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protein coding gene - shk1 (SPBC1604.14c) - PAK-related kinase Shk1

Gene summary

Standard name
shk1
Systematic ID
SPBC1604.14c
Product
PAK-related kinase Shk1
Organism
Schizosaccharomyces pombe (fission yeast)
Synonyms
pak1, orb2
UniProt ID
P50527
ORFeome ID
39/39F04
Characterisation status
biological role published
Feature type
mRNA gene
Genomic location
chromosome II: 3904616..3907593 forward strand

Annotation

PBO:0000384 - Ras1-Scd

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Complementation

PBO:0091259 - does not functionally complement S. cerevisiae CLA4

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PBO:0091849 - functionally complemented by S. cerevisiae CLA4

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PBO:0017050 - functionally complemented by S. cerevisiae STE20

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PBO:0017051 - functionally complements S. cerevisiae STE20

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Disease association

MONDO:0032568 - intellectual developmental disorder with macrocephaly, seizures, and speech delay

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MONDO:0010361 - intellectual disability, X-linked 30

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MONDO:0100119 - Knobloch syndrome 2

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MONDO:0019181 - non-syndromic X-linked intellectual disability

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GO biological process

GO:0009267 - cellular response to starvation

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GO:1903500 - negative regulation of mitotic actomyosin contractile ring assembly

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GO:1903472 - negative regulation of mitotic actomyosin contractile ring contraction

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GO:0045807 - positive regulation of endocytosis

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GO:0061173 - positive regulation of establishment of bipolar cell polarity

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GO:2000247 - positive regulation of establishment or maintenance of bipolar cell polarity regulating cell shape

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GO:0061361 - positive regulation of maintenance of bipolar cell polarity regulating cell shape

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GO:1903617 - positive regulation of mitotic cytokinesis, division site positioning

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GO:0062038 - positive regulation of pheromone response MAPK cascade

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GO:0070507 - regulation of microtubule cytoskeleton organization

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GO cellular component

GO:0071521 - Cdc42 GTPase complex

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GO:0051285 - cell cortex of cell tip

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GO:0032153 - cell division site

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GO:0051286 - cell tip

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GO:0005829 - cytosol

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GO:0110085 - mitotic actomyosin contractile ring

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GO:0120105 - mitotic actomyosin contractile ring, intermediate layer

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GO:0005876 - spindle microtubule

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GO molecular function

GO:0005515 - protein binding

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GO:0004674 - protein serine/threonine kinase activity

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Modification

MOD:00046 - O-phospho-L-serine

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MOD:00047 - O-phospho-L-threonine

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MOD:00048 - O4'-phospho-L-tyrosine

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MOD:00696 - phosphorylated residue

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MOD:01148 - ubiquitinylated lysine

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Multi-locus phenotype

FYPO:0001118 - abnormal vegetative cell morphology

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Genotypes:

FYPO:0001018 - abolished NETO

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Genotypes:

FYPO:0000082 - decreased cell population growth at high temperature

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Genotypes:

FYPO:0000708 - decreased mating efficiency

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Genotypes:

FYPO:0001838 - decreased protein phosphorylation during vegetative growth

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Genotypes:

FYPO:0004085 - decreased vegetative cell growth

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Genotypes:

FYPO:0001355 - decreased vegetative cell population growth

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Genotypes:

FYPO:0009061 - increased protein localization to cell cortex during mitotic interphase

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Genotypes:

FYPO:0002303 - inviable mononucleate monoseptate vegetative cell with anucleate compartment

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Genotypes:

FYPO:0002150 - inviable spore population

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Genotypes:

FYPO:0002414 - inviable swollen vegetative cell

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Genotypes:

FYPO:0002061 - inviable vegetative cell population

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Genotypes:

FYPO:0000118 - multiseptate vegetative cell

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Genotypes:

FYPO:0000672 - normal cell morphology

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Genotypes:

FYPO:0006008 - normal onset of protein localization to cell division site

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Genotypes:

FYPO:0003316 - normal protein localization to growing cell tip

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Genotypes:

FYPO:0001315 - normal vegetative cell morphology

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Genotypes:

FYPO:0003250 - premature septum assembly

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Genotypes:

FYPO:0000091 - sensitive to thiabendazole

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Genotypes:

FYPO:0007393 - septum mislocalized to cell tip

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Genotypes:

FYPO:0000647 - vegetative cell lysis

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Genotypes:

FYPO:0001492 - viable elongated vegetative cell

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Genotypes:

FYPO:0000648 - viable small vegetative cell

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Genotypes:

FYPO:0004103 - viable spherical vegetative cell

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Genotypes:

FYPO:0003612 - viable spore population

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Genotypes:

FYPO:0002106 - viable stubby vegetative cell

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Genotypes:

FYPO:0002060 - viable vegetative cell population

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Genotypes:

