchange with other regulatory subunits and regulating PP2A holoenzyme
CC composition. Acts as an adapter for CUL3 to target the DNA-end
CC resection factor RBBP8/CtIP for ubiquitination and subsequent
CC proteasomal degradation. Through the regulation of RBBP8/CtIP protein
CC turnover, plays a key role in DNA damage response, favoring DNA double-
CC strand repair through error-prone non-homologous end joining (NHEJ)
CC over error-free, RBBP8-mediated homologous recombination (HR).
CC {ECO:0000250|UniProtKB:Q96M94}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Homodimer. Dimerization does not affect PPP2R5B-binding, but
CC is required for its proteasomal degradation. Interacts with CUL3.
CC Directly interacts with PPP2R5B; this interaction leads to PPP2R5B
CC proteasomal degradation. Interacts with RBBP8/CtIP; this interaction
CC leads to RBBP8 proteasomal degradation. {ECO:0000250|UniProtKB:Q96M94}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q96M94}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=A2AAX3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A2AAX3-2; Sequence=VSP_058696, VSP_058698;
CC Name=3;
CC IsoId=A2AAX3-3; Sequence=VSP_058695, VSP_058697;
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DR EMBL; AK081546; BAC38253.1; -; mRNA.
DR EMBL; AK169500; BAE41202.1; -; mRNA.
DR EMBL; AL646049; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466637; EDL29751.1; -; Genomic_DNA.
DR EMBL; BC036978; AAH36978.1; -; mRNA.
DR EMBL; BC141165; AAI41166.1; -; mRNA.
DR CCDS; CCDS30278.1; -. [A2AAX3-1]
DR CCDS; CCDS30279.1; -. [A2AAX3-2]
DR CCDS; CCDS41062.1; -. [A2AAX3-3]
DR RefSeq; NP_001034148.1; NM_001039059.1. [A2AAX3-3]
DR RefSeq; NP_001034149.1; NM_001039060.1. [A2AAX3-2]
DR RefSeq; NP_001034150.1; NM_001039061.1. [A2AAX3-1]
DR RefSeq; NP_694805.1; NM_153165.2. [A2AAX3-3]
DR RefSeq; XP_006528049.1; XM_006527986.3. [A2AAX3-1]
DR RefSeq; XP_006528050.1; XM_006527987.2. [A2AAX3-1]
DR RefSeq; XP_006528051.1; XM_006527988.3. [A2AAX3-1]
DR RefSeq; XP_006528052.1; XM_006527989.3. [A2AAX3-1]
DR RefSeq; XP_006528053.1; XM_006527990.3. [A2AAX3-1]
DR RefSeq; XP_006528054.1; XM_006527991.3. [A2AAX3-3]
DR RefSeq; XP_011245883.1; XM_011247581.1. [A2AAX3-1]
DR AlphaFoldDB; A2AAX3; -.
DR SMR; A2AAX3; -.
DR STRING; 10090.ENSMUSP00000094097; -.
DR iPTMnet; A2AAX3; -.
DR PhosphoSitePlus; A2AAX3; -.
DR EPD; A2AAX3; -.
DR PaxDb; A2AAX3; -.
DR PRIDE; A2AAX3; -.
DR ProteomicsDB; 263653; -. [A2AAX3-1]
DR ProteomicsDB; 263654; -. [A2AAX3-2]
DR ProteomicsDB; 263655; -. [A2AAX3-3]
DR Antibodypedia; 24558; 94 antibodies from 26 providers.
DR DNASU; 236904; -.
DR Ensembl; ENSMUST00000096369; ENSMUSP00000094097; ENSMUSG00000043929. [A2AAX3-2]
DR Ensembl; ENSMUST00000113908; ENSMUSP00000109541; ENSMUSG00000043929. [A2AAX3-3]
DR Ensembl; ENSMUST00000113911; ENSMUSP00000109544; ENSMUSG00000043929. [A2AAX3-3]
DR Ensembl; ENSMUST00000113915; ENSMUSP00000109548; ENSMUSG00000043929. [A2AAX3-1]
DR Ensembl; ENSMUST00000113916; ENSMUSP00000109549; ENSMUSG00000043929. [A2AAX3-1]
DR Ensembl; ENSMUST00000170594; ENSMUSP00000129734; ENSMUSG00000043929. [A2AAX3-1]
DR GeneID; 236904; -.
DR KEGG; mmu:236904; -.
DR UCSC; uc009tte.1; mouse.
DR UCSC; uc009ttf.1; mouse.
DR UCSC; uc009tth.1; mouse. [A2AAX3-1]
DR CTD; 80311; -.
DR MGI; MGI:1923400; Klhl15.
DR VEuPathDB; HostDB:ENSMUSG00000043929; -.
DR eggNOG; KOG4441; Eukaryota.
DR GeneTree; ENSGT00940000159116; -.
DR HOGENOM; CLU_004253_16_1_1; -.
DR InParanoid; A2AAX3; -.
DR OMA; PRHNSWL; -.
DR OrthoDB; 250404at2759; -.
DR PhylomeDB; A2AAX3; -.
DR TreeFam; TF330633; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 236904; 2 hits in 71 CRISPR screens.
DR PRO; PR:A2AAX3; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; A2AAX3; protein.
DR Bgee; ENSMUSG00000043929; Expressed in spermatid and 227 other tissues.
DR ExpressionAtlas; A2AAX3; baseline and differential.
DR GO; GO:0031463; C:Cul3-RING ubiquitin ligase complex; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:2000042; P:negative regulation of double-strand break repair via homologous recombination; ISO:MGI.
DR GO; GO:0071630; P:nuclear protein quality control by the ubiquitin-proteasome system; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; 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; IPR030597; KLHL15.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR PANTHER; PTHR45632:SF12; PTHR45632:SF12; 1.
DR Pfam; PF07707; BACK; 1.
DR Pfam; PF00651; BTB; 1.
DR Pfam; PF01344; Kelch_1; 3.
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 2: Evidence at transcript level;
KW Alternative splicing; Kelch repeat; Nucleus; Reference proteome; Repeat;
KW Ubl conjugation pathway.
FT CHAIN 1..604
FT /note="Kelch-like protein 15"
FT /id="PRO_0000438648"
FT DOMAIN 31..98
FT /note="BTB"
FT DOMAIN 133..237
FT /note="BACK"
FT REPEAT 328..379
FT /note="Kelch 1"
FT REPEAT 381..426
FT /note="Kelch 2"
FT REPEAT 428..473
FT /note="Kelch 3"
FT REPEAT 489..542
FT /note="Kelch 4"
FT REPEAT 544..590
FT /note="Kelch 5"
FT VAR_SEQ 236..237
FT /note="VK -> TS (in isoform 3)"
FT /id="VSP_058695"
FT VAR_SEQ 237..248
FT /note="KTSEFYRYSRQL -> GTFESDRQDSSI (in isoform 2)"
FT /id="VSP_058696"
FT VAR_SEQ 238..604
FT /note="Missing (in isoform 3)"
FT /id="VSP_058697"
FT VAR_SEQ 249..604
FT /note="Missing (in isoform 2)"
FT /id="VSP_058698"
SQ SEQUENCE 604 AA; 69745 MW; 93BBD41C8577AD42 CRC64;
MAGDVEGFCS SIHDTSVSAG FRALYEEGLL LDVTLVIEDH QFQAHKALLA TQSDYFRIMF
TADMRERDQD KIHLKGLTAT GFSHVLQFMY YGTIELSMNT VHEILQAAMY VQLIEVVKFC
CSFLLAKICL ENCAEIMRLL DDFGVNIEGV REKLDAFLLD NFVPLMSRPD FLSYLSFEKL
MSYLDNDHLS RFPEIELYEA VQSWLRHDRR RWRHTDTIIQ NIRFCLMTPS SVFEKVKTSE
FYRYSRQLRY EVDQALNYFQ NVHQQPLLDM KSSRIRSAKP QTTVFRGMIG HSMVNSKILL
LKKPRVWWEL EGPQVPLRPD CLAIVNNFVF LLGGEELGPD GEFHASSKVF RYDPRQNSWL
RMADMSVPRS EFAVGVIGKF IYAVAGRTRD ETFYSTERYD ITNDKWEFVD PYPVNKYGHE
GTVLNNKLFI TGGITSSSTS KQVCVFDPSK EGTIEQRTRR TQVVTNCWEN KSKMNYARCF
HKMISYNGKL YVFGGVCVIL RASFESQGCP STEVYNPDTD QWTILASMPI GRSGHGVTVL
DKQIMVLGGL CYNGHYSDSI LTFDPDENKW KEDEYPRMPC KLDGLQVCNL HFPDYVLDEV
RRCN
