KLD10_HUMAN
ID KLD10_HUMAN Reviewed; 442 AA.
AC Q6PID8; Q86Y99; Q92554;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Kelch domain-containing protein 10 {ECO:0000305};
GN Name=KLHDC10 {ECO:0000303|PubMed:23102700, ECO:0000312|HGNC:HGNC:22194};
GN Synonyms=KIAA0265 {ECO:0000303|PubMed:9039502};
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] (ISOFORM 2).
RC TISSUE=Bone marrow;
RX PubMed=9039502; DOI=10.1093/dnares/3.5.321;
RA Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O.,
RA Tanaka A., Kotani H., Miyajima N., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. VI. The
RT coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of
RT cDNA clones from cell line KG-1 and brain.";
RL DNA Res. 3:321-329(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS GLY-183;
RP VAL-274 AND GLY-295.
RC TISSUE=Testis;
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 IDENTIFICATION, AND DEVELOPMENTAL STAGE.
RX PubMed=14962666; DOI=10.1016/j.ygeno.2003.08.016;
RA Yamada T., Mitsuya K., Kayashima T., Yamasaki K., Ohta T., Yoshiura K.,
RA Matsumoto N., Yamada H., Minakami H., Oshimura M., Niikawa N., Kishino T.;
RT "Imprinting analysis of 10 genes and/or transcripts in a 1.5-Mb MEST-
RT flanking region at human chromosome 7q32.";
RL Genomics 83:402-412(2004).
RN [6]
RP FUNCTION, INTERACTION WITH CUL2; PPP5C; ELOB AND ELOC, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF ALA-409.
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 [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).
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). 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:29779948). 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 (PubMed:29779948).
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 (By
CC similarity). {ECO:0000250|UniProtKB:Q6PAR0,
CC ECO:0000269|PubMed:23102700, ECO:0000269|PubMed:29779948}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {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 KLHDC10 (PubMed:23102700, PubMed:29779948). Interacts (via the 6 Kelch
CC repeats) with PPP5C (PubMed:23102700). {ECO:0000269|PubMed:23102700,
CC ECO:0000269|PubMed:29779948}.
CC -!- INTERACTION:
CC Q6PID8; Q8IVD9: NUDCD3; NbExp=2; IntAct=EBI-3201175, EBI-744342;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23102700}. Cytoplasm
CC {ECO:0000269|PubMed:23102700}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6PID8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6PID8-2; Sequence=VSP_031484;
CC -!- DEVELOPMENTAL STAGE: Expressed in fetal brain, liver, lung, kidney and
CC placenta. {ECO:0000269|PubMed:14962666}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA13395.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; D87454; BAA13395.1; ALT_INIT; mRNA.
DR EMBL; CH236950; EAL24096.1; -; Genomic_DNA.
DR EMBL; CH471070; EAW83744.1; -; Genomic_DNA.
DR EMBL; BC036464; AAH36464.1; -; mRNA.
DR EMBL; BC044884; AAH44884.1; -; mRNA.
DR CCDS; CCDS5815.1; -. [Q6PID8-1]
DR RefSeq; NP_055812.1; NM_014997.3. [Q6PID8-1]
DR AlphaFoldDB; Q6PID8; -.
DR SMR; Q6PID8; -.
DR BioGRID; 116652; 55.
DR IntAct; Q6PID8; 15.
DR MINT; Q6PID8; -.
DR STRING; 9606.ENSP00000334140; -.
DR iPTMnet; Q6PID8; -.
DR PhosphoSitePlus; Q6PID8; -.
DR BioMuta; KLHDC10; -.
DR DMDM; 74737721; -.
DR EPD; Q6PID8; -.
DR jPOST; Q6PID8; -.
DR MassIVE; Q6PID8; -.
DR MaxQB; Q6PID8; -.
DR PaxDb; Q6PID8; -.
DR PeptideAtlas; Q6PID8; -.
DR PRIDE; Q6PID8; -.
DR ProteomicsDB; 67150; -. [Q6PID8-1]
DR ProteomicsDB; 67151; -. [Q6PID8-2]
DR Antibodypedia; 17939; 24 antibodies from 11 providers.
DR DNASU; 23008; -.
DR Ensembl; ENST00000335420.10; ENSP00000334140.4; ENSG00000128607.14. [Q6PID8-1]
DR GeneID; 23008; -.
DR KEGG; hsa:23008; -.
