KLDC3_HUMAN
ID KLDC3_HUMAN Reviewed; 382 AA.
AC Q9BQ90; A8K2W9;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Kelch domain-containing protein 3 {ECO:0000305};
DE AltName: Full=Testis intracellular mediator protein {ECO:0000303|PubMed:12606021};
GN Name=KLHDC3 {ECO:0000303|PubMed:26138980, ECO:0000312|HGNC:HGNC:20704};
GN Synonyms=PEAS {ECO:0000303|PubMed:12606021};
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 [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Testis;
RX PubMed=12606021; DOI=10.1016/s0014-5793(03)00036-x;
RA Ohinata Y., Sutou S., Mitsui Y.;
RT "A novel testis-specific RAG2-like protein, Peas: its expression in
RT pachytene spermatocyte cytoplasm and meiotic chromatin.";
RL FEBS Lett. 537:1-5(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Umbilical cord blood;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
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].
RC TISSUE=Eye, and Lung;
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 FUNCTION.
RX PubMed=26138980; DOI=10.1126/science.aab0515;
RA Lin H.C., Ho S.C., Chen Y.Y., Khoo K.H., Hsu P.H., Yen H.C.;
RT "SELENOPROTEINS. CRL2 aids elimination of truncated selenoproteins produced
RT by failed UGA/Sec decoding.";
RL Science 349:91-95(2015).
RN [7]
RP FUNCTION, PATHWAY, AND IDENTIFICATION IN A CRL2 E3 UBIQUITIN-PROTEIN LIGASE
RP COMPLEX.
RX PubMed=29779948; DOI=10.1016/j.cell.2018.04.028;
RA Koren I., Timms R.T., Kula T., Xu Q., Li M.Z., Elledge S.J.;
RT "The eukaryotic proteome is shaped by E3 ubiquitin ligases targeting C-
RT terminal degrons.";
RL Cell 173:1622-1635(2018).
RN [8]
RP FUNCTION, PATHWAY, AND IDENTIFICATION IN A CRL2 E3 UBIQUITIN-PROTEIN LIGASE
RP COMPLEX.
RX PubMed=29775578; DOI=10.1016/j.molcel.2018.04.006;
RA Lin H.C., Yeh C.W., Chen Y.F., Lee T.T., Hsieh P.Y., Rusnac D.V., Lin S.Y.,
RA Elledge S.J., Zheng N., Yen H.S.;
RT "C-terminal end-directed protein elimination by CRL2 ubiquitin ligases.";
RL Mol. Cell 70:602-613(2018).
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 (PubMed:29779948, PubMed:29775578). The C-degron recognized
CC by the DesCEND pathway is usually a motif of less than ten residues and
CC can be present in full-length proteins, truncated proteins or
CC proteolytically cleaved forms (PubMed:29779948, PubMed:29775578). The
CC CRL2(KLHDC3) complex specifically recognizes proteins with a glycine
CC (Gly) at the C-terminus, leading to their ubiquitination and
CC degradation: recognizes the C-terminal -Arg-(Xaa)n-Arg-Gly, -Arg-
CC (Xaa)n-Lys-Gly, and -Arg-(Xaa)n-Gln-Gly degrons (PubMed:29779948,
CC PubMed:29775578). The CRL2(KLHDC3) complex mediates ubiquitination and
CC degradation of truncated SELENOV and SEPHS2 selenoproteins produced by
CC failed UGA/Sec decoding, which end with a glycine (PubMed:26138980).
CC May be involved in meiotic recombination process (PubMed:12606021).
CC {ECO:0000269|PubMed:12606021, ECO:0000269|PubMed:26138980,
CC ECO:0000269|PubMed:29775578, ECO:0000269|PubMed:29779948}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:29775578, ECO:0000269|PubMed:29779948}.
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 KLHDC3. {ECO:0000269|PubMed:29775578, ECO:0000269|PubMed:29779948}.
CC -!- INTERACTION:
CC Q9BQ90; Q13617: CUL2; NbExp=8; IntAct=EBI-1055396, EBI-456179;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12606021}.
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DR EMBL; AB055925; BAB63257.1; -; mRNA.
DR EMBL; AK290384; BAF83073.1; -; mRNA.
DR EMBL; AL136304; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX04136.1; -; Genomic_DNA.
DR EMBL; BC000295; AAH00295.1; -; mRNA.
DR EMBL; BC001789; AAH01789.1; -; mRNA.
DR EMBL; BC001793; AAH01793.1; -; mRNA.
DR EMBL; BC007296; AAH07296.1; -; mRNA.
DR EMBL; BC021546; AAH21546.1; -; mRNA.
DR CCDS; CCDS4880.1; -.
DR RefSeq; NP_476502.1; NM_057161.3.
DR AlphaFoldDB; Q9BQ90; -.
DR SMR; Q9BQ90; -.
DR BioGRID; 125478; 85.
DR IntAct; Q9BQ90; 45.
DR STRING; 9606.ENSP00000313995; -.
DR iPTMnet; Q9BQ90; -.
