KLDC1_HUMAN
ID KLDC1_HUMAN Reviewed; 406 AA.
AC Q8N7A1; B3KXD9; Q8WYI1;
DT 12-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 2.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Kelch domain-containing protein 1 {ECO:0000305};
GN Name=KLHDC1 {ECO:0000303|PubMed:16964437, ECO:0000312|HGNC:HGNC:19836};
GN ORFNames=MSTP025 {ECO:0000303|Ref.1};
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 [LARGE SCALE MRNA].
RC TISSUE=Aorta;
RA Xu Y.Y., Sun L.Z., Wu Q.Y., Liu Y.Q., Liu B., Zhao B., Wang X.Y., Song L.,
RA Ye J., Sheng H., Gao Y., Zhang C.L., Zhang J., Wei Y.J., Sun Y.H.,
RA Jiang Y.X., Zhao X.W., Liu S., Liu L.S., Ding J.F., Gao R.L., Qiang B.Q.,
RA Yuan J.G., Liew C.C., Zhao M.S., Hui R.T.;
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Hippocampus;
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].
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
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 [5]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16964437; DOI=10.1007/s11010-006-9304-6;
RA Chin K.-T., Xu H.-T., Ching Y.-P., Jin D.-Y.;
RT "Differential subcellular localization and activity of kelch repeat
RT proteins KLHDC1 and KLHDC2.";
RL Mol. Cell. Biochem. 296:109-119(2007).
RN [6]
RP FUNCTION, PATHWAY, IDENTIFICATION IN A E3 UBIQUITIN-PROTEIN LIGASE COMPLEX
RP CONTAINING CUL5, SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=32200094; DOI=10.1016/j.isci.2020.100970;
RA Okumura F., Fujiki Y., Oki N., Osaki K., Nishikimi A., Fukui Y.,
RA Nakatsukasa K., Kamura T.;
RT "Cul5-type ubiquitin ligase KLHDC1 contributes to the elimination of
RT truncated SELENOS produced by failed UGA/Sec decoding.";
RL IScience 23:100970-100970(2020).
CC -!- FUNCTION: Substrate-recognition component of a Cul5-RING (CRL5) 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:32200094). 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 (PubMed:32200094). The CRL5(KLHDC1) complex mediates
CC ubiquitination and degradation of truncated SELENOS selenoprotein
CC produced by failed UGA/Sec decoding, which ends with a glycine
CC (PubMed:32200094). {ECO:0000269|PubMed:32200094}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:32200094}.
CC -!- SUBUNIT: Component of a CRL5 E3 ubiquitin-protein ligase complex, also
CC named ECS (Elongin BC-CUL2/5-SOCS-box protein) complex, composed of
CC CUL5, Elongin BC (ELOB and ELOC), RBX1 and substrate-specific adapter
CC KLHDC1. {ECO:0000269|PubMed:32200094}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:16964437,
CC ECO:0000269|PubMed:32200094}.
CC -!- TISSUE SPECIFICITY: Widely expressed, with high levels in skeletal
CC muscle, pancreas and liver. Undetectable in peripheral blood
CC leukocytes. {ECO:0000269|PubMed:16964437}.
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DR EMBL; AF111806; AAL39008.1; -; mRNA.
DR EMBL; AK098735; BAC05398.1; -; mRNA.
DR EMBL; AK127202; BAG54451.1; -; mRNA.
DR EMBL; CH471078; EAW65753.1; -; Genomic_DNA.
DR EMBL; BC101595; AAI01596.1; -; mRNA.
DR EMBL; BC101597; AAI01598.1; -; mRNA.
DR CCDS; CCDS9692.1; -.
DR RefSeq; NP_751943.1; NM_172193.2.
DR AlphaFoldDB; Q8N7A1; -.
DR SMR; Q8N7A1; -.
DR BioGRID; 125794; 2.
DR IntAct; Q8N7A1; 2.
DR STRING; 9606.ENSP00000352282; -.
DR iPTMnet; Q8N7A1; -.
DR PhosphoSitePlus; Q8N7A1; -.
DR BioMuta; KLHDC1; -.
DR DMDM; 90110030; -.
DR MassIVE; Q8N7A1; -.
DR PaxDb; Q8N7A1; -.
