KLHL8_HUMAN
ID KLHL8_HUMAN Reviewed; 620 AA.
AC Q9P2G9; Q53XA3; Q6N018;
DT 12-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Kelch-like protein 8;
GN Name=KLHL8; Synonyms=KIAA1378;
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 1).
RC TISSUE=Brain;
RX PubMed=10718198; DOI=10.1093/dnares/7.1.65;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVI. The
RT complete sequences of 150 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:65-73(2000).
RN [2]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Cerebellum, and Fetal kidney;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ARG-520.
RC 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 [7]
RP FUNCTION, IDENTIFICATION IN A BCR (BTB-CUL3-RBX1) E3 UBIQUITIN LIGASE
RP COMPLEX, AND INTERACTION WITH RAPSN.
RX PubMed=19158078; DOI=10.1074/jbc.m808230200;
RA Nam S., Min K., Hwang H., Lee H.O., Lee J.H., Yoon J., Lee H., Park S.,
RA Lee J.;
RT "Control of rapsyn stability by the CUL-3-containing E3 ligase complex.";
RL J. Biol. Chem. 284:8195-8206(2009).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3
CC ubiquitin ligase complex required for The BCR(KLHL8) ubiquitin ligase
CC complex mediates ubiquitination and degradation of RAPSN.
CC {ECO:0000269|PubMed:19158078}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Component of the BCR(KLHL8) E3 ubiquitin ligase complex, at
CC least composed of CUL3, KLHL8 and RBX1. Interacts with RAPSN.
CC {ECO:0000269|PubMed:19158078}.
CC -!- INTERACTION:
CC Q9P2G9-2; Q7Z3E5-2: ARMC9; NbExp=3; IntAct=EBI-11959635, EBI-10256990;
CC Q9P2G9-2; P35219: CA8; NbExp=3; IntAct=EBI-11959635, EBI-718700;
CC Q9P2G9-2; Q9UER7: DAXX; NbExp=3; IntAct=EBI-11959635, EBI-77321;
CC Q9P2G9-2; P45984: MAPK9; NbExp=3; IntAct=EBI-11959635, EBI-713568;
CC Q9P2G9-2; P11086: PNMT; NbExp=3; IntAct=EBI-11959635, EBI-11305767;
CC Q9P2G9-2; Q6IPC0: PPM1F; NbExp=3; IntAct=EBI-11959635, EBI-11993088;
CC Q9P2G9-2; P12271: RLBP1; NbExp=3; IntAct=EBI-11959635, EBI-11959637;
CC Q9P2G9-2; O00204: SULT2B1; NbExp=3; IntAct=EBI-11959635, EBI-749441;
CC Q9P2G9-2; Q9BY14-2: TEX101; NbExp=3; IntAct=EBI-11959635, EBI-12306161;
CC Q9P2G9-2; Q8NBR0: TP53I13; NbExp=3; IntAct=EBI-11959635, EBI-11992976;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9P2G9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9P2G9-2; Sequence=VSP_054443;
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA92616.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AB037799; BAA92616.2; ALT_INIT; mRNA.
DR EMBL; BX640727; CAE45843.1; -; mRNA.
DR EMBL; BX640744; CAE45855.1; -; mRNA.
DR EMBL; AC092658; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC108516; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471057; EAX05982.1; -; Genomic_DNA.
DR EMBL; BC041384; AAH41384.1; -; mRNA.
DR CCDS; CCDS3617.1; -. [Q9P2G9-1]
DR CCDS; CCDS77937.1; -. [Q9P2G9-2]
DR RefSeq; NP_001278932.1; NM_001292003.1. [Q9P2G9-1]
DR RefSeq; NP_001278935.1; NM_001292006.1. [Q9P2G9-2]
DR RefSeq; NP_001278936.1; NM_001292007.1.
DR RefSeq; NP_065854.3; NM_020803.4. [Q9P2G9-1]
DR AlphaFoldDB; Q9P2G9; -.
DR SMR; Q9P2G9; -.
DR BioGRID; 121618; 107.
DR CORUM; Q9P2G9; -.
DR IntAct; Q9P2G9; 32.
DR STRING; 9606.ENSP00000273963; -.
DR GlyGen; Q9P2G9; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9P2G9; -.
DR PhosphoSitePlus; Q9P2G9; -.
DR BioMuta; KLHL8; -.
DR DMDM; 124056473; -.
DR EPD; Q9P2G9; -.
DR jPOST; Q9P2G9; -.
DR MassIVE; Q9P2G9; -.
DR MaxQB; Q9P2G9; -.
DR PaxDb; Q9P2G9; -.
DR PeptideAtlas; Q9P2G9; -.
DR PRIDE; Q9P2G9; -.
DR ProteomicsDB; 66596; -.
DR ProteomicsDB; 83814; -. [Q9P2G9-1]
DR Antibodypedia; 2897; 101 antibodies from 20 providers.
DR DNASU; 57563; -.
DR Ensembl; ENST00000273963.10; ENSP00000273963.5; ENSG00000145332.14. [Q9P2G9-1]
DR Ensembl; ENST00000498875.6; ENSP00000426451.1; ENSG00000145332.14. [Q9P2G9-2]
DR Ensembl; ENST00000512111.1; ENSP00000424131.1; ENSG00000145332.14. [Q9P2G9-1]
DR GeneID; 57563; -.