DR PhosphoSitePlus; Q9BQ90; -.
DR BioMuta; KLHDC3; -.
DR DMDM; 74752233; -.
DR EPD; Q9BQ90; -.
DR jPOST; Q9BQ90; -.
DR MassIVE; Q9BQ90; -.
DR MaxQB; Q9BQ90; -.
DR PaxDb; Q9BQ90; -.
DR PeptideAtlas; Q9BQ90; -.
DR PRIDE; Q9BQ90; -.
DR ProteomicsDB; 78644; -.
DR Antibodypedia; 30235; 67 antibodies from 20 providers.
DR DNASU; 116138; -.
DR Ensembl; ENST00000326974.9; ENSP00000313995.4; ENSG00000124702.19.
DR GeneID; 116138; -.
DR KEGG; hsa:116138; -.
DR MANE-Select; ENST00000326974.9; ENSP00000313995.4; NM_057161.4; NP_476502.1.
DR UCSC; uc003otl.4; human.
DR CTD; 116138; -.
DR GeneCards; KLHDC3; -.
DR HGNC; HGNC:20704; KLHDC3.
DR HPA; ENSG00000124702; Tissue enhanced (skeletal).
DR MIM; 611248; gene.
DR neXtProt; NX_Q9BQ90; -.
DR OpenTargets; ENSG00000124702; -.
DR PharmGKB; PA134892782; -.
DR VEuPathDB; HostDB:ENSG00000124702; -.
DR eggNOG; KOG4693; Eukaryota.
DR GeneTree; ENSGT00940000157952; -.
DR HOGENOM; CLU_045453_0_0_1; -.
DR InParanoid; Q9BQ90; -.
DR OMA; AYEQERM; -.
DR OrthoDB; 933937at2759; -.
DR PhylomeDB; Q9BQ90; -.
DR TreeFam; TF354289; -.
DR PathwayCommons; Q9BQ90; -.
DR Reactome; R-HSA-381038; XBP1(S) activates chaperone genes.
DR SignaLink; Q9BQ90; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 116138; 31 hits in 1082 CRISPR screens.
DR ChiTaRS; KLHDC3; human.
DR GeneWiki; KLHDC3; -.
DR GenomeRNAi; 116138; -.
DR Pharos; Q9BQ90; Tdark.
DR PRO; PR:Q9BQ90; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9BQ90; protein.
DR Bgee; ENSG00000124702; Expressed in right testis and 206 other tissues.
DR ExpressionAtlas; Q9BQ90; baseline and differential.
DR Genevisible; Q9BQ90; HS.
DR GO; GO:0000785; C:chromatin; IDA:UniProtKB.
DR GO; GO:0031462; C:Cul2-RING ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:1990756; F:ubiquitin ligase-substrate adaptor activity; IDA:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:0007131; P:reciprocal meiotic recombination; NAS:UniProtKB.
DR GO; GO:0140627; P:ubiquitin-dependent protein catabolic process via the C-end degron rule pathway; IDA:UniProtKB.
DR Gene3D; 2.120.10.80; -; 2.
DR InterPro; IPR015915; Kelch-typ_b-propeller.
DR InterPro; IPR006652; Kelch_1.
DR InterPro; IPR011498; Kelch_2.
DR Pfam; PF01344; Kelch_1; 1.
DR Pfam; PF07646; Kelch_2; 1.
DR SUPFAM; SSF117281; SSF117281; 2.
PE 1: Evidence at protein level;
KW Cytoplasm; Kelch repeat; Meiosis; Reference proteome; Repeat;
KW Ubl conjugation pathway.
FT CHAIN 1..382
FT /note="Kelch domain-containing protein 3"
FT /id="PRO_0000228995"
FT REPEAT 25..77
FT /note="Kelch 1"
FT REPEAT 88..138
FT /note="Kelch 2"
FT REPEAT 139..189
FT /note="Kelch 3"
FT REPEAT 191..249
FT /note="Kelch 4"
FT REPEAT 251..301
FT /note="Kelch 5"
SQ SEQUENCE 382 AA; 43088 MW; 49A3AB24BE7FFAFC CRC64;
MLRWTVHLEG GPRRVNHAAV AVGHRVYSFG GYCSGEDYET LRQIDVHIFN AVSLRWTKLP
PVKSAIRGQA PVVPYMRYGH STVLIDDTVL LWGGRNDTEG ACNVLYAFDV NTHKWFTPRV
SGTVPGARDG HSACVLGKIM YIFGGYEQQA DCFSNDIHKL DTSTMTWTLI CTKGSPARWR
DFHSATMLGS HMYVFGGRAD RFGPFHSNNE IYCNRIRVFD TRTEAWLDCP PTPVLPEGRR
SHSAFGYNGE LYIFGGYNAR LNRHFHDLWK FNPVSFTWKK IEPKGKGPCP RRRQCCCIVG
DKIVLFGGTS PSPEEGLGDE FDLIDHSDLH ILDFSPSLKT LCKLAVIQYN LDQSCLPHDI
RWELNAMTTN SNISRPIVSS HG