DR PeptideAtlas; Q8N7A1; -.
DR PRIDE; Q8N7A1; -.
DR Antibodypedia; 10289; 91 antibodies from 17 providers.
DR DNASU; 122773; -.
DR Ensembl; ENST00000359332.7; ENSP00000352282.2; ENSG00000197776.8.
DR GeneID; 122773; -.
DR KEGG; hsa:122773; -.
DR MANE-Select; ENST00000359332.7; ENSP00000352282.2; NM_172193.3; NP_751943.1.
DR UCSC; uc001www.3; human.
DR CTD; 122773; -.
DR DisGeNET; 122773; -.
DR GeneCards; KLHDC1; -.
DR HGNC; HGNC:19836; KLHDC1.
DR HPA; ENSG00000197776; Low tissue specificity.
DR MIM; 611281; gene.
DR neXtProt; NX_Q8N7A1; -.
DR OpenTargets; ENSG00000197776; -.
DR PharmGKB; PA134938689; -.
DR VEuPathDB; HostDB:ENSG00000197776; -.
DR eggNOG; KOG0379; Eukaryota.
DR GeneTree; ENSGT00940000157509; -.
DR HOGENOM; CLU_042804_0_0_1; -.
DR InParanoid; Q8N7A1; -.
DR OMA; SCGACVH; -.
DR OrthoDB; 933937at2759; -.
DR PhylomeDB; Q8N7A1; -.
DR TreeFam; TF314081; -.
DR PathwayCommons; Q8N7A1; -.
DR SignaLink; Q8N7A1; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 122773; 9 hits in 1068 CRISPR screens.
DR ChiTaRS; KLHDC1; human.
DR GenomeRNAi; 122773; -.
DR Pharos; Q8N7A1; Tbio.
DR PRO; PR:Q8N7A1; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q8N7A1; protein.
DR Bgee; ENSG00000197776; Expressed in calcaneal tendon and 166 other tissues.
DR ExpressionAtlas; Q8N7A1; baseline and differential.
DR Genevisible; Q8N7A1; HS.
DR GO; GO:0031466; C:Cul5-RING ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:1990756; F:ubiquitin ligase-substrate adaptor activity; IDA: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; IDA:UniProtKB.
DR Gene3D; 2.120.10.80; -; 2.
DR InterPro; IPR015915; Kelch-typ_b-propeller.
DR SUPFAM; SSF117281; SSF117281; 2.
PE 1: Evidence at protein level;
KW Cytoplasm; Kelch repeat; Reference proteome; Repeat;
KW Ubl conjugation pathway.
FT CHAIN 1..406
FT /note="Kelch domain-containing protein 1"
FT /id="PRO_0000119126"
FT REPEAT 24..76
FT /note="Kelch 1"
FT REPEAT 80..134
FT /note="Kelch 2"
FT REPEAT 135..181
FT /note="Kelch 3"
FT REPEAT 208..258
FT /note="Kelch 4"
FT REPEAT 260..307
FT /note="Kelch 5"
FT REPEAT 311..361
FT /note="Kelch 6"
FT CONFLICT 32
FT /note="V -> A (in Ref. 1; BAC05398)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 406 AA; 46720 MW; 73F74B22417D12E8 CRC64;
MADSQLFCVA EERSGHCAVV DGNFLYVWGG YVSIEDNEVY LPNDEIWTYD IDSGLWRMHL
MEGELPASMS GSCGACINGK LYIFGGYDDK GYSNRLYFVN LRTRDETYIW EKITDFEGQP
PTPRDKLSCW VYKDRLIYFG GYGCRRHSEL QDCFDVHDAS WEEQIFWGWH NDVHIFDTKT
QTWFQPEIKG GVPPQPRAAH TCAVLGNKGY IFGGRVLQTR MNDLHYLNLD TWTWSGRITI
NGESPKHRSW HTLTPIADDK LFLCGGLSAD NIPLSDGWIH NVTTNCWKQL THLPKTRPRL
WHTACLGKEN EIMVFGGSKD DLLALDTGHC NDLLIFQTQP YSLLRSCLDC IGKNSIMLES
QISLLPPKLL QQVLKKITFW AAANHREEQR VQKEETENKY QWISSN