Protein features

PBO:0111758 - PAK-related kinase family

Qualitative gene expression

PomGeneEx:0000019 - protein level decreased

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PomGeneEx:0000011 - RNA level increased

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Quantitative gene expression

PBO:0006310 - protein level

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PBO:0011963 - RNA level

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Single locus phenotype

FYPO:0000147 - abnormal NETO

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Genotypes:

FYPO:0005503 - abnormally monopolar protein localization to cell tip

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Genotypes:

FYPO:0005369 - abolished cell population growth at low temperature

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Genotypes:

FYPO:0001018 - abolished NETO

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Genotypes:

FYPO:0001384 - abolished protein kinase activity

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Genotypes:

FYPO:0001394 - activation of monopolar cell growth at either end

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Genotypes:

FYPO:0003314 - activation of monopolar cell growth at new end

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Genotypes:

FYPO:0003171 - binucleate monoseptate cell with mitotic cell cycle arrest before cell separation

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Genotypes:

FYPO:0005721 - curved mitotic spindle during anaphase B

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Genotypes:

FYPO:0001407 - decreased cell population growth on glucose carbon source

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Genotypes:

FYPO:0000422 - decreased endocytosis during vegetative growth

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Genotypes:

FYPO:0000708 - decreased mating efficiency

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Genotypes:

FYPO:0001382 - decreased protein kinase activity

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Genotypes:

FYPO:0006120 - decreased protein localization to actin cortical patch

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Genotypes:

FYPO:0004357 - decreased protein phosphorylation during mitosis

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Genotypes:

FYPO:0001838 - decreased protein phosphorylation during vegetative growth

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Genotypes:

FYPO:0005801 - decreased rate of protein movement within plasma membrane at cell tip

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Genotypes:

FYPO:0004109 - delayed activation of monopolar cell growth

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Genotypes:

FYPO:0002021 - dispersed actin cortical patch localization during vegetative growth

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Genotypes:

FYPO:0009061 - increased protein localization to cell cortex during mitotic interphase

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Genotypes:

FYPO:0002852 - increased protein localization to cell tip during vegetative growth

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Genotypes:

FYPO:0004428 - increased rate of cytokinesis

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Genotypes:

FYPO:0002302 - inviable after spore germination, multiple cell divisions, spheroid cell

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Genotypes:

FYPO:0005855 - inviable after spore germination, single cell division, multiseptate cell

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Genotypes:

FYPO:0004531 - inviable after spore germination, single or double cell division, small cell

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Genotypes:

FYPO:0002187 - inviable normal volume spheroid vegetative cell

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Genotypes:

FYPO:0004104 - inviable spherical vegetative cell

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Genotypes:

FYPO:0002150 - inviable spore population

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Genotypes:

FYPO:0002061 - inviable vegetative cell population

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Genotypes:

FYPO:0001019 - monopolar actin cortical patch localization during vegetative growth

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Genotypes:

FYPO:0001397 - monopolar actin cortical patch localization to old end

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Genotypes:

FYPO:0001395 - normal activation of monopolar cell growth

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Genotypes:

FYPO:0001164 - normal growth on glucose carbon source

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Genotypes:

FYPO:0001221 - normal nucleus:cytoplasm ratio

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Genotypes:

FYPO:0006008 - normal onset of protein localization to cell division site

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Genotypes:

FYPO:0001587 - normal protein localization to cell tip during vegetative growth

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Genotypes:

FYPO:0002999 - normal protein localization to medial cortical node

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Genotypes:

FYPO:0004429 - normal rate of mitotic spindle elongation

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Genotypes:

FYPO:0001120 - pear-shaped vegetative cell

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Genotypes:

FYPO:0004430 - premature actomyosin contractile ring contraction

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Genotypes:

FYPO:0007829 - premature protein localization to cell division site

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Genotypes:

FYPO:0003250 - premature septum assembly

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Genotypes:

FYPO:0000091 - sensitive to thiabendazole

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Genotypes:

FYPO:0001234 - slow vegetative cell population growth

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Genotypes:

FYPO:0000024 - stubby vegetative cell

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Genotypes:

FYPO:0003389 - viable elongated vegetative cell with swollen medial region

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Genotypes:

FYPO:0000648 - viable small vegetative cell

References:

Genotypes:

FYPO:0006822 - viable small vegetative cell with normal cell growth rate

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Genotypes:

FYPO:0004103 - viable spherical vegetative cell

References:

Genotypes:

FYPO:0002479 - viable swollen elongated vegetative cell

References:

Genotypes:

FYPO:0002060 - viable vegetative cell population

References:

Genotypes:

