KLHL4_HUMAN
ID KLHL4_HUMAN Reviewed; 718 AA.
AC Q9C0H6; B2RTW2; Q9Y3J5;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 26-SEP-2001, sequence version 2.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Kelch-like protein 4;
GN Name=KLHL4; Synonyms=KIAA1687;
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 [MRNA] (ISOFORMS 1 AND 2).
RX PubMed=11401425; DOI=10.1006/geno.2000.6478;
RA Braybrook C., Warry G., Howell G., Arnason A., Bjornsson A., Moore G.E.,
RA Ross M.T., Stanier P.;
RT "Identification and characterization of KLHL4, a novel human homologue of
RT the Drosophila Kelch gene that maps within the X-linked cleft palate and
RT ankyloglossia (CPX) critical region.";
RL Genomics 72:128-136(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=11214970; DOI=10.1093/dnares/7.6.347;
RA Nagase T., Kikuno R., Hattori A., Kondo Y., Okumura K., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIX. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:347-355(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lymph node;
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=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 133-718 (ISOFORM 1).
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 [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9C0H6-1; Sequence=Displayed;
CC Name=2; Synonyms=KLHL4c;
CC IsoId=Q9C0H6-2; Sequence=VSP_002818;
CC -!- TISSUE SPECIFICITY: Expressed in adult fibroblasts and in a range of
CC fetal tissues including tongue, palate, and mandible.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB14199.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAB21778.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF284765; AAK49441.1; -; mRNA.
DR EMBL; AF284766; AAK49442.1; -; mRNA.
DR EMBL; AB051474; BAB21778.1; ALT_INIT; mRNA.
DR EMBL; AL832514; CAI46201.1; -; mRNA.
DR EMBL; AL035424; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z95400; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471104; EAW98553.1; -; Genomic_DNA.
DR EMBL; BC140839; AAI40840.1; -; mRNA.
DR EMBL; BC140840; AAI40841.1; -; mRNA.
DR EMBL; AK022715; BAB14199.1; ALT_INIT; mRNA.
DR CCDS; CCDS14456.1; -. [Q9C0H6-2]
DR CCDS; CCDS14457.1; -. [Q9C0H6-1]
DR RefSeq; NP_061990.2; NM_019117.4. [Q9C0H6-1]
DR RefSeq; NP_476503.1; NM_057162.2. [Q9C0H6-2]
DR AlphaFoldDB; Q9C0H6; -.
DR SMR; Q9C0H6; -.
DR BioGRID; 121035; 4.
DR IntAct; Q9C0H6; 5.
DR STRING; 9606.ENSP00000362206; -.
DR iPTMnet; Q9C0H6; -.
DR PhosphoSitePlus; Q9C0H6; -.
DR BioMuta; KLHL4; -.
DR DMDM; 17378645; -.
DR EPD; Q9C0H6; -.
DR jPOST; Q9C0H6; -.
DR MassIVE; Q9C0H6; -.
DR MaxQB; Q9C0H6; -.
DR PaxDb; Q9C0H6; -.
DR PeptideAtlas; Q9C0H6; -.
DR PRIDE; Q9C0H6; -.
DR ProteomicsDB; 80044; -. [Q9C0H6-1]
DR ProteomicsDB; 80045; -. [Q9C0H6-2]
DR Antibodypedia; 28423; 152 antibodies from 24 providers.
DR DNASU; 56062; -.
DR Ensembl; ENST00000373114.4; ENSP00000362206.4; ENSG00000102271.14. [Q9C0H6-2]
DR Ensembl; ENST00000373119.9; ENSP00000362211.4; ENSG00000102271.14. [Q9C0H6-1]
DR Ensembl; ENST00000652270.1; ENSP00000498718.1; ENSG00000102271.14. [Q9C0H6-1]
DR GeneID; 56062; -.
DR KEGG; hsa:56062; -.
DR MANE-Select; ENST00000373119.9; ENSP00000362211.4; NM_019117.5; NP_061990.2.
DR UCSC; uc004efa.3; human. [Q9C0H6-1]
DR CTD; 56062; -.
DR DisGeNET; 56062; -.
DR GeneCards; KLHL4; -.
DR HGNC; HGNC:6355; KLHL4.
DR HPA; ENSG00000102271; Tissue enhanced (adrenal gland, brain).
DR MIM; 300348; gene.
DR neXtProt; NX_Q9C0H6; -.
DR OpenTargets; ENSG00000102271; -.
DR PharmGKB; PA30145; -.
DR VEuPathDB; HostDB:ENSG00000102271; -.
DR eggNOG; KOG4441; Eukaryota.
DR GeneTree; ENSGT00940000159818; -.
