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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q14203: Variant p.Gln74Pro

Dynactin subunit 1
Gene: DCTN1
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Variant information Variant position: help 74 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Glutamine (Q) to Proline (P) at position 74 (Q74P, p.Gln74Pro). 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: help Change from medium size and polar (Q) to medium size and hydrophobic (P) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -1 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: help In PERRYS; diminishes microtubule binding and lead to intracytoplasmic inclusions; significant decrease in motility of dynein-dynactin complex along microtubules; defective in inhibiting microtubule catastrophe in neurons. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 74 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 1278 The length of the canonical sequence.
Location on the sequence: help TGKWVGVILDEAKGKNDGTV Q GRKYFTCDEGHGIFVRQSQI 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         TGKWVGVILDEAKGKNDGTVQGRKYFTCDEGHGIFVRQSQI

Mouse                         TGKWVGVILDEAKGKNDGTVQGRKYFTCDEGHGIFVRQSQI

Rat                           TGKWVGVILDEAKGKNDGTVQGRKYFTCDEGHGIFVRQSQI

Pig                           TGKWVGVILDEAKGKNDGTVQGRKYFTCDEGHGIFVRQSQI

Chicken                       TGKWVGVILDEAKGKNDGTVQGRKYFTCEENHGIFVRQSQI

Xenopus laevis                TGKWVGVILDDSKGKNDGTVQGRRYFTCEENHGIFVRQSQI

Drosophila                    VGKWVGVVLDEPKGKNSGSIKGQQYFQCDENCGMFVRPTQL
Sequence annotation in neighborhood: help 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 1 – 1278 Dynactin subunit 1
Domain 48 – 90 CAP-Gly
Alternative sequence 1 – 138 MAQSKRHVYSRTPSGSRMSAEASARPLRVGSRVEVIGKGHRGTVAYVGATLFATGKWVGVILDEAKGKNDGTVQGRKYFTCDEGHGIFVRQSQIQVFEDGADTTSPETPDSSASKVLKREGTDTTAKTSKLRGLKPKK -> MMRQ. In isoform p135 and isoform 5.
Mutagenesis 68 – 68 K -> A. Abolishes interaction with CLIP1.
Mutagenesis 90 – 90 R -> E. Abolishes interaction with CLIP1.



Literature citations
DCTN1 mutations in Perry syndrome.
Farrer M.J.; Hulihan M.M.; Kachergus J.M.; Daechsel J.C.; Stoessl A.J.; Grantier L.L.; Calne S.; Calne D.B.; Lechevalier B.; Chapon F.; Tsuboi Y.; Yamada T.; Gutmann L.; Elibol B.; Bhatia K.P.; Wider C.; Vilarino-Gueell C.; Ross O.A.; Brown L.A.; Castanedes-Casey M.; Dickson D.W.; Wszolek Z.K.;
Nat. Genet. 41:163-165(2009)
Cited for: VARIANTS PERRYS ARG-71; GLU-71; ALA-71; PRO-72 AND PRO-74; CHARACTERIZATION OF VARIANTS PERRYS ARG-71 AND PRO-74; CHARACTERIZATION OF VARIANT HMND14 SER-59; Dynactin subunit p150(Glued) is a neuron-specific anti-catastrophe factor.
Lazarus J.E.; Moughamian A.J.; Tokito M.K.; Holzbaur E.L.;
PLoS Biol. 11:E1001611-E1001611(2013)
Cited for: CHARACTERIZATION OF VARIANT PERRYS PRO-74; FUNCTION; SUBUNIT; INTERACTION WITH MAPRE1; Dynactin functions as both a dynamic tether and brake during dynein-driven motility.
Ayloo S.; Lazarus J.E.; Dodda A.; Tokito M.; Ostap E.M.; Holzbaur E.L.;
Nat. Commun. 5:4807-4807(2014)
Cited for: CHARACTERIZATION OF VARIANTS PERRYS ARG-71 AND PRO-74; FUNCTION; INTERACTION WITH DYNEIN INTERMEDIATE CHAIN AND DYNEIN HEAVY CHAIN; DOMAIN CAP-GLY;
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.