KLD10_MOUSE
ID KLD10_MOUSE Reviewed; 439 AA.
AC Q6PAR0; Q6A095; Q8BH94; Q8BPK7; Q8C3Q4; Q8C7G4; Q9CWF4;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Kelch domain-containing protein 10 {ECO:0000305};
GN Name=Klhdc10 {ECO:0000303|PubMed:23102700};
GN Synonyms=Kiaa0265 {ECO:0000303|PubMed:15368895};
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] (ISOFORM 2).
RC TISSUE=Spleen;
RX PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 11:205-218(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC STRAIN=C57BL/6J;
RC TISSUE=Embryonic lung, Embryonic stem cell, Eye, Liver tumor, and
RC Spinal cord;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 FUNCTION, INTERACTION WITH PPP5C, AND SUBCELLULAR LOCATION (ISOFORM 2).
RX PubMed=23102700; DOI=10.1016/j.molcel.2012.09.018;
RA Sekine Y., Hatanaka R., Watanabe T., Sono N., Iemura S., Natsume T.,
RA Kuranaga E., Miura M., Takeda K., Ichijo H.;
RT "The Kelch repeat protein KLHDC10 regulates oxidative stress-induced ASK1
RT activation by suppressing PP5.";
RL Mol. Cell 48:692-704(2012).
RN [5]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-13, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Embryo;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27631783; DOI=10.1371/journal.pone.0163118;
RA Yamaguchi N., Sekine S., Naguro I., Sekine Y., Ichijo H.;
RT "KLHDC10 deficiency protects mice against TNFalpha-induced systemic
RT inflammation.";
RL PLoS ONE 11:e0163118-e0163118(2016).
CC -!- FUNCTION: Substrate-recognition component of a Cul2-RING (CRL2) E3
CC ubiquitin-protein ligase complex of the DesCEND (destruction via C-end
CC degrons) pathway, which recognizes a C-degron located at the extreme C
CC terminus of target proteins, leading to their ubiquitination and
CC degradation (By similarity). The C-degron recognized by the DesCEND
CC pathway is usually a motif of less than ten residues and can be present
CC in full-length proteins, truncated proteins or proteolytically cleaved
CC forms (By similarity). The CRL2(KLHDC10) complex specifically
CC recognizes proteins with a proline-glycine (Pro-Gly) at the C-terminus,
CC leading to their ubiquitination and degradation (By similarity).
CC Participates in the oxidative stress-induced cell death through MAP3K5
CC activation (PubMed:23102700). Inhibits PPP5C phosphatase activity on
CC MAP3K5 (PubMed:23102700). Acts as a regulator of necroptosis
CC (PubMed:27631783). {ECO:0000250|UniProtKB:Q6PID8,
CC ECO:0000269|PubMed:23102700, ECO:0000269|PubMed:27631783}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q6PID8}.
CC -!- SUBUNIT: Component of a CRL2 E3 ubiquitin-protein ligase complex, also
CC named ECS (Elongin BC-CUL2/5-SOCS-box protein) complex, composed of
CC CUL2, Elongin BC (ELOB and ELOC), RBX1 and substrate-specific adapter
CC KLHDC10 (By similarity). Interacts (via the 6 Kelch repeats) with PPP5C
CC (PubMed:23102700). {ECO:0000250|UniProtKB:Q6PID8,
CC ECO:0000269|PubMed:23102700}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q6PID8}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q6PID8}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC {ECO:0000269|PubMed:23102700}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q6PAR0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6PAR0-2; Sequence=VSP_031486;
CC Name=3;
CC IsoId=Q6PAR0-3; Sequence=VSP_031485;
CC -!- DISRUPTION PHENOTYPE: No visible phenotype in normal conditions
CC (PubMed:27631783). Mice are protected against TNF-alpha-induced
CC systemic inflammation: they show a reduction in the inflammatory
CC response, but not in early systemic necroptosis (PubMed:27631783).
CC {ECO:0000269|PubMed:27631783}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB27179.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC35547.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAD32201.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK172923; BAD32201.1; ALT_INIT; mRNA.
DR EMBL; AK010783; BAB27179.1; ALT_INIT; mRNA.
DR EMBL; AK039732; BAC30430.1; -; mRNA.
DR EMBL; AK050289; BAC34168.1; -; mRNA.
DR EMBL; AK053834; BAC35547.1; ALT_FRAME; mRNA.
DR EMBL; AK085116; BAC39370.1; -; mRNA.
DR EMBL; AK085130; BAC39372.1; -; mRNA.
DR EMBL; BC060132; AAH60132.1; -; mRNA.
DR CCDS; CCDS19971.1; -. [Q6PAR0-1]
DR CCDS; CCDS80509.1; -. [Q6PAR0-2]
DR RefSeq; NP_001298016.1; NM_001311087.1. [Q6PAR0-2]
DR RefSeq; NP_084018.1; NM_029742.3. [Q6PAR0-1]
DR AlphaFoldDB; Q6PAR0; -.
DR SMR; Q6PAR0; -.
DR BioGRID; 218315; 2.
DR STRING; 10090.ENSMUSP00000069669; -.
DR iPTMnet; Q6PAR0; -.
DR PhosphoSitePlus; Q6PAR0; -.
DR EPD; Q6PAR0; -.
DR MaxQB; Q6PAR0; -.
