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O14874 (BCKD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 135. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
[3-methyl-2-oxobutanoate dehydrogenase [lipoamide]] kinase, mitochondrial

EC=2.7.11.4
Alternative name(s):
Branched-chain alpha-ketoacid dehydrogenase kinase
Short name=BCKD-kinase
Short name=BCKDHKIN
Gene names
Name:BCKDK
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length412 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the phosphorylation and inactivation of the branched-chain alpha-ketoacid dehydrogenase complex, the key regulatory enzyme of the valine, leucine and isoleucine catabolic pathways. Key enzyme that regulate the activity state of the BCKD complex By similarity.

Catalytic activity

ATP + [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] = ADP + [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] phosphate.

Subunit structure

Monomer By similarity.

Subcellular location

Mitochondrion matrix.

Tissue specificity

Ubiquitous.

Post-translational modification

Autophosphorylated By similarity.

Involvement in disease

Branched-chain ketoacid dehydrogenase kinase deficiency (BCKDKD) [MIM:614923]: A metabolic disorder characterized by autism, epilepsy, intellectual disability, and reduced branched-chain amino acids.
Note: The disease is caused by mutations affecting the gene represented in this entry. A diet enriched in branched amino acids (BCAAs) allows to normalize plasma BCAA levels. This suggests that it may be possible to treat patients with mutations in BCKDK with BCAA supplementation. Ref.13

Sequence similarities

Belongs to the PDK/BCKDK protein kinase family.

Contains 1 histidine kinase domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Q9WMX22EBI-1046765,EBI-6863741From a different organism.
STAT3P407632EBI-1046765,EBI-518675

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O14874-1)

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: O14874-2)

The sequence of this isoform differs from the canonical sequence as follows:
     282-311: Missing.
     366-412: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: O14874-3)

The sequence of this isoform differs from the canonical sequence as follows:
     366-412: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 3030Mitochondrion By similarity
Chain31 – 412382[3-methyl-2-oxobutanoate dehydrogenase [lipoamide]] kinase, mitochondrial
PRO_0000023452

Regions

Domain159 – 404246Histidine kinase

Amino acid modifications

Modified residue521Phosphoserine; by autocatalysis By similarity
Modified residue1921N6-acetyllysine Ref.10
Modified residue2331N6-acetyllysine Ref.10

Natural variations

Alternative sequence282 – 31130Missing in isoform 2.
VSP_054604
Alternative sequence366 – 41247Missing in isoform 2 and isoform 3.
VSP_054605
Natural variant2241R → P in BCKDKD. Ref.13
VAR_069037

Experimental info

Sequence conflict31L → P in AK130145. Ref.2
Sequence conflict1141F → S in AK130145. Ref.2
Sequence conflict2181V → F in AAB82714. Ref.1
Sequence conflict2271P → S in AK130145. Ref.2

Sequences

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

Last modified June 6, 2002. Version 2.
Checksum: AC97CF5D151FEFB4

FASTA41246,360
        10         20         30         40         50         60 
MILASVLRSG PGGGLPLRPL LGPALALRAR STSATDTHHV EMARERSKTV TSFYNQSAID 

        70         80         90        100        110        120 
AAAEKPSVRL TPTMMLYAGR SQDGSHLLKS ARYLQQELPV RIAHRIKGFR CLPFIIGCNP 

       130        140        150        160        170        180 
TILHVHELYI RAFQKLTDFP PIKDQADEAQ YCQLVRQLLD DHKDVVTLLA EGLRESRKHI 

       190        200        210        220        230        240 
EDEKLVRYFL DKTLTSRLGI RMLATHHLAL HEDKPDFVGI ICTRLSPKKI IEKWVDFARR 

       250        260        270        280        290        300 
LCEHKYGNAP RVRINGHVAA RFPFIPMPLD YILPELLKNA MRATMESHLD TPYNVPDVVI 

       310        320        330        340        350        360 
TIANNDVDLI IRISDRGGGI AHKDLDRVMD YHFTTAEAST QDPRISPLFG HLDMHSGAQS 

       370        380        390        400        410 
GPMHGFGFGL PTSRAYAEYL GGSLQLQSLQ GIGTDVYLRL RHIDGREESF RI 

« Hide

Isoform 2 [UniParc].

Checksum: B66E1F96C0718C57
Show »

FASTA33537,768
Isoform 3 [UniParc].

