KLH40_MOUSE
ID KLH40_MOUSE Reviewed; 621 AA.
AC Q9D783; B9EHG6; Q059P8; Q3TUF0;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Kelch-like protein 40 {ECO:0000305};
DE AltName: Full=Kelch repeat and BTB domain-containing protein 5 {ECO:0000303|PubMed:24361185, ECO:0000303|PubMed:25940086};
GN Name=Klhl40 {ECO:0000312|MGI:MGI:1919580};
GN Synonyms=Kbtbd5 {ECO:0000303|PubMed:24361185, ECO:0000303|PubMed:25940086};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Head, and Tongue;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=23746549; DOI=10.1016/j.ajhg.2013.05.004;
RA Ravenscroft G., Miyatake S., Lehtokari V.L., Todd E.J., Vornanen P.,
RA Yau K.S., Hayashi Y.K., Miyake N., Tsurusaki Y., Doi H., Saitsu H.,
RA Osaka H., Yamashita S., Ohya T., Sakamoto Y., Koshimizu E., Imamura S.,
RA Yamashita M., Ogata K., Shiina M., Bryson-Richardson R.J., Vaz R.,
RA Ceyhan O., Brownstein C.A., Swanson L.C., Monnot S., Romero N.B.,
RA Amthor H., Kresoje N., Sivadorai P., Kiraly-Borri C., Haliloglu G.,
RA Talim B., Orhan D., Kale G., Charles A.K., Fabian V.A., Davis M.R.,
RA Lammens M., Sewry C.A., Manzur A., Muntoni F., Clarke N.F., North K.N.,
RA Bertini E., Nevo Y., Willichowski E., Silberg I.E., Topaloglu H.,
RA Beggs A.H., Allcock R.J., Nishino I., Wallgren-Pettersson C., Matsumoto N.,
RA Laing N.G.;
RT "Mutations in KLHL40 are a frequent cause of severe autosomal-recessive
RT nemaline myopathy.";
RL Am. J. Hum. Genet. 93:6-18(2013).
RN [5]
RP DEVELOPMENTAL STAGE, INDUCTION, AND IDENTIFICATION IN THE BCR(KLHL40)
RP COMPLEX.
RX PubMed=24361185; DOI=10.1016/j.diff.2013.08.002;
RA Bowlin K.M., Embree L.J., Garry M.G., Garry D.J., Shi X.;
RT "Kbtbd5 is regulated by MyoD and restricted to the myogenic lineage.";
RL Differentiation 86:184-191(2013).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH LMOD3, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=24960163; DOI=10.1172/jci74994;
RA Garg A., O'Rourke J., Long C., Doering J., Ravenscroft G.,
RA Bezprozvannaya S., Nelson B.R., Beetz N., Li L., Chen S., Laing N.G.,
RA Grange R.W., Bassel-Duby R., Olson E.N.;
RT "KLHL40 deficiency destabilizes thin filament proteins and promotes
RT nemaline myopathy.";
RL J. Clin. Invest. 124:3529-3539(2014).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=25940086; DOI=10.1074/jbc.m114.629956;
RA Gong W., Gohla R.M., Bowlin K.M., Koyano-Nakagawa N., Garry D.J., Shi X.;
RT "Kelch repeat and BTB domain containing protein 5 (Kbtbd5) regulates
RT skeletal muscle myogenesis through the E2F1-DP1 complex.";
RL J. Biol. Chem. 290:15350-15361(2015).
CC -!- FUNCTION: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3
CC ubiquitin ligase complex that acts as a key regulator of skeletal
CC muscle development (PubMed:25940086). The BCR(KLHL40) complex acts by
CC mediating ubiquitination and degradation of TFDP1, thereby regulating
CC the activity of the E2F:DP transcription factor complex
CC (PubMed:25940086). Promotes stabilization of LMOD3 by acting as a
CC negative regulator of LMOD3 ubiquitination; the molecular process by
CC which it negatively regulates ubiquitination of LMOD3 is however
CC unclear (PubMed:24960163). {ECO:0000269|PubMed:24960163,
CC ECO:0000269|PubMed:25940086}.
