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Protein

Kelch-like protein 40

Gene

KLHL40

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Required for skeletal muscle development.1 Publication

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Names & Taxonomyi

Protein namesi
Recommended name:
Kelch-like protein 40
Alternative name(s):
Kelch repeat and BTB domain-containing protein 5
Sarcosynapsin
Gene namesi
Name:KLHL40
Synonyms:KBTBD5, SRYP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:30372. KLHL40.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Nemaline myopathy 8 (NEM8)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA severe form of nemaline myopathy. Nemaline myopathies are muscular disorders characterized by muscle weakness of varying severity and onset, and abnormal thread-like or rod-shaped structures in muscle fibers on histologic examination. NEM8 is characterized by fetal akinesia or hypokinesia, followed by contractures, fractures, respiratory failure, and swallowing difficulties apparent at birth. Most patients die in infancy. Skeletal muscle biopsy shows numerous small nemaline bodies, often with no normal myofibrils.
See also OMIM:615348
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06983634D → H in NEM8. 1 PublicationCorresponds to variant rs778565563dbSNPEnsembl.1
Natural variantiVAR_06983786L → P in NEM8. 1 Publication1
Natural variantiVAR_069838194V → E in NEM8. 1 Publication1
Natural variantiVAR_069839201W → L in NEM8. 1 PublicationCorresponds to variant rs397509420dbSNPEnsembl.1
Natural variantiVAR_069840311R → L in NEM8. 1 Publication1
Natural variantiVAR_069841397P → L in NEM8. 1 PublicationCorresponds to variant rs773649133dbSNPEnsembl.1
Natural variantiVAR_069842455H → R in NEM8. 1 PublicationCorresponds to variant rs770866675dbSNPEnsembl.1
Natural variantiVAR_069843469G → C in NEM8. 1 PublicationCorresponds to variant rs367579275dbSNPEnsembl.1
Natural variantiVAR_069844506T → P in NEM8. 1 PublicationCorresponds to variant rs778022582dbSNPEnsembl.1
Natural variantiVAR_069845528E → K in NEM8. 1 PublicationCorresponds to variant rs397509419dbSNPEnsembl.1
Natural variantiVAR_069846538A → P in NEM8. 1 PublicationCorresponds to variant rs397509421dbSNPEnsembl.1
Natural variantiVAR_069847588E → K in NEM8. 1 PublicationCorresponds to variant rs201856772dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation, Nemaline myopathy

Organism-specific databases

DisGeNETi131377.
MalaCardsiKLHL40.
MIMi615348. phenotype.
OpenTargetsiENSG00000157119.
Orphaneti171430. Severe congenital nemaline myopathy.
PharmGKBiPA134908127.

Polymorphism and mutation databases

DMDMi125950763.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002742351 – 621Kelch-like protein 40Add BLAST621

Proteomic databases

PaxDbiQ2TBA0.
PeptideAtlasiQ2TBA0.
PRIDEiQ2TBA0.

PTM databases

iPTMnetiQ2TBA0.
PhosphoSitePlusiQ2TBA0.

Expressioni

Tissue specificityi

Highly expressed in fetal (19, 23 and 31 weeks of gestation) and adult skeletal muscle; expression levels tend to be higher in fetal compared to postnatal muscles (at protein level). Aslo expressed in fetal and adult heart.1 Publication

Gene expression databases

BgeeiENSG00000157119.
CleanExiHS_KBTBD5.
GenevisibleiQ2TBA0. HS.

Organism-specific databases

HPAiHPA024463.
HPA052201.

Interactioni

Protein-protein interaction databases

BioGridi126278. 42 interactors.
IntActiQ2TBA0. 4 interactors.
MINTiMINT-8330030.
STRINGi9606.ENSP00000287777.

