Cyclin-G-associated kinase (GAK)

The protein contains 1311 amino acids for an estimated molecular weight of 143191 Da.

 

Associates with cyclin G and CDK5. Seems to act as an auxilin homolog that is involved in the uncoating of clathrin-coated vesicles by Hsc70 in non-neuronal cells. Expression oscillates slightly during the cell cycle, peaking at G1. (updated: March 4, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  3. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  4. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  5. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

Interpro domains
Total structural coverage: 44%
Model score: 0
No model available.

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VariantDescription
dbSNP:rs768962219
dbSNP:rs34255232
dbSNP:rs34585705
dbSNP:rs149842313
a lung neuroendocrine carcinoma sample
dbSNP:rs35227944
dbSNP:rs55801437
dbSNP:rs56169884
dbSNP:rs56326341
dbSNP:rs2306242
dbSNP:rs1134921

The reference OMIM entry for this protein is 602052

Cyclin g-associated kinase; gak

CLONING

In all eukaryotes, the cell cycle is governed by cyclin-dependent protein kinases (CDKs), whose activities are regulated by cyclins and CDK inhibitors in a diverse array of mechanisms that involve the control of phosphorylation-dephosphorylation of ser/thr or tyr residues. Cyclins are molecules that possess a consensus domain called the 'cyclin box.' In mammalian cells, 9 cyclin species have been identified to this time, and they are referred to as cyclins A (123835) through I. Cyclin G (601578) is a direct transcriptional target of the p53 tumor suppressor gene product (191170) and thus functions downstream of p53. Kimura et al. (1997) reported the cloning of a cDNA encoding the human homolog of GAK, an association partner of cyclin G and CDK5 (123831), which had previously been cloned in the rat. They showed that the cDNA encodes a protein of 1,311 amino acids containing all the unique motifs characteristic of rat GAK. The expression profiles of GAK and cyclin G during the synchronized HeLa cell cycle showed that GAK expression oscillates slightly, peaking at the G1 phase, although histone H1 kinase activity remained constant throughout the cell cycle. Northern blot analysis showed that GAK is expressed ubiquitously, with the highest level of expression being observed in the testis.

MAPPING

By fluorescence in situ hybridization, Kimura et al. (1997) assigned the GAK gene to chromosome 4p16.

MOLECULAR GENETICS

For a discussion of a possible association between variation in the GAK gene and susceptibility to the development of Parkinson disease, see 168600. ... More on the omim web site

Subscribe to this protein entry history

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 602052 was added.

Jan. 28, 2016: Protein entry updated
Automatic update: model status changed

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed