LOCUS       NP_065854                620 aa            linear   PRI 20-SEP-2024
DEFINITION  kelch-like protein 8 isoform 1 [Homo sapiens].
ACCESSION   NP_065854
VERSION     NP_065854.3
DBSOURCE    REFSEQ: accession NM_020803.5
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 620)
  AUTHORS   Swaney,D.L., Ramms,D.J., Wang,Z., Park,J., Goto,Y., Soucheray,M.,
            Bhola,N., Kim,K., Zheng,F., Zeng,Y., McGregor,M., Herrington,K.A.,
            O'Keefe,R., Jin,N., VanLandingham,N.K., Foussard,H., Von Dollen,J.,
            Bouhaddou,M., Jimenez-Morales,D., Obernier,K., Kreisberg,J.F.,
            Kim,M., Johnson,D.E., Jura,N., Grandis,J.R., Gutkind,J.S.,
            Ideker,T. and Krogan,N.J.
  TITLE     A protein network map of head and neck cancer reveals PIK3CA mutant
            drug sensitivity
  JOURNAL   Science 374 (6563), eabf2911 (2021)
   PUBMED   34591642
REFERENCE   2  (residues 1 to 620)
  AUTHORS   Huttlin,E.L., Bruckner,R.J., Navarrete-Perea,J., Cannon,J.R.,
            Baltier,K., Gebreab,F., Gygi,M.P., Thornock,A., Zarraga,G., Tam,S.,
            Szpyt,J., Gassaway,B.M., Panov,A., Parzen,H., Fu,S., Golbazi,A.,
            Maenpaa,E., Stricker,K., Guha Thakurta,S., Zhang,T., Rad,R.,
            Pan,J., Nusinow,D.P., Paulo,J.A., Schweppe,D.K., Vaites,L.P.,
            Harper,J.W. and Gygi,S.P.
  TITLE     Dual proteome-scale networks reveal cell-specific remodeling of the
            human interactome
  JOURNAL   Cell 184 (11), 3022-3040 (2021)
   PUBMED   33961781
REFERENCE   3  (residues 1 to 620)
  AUTHORS   Luck,K., Kim,D.K., Lambourne,L., Spirohn,K., Begg,B.E., Bian,W.,
            Brignall,R., Cafarelli,T., Campos-Laborie,F.J., Charloteaux,B.,
            Choi,D., Cote,A.G., Daley,M., Deimling,S., Desbuleux,A., Dricot,A.,
            Gebbia,M., Hardy,M.F., Kishore,N., Knapp,J.J., Kovacs,I.A.,
            Lemmens,I., Mee,M.W., Mellor,J.C., Pollis,C., Pons,C.,
            Richardson,A.D., Schlabach,S., Teeking,B., Yadav,A., Babor,M.,
            Balcha,D., Basha,O., Bowman-Colin,C., Chin,S.F., Choi,S.G.,
            Colabella,C., Coppin,G., D'Amata,C., De Ridder,D., De Rouck,S.,
            Duran-Frigola,M., Ennajdaoui,H., Goebels,F., Goehring,L., Gopal,A.,
            Haddad,G., Hatchi,E., Helmy,M., Jacob,Y., Kassa,Y., Landini,S.,
            Li,R., van Lieshout,N., MacWilliams,A., Markey,D., Paulson,J.N.,
            Rangarajan,S., Rasla,J., Rayhan,A., Rolland,T., San-Miguel,A.,
            Shen,Y., Sheykhkarimli,D., Sheynkman,G.M., Simonovsky,E., Tasan,M.,
            Tejeda,A., Tropepe,V., Twizere,J.C., Wang,Y., Weatheritt,R.J.,
            Weile,J., Xia,Y., Yang,X., Yeger-Lotem,E., Zhong,Q., Aloy,P.,
            Bader,G.D., De Las Rivas,J., Gaudet,S., Hao,T., Rak,J.,
            Tavernier,J., Hill,D.E., Vidal,M., Roth,F.P. and Calderwood,M.A.
  TITLE     A reference map of the human binary protein interactome
  JOURNAL   Nature 580 (7803), 402-408 (2020)
   PUBMED   32296183
REFERENCE   4  (residues 1 to 620)
  AUTHORS   Mena,E.L., Kjolby,R.A.S., Saxton,R.A., Werner,A., Lew,B.G.,
            Boyle,J.M., Harland,R. and Rape,M.
  TITLE     Dimerization quality control ensures neuronal development and
            survival
  JOURNAL   Science 362 (6411) (2018)
   PUBMED   30190310
REFERENCE   5  (residues 1 to 620)
  AUTHORS   Willer,C.J., Schmidt,E.M., Sengupta,S., Peloso,G.M., Gustafsson,S.,
            Kanoni,S., Ganna,A., Chen,J., Buchkovich,M.L., Mora,S.,
            Beckmann,J.S., Bragg-Gresham,J.L., Chang,H.Y., Demirkan,A., Den
            Hertog,H.M., Do,R., Donnelly,L.A., Ehret,G.B., Esko,T.,
            Feitosa,M.F., Ferreira,T., Fischer,K., Fontanillas,P., Fraser,R.M.,
            Freitag,D.F., Gurdasani,D., Heikkila,K., Hypponen,E., Isaacs,A.,
            Jackson,A.U., Johansson,A., Johnson,T., Kaakinen,M., Kettunen,J.,
            Kleber,M.E., Li,X., Luan,J., Lyytikainen,L.P., Magnusson,P.K.E.,
            Mangino,M., Mihailov,E., Montasser,M.E., Muller-Nurasyid,M.,
            Nolte,I.M., O'Connell,J.R., Palmer,C.D., Perola,M., Petersen,A.K.,
            Sanna,S., Saxena,R., Service,S.K., Shah,S., Shungin,D., Sidore,C.,
            Song,C., Strawbridge,R.J., Surakka,I., Tanaka,T., Teslovich,T.M.,
            Thorleifsson,G., Van den Herik,E.G., Voight,B.F., Volcik,K.A.,
            Waite,L.L., Wong,A., Wu,Y., Zhang,W., Absher,D., Asiki,G.,
            Barroso,I., Been,L.F., Bolton,J.L., Bonnycastle,L.L., Brambilla,P.,
            Burnett,M.S., Cesana,G., Dimitriou,M., Doney,A.S.F., Doring,A.,
            Elliott,P., Epstein,S.E., Ingi Eyjolfsson,G., Gigante,B.,
            Goodarzi,M.O., Grallert,H., Gravito,M.L., Groves,C.J., Hallmans,G.,
            Hartikainen,A.L., Hayward,C., Hernandez,D., Hicks,A.A., Holm,H.,
            Hung,Y.J., Illig,T., Jones,M.R., Kaleebu,P., Kastelein,J.J.P.,
            Khaw,K.T., Kim,E., Klopp,N., Komulainen,P., Kumari,M.,
            Langenberg,C., Lehtimaki,T., Lin,S.Y., Lindstrom,J., Loos,R.J.F.,
            Mach,F., McArdle,W.L., Meisinger,C., Mitchell,B.D., Muller,G.,
            Nagaraja,R., Narisu,N., Nieminen,T.V.M., Nsubuga,R.N., Olafsson,I.,
            Ong,K.K., Palotie,A., Papamarkou,T., Pomilla,C., Pouta,A.,
            Rader,D.J., Reilly,M.P., Ridker,P.M., Rivadeneira,F., Rudan,I.,
            Ruokonen,A., Samani,N., Scharnagl,H., Seeley,J., Silander,K.,
            Stancakova,A., Stirrups,K., Swift,A.J., Tiret,L.,
            Uitterlinden,A.G., van Pelt,L.J., Vedantam,S., Wainwright,N.,
            Wijmenga,C., Wild,S.H., Willemsen,G., Wilsgaard,T., Wilson,J.F.,
            Young,E.H., Zhao,J.H., Adair,L.S., Arveiler,D., Assimes,T.L.,
            Bandinelli,S., Bennett,F., Bochud,M., Boehm,B.O., Boomsma,D.I.,
            Borecki,I.B., Bornstein,S.R., Bovet,P., Burnier,M., Campbell,H.,
            Chakravarti,A., Chambers,J.C., Chen,Y.I., Collins,F.S.,
            Cooper,R.S., Danesh,J., Dedoussis,G., de Faire,U., Feranil,A.B.,
            Ferrieres,J., Ferrucci,L., Freimer,N.B., Gieger,C., Groop,L.C.,
            Gudnason,V., Gyllensten,U., Hamsten,A., Harris,T.B., Hingorani,A.,
            Hirschhorn,J.N., Hofman,A., Hovingh,G.K., Hsiung,C.A.,
            Humphries,S.E., Hunt,S.C., Hveem,K., Iribarren,C., Jarvelin,M.R.,
            Jula,A., Kahonen,M., Kaprio,J., Kesaniemi,A., Kivimaki,M.,