Structurei

Secondary structure

1621
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi317 – 324Combined sources8
Beta strandi327 – 332Combined sources6
Turni333 – 336Combined sources4
Beta strandi337 – 342Combined sources6
Beta strandi349 – 355Combined sources7
Beta strandi361 – 369Combined sources9
Beta strandi374 – 376Combined sources3
Beta strandi378 – 386Combined sources9
Turni387 – 390Combined sources4
Beta strandi391 – 394Combined sources4
Beta strandi398 – 400Combined sources3
Beta strandi402 – 404Combined sources3
Beta strandi406 – 410Combined sources5
Beta strandi413 – 417Combined sources5
Beta strandi420 – 423Combined sources4
Beta strandi432 – 436Combined sources5
Turni437 – 440Combined sources4
Beta strandi441 – 444Combined sources4
Beta strandi456 – 460Combined sources5
Beta strandi463 – 467Combined sources5
Beta strandi480 – 484Combined sources5
Turni485 – 488Combined sources4
Beta strandi489 – 492Combined sources4
Beta strandi504 – 508Combined sources5
Beta strandi511 – 518Combined sources8
Beta strandi520 – 531Combined sources12
Turni532 – 535Combined sources4
Beta strandi536 – 540Combined sources5
Beta strandi551 – 555Combined sources5
Beta strandi558 – 569Combined sources12
Beta strandi575 – 587Combined sources13
Turni588 – 591Combined sources4
Beta strandi592 – 598Combined sources7
Beta strandi607 – 613Combined sources7
Helixi615 – 617Combined sources3
Beta strandi618 – 620Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4ASCX-ray1.78A314-621[»]
ProteinModelPortaliQ2TBA0.
SMRiQ2TBA0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

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

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi270 – 275Poly-Lys6

Sequence similaritiesi

Contains 1 BTB (POZ) domain.PROSITE-ProRule annotation
Contains 5 Kelch repeats.Curated

Keywords - Domaini

Kelch repeat, Repeat

Phylogenomic databases

eggNOGiKOG4441. Eukaryota.
ENOG410XNX8. LUCA.
GeneTreeiENSGT00850000132244.
HOGENOMiHOG000231966.
HOVERGENiHBG052215.
InParanoidiQ2TBA0.
KOiK10473.
OMAiYSITDNK.
OrthoDBiEOG091G0C3Y.
PhylomeDBiQ2TBA0.
TreeFamiTF351653.

Family and domain databases

Gene3Di2.120.10.80. 1 hit.
InterProiIPR011705. BACK.
IPR017096. BTB-kelch_protein.
IPR000210. BTB/POZ_dom.
IPR015915. Kelch-typ_b-propeller.
IPR006652. Kelch_1.
IPR030607. KLHL40.
IPR011333. SKP1/BTB/POZ.
[Graphical view]
PANTHERiPTHR24412:SF22. PTHR24412:SF22. 1 hit.
PfamiPF07707. BACK. 1 hit.
PF00651. BTB. 1 hit.
PF01344. Kelch_1. 3 hits.
[Graphical view]
PIRSFiPIRSF037037. Kelch-like_protein_gigaxonin. 1 hit.
SMARTiSM00875. BACK. 1 hit.
SM00225. BTB. 1 hit.
SM00612. Kelch. 4 hits.
[Graphical view]
SUPFAMiSSF54695. SSF54695. 1 hit.
PROSITEiPS50097. BTB. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q2TBA0-1) [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
MALGLEQAEE QRLYQQTLLQ DGLKDMLDHG KFLDCVVRAG EREFPCHRLV
60 70 80 90 100
LAACSPYFRA RFLAEPERAG ELHLEEVSPD VVAQVLHYLY TSEIALDEAS
110 120 130 140 150
VQDLFAAAHR FQIPSIFTIC VSFLQKRLCL SNCLAVFRLG LLLDCARLAV
160 170 180 190 200
AARDFICAHF TLVARDADFL GLSADELIAI ISSDGLNVEK EEAVFEAVMR
210 220 230 240 250
WAGSGDAEAQ AERQRALPTV FESVRCRLLP RAFLESRVER HPLVRAQPEL
260 270 280 290 300
LRKVQMVKDA HEGRITTLRK KKKGKDGAGA KEADKGTSKA KAEEDEEAER
310 320 330 340 350
ILPGILNDTL RFGMFLQDLI FMISEEGAVA YDPAANECYC ASLSNQVPKN
360 370 380 390 400
HVSLVTKENQ VFVAGGLFYN EDNKEDPMSA YFLQFDHLDS EWLGMPPLPS
410 420 430 440 450
PRCLFGLGEA LNSIYVVGGR EIKDGERCLD SVMCYDRLSF KWGESDPLPY
460 470 480 490 500
VVYGHTVLSH MDLVYVIGGK GSDRKCLNKM CVYDPKKFEW KELAPMQTAR
510 520 530 540 550
SLFGATVHDG RIIVAAGVTD TGLTSSAEVY SITDNKWAPF EAFPQERSSL
560 570 580 590 600
SLVSLVGTLY AIGGFATLET ESGELVPTEL NDIWRYNEEE KKWEGVLREI
610 620
AYAAGATFLP VRLNVLCLTK M
Length:621
Mass (Da):69,257
Last modified:February 6, 2007 - v2
Checksum:i53492478F08A5A2D
GO
Isoform 2 (identifier: Q2TBA0-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     444-604: ESDPLPYVVY...GVLREIAYAA → HRHRADQFCRSVQHHRQQVGTLRGLPTGA
     605-621: Missing.

Note: No experimental confirmation available.
Show »
Length:472
Mass (Da):52,893
Checksum:i6A64676A03325797
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06983634D → H in NEM8. 1 PublicationCorresponds to variant rs778565563dbSNPEnsembl.1
Natural variantiVAR_06983786L → P in NEM8. 1 Publication1
Natural variantiVAR_069838194V → E in NEM8. 1 Publication1
Natural variantiVAR_069839201W → L in NEM8. 1 PublicationCorresponds to variant rs397509420dbSNPEnsembl.1
Natural variantiVAR_069840311R → L in NEM8. 1 Publication1
Natural variantiVAR_030214345N → S.2 PublicationsCorresponds to variant rs6805421dbSNPEnsembl.1
Natural variantiVAR_069841397P → L in NEM8. 1 PublicationCorresponds to variant rs773649133dbSNPEnsembl.1
Natural variantiVAR_069842455H → R in NEM8. 1 PublicationCorresponds to variant rs770866675dbSNPEnsembl.1
Natural variantiVAR_069843469G → C in NEM8. 1 PublicationCorresponds to variant rs367579275dbSNPEnsembl.1
Natural variantiVAR_069844506T → P in NEM8. 1 PublicationCorresponds to variant rs778022582dbSNPEnsembl.1
Natural variantiVAR_069845528E → K in NEM8. 1 PublicationCorresponds to variant rs397509419dbSNPEnsembl.1
Natural variantiVAR_069846538A → P in NEM8. 1 PublicationCorresponds to variant rs397509421dbSNPEnsembl.1
Natural variantiVAR_069847588E → K in NEM8. 1 PublicationCorresponds to variant rs201856772dbSNPEnsembl.1
Natural variantiVAR_030215617C → R.1 PublicationCorresponds to variant rs123509dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_022681444 – 604ESDPL…IAYAA → HRHRADQFCRSVQHHRQQVG TLRGLPTGA in isoform 2. 1 PublicationAdd BLAST161
Alternative sequenceiVSP_022682605 – 621Missing in isoform 2. 1 PublicationAdd BLAST17

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY177390 mRNA. Translation: AAO06908.1.
AY176040 mRNA. Translation: AAO22141.1.
AK056577 mRNA. Translation: BAB71222.1.
BC110491 mRNA. Translation: AAI10492.1.
CCDSiCCDS2703.1. [Q2TBA0-1]
RefSeqiNP_689606.2. NM_152393.3. [Q2TBA0-1]
UniGeneiHs.350288.

Genome annotation databases

EnsembliENST00000287777; ENSP00000287777; ENSG00000157119. [Q2TBA0-1]
GeneIDi131377.
KEGGihsa:131377.
UCSCiuc003clv.2. human. [Q2TBA0-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY177390 mRNA. Translation: AAO06908.1.
AY176040 mRNA. Translation: AAO22141.1.
AK056577 mRNA. Translation: BAB71222.1.
BC110491 mRNA. Translation: AAI10492.1.
CCDSiCCDS2703.1. [Q2TBA0-1]
RefSeqiNP_689606.2. NM_152393.3. [Q2TBA0-1]
UniGeneiHs.350288.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4ASCX-ray1.78A314-621[»]
ProteinModelPortaliQ2TBA0.
SMRiQ2TBA0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi126278. 42 interactors.
IntActiQ2TBA0. 4 interactors.
MINTiMINT-8330030.
STRINGi9606.ENSP00000287777.

PTM databases

iPTMnetiQ2TBA0.
PhosphoSitePlusiQ2TBA0.

Polymorphism and mutation databases

DMDMi125950763.

Proteomic databases

PaxDbiQ2TBA0.
PeptideAtlasiQ2TBA0.
PRIDEiQ2TBA0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000287777; ENSP00000287777; ENSG00000157119. [Q2TBA0-1]
GeneIDi131377.
KEGGihsa:131377.
UCSCiuc003clv.2. human. [Q2TBA0-1]

Organism-specific databases

CTDi131377.
DisGeNETi131377.
GeneCardsiKLHL40.
HGNCiHGNC:30372. KLHL40.
HPAiHPA024463.
HPA052201.
MalaCardsiKLHL40.
MIMi615340. gene.
615348. phenotype.
neXtProtiNX_Q2TBA0.
OpenTargetsiENSG00000157119.
Orphaneti171430. Severe congenital nemaline myopathy.
PharmGKBiPA134908127.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4441. Eukaryota.
ENOG410XNX8. LUCA.
GeneTreeiENSGT00850000132244.
HOGENOMiHOG000231966.
HOVERGENiHBG052215.
InParanoidiQ2TBA0.
KOiK10473.
OMAiYSITDNK.
OrthoDBiEOG091G0C3Y.
PhylomeDBiQ2TBA0.
TreeFamiTF351653.

Miscellaneous databases

GenomeRNAii131377.
PROiQ2TBA0.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000157119.
CleanExiHS_KBTBD5.
GenevisibleiQ2TBA0. HS.

Family and domain databases

Gene3Di2.120.10.80. 1 hit.
InterProiIPR011705. BACK.
IPR017096. BTB-kelch_protein.
IPR000210. BTB/POZ_dom.
IPR015915. Kelch-typ_b-propeller.
IPR006652. Kelch_1.
IPR030607. KLHL40.
IPR011333. SKP1/BTB/POZ.
[Graphical view]
PANTHERiPTHR24412:SF22. PTHR24412:SF22. 1 hit.
PfamiPF07707. BACK. 1 hit.
PF00651. BTB. 1 hit.
PF01344. Kelch_1. 3 hits.
[Graphical view]
PIRSFiPIRSF037037. Kelch-like_protein_gigaxonin. 1 hit.
SMARTiSM00875. BACK. 1 hit.
SM00225. BTB. 1 hit.
SM00612. Kelch. 4 hits.
[Graphical view]
SUPFAMiSSF54695. SSF54695. 1 hit.
PROSITEiPS50097. BTB. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKLH40_HUMAN
AccessioniPrimary (citable) accession number: Q2TBA0
Secondary accession number(s): Q86SI1, Q96MR2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 6, 2007
Last sequence update: February 6, 2007
Last modified: November 30, 2016
This is version 94 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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.