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Protein

Kelch-like protein 40

Gene

Klhl40

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a key regulator of skeletal muscle development (PubMed:25940086). The BCR(KLHL40) complex acts by mediating ubiquitination and degradation of TFDP1, thereby regulating the activity of the E2F:DP transcription factor complex (PubMed:25940086). Promotes stabilization of LMOD3 by acting as a negative regulator of LMOD3 ubiquitination; the molecular process by which it negatively regulates ubiquitination of LMOD3 is however unclear (PubMed:24960163).2 Publications

GO - Biological processi

  • negative regulation of proteasomal ubiquitin-dependent protein catabolic process Source: MGI
  • negative regulation of protein ubiquitination Source: MGI
  • positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
  • positive regulation of protein ubiquitination Source: UniProtKB
  • protein ubiquitination Source: GOC
  • skeletal muscle fiber development Source: UniProtKB
  • skeletal muscle fiber differentiation Source: UniProtKB

Keywordsi

Molecular functionDevelopmental protein
Biological processUbl conjugation pathway

Names & Taxonomyi

Protein namesi
Recommended name:
Kelch-like protein 40Curated
Alternative name(s):
Kelch repeat and BTB domain-containing protein 52 Publications
Gene namesi
Name:Klhl40Imported
Synonyms:Kbtbd52 Publications
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1919580. Klhl40.

Subcellular locationi

GO - Cellular componenti

  • A band Source: MGI
  • Cul3-RING ubiquitin ligase complex Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • I band Source: MGI

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Disruption phenotypei

Neonates are normal in size at birth and were born with the expected Mendelian ratio (PubMed:24960163, PubMed:25940086). They however fail to gain weight and do not survive to weaning (PubMed:24960163, PubMed:25940086). Defects are due to smaller muscle fibers and a disorganized sarcomeric structure (PubMed:24960163, PubMed:25940086).2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002742361 – 621Kelch-like protein 40Add BLAST621

Proteomic databases

PaxDbiQ9D783.
PRIDEiQ9D783.

PTM databases

iPTMnetiQ9D783.
PhosphoSitePlusiQ9D783.

Expressioni

Tissue specificityi

Specifically expressed in skeletal muscles in embryonic, neonatal and adults (PubMed:24960163, PubMed:25940086). Expressed in various types of muscles, including extensor digitorum longus, gastrocnemius, soleus, diaphragm, masseter and heart (at protein level). Not detected in brain, liver and lung (at protein level).3 Publications

Developmental stagei

Absent early during embryogenesis (E7), present at the middle stage (E11) and highly expressed at the later stages (E15 and E17) (PubMed:24361185). Specifically expressed in the somites at E11.5 and in the skeletal muscle at E15.5 (PubMed:24361185).1 Publication

Inductioni

Up-regulated during myogenic differentiation (PubMed:24361185). Induced during the differentiation of myoblasts into myotubes (PubMed:23746549).2 Publications

Gene expression databases

BgeeiENSMUSG00000074001.
CleanExiMM_KBTBD5.

Interactioni

Subunit structurei

Component of the BCR(KLHL40) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL40 and RBX1 (PubMed:24361185). Interacts with LMOD3 (PubMed:24960163).2 Publications

Protein-protein interaction databases

BioGridi215313. 12 interactors.
STRINGi10090.ENSMUSP00000095873.

Structurei

3D structure databases

ProteinModelPortaliQ9D783.
SMRiQ9D783.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini33 – 98BTBPROSITE-ProRule annotationAdd BLAST66
Domaini133 – 239BACKSequence analysisAdd BLAST107
Repeati360 – 412Kelch 1Sequence analysisAdd BLAST53
Repeati413 – 462Kelch 2Sequence analysisAdd BLAST50
Repeati463 – 510Kelch 3Sequence analysisAdd BLAST48
Repeati512 – 557Kelch 4Sequence analysisAdd BLAST46
Repeati559 – 613Kelch 5Sequence analysisAdd BLAST55

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi270 – 275Poly-LysSequence analysis6

Sequence similaritiesi

Belongs to the KLHL40 family.Curated

Keywords - Domaini

Kelch repeat, Repeat

Phylogenomic databases

eggNOGiKOG4441. Eukaryota.
ENOG410XNX8. LUCA.
HOGENOMiHOG000231966.
HOVERGENiHBG052215.
InParanoidiQ9D783.
KOiK10473.
PhylomeDBiQ9D783.
TreeFamiTF351653.