CC -!- SUBUNIT: Component of the BCR(KLHL40) E3 ubiquitin ligase complex, at
CC least composed of CUL3, KLHL40 and RBX1 (PubMed:24361185). Interacts
CC with LMOD3 (PubMed:24960163). {ECO:0000269|PubMed:24361185,
CC ECO:0000269|PubMed:24960163}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:25940086}.
CC Cytoplasm, myofibril, sarcomere, A band {ECO:0000269|PubMed:24960163}.
CC Cytoplasm, myofibril, sarcomere, I band {ECO:0000269|PubMed:24960163}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9D783-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9D783-2; Sequence=VSP_022683, VSP_022684;
CC -!- TISSUE SPECIFICITY: Specifically expressed in skeletal muscles in
CC embryonic, neonatal and adults (PubMed:24960163, PubMed:25940086).
CC Expressed in various types of muscles, including extensor digitorum
CC longus, gastrocnemius, soleus, diaphragm, masseter and heart (at
CC protein level). Not detected in brain, liver and lung (at protein
CC level). {ECO:0000269|PubMed:23746549, ECO:0000269|PubMed:24960163,
CC ECO:0000269|PubMed:25940086}.
CC -!- DEVELOPMENTAL STAGE: Absent early during embryogenesis (7 dpc), present
CC at the middle stage (11 dpc) and highly expressed at the later stages
CC (15 dpc and 17 dpc) (PubMed:24361185). Specifically expressed in the
CC somites at 11.5 dpc and in the skeletal muscle at 15.5 dpc
CC (PubMed:24361185). {ECO:0000269|PubMed:24361185}.
CC -!- INDUCTION: Up-regulated during myogenic differentiation
CC (PubMed:24361185). Induced during the differentiation of myoblasts into
CC myotubes (PubMed:23746549). {ECO:0000269|PubMed:23746549,
CC ECO:0000269|PubMed:24361185}.
CC -!- DISRUPTION PHENOTYPE: Neonates are normal in size at birth and were
CC born with the expected Mendelian ratio (PubMed:24960163,
CC PubMed:25940086). They however fail to gain weight and do not survive
CC to weaning (PubMed:24960163, PubMed:25940086). Defects are due to
CC smaller muscle fibers and a disorganized sarcomeric structure
CC (PubMed:24960163, PubMed:25940086). {ECO:0000269|PubMed:24960163,
CC ECO:0000269|PubMed:25940086}.
CC -!- SIMILARITY: Belongs to the KLHL40 family. {ECO:0000305}.
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DR EMBL; AK009491; BAB26321.1; -; mRNA.
DR EMBL; AK160799; BAE36021.1; -; mRNA.
DR EMBL; BC125576; AAI25577.1; -; mRNA.
DR EMBL; BC137889; AAI37890.1; -; mRNA.
DR CCDS; CCDS23637.1; -. [Q9D783-1]
DR RefSeq; NP_082478.1; NM_028202.3.
DR AlphaFoldDB; Q9D783; -.
DR SMR; Q9D783; -.
DR BioGRID; 215313; 13.
DR STRING; 10090.ENSMUSP00000095873; -.
DR iPTMnet; Q9D783; -.
DR PhosphoSitePlus; Q9D783; -.
DR MaxQB; Q9D783; -.
DR PaxDb; Q9D783; -.
DR PRIDE; Q9D783; -.
DR ProteomicsDB; 264849; -. [Q9D783-1]
DR ProteomicsDB; 264850; -. [Q9D783-2]
DR GeneID; 72330; -.
DR KEGG; mmu:72330; -.
DR UCSC; uc009sdv.2; mouse. [Q9D783-1]
DR UCSC; uc029xgr.1; mouse. [Q9D783-2]
DR CTD; 131377; -.
DR MGI; MGI:1919580; Klhl40.
DR eggNOG; KOG4441; Eukaryota.
DR InParanoid; Q9D783; -.
DR OrthoDB; 946131at2759; -.
DR PhylomeDB; Q9D783; -.
DR TreeFam; TF351653; -.
DR BioGRID-ORCS; 72330; 2 hits in 72 CRISPR screens.
DR PRO; PR:Q9D783; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q9D783; protein.
DR GO; GO:0031672; C:A band; IDA:MGI.
DR GO; GO:0031463; C:Cul3-RING ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0031674; C:I band; IDA:MGI.
