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UniProtKB/Swiss-Prot Q14203: Variant p.Gly59Ser

Dynactin subunit 1
Gene: DCTN1
Variant information

Variant position:  59
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Glycine (G) to Serine (S) at position 59 (G59S, p.Gly59Ser).
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:  Change from glycine (G) to small size and polar (S)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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

Involvement in disease:  Neuronopathy, distal hereditary motor, 7B (HMN7B) [MIM:607641]: A neuromuscular disorder. Distal hereditary motor neuronopathies constitute a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. {ECO:0000269|PubMed:12627231, ECO:0000269|PubMed:16505168, ECO:0000269|PubMed:19136952, ECO:0000269|PubMed:19279216, ECO:0000269|PubMed:22777741}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In HMN7B; reduced affinity for microtubules which has been suggested to impair axonal transport; the effect is identical to that of complete loss of the CAP-Gly domain; decreased interaction with MAPRE1; no effect on its interaction with TBCB.
Any additional useful information about the variant.

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



Sequence information

Variant position:  59
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1278
The length of the canonical sequence.

Location on the sequence:   GHRGTVAYVGATLFATGKWV  G VILDEAKGKNDGTVQGRKYF
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                         GHRGTVAYVGATLFATGKWVGVILDEAKGKNDGTVQGRKYF

Mouse                         GHRGTVAYVGATLFATGKWVGVILDEAKGKNDGTVQGRKYF

Rat                           GHRGTVAYVGATLFATGKWVGVILDEAKGKNDGTVQGRKYF

Chicken                       GHRGTVAYVGATLXATGKWVGVILDEAKGKNDGTVQGRKYF

Xenopus laevis                GYRGTVAYVGATLFATGKWVGVILDDSKGKNDGTVQGRRYF

Drosophila                    DLLGTVAYVGMTSFAVGKWVGVVLDEPKGKNSGSIKGQQYF

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 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.
Beta strand 57 – 65


Literature citations

Mutant dynactin in motor neuron disease.
Puls I.; Jonnakuty C.; LaMonte B.H.; Holzbaur E.L.; Tokito M.; Mann E.; Floeter M.K.; Bidus K.; Drayna D.; Oh S.J.; Brown R.H. Jr.; Ludlow C.L.; Fischbeck K.H.;
Nat. Genet. 33:455-456(2003)
Cited for: VARIANT HMN7B SER-59;

A motor neuron disease-associated mutation in p150Glued perturbs dynactin function and induces protein aggregation.
Levy J.R.; Sumner C.J.; Caviston J.P.; Tokito M.K.; Ranganathan S.; Ligon L.A.; Wallace K.E.; LaMonte B.H.; Harmison G.G.; Puls I.; Fischbeck K.H.; Holzbaur E.L.F.;
J. Cell Biol. 172:733-745(2006)
Cited for: CHARACTERIZATION OF VARIANT HMN7B SER-59; INTERACTION WITH MAPRE1;

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 HMN7B SER-59;

Neurodegeneration mutations in dynactin impair dynein-dependent nuclear migration.
Moore J.K.; Sept D.; Cooper J.A.;
Proc. Natl. Acad. Sci. U.S.A. 106:5147-5152(2009)
Cited for: CHARACTERIZATION OF VARIANT HMN7B SER-59;

Tubulin-binding cofactor B is a direct interaction partner of the dynactin subunit p150(Glued).
Kuh G.F.; Stockmann M.; Meyer-Ohlendorf M.; Linta L.; Proepper C.; Ludolph A.C.; Bockmann J.; Boeckers T.M.; Liebau S.;
Cell Tissue Res. 350:13-26(2012)
Cited for: CHARACTERIZATION OF VARIANT HMN7B SER-59; CHARACTERIZATION OF VARIANT 196-ILE; INTERACTION WITH TBCB; SUBCELLULAR LOCATION;

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.