KLH41_HUMAN
ID KLH41_HUMAN Reviewed; 606 AA.
AC O60662; Q53R42;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 2.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Kelch-like protein 41;
DE AltName: Full=Kel-like protein 23;
DE AltName: Full=Kelch repeat and BTB domain-containing protein 10;
DE AltName: Full=Kelch-related protein 1;
DE AltName: Full=Sarcosin;
GN Name=KLHL41; Synonyms=KBTBD10, KRP1;
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] (ISOFORM SHORT).
RX PubMed=9655184; DOI=10.1023/a:1006824331819;
RA Taylor A., Obholz K., Linden G., Sadiev S., Klaus S., Carlson K.D.;
RT "DNA sequence and muscle-specific expression of human sarcosin
RT transcripts.";
RL Mol. Cell. Biochem. 183:105-112(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
RC TISSUE=Skeletal muscle;
RX PubMed=10713668; DOI=10.1038/sj.onc.1203433;
RA Spence H.J., Johnston I.P., Ewart K., Buchanan S.J., Fitzgerald U.,
RA Ozanne B.W.;
RT "Krp1, a novel kelch related protein that is involved in pseudopod
RT elongation in transformed cells.";
RL Oncogene 19:1266-1276(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
RA Zhuang D., Gunnarsson D., Toffia O., Lind M., Lundgren P., Selstam G.;
RT "Mammalian Kel or Kel-like proteins related to ovarian development and
RT differentiation.";
RL Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases.
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 MRNA] (ISOFORM LONG).
RC TISSUE=Muscle;
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 [6]
RP IDENTIFICATION IN A COMPLEX WITH CUL3 AND RBX1, AND UBIQUITINATION.
RX PubMed=15983046; DOI=10.1074/jbc.m501279200;
RA Zhang D.D., Lo S.C., Sun Z., Habib G.M., Lieberman M.W., Hannink M.;
RT "Ubiquitination of Keap1, a BTB-Kelch substrate adaptor protein for Cul3,
RT targets Keap1 for degradation by a proteasome-independent pathway.";
RL J. Biol. Chem. 280:30091-30099(2005).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=19424503; DOI=10.1371/journal.pone.0005492;
RA Wang X.J., Zhang D.D.;
RT "Ectodermal-neural cortex 1 down-regulates Nrf2 at the translational
RT level.";
RL PLoS ONE 4:E5492-E5492(2009).
RN [8]
RP SUBCELLULAR LOCATION, AND VARIANTS NEM9 LEU-153 INS AND LEU-413.
RX PubMed=24268659; DOI=10.1016/j.ajhg.2013.10.020;
RA Gupta V.A., Ravenscroft G., Shaheen R., Todd E.J., Swanson L.C., Shiina M.,
RA Ogata K., Hsu C., Clarke N.F., Darras B.T., Farrar M.A., Hashem A.,
RA Manton N.D., Muntoni F., North K.N., Sandaradura S.A., Nishino I.,
RA Hayashi Y.K., Sewry C.A., Thompson E.M., Yau K.S., Brownstein C.A.,
RA Yu T.W., Allcock R.J., Davis M.R., Wallgren-Pettersson C., Matsumoto N.,
RA Alkuraya F.S., Laing N.G., Beggs A.H.;
RT "Identification of KLHL41 mutations implicates BTB-Kelch-mediated
RT ubiquitination as an alternate pathway to myofibrillar disruption in
RT nemaline myopathy.";
RL Am. J. Hum. Genet. 93:1108-1117(2013).
CC -!- FUNCTION: Involved in skeletal muscle development and differentiation.
CC Regulates proliferation and differentiation of myoblasts and plays a
CC role in myofibril assembly by promoting lateral fusion of adjacent thin
CC fibrils into mature, wide myofibrils. Required for pseudopod elongation
CC in transformed cells. {ECO:0000250|UniProtKB:A2AUC9}.
CC -!- SUBUNIT: Interacts with NRAP. Interacts with LASP1. Part of a complex
CC that contains CUL3, RBX1 and KLHL41. {ECO:0000250|UniProtKB:Q9ER30,
CC ECO:0000269|PubMed:15983046}.
CC -!- INTERACTION:
CC O60662; Q96LM5: C4orf45; NbExp=3; IntAct=EBI-5353084, EBI-12020542;
CC O60662; P20929: NEB; NbExp=8; IntAct=EBI-5353084, EBI-1049657;
CC O60662; P20929-4: NEB; NbExp=5; IntAct=EBI-5353084, EBI-9531519;
CC O60662; Q96PM5: RCHY1; NbExp=6; IntAct=EBI-5353084, EBI-947779;
CC O60662; P40337-2: VHL; NbExp=3; IntAct=EBI-5353084, EBI-12157263;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19424503}.