DR KEGG; hsa:57563; -.
DR MANE-Select; ENST00000273963.10; ENSP00000273963.5; NM_020803.5; NP_065854.3.
DR UCSC; uc003hql.2; human. [Q9P2G9-1]
DR CTD; 57563; -.
DR DisGeNET; 57563; -.
DR GeneCards; KLHL8; -.
DR HGNC; HGNC:18644; KLHL8.
DR HPA; ENSG00000145332; Tissue enhanced (epididymis).
DR MIM; 611967; gene.
DR neXtProt; NX_Q9P2G9; -.
DR OpenTargets; ENSG00000145332; -.
DR PharmGKB; PA38616; -.
DR VEuPathDB; HostDB:ENSG00000145332; -.
DR eggNOG; KOG4441; Eukaryota.
DR GeneTree; ENSGT00940000157583; -.
DR InParanoid; Q9P2G9; -.
DR OMA; ADQFACE; -.
DR PhylomeDB; Q9P2G9; -.
DR TreeFam; TF329218; -.
DR PathwayCommons; Q9P2G9; -.
DR SignaLink; Q9P2G9; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 57563; 14 hits in 1118 CRISPR screens.
DR ChiTaRS; KLHL8; human.
DR GeneWiki; KLHL8; -.
DR GenomeRNAi; 57563; -.
DR Pharos; Q9P2G9; Tdark.
DR PRO; PR:Q9P2G9; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q9P2G9; protein.
DR Bgee; ENSG00000145332; Expressed in corpus epididymis and 188 other tissues.
DR ExpressionAtlas; Q9P2G9; baseline and differential.
DR Genevisible; Q9P2G9; HS.
DR GO; GO:0031463; C:Cul3-RING ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR Gene3D; 2.120.10.80; -; 2.
DR Gene3D; 3.30.710.10; -; 1.
DR InterPro; IPR011705; BACK.
DR InterPro; IPR017096; BTB-kelch_protein.
DR InterPro; IPR000210; BTB/POZ_dom.
DR InterPro; IPR011043; Gal_Oxase/kelch_b-propeller.
DR InterPro; IPR015915; Kelch-typ_b-propeller.
DR InterPro; IPR006652; Kelch_1.
DR InterPro; IPR030605; KLHL8.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR PANTHER; PTHR24412:SF403; PTHR24412:SF403; 1.
DR Pfam; PF07707; BACK; 1.
DR Pfam; PF00651; BTB; 1.
DR Pfam; PF01344; Kelch_1; 6.
DR PIRSF; PIRSF037037; Kelch-like_protein_gigaxonin; 1.
DR SMART; SM00875; BACK; 1.
DR SMART; SM00225; BTB; 1.
DR SMART; SM00612; Kelch; 6.
DR SUPFAM; SSF50965; SSF50965; 1.
DR SUPFAM; SSF54695; SSF54695; 1.
DR PROSITE; PS50097; BTB; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Kelch repeat; Reference proteome;
KW Repeat; Ubl conjugation pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..620
FT /note="Kelch-like protein 8"
FT /id="PRO_0000119108"
FT DOMAIN 67..134
FT /note="BTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT DOMAIN 169..270
FT /note="BACK"
FT REPEAT 319..366
FT /note="Kelch 1"
FT REPEAT 367..413
FT /note="Kelch 2"
FT REPEAT 415..460
FT /note="Kelch 3"
FT REPEAT 462..507
FT /note="Kelch 4"
FT REPEAT 508..554
FT /note="Kelch 5"
FT REPEAT 556..601
FT /note="Kelch 6"
FT REGION 1..35
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT VAR_SEQ 73..148
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_054443"
FT VARIANT 520
FT /note="P -> R (in dbSNP:rs17854114)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_030012"
SQ SEQUENCE 620 AA; 68802 MW; 6C3C3C78CEC6FE84 CRC64;
MASDSMSSKQ ARNHITKGKR QQQHQQIKNR SSISDGDGED SFIFEANEAW KDFHGSLLRF
YENGELCDVT LKVGSKLISC HKLVLACVIP YFRAMFLSEM AEAKQTLIEI RDFDGDAIED
LVKFVYSSRL TLTVDNVQPL LYAACILQVE LVARACCEYM KLHFHPSNCL AVRAFAESHN
RIDLMDMADQ YACDHFTEVV ECEDFVSVSP QHLHKLLSSS DLNIENEKQV YNAAIKWLLA
NPQHHSKWLD ETLAQVRLPL LPVDFLMGVV AKEQIVKQNL KCRDLLDEAR NYHLHLSSRA
VPDFEYSIRT TPRKHTAGVL FCVGGRGGSG DPFRSIECYS INKNSWFFGP EMNSRRRHVG
VISVEGKVYA VGGHDGNEHL GSMEMFDPLT NKWMMKASMN TKRRGIALAS LGGPIYAIGG
LDDNTCFNDV ERYDIESDQW STVAPMNTPR GGVGSVALVN HVYAVGGNDG MASLSSVERY
DPHLDKWIEV KEMGQRRAGN GVSKLHGCLY VVGGFDDNSP LSSVERYDPR SNKWDYVAAL
TTPRGGVGIA TVMGKIFAVG GHNGNAYLNT VEAFDPVLNR WELVGSVSHC RAGAGVAVCS
CLTSQIRDVG HGSNNVVDCM
