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 27-MAR-2024, entry version 173. 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; Q13618: CUL3; NbExp=7; IntAct=EBI-949008, EBI-456129; 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 110. DR ComplexPortal; CPX-8085; CRL3 E3 ubiquitin ligase complex, KLHL8 variant. DR CORUM; Q9P2G9; -. DR IntAct; Q9P2G9; 32. DR MINT; Q9P2G9; -. 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; 9606-ENSP00000273963; -. DR PeptideAtlas; Q9P2G9; -. DR ProteomicsDB; 66596; -. DR ProteomicsDB; 83814; -. [Q9P2G9-1] DR Pumba; Q9P2G9; -. DR Antibodypedia; 2897; 112 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 AGR; HGNC:18644; -. 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; YRAAIKW; -. DR OrthoDB; 5472491at2759; -. DR PhylomeDB; Q9P2G9; -. DR TreeFam; TF329218; -. DR PathwayCommons; Q9P2G9; -. DR SignaLink; Q9P2G9; -. DR SIGNOR; Q9P2G9; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 57563; 14 hits in 1194 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 190 other cell types or tissues. DR ExpressionAtlas; Q9P2G9; baseline and differential. 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 CDD; cd18448; BACK_KLHL8; 1. DR CDD; cd18238; BTB_POZ_KLHL8; 1. DR Gene3D; 1.25.40.420; -; 1. DR Gene3D; 2.120.10.80; Kelch-type beta propeller; 2. 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; IPR011333; SKP1/BTB/POZ_sf. DR PANTHER; PTHR24412:SF35; ACTIN-BINDING PROTEIN IPP; 1. DR PANTHER; PTHR24412; KELCH PROTEIN; 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 PRINTS; PR00501; KELCHREPEAT. DR SMART; SM00875; BACK; 1. DR SMART; SM00225; BTB; 1. DR SMART; SM00612; Kelch; 6. DR SUPFAM; SSF50965; Galactose oxidase, central domain; 1. DR SUPFAM; SSF54695; POZ domain; 1. DR PROSITE; PS50097; BTB; 1. DR Genevisible; Q9P2G9; HS. 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 //