DR MANE-Select; ENST00000335420.10; ENSP00000334140.4; NM_014997.4; NP_055812.1.
DR UCSC; uc003vpj.3; human. [Q6PID8-1]
DR CTD; 23008; -.
DR DisGeNET; 23008; -.
DR GeneCards; KLHDC10; -.
DR HGNC; HGNC:22194; KLHDC10.
DR HPA; ENSG00000128607; Low tissue specificity.
DR MIM; 615152; gene.
DR neXtProt; NX_Q6PID8; -.
DR OpenTargets; ENSG00000128607; -.
DR PharmGKB; PA164721976; -.
DR VEuPathDB; HostDB:ENSG00000128607; -.
DR eggNOG; KOG0379; Eukaryota.
DR GeneTree; ENSGT00940000155977; -.
DR HOGENOM; CLU_030914_0_0_1; -.
DR InParanoid; Q6PID8; -.
DR OMA; HCDMPEE; -.
DR OrthoDB; 564212at2759; -.
DR PhylomeDB; Q6PID8; -.
DR TreeFam; TF314081; -.
DR PathwayCommons; Q6PID8; -.
DR SignaLink; Q6PID8; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 23008; 13 hits in 1083 CRISPR screens.
DR ChiTaRS; KLHDC10; human.
DR GenomeRNAi; 23008; -.
DR Pharos; Q6PID8; Tdark.
DR PRO; PR:Q6PID8; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q6PID8; protein.
DR Bgee; ENSG00000128607; Expressed in endothelial cell and 211 other tissues.
DR ExpressionAtlas; Q6PID8; baseline and differential.
DR Genevisible; Q6PID8; HS.
DR GO; GO:0031462; C:Cul2-RING ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:1990756; F:ubiquitin ligase-substrate adaptor activity; IDA: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; IDA: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..442
FT /note="Kelch domain-containing protein 10"
FT /id="PRO_0000319436"
FT REPEAT 103..164
FT /note="Kelch 1"
FT REPEAT 166..217
FT /note="Kelch 2"
FT REPEAT 218..270
FT /note="Kelch 3"
FT REPEAT 271..319
FT /note="Kelch 4"
FT REPEAT 327..373
FT /note="Kelch 5"
FT REPEAT 376..419
FT /note="Kelch 6"
FT REGION 1..57
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 401..442
FT /note="Interaction with CUL2"
FT /evidence="ECO:0000269|PubMed:23102700"
FT MOD_RES 13
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q6PAR0"
FT VAR_SEQ 1..143
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9039502"
FT /id="VSP_031484"
FT VARIANT 2
FT /note="S -> L (in dbSNP:rs3734928)"
FT /id="VAR_039005"
FT VARIANT 183
FT /note="D -> G (in dbSNP:rs17854337)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_039006"
FT VARIANT 274
FT /note="I -> V (in dbSNP:rs17854336)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_039007"
FT VARIANT 295
FT /note="E -> G (in dbSNP:rs17857292)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_039008"
FT VARIANT 437
FT /note="L -> I (in dbSNP:rs10241894)"
FT /id="VAR_039009"
FT MUTAGEN 409
FT /note="A->P: Loss of interaction with CUL2. No effect on
FT MAP3K5 activation."
FT /evidence="ECO:0000269|PubMed:23102700"
SQ SEQUENCE 442 AA; 49098 MW; 8D8AF4A6302A7A86 CRC64;
MSAAQGWDRN RRRGGGAAGA GGGGSGAGGG SGGSGGRGTG QLNRFVQLSG RPHLPGKKKI
RWDPVRRRFI QSCPIIRIPN RFLRGHRPPP ARSGHRCVAD NTNLYVFGGY NPDYDESGGP
DNEDYPLFRE LWRYHFATGV WHQMGTDGYM PRELASMSLV LHGNNLLVFG GTGIPFGESN
GNDVHVCNVK YKRWALLSCR GKKPSRIYGQ AMAIINGSLY VFGGTTGYIY STDLHKLDLN
TREWTQLKPN NLSCDLPEER YRHEIAHDGQ RIYILGGGTS WTAYSLNKIH AYNLETNAWE
EIATKPHEKI GFPAARRCHS CVQIKNDVFI CGGYNGEVIL GDIWKLNLQT FQWVKLPATM
PEPVYFHCAA VTPAGCMYIH GGVVNIHENK RTGSLFKIWL VVPSLLELAW EKLLAAFPNL
ANLSRTQLLH LGLTQGLIER LK