Checksum: 8702A3E7E94341DC
Show »

FASTA36541,090

References

« Hide 'large scale' references
[1]Chuang J.C., Cox R.P., Chuang D.T.
Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[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 3).
[3]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]"The sequence and analysis of duplication-rich human chromosome 16."
Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. expand/collapse author list , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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] (ISOFORMS 1 AND 2).
Tissue: Lung and Placenta.
[7]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[8]"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-192 AND LYS-233, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[12]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"Mutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy."
Novarino G., El-Fishawy P., Kayserili H., Meguid N.A., Scott E.M., Schroth J., Silhavy J.L., Kara M., Khalil R.O., Ben-Omran T., Ercan-Sencicek A.G., Hashish A.F., Sanders S.J., Gupta A.R., Hashem H.S., Matern D., Gabriel S., Sweetman L. expand/collapse author list , Rahimi Y., Harris R.A., State M.W., Gleeson J.G.
Science 338:394-397(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT BCKDKD PRO-224.
+Additional computationally mapped references.

Web resources

Protein Spotlight

The silence within - Issue 147 of March 2013

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF026548 mRNA. Translation: AAB82714.1.
AK130145 mRNA. No translation available.
CR542093 mRNA. Translation: CAG46890.1.
AC135050 Genomic DNA. No translation available.
CH471192 Genomic DNA. Translation: EAW52160.1.
CH471192 Genomic DNA. Translation: EAW52161.1.
CH471192 Genomic DNA. Translation: EAW52163.1.
BC007363 mRNA. Translation: AAH07363.1.
BC009872 mRNA. Translation: AAH09872.1.
CCDSCCDS10705.1.
RefSeqNP_001116429.1. NM_001122957.2. [O14874-3]
NP_001258855.1. NM_001271926.1. [O14874-2]
NP_005872.2. NM_005881.3. [O14874-1]
UniGeneHs.513520.

3D structure databases

ProteinModelPortalO14874.
SMRO14874. Positions 68-408.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115583. 14 interactions.
IntActO14874. 4 interactions.
MINTMINT-2998419.
STRING9606.ENSP00000219794.

PTM databases

PhosphoSiteO14874.

Proteomic databases

MaxQBO14874.
PaxDbO14874.
PRIDEO14874.

Protocols and materials databases

DNASU10295.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000219794; ENSP00000219794; ENSG00000103507.
ENST00000287507; ENSP00000287507; ENSG00000103507.
ENST00000394950; ENSP00000378404; ENSG00000103507.
ENST00000394951; ENSP00000378405; ENSG00000103507.
GeneID10295.
KEGGhsa:10295.
UCSCuc002eav.5. human. [O14874-1]

Organism-specific databases

CTD10295.
GeneCardsGC16P031117.
HGNCHGNC:16902. BCKDK.
HPAHPA017995.
HPA056067.
MIM614901. gene.
614923. phenotype.
neXtProtNX_O14874.
Orphanet308410. Autism-epilepsy syndrome due to branched chain ketoacid dehydrogenase kinase deficiency.
PharmGKBPA134899581.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0642.
HOGENOMHOG000164315.
HOVERGENHBG004829.
InParanoidO14874.
KOK00905.
OMATIANNDV.
OrthoDBEOG7TQV0S.
PhylomeDBO14874.
TreeFamTF331303.

Gene expression databases

ArrayExpressO14874.
BgeeO14874.
CleanExHS_BCKDK.
GenevestigatorO14874.

Family and domain databases

Gene3D1.20.140.20. 1 hit.
3.30.565.10. 1 hit.
InterProIPR018955. BCDHK/PDK_N.
IPR003594. HATPase_ATP-bd.
IPR004358. Sig_transdc_His_kin-like_C.
IPR005467. Sig_transdc_His_kinase_core.
[Graphical view]
PfamPF10436. BCDHK_Adom3. 1 hit.
PF02518. HATPase_c. 1 hit.
[Graphical view]
PRINTSPR00344. BCTRLSENSOR.
SMARTSM00387. HATPase_c. 1 hit.
[Graphical view]
SUPFAMSSF55874. SSF55874. 1 hit.
SSF69012. SSF69012. 1 hit.
PROSITEPS50109. HIS_KIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiBCKDK.
GenomeRNAi10295.
NextBio39014.
PROO14874.
SOURCESearch...

Entry information

Entry nameBCKD_HUMAN
AccessionPrimary (citable) accession number: O14874
Secondary accession number(s): A8MY43 expand/collapse secondary AC list , Q6FGL4, Q96G95, Q96IN5
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: June 6, 2002
Last modified: July 9, 2014
This is version 135 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

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

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 16

Human chromosome 16: entries, gene names and cross-references to MIM