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Q2TBA0 (KLH40_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 69. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Kelch-like protein 40
Alternative name(s):
Kelch repeat and BTB domain-containing protein 5
Sarcosynapsin
Gene names
Name:KLHL40
Synonyms:KBTBD5, SRYP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length621 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Required for skeletal muscle development. Ref.5

Subcellular location

CytoplasmmyofibrilsarcomereA band Ref.5.

Tissue specificity

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. Ref.5

Involvement in disease

Nemaline myopathy 8 (NEM8) [MIM:615348]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5

Sequence similarities

Contains 1 BACK (BTB/Kelch associated) domain.

Contains 1 BTB (POZ) domain.

Contains 5 Kelch repeats.

Ontologies

Keywords
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Nemaline myopathy
   DomainKelch repeat
Repeat
   Molecular functionDevelopmental protein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processmulticellular organismal development

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentA band

Inferred from electronic annotation. Source: UniProtKB-SubCell

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q2TBA0-1)

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.
Isoform 2 (identifier: Q2TBA0-2)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 621621Kelch-like protein 40
PRO_0000274235

Regions

Domain33 – 9866BTB
Domain133 – 239107BACK
Repeat360 – 41253Kelch 1
Repeat413 – 46250Kelch 2
Repeat463 – 51048Kelch 3
Repeat512 – 55746Kelch 4
Repeat559 – 61355Kelch 5
Compositional bias270 – 2756Poly-Lys

Natural variations

Alternative sequence444 – 604161ESDPL…IAYAA → HRHRADQFCRSVQHHRQQVG TLRGLPTGA in isoform 2.
VSP_022681
Alternative sequence605 – 62117Missing in isoform 2.
VSP_022682
Natural variant341D → H in NEM8. Ref.5
VAR_069836
Natural variant861L → P in NEM8. Ref.5
VAR_069837
Natural variant1941V → E in NEM8. Ref.5
VAR_069838
Natural variant2011W → L in NEM8. Ref.5
VAR_069839
Natural variant3111R → L in NEM8. Ref.5
VAR_069840
Natural variant3451N → S. Ref.2 Ref.3
Corresponds to variant rs6805421 [ dbSNP | Ensembl ].
VAR_030214
Natural variant3971P → L in NEM8. Ref.5
VAR_069841
Natural variant4551H → R in NEM8. Ref.5
VAR_069842
Natural variant4691G → C in NEM8. Ref.5
VAR_069843
Natural variant5061T → P in NEM8. Ref.5
VAR_069844
Natural variant5281E → K in NEM8. Ref.5
VAR_069845
Natural variant5381A → P in NEM8. Ref.5
VAR_069846
Natural variant5881E → K in NEM8. Ref.5
VAR_069847
Natural variant6171C → R. Ref.3
Corresponds to variant rs123509 [ dbSNP | Ensembl ].
VAR_030215

Secondary structure

............................................................ 621
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 6, 2007. Version 2.
Checksum: 53492478F08A5A2D

FASTA62169,257
        10         20         30         40         50         60 
MALGLEQAEE QRLYQQTLLQ DGLKDMLDHG KFLDCVVRAG EREFPCHRLV LAACSPYFRA 

        70         80         90        100        110        120 
RFLAEPERAG ELHLEEVSPD VVAQVLHYLY TSEIALDEAS VQDLFAAAHR FQIPSIFTIC 

       130        140        150        160        170        180 
VSFLQKRLCL SNCLAVFRLG LLLDCARLAV AARDFICAHF TLVARDADFL GLSADELIAI 

       190        200        210        220        230        240 
ISSDGLNVEK EEAVFEAVMR WAGSGDAEAQ AERQRALPTV FESVRCRLLP RAFLESRVER 

       250        260        270        280        290        300 
HPLVRAQPEL LRKVQMVKDA HEGRITTLRK KKKGKDGAGA KEADKGTSKA KAEEDEEAER 

       310        320        330        340        350        360 
ILPGILNDTL RFGMFLQDLI FMISEEGAVA YDPAANECYC ASLSNQVPKN HVSLVTKENQ 

       370        380        390        400        410        420 
VFVAGGLFYN EDNKEDPMSA YFLQFDHLDS EWLGMPPLPS PRCLFGLGEA LNSIYVVGGR 

       430        440        450        460        470        480 
EIKDGERCLD SVMCYDRLSF KWGESDPLPY VVYGHTVLSH MDLVYVIGGK GSDRKCLNKM 

       490        500        510        520        530        540 
CVYDPKKFEW KELAPMQTAR SLFGATVHDG RIIVAAGVTD TGLTSSAEVY SITDNKWAPF 

       550        560        570        580        590        600 
EAFPQERSSL SLVSLVGTLY AIGGFATLET ESGELVPTEL NDIWRYNEEE KKWEGVLREI 

       610        620 
AYAAGATFLP VRLNVLCLTK M 

« Hide

Isoform 2 [UniParc].