            Kooner,J.S., Koudstaal,P.J., Krauss,R.M., Kuh,D., Kuusisto,J.,
            Kyvik,K.O., Laakso,M., Lakka,T.A., Lind,L., Lindgren,C.M.,
            Martin,N.G., Marz,W., McCarthy,M.I., McKenzie,C.A., Meneton,P.,
            Metspalu,A., Moilanen,L., Morris,A.D., Munroe,P.B., Njolstad,I.,
            Pedersen,N.L., Power,C., Pramstaller,P.P., Price,J.F., Psaty,B.M.,
            Quertermous,T., Rauramaa,R., Saleheen,D., Salomaa,V.,
            Sanghera,D.K., Saramies,J., Schwarz,P.E.H., Sheu,W.H.,
            Shuldiner,A.R., Siegbahn,A., Spector,T.D., Stefansson,K.,
            Strachan,D.P., Tayo,B.O., Tremoli,E., Tuomilehto,J., Uusitupa,M.,
            van Duijn,C.M., Vollenweider,P., Wallentin,L., Wareham,N.J.,
            Whitfield,J.B., Wolffenbuttel,B.H.R., Ordovas,J.M., Boerwinkle,E.,
            Palmer,C.N.A., Thorsteinsdottir,U., Chasman,D.I., Rotter,J.I.,
            Franks,P.W., Ripatti,S., Cupples,L.A., Sandhu,M.S., Rich,S.S.,
            Boehnke,M., Deloukas,P., Kathiresan,S., Mohlke,K.L., Ingelsson,E.
            and Abecasis,G.R.
  CONSRTM   Global Lipids Genetics Consortium
  TITLE     Discovery and refinement of loci associated with lipid levels
  JOURNAL   Nat Genet 45 (11), 1274-1283 (2013)
   PUBMED   24097068
REFERENCE   6  (residues 1 to 620)
  AUTHORS   Bennett,E.J., Rush,J., Gygi,S.P. and Harper,J.W.
  TITLE     Dynamics of cullin-RING ubiquitin ligase network revealed by
            systematic quantitative proteomics
  JOURNAL   Cell 143 (6), 951-965 (2010)
   PUBMED   21145461
REFERENCE   7  (residues 1 to 620)
  AUTHORS   Flachsbart,F., Franke,A., Kleindorp,R., Caliebe,A., Blanche,H.,
            Schreiber,S. and Nebel,A.
  TITLE     Investigation of genetic susceptibility factors for human longevity
            - a targeted nonsynonymous SNP study
  JOURNAL   Mutat Res 694 (1-2), 13-19 (2010)
   PUBMED   20800603
  REMARK    GeneRIF: Observational study of gene-disease association. (HuGE
            Navigator)
REFERENCE   8  (residues 1 to 620)
  AUTHORS   Teslovich,T.M., Musunuru,K., Smith,A.V., Edmondson,A.C.,
            Stylianou,I.M., Koseki,M., Pirruccello,J.P., Ripatti,S.,
            Chasman,D.I., Willer,C.J., Johansen,C.T., Fouchier,S.W., Isaacs,A.,
            Peloso,G.M., Barbalic,M., Ricketts,S.L., Bis,J.C., Aulchenko,Y.S.,
            Thorleifsson,G., Feitosa,M.F., Chambers,J., Orho-Melander,M.,
            Melander,O., Johnson,T., Li,X., Guo,X., Li,M., Shin Cho,Y., Jin
            Go,M., Jin Kim,Y., Lee,J.Y., Park,T., Kim,K., Sim,X., Twee-Hee
            Ong,R., Croteau-Chonka,D.C., Lange,L.A., Smith,J.D., Song,K., Hua
            Zhao,J., Yuan,X., Luan,J., Lamina,C., Ziegler,A., Zhang,W.,
            Zee,R.Y., Wright,A.F., Witteman,J.C., Wilson,J.F., Willemsen,G.,
            Wichmann,H.E., Whitfield,J.B., Waterworth,D.M., Wareham,N.J.,
            Waeber,G., Vollenweider,P., Voight,B.F., Vitart,V.,
            Uitterlinden,A.G., Uda,M., Tuomilehto,J., Thompson,J.R., Tanaka,T.,
            Surakka,I., Stringham,H.M., Spector,T.D., Soranzo,N., Smit,J.H.,
            Sinisalo,J., Silander,K., Sijbrands,E.J., Scuteri,A., Scott,J.,