DR GO; GO:0032435; P:negative regulation of proteasomal ubiquitin-dependent protein catabolic process; IDA:MGI.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; IDA:MGI.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:MGI.
DR GO; GO:0016567; P:protein ubiquitination; IDA:MGI.
DR GO; GO:0048741; P:skeletal muscle fiber development; IMP:UniProtKB.
DR GO; GO:0098528; P:skeletal muscle fiber differentiation; IMP:UniProtKB.
DR Gene3D; 2.120.10.80; -; 1.
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; IPR015915; Kelch-typ_b-propeller.
DR InterPro; IPR006652; Kelch_1.
DR InterPro; IPR030607; KLHL40.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR PANTHER; PTHR24412:SF22; PTHR24412:SF22; 1.
DR Pfam; PF07707; BACK; 1.
DR Pfam; PF00651; BTB; 1.
DR Pfam; PF01344; Kelch_1; 3.
DR PIRSF; PIRSF037037; Kelch-like_protein_gigaxonin; 1.
DR SMART; SM00875; BACK; 1.
DR SMART; SM00225; BTB; 1.
DR SMART; SM00612; Kelch; 4.
DR SUPFAM; SSF117281; SSF117281; 1.
DR SUPFAM; SSF54695; SSF54695; 1.
DR PROSITE; PS50097; BTB; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Developmental protein; Kelch repeat;
KW Reference proteome; Repeat; Ubl conjugation pathway.
FT CHAIN 1..621
FT /note="Kelch-like protein 40"
FT /id="PRO_0000274236"
FT DOMAIN 33..98
FT /note="BTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT DOMAIN 133..239
FT /note="BACK"
FT /evidence="ECO:0000255"
FT REPEAT 360..412
FT /note="Kelch 1"
FT /evidence="ECO:0000255"
FT REPEAT 413..462
FT /note="Kelch 2"
FT /evidence="ECO:0000255"
FT REPEAT 463..510
FT /note="Kelch 3"
FT /evidence="ECO:0000255"
FT REPEAT 512..557
FT /note="Kelch 4"
FT /evidence="ECO:0000255"
FT REPEAT 559..613
FT /note="Kelch 5"
FT /evidence="ECO:0000255"
FT REGION 265..298
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 385..445
FT /note="FDHLDSEWLGMPPLPSPRCLFGLGEALNAIYVVGGRELKDSEDSLDSVLCYD
FT RLSFKWGES -> VPGQS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_022683"
FT VAR_SEQ 446..621
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_022684"
FT CONFLICT 616
FT /note="V -> L (in Ref. 1; BAE36021)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 621 AA; 69589 MW; D8D4BEA104526E5F CRC64;
MTLGLEQAEE QRLYQQTLLQ DGLKDMLDHG KFLDCVVRVG EREFPCHRLV LAACSPYFRA
RFLAEPDSAG EVRLEEVSPD VVSQVLHYLY TSEIALDEAS VQDLFAAAHR FQIPSIFTIC
VSFLQKRLCL ANCLAVFRLG LLLDCARLAV AARDFICARF PLVARDNDFL GLSADELIAI
ISSDGLNVEK EEAVFEAVMR WASSGDAEAQ AERQRALPTV FESVRCRLLP RAFLETRVER
HPLVRSQPEL LRKVQMVKDA HEGRLTTLRK KKKEKGEQTA RAKEANQGTE DTKAEDDEER
VLPGILNDTL RFGMFLQDLI FMISEEGAVA YDPAANECYC ASLSTQIPKN HVSLVTKENQ
VFVAGGLFYN EDNKEDPMSA YFLQFDHLDS EWLGMPPLPS PRCLFGLGEA LNAIYVVGGR
ELKDSEDSLD SVLCYDRLSF KWGESDPLPY AVYGHTVLSH MDLVYVIGGK GKDRKCLNKM
CVYDPKKFEW KELAPMQTAR SLFGATVHDG RIFVAAGVTD TGLTSSSEVY SIADNKWTSF
EAFPQERSSL SLVSLAGTLY ALGGFATLET ESGELVPTEL NDIWRYNEDE KKWEGVLREI
AYAAGATFLP VRLNVVRLTK M