DR HOGENOM; CLU_004253_12_0_1; -.
DR InParanoid; Q9C0H6; -.
DR OMA; AWTVMPP; -.
DR OrthoDB; 709680at2759; -.
DR PhylomeDB; Q9C0H6; -.
DR TreeFam; TF329218; -.
DR PathwayCommons; Q9C0H6; -.
DR SignaLink; Q9C0H6; -.
DR BioGRID-ORCS; 56062; 9 hits in 739 CRISPR screens.
DR ChiTaRS; KLHL4; human.
DR GenomeRNAi; 56062; -.
DR Pharos; Q9C0H6; Tdark.
DR PRO; PR:Q9C0H6; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q9C0H6; protein.
DR Bgee; ENSG00000102271; Expressed in right adrenal gland cortex and 104 other tissues.
DR ExpressionAtlas; Q9C0H6; baseline and differential.
DR Genevisible; Q9C0H6; HS.
DR GO; GO:0034451; C:centriolar satellite; IDA:HPA.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:HPA.
DR GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW.
DR Gene3D; 2.120.10.80; -; 2.
DR Gene3D; 3.30.710.10; -; 1.
DR InterPro; IPR011705; BACK.
DR InterPro; IPR000210; BTB/POZ_dom.
DR InterPro; IPR015915; Kelch-typ_b-propeller.
DR InterPro; IPR006652; Kelch_1.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR Pfam; PF07707; BACK; 1.
DR Pfam; PF00651; BTB; 1.
DR Pfam; PF01344; Kelch_1; 6.
DR SMART; SM00875; BACK; 1.
DR SMART; SM00225; BTB; 1.
DR SMART; SM00612; Kelch; 6.
DR SUPFAM; SSF117281; SSF117281; 2.
DR SUPFAM; SSF54695; SSF54695; 1.
DR PROSITE; PS50097; BTB; 1.
PE 1: Evidence at protein level;
KW Actin-binding; Alternative splicing; Cytoplasm; Cytoskeleton; Kelch repeat;
KW Reference proteome; Repeat.
FT CHAIN 1..718
FT /note="Kelch-like protein 4"
FT /id="PRO_0000119104"
FT DOMAIN 182..249
FT /note="BTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT REPEAT 430..476
FT /note="Kelch 1"
FT REPEAT 477..523
FT /note="Kelch 2"
FT REPEAT 525..570
FT /note="Kelch 3"
FT REPEAT 571..617
FT /note="Kelch 4"
FT REPEAT 619..670
FT /note="Kelch 5"
FT REPEAT 671..717
FT /note="Kelch 6"
FT REGION 46..69
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 46..65
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 700..718
FT /note="EVPVNIGRAGACVVVVKLP -> SMQELLQNFYTTQKLKETLGH (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:11401425,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_002818"
SQ SEQUENCE 718 AA; 80245 MW; D7385BAAD63B150A CRC64;
MSVSGKKEFD VKQILRLRWR WFSHPFQGST NTGSCLQQEG YEHRGTPVQG RLKSHSRDRN
GLKKSNSPVH HNILAPVPGP APAHQRAVQN LQQHNLIVHF QANEDTPKSV PEKNLFKEAC
EKRAQDLEMM ADDNIEDSTA RLDTQHSEDM NATRSEEQFH VINHAEQTLR KMENYLKEKQ
LCDVLLIAGH LRIPAHRLVL SAVSDYFAAM FTNDVLEAKQ EEVRMEGVDP NALNSLVQYA
YTGVLQLKED TIESLLAAAC LLQLTQVIDV CSNFLIKQLH PSNCLGIRSF GDAQGCTELL
NVAHKYTMEH FIEVIKNQEF LLLPANEISK LLCSDDINVP DEETIFHALM QWVGHDVQNR
QGELGMLLSY IRLPLLPPQL LADLETSSMF TGDLECQKLL MEAMKYHLLP ERRSMMQSPR
TKPRKSTVGA LYAVGGMDAM KGTTTIEKYD LRTNSWLHIG TMNGRRLQFG VAVIDNKLYV
VGGRDGLKTL NTVECFNPVG KIWTVMPPMS THRHGLGVAT LEGPMYAVGG HDGWSYLNTV
ERWDPEGRQW NYVASMSTPR STVGVVALNN KLYAIGGRDG SSCLKSMEYF DPHTNKWSLC
APMSKRRGGV GVATYNGFLY VVGGHDAPAS NHCSRLSDCV ERYDPKGDSW STVAPLSVPR
DAVAVCPLGD KLYVVGGYDG HTYLNTVESY DAQRNEWKEE VPVNIGRAGA CVVVVKLP