            Schlessinger,D., Sanna,S., Salomaa,V., Saharinen,J., Sabatti,C.,
            Ruokonen,A., Rudan,I., Rose,L.M., Roberts,R., Rieder,M.,
            Psaty,B.M., Pramstaller,P.P., Pichler,I., Perola,M., Penninx,B.W.,
            Pedersen,N.L., Pattaro,C., Parker,A.N., Pare,G., Oostra,B.A.,
            O'Donnell,C.J., Nieminen,M.S., Nickerson,D.A., Montgomery,G.W.,
            Meitinger,T., McPherson,R., McCarthy,M.I., McArdle,W., Masson,D.,
            Martin,N.G., Marroni,F., Mangino,M., Magnusson,P.K., Lucas,G.,
            Luben,R., Loos,R.J., Lokki,M.L., Lettre,G., Langenberg,C.,
            Launer,L.J., Lakatta,E.G., Laaksonen,R., Kyvik,K.O., Kronenberg,F.,
            Konig,I.R., Khaw,K.T., Kaprio,J., Kaplan,L.M., Johansson,A.,
            Jarvelin,M.R., Janssens,A.C., Ingelsson,E., Igl,W., Kees
            Hovingh,G., Hottenga,J.J., Hofman,A., Hicks,A.A., Hengstenberg,C.,
            Heid,I.M., Hayward,C., Havulinna,A.S., Hastie,N.D., Harris,T.B.,
            Haritunians,T., Hall,A.S., Gyllensten,U., Guiducci,C., Groop,L.C.,
            Gonzalez,E., Gieger,C., Freimer,N.B., Ferrucci,L., Erdmann,J.,
            Elliott,P., Ejebe,K.G., Doring,A., Dominiczak,A.F., Demissie,S.,
            Deloukas,P., de Geus,E.J., de Faire,U., Crawford,G., Collins,F.S.,
            Chen,Y.D., Caulfield,M.J., Campbell,H., Burtt,N.P.,
            Bonnycastle,L.L., Boomsma,D.I., Boekholdt,S.M., Bergman,R.N.,
            Barroso,I., Bandinelli,S., Ballantyne,C.M., Assimes,T.L.,
            Quertermous,T., Altshuler,D., Seielstad,M., Wong,T.Y., Tai,E.S.,
            Feranil,A.B., Kuzawa,C.W., Adair,L.S., Taylor,H.A. Jr.,
            Borecki,I.B., Gabriel,S.B., Wilson,J.G., Holm,H.,
            Thorsteinsdottir,U., Gudnason,V., Krauss,R.M., Mohlke,K.L.,
            Ordovas,J.M., Munroe,P.B., Kooner,J.S., Tall,A.R., Hegele,R.A.,
            Kastelein,J.J., Schadt,E.E., Rotter,J.I., Boerwinkle,E.,
            Strachan,D.P., Mooser,V., Stefansson,K., Reilly,M.P., Samani,N.J.,
            Schunkert,H., Cupples,L.A., Sandhu,M.S., Ridker,P.M., Rader,D.J.,
            van Duijn,C.M., Peltonen,L., Abecasis,G.R., Boehnke,M. and
            Kathiresan,S.
  TITLE     Biological, clinical and population relevance of 95 loci for blood
            lipids
  JOURNAL   Nature 466 (7307), 707-713 (2010)
   PUBMED   20686565
REFERENCE   9  (residues 1 to 620)
  AUTHORS   Nam,S., Min,K., Hwang,H., Lee,H.O., Lee,J.H., Yoon,J., Lee,H.,
            Park,S. and Lee,J.
  TITLE     Control of rapsyn stability by the CUL-3-containing E3 ligase
            complex
  JOURNAL   J Biol Chem 284 (12), 8195-8206 (2009)
   PUBMED   19158078
REFERENCE   10 (residues 1 to 620)
  AUTHORS   Lim,J., Hao,T., Shaw,C., Patel,A.J., Szabo,G., Rual,J.F.,
            Fisk,C.J., Li,N., Smolyar,A., Hill,D.E., Barabasi,A.L., Vidal,M.
            and Zoghbi,H.Y.
  TITLE     A protein-protein interaction network for human inherited ataxias
            and disorders of Purkinje cell degeneration
  JOURNAL   Cell 125 (4), 801-814 (2006)
   PUBMED   16713569
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            AC092658.2, CN290430.1, BX640727.1, BX647454.1, BX538173.1,
            BX640744.1 and AA878129.1.
