Serine/threonine-protein kinase N1 (PKN1)

The protein contains 942 amino acids for an estimated molecular weight of 103932 Da.

 

PKC-related serine/threonine-protein kinase involved in various processes such as regulation of the intermediate filaments of the actin cytoskeleton, cell migration, tumor cell invasion and transcription regulation. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. Regulates the cytoskeletal network by phosphorylating proteins such as VIM and neurofilament proteins NEFH, NEFL and NEFM, leading to inhibit their polymerization. Phosphorylates 'Ser-575', 'Ser-637' and 'Ser-669' of MAPT/Tau, lowering its ability to bind to microtubules, resulting in disruption of tubulin assembly. Acts as a key coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and specifically mediating phosphorylation of 'Thr-11' of histone H3 (H3T11ph), a specific tag for epigenetic transcriptional activation that promotes demethylation of histone H3 'Lys-9' (H3K9me) by KDM4C/JMJD2C. Phosphorylates HDAC5, HDAC7 and HDAC9, leading to impair their import in the nucleus. Phosphorylates 'Thr-38' of PPP1R14A, 'Ser-159', 'Ser-163' and 'Ser-170' of MARCKS, and GFAP. Able to phosphorylate RPS6 in vitro. (updated: April 7, 2021)

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. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. 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.

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)

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.


Interpro domains
Total structural coverage: 72%
Model score: 0
MODL_I-TASSER-3.0

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VariantDescription
a metastatic melanoma sample
dbSNP:rs1287763348
dbSNP:rs35132656
dbSNP:rs56273055
dbSNP:rs34309238
dbSNP:rs35416389
dbSNP:rs2230539
a breast infiltrating ductal carcinoma sample; somatic mutation
dbSNP:rs10846
a colorectal adenocarcinoma sample; somatic mutation

The reference OMIM entry for this protein is 601032

Protein kinase n1; pkn1
Protein kinase c-related kinase 1; prk1
Serine/threonine protein kinase n; pkn
Pkn-alpha
Protein kinase c-like 1; prkcl1
Pak1, rat, homolog of

CLONING

Mukai and Ono (1994) isolated a cDNA for the protein kinase PRK1, which they designated PKN, from a human hippocampus cDNA library. The putative 942-amino acid protein has leucine zipper-like sequences at its N terminus and contains a domain with strong similarity to that of the protein kinase C (PKC) family. Ubiquitous expression in human tissues was shown. Antisera detected a 120-kD recombinantly expressed protein on Western blots. The protein showed intrinsic protein kinase activity that was abolished by a mutation in the predicted ATP binding site. Palmer et al. (1994) used degenerate PCR to isolate 3 novel members of the closely related PKC family, termed PRK1, PRK2 (602549), and PRK3 (610714). Palmer et al. (1995) cloned a full-length cDNA of PRK1 from a human fetal brain library. Using Northern blot and RT-PCR analyses, Palmer et al. (1995) detected expression of PRK1 in all tissues and cell lines tested.

GENE FUNCTION

In a study of proteins that bind to the rho GTPase (see Ridley and Hall, 1992), Amano et al. (1996) discovered a protein that had partial amino acid sequences identical to PKN. They found that rho binds directly to a polybasic region of the N-terminal regulatory domain that precedes the leucine zipper-like motif. The authors speculated that through this activity, PKN may mediate the rho-dependent signaling pathway. Metzger et al. (2003) found that androgen receptor (AR; 313700) and PRK1 interact in vitro and in vivo. Stimulation of the PRK1 signaling cascade resulted in ligand-dependent superactivation of AR in human prostate carcinoma cells, and PRK1 promoted a functional complex of AR with the coactivator TIF2 (NCOA2; 601993). PRK1 signaling stimulated AR activity in the presence of adrenal androgens and in the presence of an AR antagonist. Metzger et al. (2003) concluded that AR is controlled by PRK1 signaling as well as by ligand binding.

MAPPING

Bartsch et al. (1998) used fluorescence in situ hybridization to map the PRKCL1 gene to 19p13.1-p12 and radiation hybrid mapping to localize the gene in subband 19p12. By segregation analysis, they mapped the corresponding mouse gene (Prkcl1) to chromosome 8. ... More on the omim web site

Subscribe to this protein entry history

April 10, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.

May 12, 2019: Protein entry updated
Automatic update: model status changed

Nov. 17, 2018: Protein entry updated
Automatic update: model status changed

Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

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

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

Oct. 27, 2017: Protein entry updated
Automatic update: model status changed

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 601032 was added.

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