KLDC2_MOUSE
ID KLDC2_MOUSE Reviewed; 406 AA.
AC Q4G5Y1; E9QKN6; Q99JY2; Q9D784;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Kelch domain-containing protein 2 {ECO:0000305};
DE AltName: Full=Endothelial differentiation inhibitory protein TNG {ECO:0000303|PubMed:16008511};
GN Name=Klhdc2 {ECO:0000312|MGI:MGI:1916804};
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 [MRNA].
RX PubMed=16008511; DOI=10.1089/dna.2005.24.432;
RA Ishii H., Mimori K., Mori M., Vecchione A.;
RT "Differentially expressed genes in endothelial differentiation.";
RL DNA Cell Biol. 24:432-437(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Tongue;
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 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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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).
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. The C-degron recognized by the DesCEND pathway is usually
CC a motif of less than ten residues and can be present in full-length
CC proteins, truncated proteins or proteolytically cleaved forms. The
CC CRL2(KLHDC2) complex specifically recognizes proteins with a diglycine
CC (Gly-Gly) at the C-terminus, leading to their ubiquitination and
CC degradation. The CRL2(KLHDC2) complex mediates ubiquitination and
CC degradation of truncated SELENOK and SELENOS selenoproteins produced by
CC failed UGA/Sec decoding, which end with a diglycine. The CRL2(KLHDC2)
CC complex also recognizes proteolytically cleaved proteins ending with
CC Gly-Gly, such as the N-terminal fragment of USP1, leading to their
CC degradation. May also act as an indirect repressor of CREB3-mediated
CC transcription by interfering with CREB3-DNA-binding.
CC {ECO:0000250|UniProtKB:Q9Y2U9}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q9Y2U9}.
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 KLHDC2. Interacts with CREB3; interaction is direct and specific as it
CC does not interact with CREB1, ATF4, ATF6, JUN, FOS, CEBPA or herpes
CC simplex virus transactivator VP16. {ECO:0000250|UniProtKB:Q9Y2U9}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9Y2U9}.
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DR EMBL; AY513272; AAS82954.1; -; mRNA.
DR EMBL; AK009481; BAB26317.1; -; mRNA.
DR EMBL; AC099934; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC005581; AAH05581.1; -; mRNA.
DR CCDS; CCDS25950.1; -.
DR RefSeq; NP_081393.2; NM_027117.3.
DR AlphaFoldDB; Q4G5Y1; -.
DR SMR; Q4G5Y1; -.
DR BioGRID; 213528; 1.
DR IntAct; Q4G5Y1; 1.
DR MINT; Q4G5Y1; -.
DR STRING; 10090.ENSMUSP00000021362; -.
DR iPTMnet; Q4G5Y1; -.
DR PhosphoSitePlus; Q4G5Y1; -.
DR EPD; Q4G5Y1; -.
DR MaxQB; Q4G5Y1; -.
DR PaxDb; Q4G5Y1; -.
DR PeptideAtlas; Q4G5Y1; -.
DR PRIDE; Q4G5Y1; -.
DR ProteomicsDB; 264946; -.
DR Antibodypedia; 23574; 95 antibodies from 19 providers.
DR DNASU; 69554; -.
DR Ensembl; ENSMUST00000021362; ENSMUSP00000021362; ENSMUSG00000020978.
DR GeneID; 69554; -.
DR KEGG; mmu:69554; -.
DR UCSC; uc007nrz.2; mouse.
DR CTD; 23588; -.
DR MGI; MGI:1916804; Klhdc2.
DR VEuPathDB; HostDB:ENSMUSG00000020978; -.
DR eggNOG; KOG0379; Eukaryota.
DR GeneTree; ENSGT00940000157150; -.
DR HOGENOM; CLU_042804_0_0_1; -.
DR InParanoid; Q4G5Y1; -.
DR OMA; YNDGNCH; -.
DR OrthoDB; 1263405at2759; -.
DR PhylomeDB; Q4G5Y1; -.
DR TreeFam; TF314081; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 69554; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Klhdc2; mouse.
DR PRO; PR:Q4G5Y1; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q4G5Y1; protein.
DR Bgee; ENSMUSG00000020978; Expressed in respiratory primordium and 263 other tissues.
DR Genevisible; Q4G5Y1; MM.
DR GO; GO:0031462; C:Cul2-RING ubiquitin ligase complex; ISS:UniProtKB.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0031965; C:nuclear membrane; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:1990756; F:ubiquitin ligase-substrate adaptor activity; ISS:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
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; IPR011043; Gal_Oxase/kelch_b-propeller.
DR InterPro; IPR015915; Kelch-typ_b-propeller.
DR SUPFAM; SSF117281; SSF117281; 1.
DR SUPFAM; SSF50965; SSF50965; 1.
PE 2: Evidence at transcript level;
KW Kelch repeat; Nucleus; Reference proteome; Repeat; Ubl conjugation pathway.
FT CHAIN 1..406
FT /note="Kelch domain-containing protein 2"
FT /id="PRO_0000228993"
FT REPEAT 43..89
FT /note="Kelch 1"
FT REPEAT 102..155
FT /note="Kelch 2"
FT REPEAT 157..202
FT /note="Kelch 3"
FT REPEAT 229..278
FT /note="Kelch 4"
FT REPEAT 280..329
FT /note="Kelch 5"
FT REPEAT 331..377
FT /note="Kelch 6"
FT CONFLICT 22
FT /note="E -> G (in Ref. 2; BAB26317)"
FT /evidence="ECO:0000305"
FT CONFLICT 72
FT /note="N -> Y (in Ref. 4; AAH05581)"
FT /evidence="ECO:0000305"
FT CONFLICT 368
FT /note="S -> I (in Ref. 2; BAB26317)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 406 AA; 45909 MW; 9CD61E844607ACEF CRC64;
MADGNEDARA EDLPGPAFEN YEAMELACPA ERSGHVAVSD GRHMFVWGGY KSNQVRGLYD
FYLPREELWI YNMETGRWKK INTEGDVPPS MSGSCAVCVD RVLYLFGGHH SRGNTNKFYM
LDSRSADRGL QWERIDCQGI PPSSKDKLGV WVYKNKLIFF GGYGYLPEDK VLGTFEFDET
SFWNSSHPRG WNDHVHILDT ETFAWSQPIT TGKAPSPRAA HACATVGNKG FVFGGRYRDA
RMNDLHYLNL DTWEWNELIP QGVCPVGRSW HSLTPVSSDH LFLFGGFTTE KQPLSDAWTY
CISKNEWIQF NHPYVEKPRL WHTACASDEG EVIVFGGCAN NLLVHHRAAH SNEVLIFSVQ
PKSLVRLSLE AVICFKEMLA NSWSCLPKHL LHSVNQRFGS NNTSGS