            
            On Aug 22, 2003 this sequence version replaced NP_065854.2.
            
            Transcript Variant: This variant (2) differs in the 5' UTR compared
            to variant 1. Variants 1 and 2 encode the same isoform (1).
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR1803614.259598.1,
                                           SRR1660803.9680.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000273963.10/ ENSP00000273963.5
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..620
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="4"
                     /map="4q22.1"
     Protein         1..620
                     /product="kelch-like protein 8 isoform 1"
                     /note="kelch-like protein 8; kelch-like 8"
                     /calculated_mol_wt=68671
     Region          1..35
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9P2G9.4)"
     Site            2
                     /site_type="acetylation"
                     /note="N-acetylalanine.
                     /evidence=ECO:0007744|PubMed:22814378; propagated from
                     UniProtKB/Swiss-Prot (Q9P2G9.4)"
     Region          52..171
                     /region_name="BTB_POZ_KLHL8"
                     /note="BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ
                     (poxvirus and zinc finger) domain found in Kelch-like
                     protein 8 (KLHL8); cd18238"
                     /db_xref="CDD:349547"
     Region          60..535
                     /region_name="PHA03098"
                     /note="kelch-like protein; Provisional"
                     /db_xref="CDD:222983"
     Region          319..366
                     /region_name="Kelch 1"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9P2G9.4)"
     Region          356..399
                     /region_name="KELCH repeat"
                     /note="KELCH repeat [structural motif]"
                     /db_xref="CDD:276965"
     Region          367..413
                     /region_name="Kelch 2"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9P2G9.4)"
     Region          403..447
                     /region_name="KELCH repeat"
                     /note="KELCH repeat [structural motif]"
                     /db_xref="CDD:276965"
     Region          415..460
                     /region_name="Kelch 3"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9P2G9.4)"
     Region          450..495
                     /region_name="KELCH repeat"
                     /note="KELCH repeat [structural motif]"
                     /db_xref="CDD:276965"
     Region          462..507
                     /region_name="Kelch 4"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9P2G9.4)"
     Region          497..542
                     /region_name="KELCH repeat"
                     /note="KELCH repeat [structural motif]"
                     /db_xref="CDD:276965"
     Region          508..554
                     /region_name="Kelch 5"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9P2G9.4)"
     Region          544..586
                     /region_name="KELCH repeat"
                     /note="KELCH repeat [structural motif]"
                     /db_xref="CDD:276965"
     Region          555..599
                     /region_name="Kelch"
                     /note="Kelch domain; smart00612"
                     /db_xref="CDD:128874"
     Region          556..601
                     /region_name="Kelch 6"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9P2G9.4)"
     CDS             1..620
                     /gene="KLHL8"
                     /coded_by="NM_020803.5:353..2215"
                     /note="isoform 1 is encoded by transcript variant 2"
                     /db_xref="CCDS:CCDS3617.1"
                     /db_xref="GeneID:57563"
                     /db_xref="HGNC:HGNC:18644"
                     /db_xref="MIM:611967"
ORIGIN      
        1 masdsmsskq arnhitkgkr qqqhqqiknr ssisdgdged sfifeaneaw kdfhgsllrf
       61 yengelcdvt lkvgsklisc hklvlacvip yframflsem aeakqtliei rdfdgdaied
      121 lvkfvyssrl tltvdnvqpl lyaacilqve lvaracceym klhfhpsncl avrafaeshn
      181 ridlmdmadq yacdhftevv ecedfvsvsp qhlhkllsss dlnienekqv ynaaikwlla
      241 npqhhskwld etlaqvrlpl lpvdflmgvv akeqivkqnl kcrdlldear nyhlhlssra
      301 vpdfeysirt tprkhtagvl fcvggrggsg dpfrsiecys inknswffgp emnsrrrhvg
      361 visvegkvya vgghdgnehl gsmemfdplt nkwmmkasmn tkrrgialas lggpiyaigg
      421 lddntcfndv erydiesdqw stvapmntpr ggvgsvalvn hvyavggndg maslssvery
      481 dphldkwiev kemgqrragn gvsklhgcly vvggfddnsp lssverydpr snkwdyvaal
      541 ttprggvgia tvmgkifavg ghngnaylnt veafdpvlnr welvgsvshc ragagvavcs
      601 cltsqirdvg hgsnnvvdcm
//
