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UniProtKB/Swiss-Prot Q9BXM7: Variant p.Leu347Pro

Serine/threonine-protein kinase PINK1, mitochondrial
Gene: PINK1
Variant information

Variant position:  347
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change:  From Leucine (L) to Proline (P) at position 347 (L347P, p.Leu347Pro).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Variant description:  In PARK6; strongly reduces interaction with PRKN; reduced ubiquitination of MIRO1.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  347
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  581
The length of the canonical sequence.

Location on the sequence:   QYLCVNTPSPRLAAMMLLQL  L EGVDHLVQQGIAHRDLKSDN
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         QYLCVNTPSPRLAAMMLLQLLEGVDHLVQQGIAHRDLKSDN

Mouse                         QYLEEQTPSSRLATMMTLQLLEGVDHLVQQGIAHRDLKSDN

Rat                           QYLEEQTPSSRLATMMTLQLLEGVDHLVQQGIAHRDLKSDN

Caenorhabditis elegans        EYVWTRHRNYWTGRVIIAQLLEACTYLHKHKVAQRDMKSDN

Drosophila                    GLLDSQDLSTRNRILLLAQMLEAVNHLSRHGVAHRDLKSDN

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 78 – 581 Serine/threonine-protein kinase PINK1, mitochondrial
Topological domain 111 – 581 Cytoplasmic
Domain 156 – 511 Protein kinase
Active site 362 – 362 Proton acceptor
Mutagenesis 362 – 362 D -> A. Abolishes MFN2 phosphorylation and interaction with PRKN; when associated with A-219 and A-384. Loss of enzyme activity and impaired localization of PRKN to mitochondria; when associated with M-219 and A-384.


Literature citations

The PINK1/Parkin-mediated mitophagy is compromised by PD-associated mutations.
Geisler S.; Holmstrom K.M.; Treis A.; Skujat D.; Weber S.S.; Fiesel F.C.; Kahle P.J.; Springer W.;
Autophagy 6:871-878(2010)
Cited for: FUNCTION IN MITOCHONDRIAL AUTOPHAGY; SUBCELLULAR LOCATION; INTERACTION WITH PRKN; CHARACTERIZATION OF VARIANTS PARK6 PRO-126; ASP-309 AND PRO-347;

Parkinson's disease-associated kinase PINK1 regulates Miro protein level and axonal transport of mitochondria.
Liu S.; Sawada T.; Lee S.; Yu W.; Silverio G.; Alapatt P.; Millan I.; Shen A.; Saxton W.; Kanao T.; Takahashi R.; Hattori N.; Imai Y.; Lu B.;
PLoS Genet. 8:E1002537-E1002537(2012)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANT PARK6 PRO-347;

Novel PINK1 mutations in early-onset parkinsonism.
Hatano Y.; Li Y.; Sato K.; Asakawa S.; Yamamura Y.; Tomiyama H.; Yoshino H.; Asahina M.; Kobayashi S.; Hassin-Baer S.; Lu C.-S.; Ng A.R.; Rosales R.L.; Shimizu N.; Toda T.; Mizuno Y.; Hattori N.;
Ann. Neurol. 56:424-427(2004)
Cited for: VARIANTS PARK6 GLN-271; PRO-347 AND GLY-417;

Analysis of the PINK1 gene in a large cohort of cases with Parkinson disease.
Rogaeva E.; Johnson J.; Lang A.E.; Gulick C.; Gwinn-Hardy K.; Kawarai T.; Sato C.; Morgan A.; Werner J.; Nussbaum R.; Petit A.; Okun M.S.; McInerney A.; Mandel R.; Groen J.L.; Fernandez H.H.; Postuma R.; Foote K.D.; Salehi-Rad S.; Liang Y.; Reimsnider S.; Tandon A.; Hardy J.; St George-Hyslop P.; Singleton A.B.;
Arch. Neurol. 61:1898-1904(2004)
Cited for: VARIANTS PARK6 LYS-240; PRO-347 AND PRO-489; VARIANTS GLY-231; ILE-235; GLY-263; LEU-318; THR-339; THR-340; HIS-362; SER-425; LYS-476 AND THR-521;

Systematic review and UK-based study of PARK2 (parkin), PINK1, PARK7 (DJ-1) and LRRK2 in early-onset Parkinson's disease.
Kilarski L.L.; Pearson J.P.; Newsway V.; Majounie E.; Knipe M.D.; Misbahuddin A.; Chinnery P.F.; Burn D.J.; Clarke C.E.; Marion M.H.; Lewthwaite A.J.; Nicholl D.J.; Wood N.W.; Morrison K.E.; Williams-Gray C.H.; Evans J.R.; Sawcer S.J.; Barker R.A.; Wickremaratchi M.M.; Ben-Shlomo Y.; Williams N.M.; Morris H.R.;
Mov. Disord. 27:1522-1529(2012)
Cited for: VARIANT PARK6 PRO-347;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.