ADCK3_HUMAN » Atypical kinase ADCK3, mitochondrial

ADCK3_HUMAN » Atypical kinase ADCK3, mitochondrial
Magnify ADCK3_HUMAN » Atypical kinase ADCK3, mitochondrialEnlarged view of image
3D view in GLMol or JMol

gray dot

Download Coordinates

gray dot

Topology in Mitochondrial inner membrane
Topologyintermembrane space
mitochondrial matrix side
ADCK3_HUMAN » Atypical kinase ADCK3, mitochondrial »
Hydrophobic Thickness 25.2 ± 1.4 Å
Tilt Angle 1 ± 0°
ΔGtransfer -26.7 kcal/mol
ΔGfold -5.2 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC
Topology In
TM Segments 214-237 (213-238)
Pathways none
PDB 4ped (256-647)
OPM none
Complexes none
Interactions

EGFR, Complex: EGFR:ADCK3

Domains

AA: 318-434, PDBID: 4PED, Subunit A, Seq Identity:100%, ABC1 family

UniProt annotation for ADCK3_HUMAN » Atypical kinase ADCK3, mitochondrial
FUNCTION: Atypical kinase involved in the biosynthesis of coenzyme Q, also named ubiquinone, an essential lipid-soluble electron transporter for aerobic cellular respiration (PubMed). Its substrate specificity is unclear: either acts as protein kinase that phosphorylates other proteins in the CoQ complex to stabilize their interactions or acts as a small molecule kinase that phosphorylates a prenyl lipid in the ubiquinone biosynthesis pathway (PubMed). Shows an unusual selectivity for binding ADP over ATP (PubMed).

ENZYME REGULATION: Autoinhibited by the N-terminal domain, containing the KxGQ motif, that completely occludes the typical substrate binding pocket.

SUBUNIT: Homodimer; homodimerizes via its transmembrane region.

TISSUE SPECIFICITY: Widely expressed, with highest levels in adrenal gland, heart, pancreas, nasal mucosa, stomach, uterus and skeletal muscle.

INDUCTION: By p53/TP53.

DOMAIN: Adopts an atypical protein kinase-like fold: while it adopts a core fold similar to that of well-characterized protein kinase-like domains, a number of features are positioned to inhibit the kinase activity: (1) an atypical AAAS motif in an alanine-rich (A-rich) loop that replaces the canonical glycine- rich (G-rich) nucleotide-binding loop and limits ATP binding by establishing an unusual selectivity for ADP and (2) an N-terminal domain, containing the KxGQ motif, that completely occludes the typical substrate binding pocket.

DISEASE: Coenzyme Q10 deficiency, primary, 4 (COQ10D4) OMIM: An autosomal recessive disorder characterized by childhood-onset of cerebellar ataxia and exercise intolerance. Patient manifest gait ataxia and cerebellar atrophy with slow progression. Additional features include brisk tendon reflexes and Hoffmann sign, variable psychomotor retardation and variable seizures. mutations affecting the gene represented in this entry.

UniProt features for ADCK3_HUMAN » Atypical kinase ADCK3, mitochondrial
TRANSIT 1 162 Mitochondrion.
CHAIN 163 647 Atypical kinase ADCK3, mitochondrial.
DOMAIN 329 518 Protein kinase.
MOTIF 276 279 KxGQ motif.
MOTIF 337 340 AAAS motif.
ACT_SITE 488 488 Proton acceptor.
Amino Acid Sequence for ADCK3_HUMAN » Atypical kinase ADCK3, mitochondrial
MAAILGDTIM VAKGLVKLTQ AAVETHLQHL GIGGELIMAA RALQSTAVEQ IGMFLGKVQG QDKHEEYFAE NFGGPEGEFH FSVPHAAGAS TDFSSASAPD QSAPPSLGHA HSEGPAPAYV ASGPFREAGF PGQASSPLGR ANGRLFANPR DSFSAMGFQR RFFHQDQSPV GGLTAEDIEK ARQAKARPEN KQHKQTLSEH ARERKVPVTR IGRLANFGGL AVGLGFGALA EVAKKSLRSE DPSGKKAVLG SSPFLSEANA ERIVRTLCKV RGAALKLGQM LSIQDDAFIN PHLAKIFERV RQSADFMPLK QMMKTLNNDL GPNWRDKLEY FEERPFAAAS IGQVHLARMK GGREVAMKIQ YPGVAQSINS DVNNLMAVLN MSNMLPEGLF PEHLIDVLRR ELALECDYQR EAACARKFRD LLKGHPFFYV PEIVDELCSP HVLTTELVSG FPLDQAEGLS QEIRNEICYN ILVLCLRELF EFHFMQTDPN WSNFFYDPQQ HKVALLDFGA TREYDRSFTD LYIQIIRAAA DRDRETVRAK SIEMKFLTGY EVKVMEDAHL DAILILGEAF ASDEPFDFGT QSTTEKIHNL IPVMLRHRLV PPPEETYSLH RKMGGSFLIC SKLKARFPCK AMFEEAYSNY CKRQAQQ