Checksum: 6A64676A03325797
Show »

FASTA47252,893

References

« Hide 'large scale' references
[1]"Structure, gene organization and expression analysis of human sarcosynapsin."
Goudou D., Bitoun M., Rieger F., Perin J.-P., Alliel P.M.
Submitted (NOV-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Heart.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT SER-345.
Tissue: Tongue.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS SER-345 AND ARG-617.
[4]"Structural basis for Cul3 assembly with the BTB-Kelch family of E3 ubiquitin ligases."
Canning P., Cooper C.D., Krojer T., Murray J.W., Pike A.C., Chaikuad A., Keates T., Thangaratnarajah C., Hojzan V., Marsden B.D., Gileadi O., Knapp S., von Delft F., Bullock A.N.
J. Biol. Chem. 288:7803-7814(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.78 ANGSTROMS) OF 314-621.
[5]"Mutations in KLHL40 are a frequent cause of severe autosomal-recessive nemaline myopathy."
Ravenscroft G., Miyatake S., Lehtokari V.L., Todd E.J., Vornanen P., Yau K.S., Hayashi Y.K., Miyake N., Tsurusaki Y., Doi H., Saitsu H., Osaka H., Yamashita S., Ohya T., Sakamoto Y., Koshimizu E., Imamura S., Yamashita M. expand/collapse author list , Ogata K., Shiina M., Bryson-Richardson R.J., Vaz R., Ceyhan O., Brownstein C.A., Swanson L.C., Monnot S., Romero N.B., Amthor H., Kresoje N., Sivadorai P., Kiraly-Borri C., Haliloglu G., Talim B., Orhan D., Kale G., Charles A.K., Fabian V.A., Davis M.R., Lammens M., Sewry C.A., Manzur A., Muntoni F., Clarke N.F., North K.N., Bertini E., Nevo Y., Willichowski E., Silberg I.E., Topaloglu H., Beggs A.H., Allcock R.J., Nishino I., Wallgren-Pettersson C., Matsumoto N., Laing N.G.
Am. J. Hum. Genet. 93:6-18(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NEM8 HIS-34; PRO-86; GLU-194; LEU-201; LEU-311; LEU-397; ARG-455; CYS-469; PRO-506; LYS-528; PRO-538 AND LYS-588, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY177390 mRNA. Translation: AAO06908.1.
AY176040 mRNA. Translation: AAO22141.1.
AK056577 mRNA. Translation: BAB71222.1.
BC110491 mRNA. Translation: AAI10492.1.
CCDSCCDS2703.1. [Q2TBA0-1]
RefSeqNP_689606.2. NM_152393.3. [Q2TBA0-1]
UniGeneHs.350288.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4ASCX-ray1.78A314-621[»]
ProteinModelPortalQ2TBA0.
SMRQ2TBA0. Positions 29-262, 314-621.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ2TBA0. 1 interaction.
MINTMINT-8330030.

PTM databases

PhosphoSiteQ2TBA0.

Polymorphism databases

DMDM125950763.

Proteomic databases

PaxDbQ2TBA0.
PRIDEQ2TBA0.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000287777; ENSP00000287777; ENSG00000157119. [Q2TBA0-1]
GeneID131377.
KEGGhsa:131377.
UCSCuc003clv.1. human. [Q2TBA0-1]

Organism-specific databases

CTD131377.
GeneCardsGC03P042727.
HGNCHGNC:30372. KLHL40.
HPAHPA024463.
MIM615340. gene.
615348. phenotype.
neXtProtNX_Q2TBA0.
Orphanet171430. Severe congenital nemaline myopathy.
PharmGKBPA134908127.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG290520.
HOGENOMHOG000231966.
HOVERGENHBG052215.
InParanoidQ2TBA0.
KOK10473.
OMAVYGHAVL.
OrthoDBEOG7M6D6S.
PhylomeDBQ2TBA0.
TreeFamTF351653.

Gene expression databases

BgeeQ2TBA0.
CleanExHS_KBTBD5.
GenevestigatorQ2TBA0.

Family and domain databases

Gene3D2.120.10.80. 1 hit.
3.30.710.10. 1 hit.
InterProIPR011705. BACK.
IPR000210. BTB/POZ-like.
IPR011333. BTB/POZ_fold.
IPR013069. BTB_POZ.
IPR017096. Kelch-like_gigaxonin-typ.
IPR015915. Kelch-typ_b-propeller.
IPR006652. Kelch_1.
[Graphical view]
PfamPF07707. BACK. 1 hit.
PF00651. BTB. 1 hit.
PF01344. Kelch_1. 3 hits.
[Graphical view]
PIRSFPIRSF037037. Kelch-like_protein_gigaxonin. 1 hit.
SMARTSM00875. BACK. 1 hit.
SM00225. BTB. 1 hit.
SM00612. Kelch. 4 hits.
[Graphical view]
SUPFAMSSF54695. SSF54695. 1 hit.
PROSITEPS50097. BTB. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSKBTBD5. human.
GenomeRNAi131377.
NextBio82900.
PROQ2TBA0.
SOURCESearch...

Entry information

Entry nameKLH40_HUMAN
AccessionPrimary (citable) accession number: Q2TBA0
Secondary accession number(s): Q86SI1, Q96MR2
Entry history
Integrated into UniProtKB/Swiss-Prot: February 6, 2007
Last sequence update: February 6, 2007
Last modified: July 9, 2014
This is version 69 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM