ID   KLH15_RAT               Reviewed;         604 AA.
AC   D3ZA50;
DT   18-JAN-2017, integrated into UniProtKB/Swiss-Prot.
DT   20-APR-2010, sequence version 1.
DT   03-AUG-2022, entry version 92.
DE   RecName: Full=Kelch-like protein 15;
GN   Name=Klhl15;
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;
RX   PubMed=15057822; DOI=10.1038/nature02426;
RA   Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA   Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA   Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA   Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA   Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA   Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA   Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA   Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA   Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA   Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA   Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA   Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA   Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA   Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA   Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA   Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA   Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA   Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA   Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA   Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA   Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA   Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA   Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA   Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA   Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA   Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA   Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA   Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA   Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA   Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA   Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA   Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA   Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA   Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA   Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA   Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA   Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA   Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA   Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA   Mockrin S., Collins F.S.;
RT   "Genome sequence of the Brown Norway rat yields insights into mammalian
RT   evolution.";
RL   Nature 428:493-521(2004).
RN   [2]
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   [3]
RP   TISSUE SPECIFICITY.
RX   PubMed=23135275; DOI=10.1074/jbc.m112.420281;
RA   Oberg E.A., Nifoussi S.K., Gingras A.C., Strack S.;
RT   "Selective proteasomal degradation of the B'beta subunit of protein
RT   phosphatase 2A by the E3 ubiquitin ligase adaptor Kelch-like 15.";
RL   J. Biol. Chem. 287:43378-43389(2012).
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   -!- TISSUE SPECIFICITY: Widely expressed at the mRNA level, with the
CC       highest levels in lung, muscle, and spleen.
CC       {ECO:0000269|PubMed:23135275}.
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DR   EMBL; AABR07038874; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AABR07038875; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AABR07038876; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AABR07038877; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH473966; EDL96006.1; -; Genomic_DNA.
DR   RefSeq; NP_001101491.1; NM_001108021.1.
DR   RefSeq; XP_017457528.1; XM_017602039.1.
DR   RefSeq; XP_017457529.1; XM_017602040.1.
DR   RefSeq; XP_017457530.1; XM_017602041.1.
DR   RefSeq; XP_017457531.1; XM_017602042.1.
DR   RefSeq; XP_017457532.1; XM_017602043.1.
DR   RefSeq; XP_017457533.1; XM_017602044.1.
DR   RefSeq; XP_017457534.1; XM_017602045.1.
DR   AlphaFoldDB; D3ZA50; -.
DR   SMR; D3ZA50; -.
DR   STRING; 10116.ENSRNOP00000068396; -.
DR   PhosphoSitePlus; D3ZA50; -.
DR   PaxDb; D3ZA50; -.
DR   PRIDE; D3ZA50; -.
DR   Ensembl; ENSRNOT00000008558; ENSRNOP00000008558; ENSRNOG00000006515.
DR   GeneID; 314111; -.
DR   KEGG; rno:314111; -.
DR   CTD; 80311; -.
DR   RGD; 1563101; Klhl15.
DR   eggNOG; KOG4441; Eukaryota.
DR   GeneTree; ENSGT00940000159116; -.
DR   HOGENOM; CLU_004253_16_1_1; -.
DR   InParanoid; D3ZA50; -.
DR   OMA; PRHNSWL; -.
DR   OrthoDB; 250404at2759; -.
DR   PhylomeDB; D3ZA50; -.
DR   TreeFam; TF328485; -.
DR   UniPathway; UPA00143; -.
DR   PRO; PR:D3ZA50; -.
DR   Proteomes; UP000002494; Chromosome X.
DR   Proteomes; UP000234681; Chromosome x.
DR   Bgee; ENSRNOG00000006515; Expressed in testis and 18 other tissues.
DR   ExpressionAtlas; D3ZA50; baseline and differential.
DR   GO; GO:0031463; C:Cul3-RING ubiquitin ligase complex; IEA:Ensembl.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:2000042; P:negative regulation of double-strand break repair via homologous recombination; ISO:RGD.
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   Kelch repeat; Nucleus; Reference proteome; Repeat; Ubl conjugation pathway.
FT   CHAIN           1..604
FT                   /note="Kelch-like protein 15"
FT                   /id="PRO_0000438649"
FT   DOMAIN          31..98
FT                   /note="BTB"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
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"
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