Family and domain databases

Gene3Di2.120.10.80. 1 hit.
InterProiView protein in InterPro
IPR011705. BACK.
IPR017096. BTB-kelch_protein.
IPR000210. BTB/POZ_dom.
IPR015915. Kelch-typ_b-propeller.
IPR006652. Kelch_1.
IPR030607. KLHL40.
IPR011333. SKP1/BTB/POZ.
PANTHERiPTHR24412:SF360. PTHR24412:SF360. 1 hit.
PfamiView protein in Pfam
PF07707. BACK. 1 hit.
PF00651. BTB. 1 hit.
PF01344. Kelch_1. 3 hits.
PIRSFiPIRSF037037. Kelch-like_protein_gigaxonin. 1 hit.
SMARTiView protein in SMART
SM00875. BACK. 1 hit.
SM00225. BTB. 1 hit.
SM00612. Kelch. 4 hits.
SUPFAMiSSF54695. SSF54695. 1 hit.
PROSITEiView protein in PROSITE
PS50097. BTB. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9D783-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MTLGLEQAEE QRLYQQTLLQ DGLKDMLDHG KFLDCVVRVG EREFPCHRLV
60 70 80 90 100
LAACSPYFRA RFLAEPDSAG EVRLEEVSPD VVSQVLHYLY TSEIALDEAS
110 120 130 140 150
VQDLFAAAHR FQIPSIFTIC VSFLQKRLCL ANCLAVFRLG LLLDCARLAV
160 170 180 190 200
AARDFICARF PLVARDNDFL GLSADELIAI ISSDGLNVEK EEAVFEAVMR
210 220 230 240 250
WASSGDAEAQ AERQRALPTV FESVRCRLLP RAFLETRVER HPLVRSQPEL
260 270 280 290 300
LRKVQMVKDA HEGRLTTLRK KKKEKGEQTA RAKEANQGTE DTKAEDDEER
310 320 330 340 350
VLPGILNDTL RFGMFLQDLI FMISEEGAVA YDPAANECYC ASLSTQIPKN
360 370 380 390 400
HVSLVTKENQ VFVAGGLFYN EDNKEDPMSA YFLQFDHLDS EWLGMPPLPS
410 420 430 440 450
PRCLFGLGEA LNAIYVVGGR ELKDSEDSLD SVLCYDRLSF KWGESDPLPY
460 470 480 490 500
AVYGHTVLSH MDLVYVIGGK GKDRKCLNKM CVYDPKKFEW KELAPMQTAR
510 520 530 540 550
SLFGATVHDG RIFVAAGVTD TGLTSSSEVY SIADNKWTSF EAFPQERSSL
560 570 580 590 600
SLVSLAGTLY ALGGFATLET ESGELVPTEL NDIWRYNEDE KKWEGVLREI
610 620
AYAAGATFLP VRLNVVRLTK M
Length:621
Mass (Da):69,589
Last modified:June 1, 2001 - v1
Checksum:iD8D4BEA104526E5F
GO
Isoform 2 (identifier: Q9D783-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     385-445: FDHLDSEWLGMPPLPSPRCLFGLGEALNAIYVVGGRELKDSEDSLDSVLCYDRLSFKWGES → VPGQS
     446-621: Missing.

Note: No experimental confirmation available.
Show »
Length:389
Mass (Da):43,713
Checksum:i4F5EFFD1A675D51F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti616V → L in BAE36021 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_022683385 – 445FDHLD…KWGES → VPGQS in isoform 2. 1 PublicationAdd BLAST61
Alternative sequenceiVSP_022684446 – 621Missing in isoform 2. 1 PublicationAdd BLAST176

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK009491 mRNA. Translation: BAB26321.1.
AK160799 mRNA. Translation: BAE36021.1.
BC125576 mRNA. Translation: AAI25577.1.
BC137889 mRNA. Translation: AAI37890.1.
CCDSiCCDS23637.1. [Q9D783-1]
RefSeqiNP_082478.1. NM_028202.3.
UniGeneiMm.45734.

Genome annotation databases

GeneIDi72330.
KEGGimmu:72330.
UCSCiuc009sdv.2. mouse. [Q9D783-1]
uc029xgr.1. mouse. [Q9D783-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiKLH40_MOUSE
AccessioniPrimary (citable) accession number: Q9D783
Secondary accession number(s): B9EHG6, Q059P8, Q3TUF0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 6, 2007
Last sequence update: June 1, 2001
Last modified: May 10, 2017
This is version 102 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families