CC Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:A2AUC9}. Cell
CC projection, pseudopodium {ECO:0000250|UniProtKB:Q9ER30}. Cell
CC projection, ruffle {ECO:0000250|UniProtKB:Q9ER30}. Cytoplasm,
CC myofibril, sarcomere, M line {ECO:0000250|UniProtKB:A2AUC9}.
CC Sarcoplasmic reticulum membrane {ECO:0000269|PubMed:24268659}.
CC Endoplasmic reticulum membrane {ECO:0000269|PubMed:24268659}.
CC Note=Predominantly cytoplasmic but can colocalize with F-actin at the
CC membrane ruffle-like structures at the tips of transformation-specific
CC pseudopodia. {ECO:0000269|PubMed:19424503}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=O60662-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=O60662-2; Sequence=VSP_002819;
CC -!- TISSUE SPECIFICITY: Sarcomeric muscle.
CC -!- PTM: Ubiquitinated by E3 ubiquitin ligase complex formed by CUL3 and
CC RBX1 and probably targeted for proteasome-independent degradation.
CC Quinone-induced oxidative stress increases its ubiquitination.
CC {ECO:0000269|PubMed:15983046}.
CC -!- DISEASE: Nemaline myopathy 9 (NEM9) [MIM:615731]: An autosomal
CC recessive form of nemaline myopathy. Nemaline myopathies are muscular
CC disorders characterized by muscle weakness of varying severity and
CC onset, and abnormal thread-like or rod-shaped structures in muscle
CC fibers on histologic examination. NEM9 phenotype is highly variable,
CC ranging from death in infancy due to lack of antigravity movements, to
CC slowly progressive distal muscle weakness with preserved ambulation
CC later in childhood. {ECO:0000269|PubMed:24268659}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
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DR EMBL; AF056929; AAC13686.1; -; mRNA.
DR EMBL; AF333387; AAG52886.1; -; mRNA.
DR EMBL; AC093899; AAY24117.1; -; Genomic_DNA.
DR EMBL; BC006534; AAH06534.1; -; mRNA.
DR CCDS; CCDS2234.1; -. [O60662-1]
DR RefSeq; NP_006054.2; NM_006063.2. [O60662-1]
DR AlphaFoldDB; O60662; -.
DR SMR; O60662; -.
DR BioGRID; 115607; 22.
DR IntAct; O60662; 14.
DR STRING; 9606.ENSP00000284669; -.
DR iPTMnet; O60662; -.
DR PhosphoSitePlus; O60662; -.
DR BioMuta; KLHL41; -.
DR jPOST; O60662; -.
DR MassIVE; O60662; -.
DR MaxQB; O60662; -.
DR PaxDb; O60662; -.
DR PeptideAtlas; O60662; -.
DR PRIDE; O60662; -.
DR ProteomicsDB; 49504; -. [O60662-1]
DR ProteomicsDB; 49505; -. [O60662-2]
DR Antibodypedia; 35006; 208 antibodies from 26 providers.
DR DNASU; 10324; -.
DR Ensembl; ENST00000284669.2; ENSP00000284669.1; ENSG00000239474.7. [O60662-1]
DR GeneID; 10324; -.
DR KEGG; hsa:10324; -.
DR MANE-Select; ENST00000284669.2; ENSP00000284669.1; NM_006063.3; NP_006054.2.
DR UCSC; uc002ueu.1; human. [O60662-1]
DR CTD; 10324; -.
DR DisGeNET; 10324; -.
DR GeneCards; KLHL41; -.
DR HGNC; HGNC:16905; KLHL41.
DR HPA; ENSG00000239474; Group enriched (skeletal muscle, tongue).
DR MalaCards; KLHL41; -.
DR MIM; 607701; gene.
DR MIM; 615731; phenotype.
DR neXtProt; NX_O60662; -.
DR OpenTargets; ENSG00000239474; -.
DR Orphanet; 171439; Childhood-onset nemaline myopathy.
DR Orphanet; 171433; Intermediate nemaline myopathy.
DR Orphanet; 171430; Severe congenital nemaline myopathy.
DR Orphanet; 171436; Typical nemaline myopathy.
DR PharmGKB; PA134950205; -.
DR VEuPathDB; HostDB:ENSG00000239474; -.
DR eggNOG; KOG4441; Eukaryota.
DR GeneTree; ENSGT00940000158859; -.
DR HOGENOM; CLU_004253_14_4_1; -.
DR InParanoid; O60662; -.
DR OMA; FQSYFFQ; -.
DR OrthoDB; 946131at2759; -.
DR PhylomeDB; O60662; -.
DR TreeFam; TF351653; -.
DR PathwayCommons; O60662; -.
DR Reactome; R-HSA-8951664; Neddylation.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; O60662; -.
DR BioGRID-ORCS; 10324; 15 hits in 1105 CRISPR screens.
DR GeneWiki; KBTBD10; -.
DR GenomeRNAi; 10324; -.
DR Pharos; O60662; Tbio.
DR PRO; PR:O60662; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; O60662; protein.
DR Bgee; ENSG00000239474; Expressed in tibialis anterior and 117 other tissues.
DR Genevisible; O60662; HS.
DR GO; GO:0031463; C:Cul3-RING ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0031430; C:M band; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0031143; C:pseudopodium; IEA:UniProtKB-SubCell.
DR GO; GO:0001726; C:ruffle; IEA:UniProtKB-SubCell.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0030239; P:myofibril assembly; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0031269; P:pseudopodium assembly; IEA:Ensembl.
DR GO; GO:0045661; P:regulation of myoblast differentiation; ISS:UniProtKB.
DR GO; GO:2000291; P:regulation of myoblast proliferation; ISS:UniProtKB.
DR GO; GO:2001014; P:regulation of skeletal muscle cell differentiation; IBA:GO_Central.
DR GO; GO:0045214; P:sarcomere organization; IEA:InterPro.
DR GO; GO:0035914; P:skeletal muscle cell differentiation; ISS:UniProtKB.
DR GO; GO:0048741; P:skeletal muscle fiber development; IEA:InterPro.
DR GO; GO:0006941; P:striated muscle contraction; TAS:ProtInc.
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; IPR030571; KLHL41.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR PANTHER; PTHR24412:SF146; PTHR24412:SF146; 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 1: Evidence at protein level;
KW Alternative splicing; Cell projection; Cytoplasm; Cytoskeleton;
KW Disease variant; Endoplasmic reticulum; Kelch repeat; Membrane;
KW Nemaline myopathy; Phosphoprotein; Reference proteome; Repeat;
KW Sarcoplasmic reticulum; Ubl conjugation.
FT CHAIN 1..606
FT /note="Kelch-like protein 41"
FT /id="PRO_0000119088"
FT DOMAIN 33..100
FT /note="BTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT DOMAIN 135..237
FT /note="BACK"
FT REPEAT 346..398
FT /note="Kelch 1"
FT REPEAT 399..447
FT /note="Kelch 2"
FT REPEAT 448..495
FT /note="Kelch 3"
FT REPEAT 497..542
FT /note="Kelch 4"
FT REPEAT 544..599
FT /note="Kelch 5"
FT MOD_RES 3
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9ER30"
FT VAR_SEQ 1..11
FT /note="MDSQRELAEEL -> M (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:9655184"
FT /id="VSP_002819"
FT VARIANT 153
FT /note="S -> SL (in NEM9)"
FT /evidence="ECO:0000269|PubMed:24268659"
FT /id="VAR_071823"
FT VARIANT 271
FT /note="A -> T (in dbSNP:rs28763868)"
FT /id="VAR_050046"
FT VARIANT 413
FT /note="S -> L (in NEM9; dbSNP:rs730882260)"
FT /evidence="ECO:0000269|PubMed:24268659"
FT /id="VAR_071824"
FT VARIANT 481
FT /note="M -> V (in dbSNP:rs34623017)"
FT /id="VAR_050047"
FT CONFLICT 304
FT /note="D -> G (in Ref. 1; AAC13686)"
FT /evidence="ECO:0000305"
FT CONFLICT 358
FT /note="E -> K (in Ref. 1; AAC13686)"
FT /evidence="ECO:0000305"
FT CONFLICT 361
FT /note="D -> V (in Ref. 1; AAC13686)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 606 AA; 68037 MW; 8C7BC13EB6E01034 CRC64;
MDSQRELAEE LRLYQSTLLQ DGLKDLLDEK KFIDCTLKAG DKSLPCHRLI LSACSPYFRE
YFLSEIDEAK KKEVVLDNVD PAILDLIIKY LYSASIDLND GNVQDIFALA SRFQIPSVFT
VCVSYLQKRL APGNCLAILR LGLLLDCPRL AISAREFVSD RFVQICKEED FMQLSPQELI
SVISNDSLNV EKEEAVFEAV MKWVRTDKEN RVKNLSEVFD CIRFRLMTEK YFKDHVEKDD
IIKSNPDLQK KIKVLKDAFA GKLPEPSKNA AKTGAGEVNG DVGDEDLLPG YLNDIPRHGM
FVKDLILLVN DTAAVAYDPT ENECYLTALA EQIPRNHSSI VTQQNQIYVV GGLYVDEENK
DQPLQSYFFQ LDSIASEWVG LPPLPSARCL FGLGEVDDKI YVVAGKDLQT EASLDSVLCY
DPVAAKWNEV KKLPIKVYGH NVISHKGMIY CLGGKTDDKK CTNRVFIFNP KKGDWKDLAP
MKIPRSMFGV AVHKGKIVIA GGVTEDGLSA SVEAFDLTTN KWDVMTEFPQ ERSSISLVSL
AGSLYAIGGF AMIQLESKEF APTEVNDIWK YEDDKKEWAG MLKEIRYASG ASCLATRLNL
FKLSKL
