KL40A_DANRE
ID KL40A_DANRE Reviewed; 612 AA.
AC B3DIV9; B8JL77; Q66L56;
DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT 16-OCT-2013, sequence version 2.
DT 03-AUG-2022, entry version 89.
DE RecName: Full=Kelch-like protein 40a;
DE AltName: Full=Kelch repeat and BTB domain-containing protein 5a;
GN Name=klhl40a; Synonyms=kbtbd5a;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (APR-2008) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
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).
CC -!- FUNCTION: ubstrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3
CC ubiquitin ligase complex (By similarity). Required for skeletal muscle
CC development (PubMed:23746549). {ECO:0000250|UniProtKB:Q9D783,
CC ECO:0000269|PubMed:23746549}.
CC -!- SUBUNIT: Component of the BCR(KLHL40) E3 ubiquitin ligase complex.
CC {ECO:0000250|UniProtKB:Q9D783}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9D783}.
CC Cytoplasm, myofibril, sarcomere, A band {ECO:0000250|UniProtKB:Q9D783}.
CC Cytoplasm, myofibril, sarcomere, I band {ECO:0000250|UniProtKB:Q9D783}.
CC -!- TISSUE SPECIFICITY: Expressed in skeletal muscle and heart. Detected,
CC although at much lower levels, in brain, eye and fin.
CC {ECO:0000269|PubMed:23746549}.
CC -!- DEVELOPMENTAL STAGE: At 16 and 24 hpf, restricted to muscle precursor
CC cells in somites. Also detected at 48 hpf.
CC {ECO:0000269|PubMed:23746549}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown of the protein results in a
CC curved trunk and small head at 48 hpf. Morphants show disruption of
CC skeletal muscle patterning with an irregular, wavy appearance of the
CC striated myofibers and extensive gaps between the myofibers. Myofibers
CC show disorganized and irregular patterns with small aggregates of
CC alpha-actinin, suggesting nemaline bodies. Animals exhibit sporadic
CC muscle tremor and coordinated swimming is not observed.
CC {ECO:0000269|PubMed:23746549}.
CC -!- SIMILARITY: Belongs to the KLHL40 family. {ECO:0000305}.
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DR EMBL; CU464125; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC078427; AAH78427.1; -; mRNA.
DR EMBL; BC163267; AAI63267.1; -; mRNA.
DR RefSeq; NP_001122154.1; NM_001128682.1.
DR AlphaFoldDB; B3DIV9; -.
DR SMR; B3DIV9; -.
DR STRING; 7955.ENSDARP00000057021; -.
DR PaxDb; B3DIV9; -.
DR PRIDE; B3DIV9; -.
DR Ensembl; ENSDART00000057022; ENSDARP00000057021; ENSDARG00000039052.
DR GeneID; 553257; -.
DR KEGG; dre:553257; -.
DR CTD; 553257; -.
DR ZFIN; ZDB-GENE-050916-1; klhl40a.
DR eggNOG; KOG4441; Eukaryota.
DR GeneTree; ENSGT00940000156360; -.
DR HOGENOM; CLU_004253_14_4_1; -.
DR OMA; MVLGNCL; -.
DR OrthoDB; 946131at2759; -.
DR PhylomeDB; B3DIV9; -.
DR TreeFam; TF351653; -.
DR PRO; PR:B3DIV9; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 2.
DR Bgee; ENSDARG00000039052; Expressed in muscle tissue and 11 other tissues.
DR GO; GO:0031672; C:A band; IEA:UniProtKB-SubCell.
DR GO; GO:0031463; C:Cul3-RING ubiquitin ligase complex; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0031674; C:I band; IEA:UniProtKB-SubCell.
DR GO; GO:0061061; P:muscle structure development; IMP:ZFIN.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; IEA:InterPro.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0048741; P:skeletal muscle fiber development; IMP:ZFIN.
DR GO; GO:0098528; P:skeletal muscle fiber differentiation; ISS:UniProtKB.
DR GO; GO:0036268; P:swimming; IGI:ZFIN.
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; 4.
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 2: Evidence at transcript level;
KW Cytoplasm; Developmental protein; Kelch repeat; Reference proteome; Repeat;
KW Ubl conjugation pathway.
FT CHAIN 1..612
FT /note="Kelch-like protein 40a"
FT /id="PRO_0000423863"
FT DOMAIN 34..101
FT /note="BTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT DOMAIN 136..238
FT /note="BACK"
FT REPEAT 350..402
FT /note="Kelch 1"
FT REPEAT 403..452
FT /note="Kelch 2"
FT REPEAT 453..500
FT /note="Kelch 3"
FT REPEAT 502..547
FT /note="Kelch 4"
FT REPEAT 549..604
FT /note="Kelch 5"
FT REGION 266..290
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 26
FT /note="D -> G (in Ref. 2; AAH78427)"
FT /evidence="ECO:0000305"
FT CONFLICT 84
FT /note="V -> I (in Ref. 2; AAI63267)"
FT /evidence="ECO:0000305"
FT CONFLICT 587
FT /note="I -> V (in Ref. 2; AAH78427)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 612 AA; 69704 MW; 7F1114E83C61F265 CRC64;
MASMSVDPVT EPRMYQQTLL QDGLCDLLDA NKFVDCILKI KDKEFPCHRL VLAATSPYFK
AMFLSDLEES KKREIVLKDI EPGVMGMILR YIYTSDINLT EQNVQDIFMA ANMYQIPSIF
SVCVSYLQQK LVLSNCLAIF RLGLLLDCPR LAMEARDFIC DRYLLIIRDQ DFHQLGPSEL
AAIITCDSLN VEREESVFES LMDWVEYDTD ERTKELPELL HCVRFRLMPT SYFKEKVEGH
RLIRTNQELK KELQLIKDAQ KGLLHRVKRS SHRKEGKSAE FESDDDDEDG LLPGILNDNP
RFGMFQSDLI LMINDAGTVA YDVGANECFV ASSSTEIPKN HCSLVTKENQ IFVVGGLRYN
EENKDQPFSS YFLQFDPMSS EWLGMPSLPN PRCLFGLVEA ENSIYVVGGK ELKEGERALD
SVMIYDRQSF KWGESDPLPY AVYGHGIVSH KGLVYVIGGK TESKKCLRRV CVYDPSKFEW
KDLAPMKTAR SLFGTAVHKN KIYVVTGVTD NGLTSTVEVY DIASNSWSEF VDFPQERSSL
NLVELGGFLY AIGGFAMMPN ETTEKLEPTE MNDIWKFDEE ENCWNGILRE IRYAAGATVL
GVRLNTLRLT KI