DR PaxDb; Q6PAR0; -.
DR PeptideAtlas; Q6PAR0; -.
DR PRIDE; Q6PAR0; -.
DR ProteomicsDB; 264941; -. [Q6PAR0-1]
DR ProteomicsDB; 264942; -. [Q6PAR0-2]
DR ProteomicsDB; 264943; -. [Q6PAR0-3]
DR Antibodypedia; 17939; 24 antibodies from 11 providers.
DR DNASU; 76788; -.
DR Ensembl; ENSMUST00000068240; ENSMUSP00000064594; ENSMUSG00000029775. [Q6PAR0-2]
DR Ensembl; ENSMUST00000068259; ENSMUSP00000069669; ENSMUSG00000029775. [Q6PAR0-1]
DR Ensembl; ENSMUST00000144272; ENSMUSP00000145063; ENSMUSG00000029775. [Q6PAR0-3]
DR GeneID; 76788; -.
DR KEGG; mmu:76788; -.
DR UCSC; uc009bfe.1; mouse. [Q6PAR0-1]
DR UCSC; uc009bff.1; mouse. [Q6PAR0-2]
DR CTD; 23008; -.
DR MGI; MGI:1924038; Klhdc10.
DR VEuPathDB; HostDB:ENSMUSG00000029775; -.
DR eggNOG; KOG0379; Eukaryota.
DR GeneTree; ENSGT00940000155977; -.
DR HOGENOM; CLU_030914_0_0_1; -.
DR InParanoid; Q6PAR0; -.
DR OMA; HCDMPEE; -.
DR OrthoDB; 564212at2759; -.
DR PhylomeDB; Q6PAR0; -.
DR TreeFam; TF314081; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 76788; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Klhdc10; mouse.
DR PRO; PR:Q6PAR0; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q6PAR0; protein.
DR Bgee; ENSMUSG00000029775; Expressed in internal carotid artery and 223 other tissues.
DR ExpressionAtlas; Q6PAR0; baseline and differential.
DR Genevisible; Q6PAR0; MM.
DR GO; GO:0031462; C:Cul2-RING ubiquitin ligase complex; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:1990756; F:ubiquitin ligase-substrate adaptor activity; ISS:UniProtKB.
DR GO; GO:0032874; P:positive regulation of stress-activated MAPK cascade; IBA:GO_Central.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:0140627; P:ubiquitin-dependent protein catabolic process via the C-end degron rule pathway; ISS:UniProtKB.
DR Gene3D; 2.120.10.80; -; 2.
DR InterPro; IPR015915; Kelch-typ_b-propeller.
DR InterPro; IPR006652; Kelch_1.
DR Pfam; PF01344; Kelch_1; 1.
DR SMART; SM00612; Kelch; 2.
DR SUPFAM; SSF117281; SSF117281; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Kelch repeat; Methylation; Nucleus;
KW Reference proteome; Repeat; Ubl conjugation pathway.
FT CHAIN 1..439
FT /note="Kelch domain-containing protein 10"
FT /id="PRO_0000319437"
FT REPEAT 100..161
FT /note="Kelch 1"
FT REPEAT 163..214
FT /note="Kelch 2"
FT REPEAT 215..267
FT /note="Kelch 3"
FT REPEAT 268..316
FT /note="Kelch 4"
FT REPEAT 324..370
FT /note="Kelch 5"
FT REPEAT 373..416
FT /note="Kelch 6"
FT REGION 1..50
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 398..439
FT /note="Interaction with CUL2"
FT /evidence="ECO:0000250|UniProtKB:Q6PID8"
FT MOD_RES 13
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT VAR_SEQ 1..140
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_031485"
FT VAR_SEQ 53..81
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15368895,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_031486"
FT CONFLICT 12
FT /note="R -> W (in Ref. 2; BAC39372)"
FT /evidence="ECO:0000305"
FT CONFLICT 47
FT /note="G -> R (in Ref. 2; BAC35547)"
FT /evidence="ECO:0000305"
FT CONFLICT 266
FT /note="G -> R (in Ref. 2; BAC35547)"
FT /evidence="ECO:0000305"
FT CONFLICT 305
FT /note="E -> K (in Ref. 2; BAB27179)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 439 AA; 49012 MW; CC5BD6C28FFF40E6 CRC64;
MSAAQGWDRN RRRGGGAAGG ASGVSGAGAA GGGRGTGQLN RFVQLSGRPH LPGKKKIRWD
PVRRRFIQSC PIIRIPNRFL RGHRPPPARS GHRCVADNTN LYVFGGYNPD YDESGGPDNE
DYPLFRELWR YHFATGVWHQ MGTDGYMPRE LASMSLVLHG NNLLVFGGTG IPFGESNGND
VHVCNVKYKR WALLSCRGKR PSRIYGQAMA LINGSLYVFG GTTGYIYSTD LHKLDLNTMV
WTQLKPNNLS CDLPEERYRH EIAHDGQRIY ILGGGTSWTA YSLNKIHAYN LETNAWEEIA
TKPHEKIGFP AARRCHSCVQ IKNDVFICGG YNGEVILGDI WKLNLQTFQW VKLPATMPEP
VYFHCAAVTP AGCMYIHGGV VNIHENKRTG SLFKIWLVVP SLLELAWEKL LAAFPNLANL
SRTQLLHLGL TQELIERLK