Taxonomic conservation

PBO:0011065 - conserved in eukaryotes

PBO:0011071 - conserved in eukaryotes only

PBO:0011064 - conserved in fungi

PBO:0011069 - conserved in metazoa

PBO:0011070 - conserved in vertebrates

Protein features

IDNameInterPro nameDB name
PF00069PkinaseProt_kinase_domPfam
PF00786PBDCRIB_domPfam
cd01093CRIB_PAK_likePAK_BDCDD
cd06614STKc_PAKCDD
PS00107PROTEIN_KINASE_ATPProtein_kinase_ATP_BSPROSITE patterns
PS00108PROTEIN_KINASE_STSer/Thr_kinase_ASPROSITE patterns
PS50011PROTEIN_KINASE_DOMProt_kinase_domPROSITE profiles
PS50108CRIBCRIB_domPROSITE profiles
SM00220S_TKcProt_kinase_domSMART
SM00285PBDCRIB_domSMART
G3DSA:1.10.510.10:FF:000011CATH-FunFam
G3DSA:1.10.510.10CATH-Gene3D
G3DSA:3.30.200.20CATH-Gene3D
G3DSA:3.90.810.10CRIB_dom_sfCATH-Gene3D
SSF47912WAS_CSUPERFAMILY
SSF56112Kinase-like_dom_sfSUPERFAMILY
PTHR45832PAK3-likePANTHER
mobidb-lite-Disorderdisorder_predictionMobiDB-Disorder
mobidb-lite-Low-complexitydisorder_predictionMobiDB-Low-complexity
mobidb-lite-Polardisorder_predictionMobiDB-Polar

Orthologs

References / Literature

PMID:21849474 - Spatial control of Cdc42 activation determines cell width in fission yeast.
Kelly FD et al. Mol Biol Cell 2011 Oct;22(20):3801-11
PMID:17998401 - Nuclear size control in fission yeast.
Neumann FR et al. J Cell Biol 2007 Nov 19;179(4):593-600
PMID:19029336 - Schizosaccharomyces pombe Pak-related protein, Pak1p/Orb2p, phosphorylates myosin regulatory light chain to inhibit cytokinesis.
Loo TH et al. J Cell Biol 2008 Dec 01;183(5):785-93
PMID:39012625 - Arp2/3-dependent endocytosis ensures Cdc42 oscillations by removing Pak1-mediated negative feedback.
Harrell MA et al. J Cell Biol 2024 Sep 02;223(10)
PMID:29996109 - Quantitative Phosphoproteomics Reveals the Signaling Dynamics of Cell-Cycle Kinases in the Fission Yeast Schizosaccharomyces pombe.
Swaffer MP et al. Cell Rep 2018 Jul 10;24(2):503-514
GO_REF:0000033 - Annotation inferences using phylogenetic trees
PMID:27298342 - Identification of S-phase DNA damage-response targets in fission yeast reveals conservation of damage-response networks.
Willis NA et al. Proc Natl Acad Sci U S A 2016 Jun 28;113(26):E3676-85
PMID:12409291 - The Cdc42 binding and scaffolding activities of the fission yeast adaptor protein Scd2.
Endo M et al. J Biol Chem 2003 Jan 10;278(2):843-52
PMID:23697806 - A genome-wide resource of cell cycle and cell shape genes of fission yeast.
Hayles J et al. Open Biol 2013 May 22;3(5):130053
PMID:36749320 - Multiple polarity kinases inhibit phase separation of F-BAR protein Cdc15 and antagonize cytokinetic ring assembly in fission yeast.
Bhattacharjee R et al. Elife 2023 Feb 07;12
PMID:16823372 - ORFeome cloning and global analysis of protein localization in the fission yeast Schizosaccharomyces pombe.
Matsuyama A et al. Nat Biotechnol 2006 Jul;24(7):841-7
PMID:28914606 - Nanoscale architecture of the Schizosaccharomyces pombe contractile ring.
McDonald NA et al. Elife 2017 Sep 15;6
PMID:10593886 - Direct activation of the fission yeast PAK Shk1 by the novel SH3 domain protein, Skb5.
Yang P et al. J Biol Chem 1999 Dec 17;274(51):36052-7
PMID:33823663 - A TOR (target of rapamycin) and nutritional phosphoproteome of fission yeast reveals novel targets in networks conserved in humans.
Halova L et al. Open Biol 2021 Apr;11(4):200405
PMID:8187760 - Genetic analysis of cell morphogenesis in fission yeast--a role for casein kinase II in the establishment of polarized growth.
Snell V et al. EMBO J 1994 May 01;13(9):2066-74
PMID:12764130 - The kelch repeat protein, Tea1, is a potential substrate target of the p21-activated kinase, Shk1, in the fission yeast, Schizosaccharomyces pombe.
Kim H et al. J Biol Chem 2003 Aug 08;278(32):30074-82
PMID:37039135 - Cdc42 prevents precocious Rho1 activation during cytokinesis in a Pak1-dependent manner.
Onwubiko UN et al. J Cell Sci 2023 Apr 15;136(8)
PMID:9315645 - Multiple regulatory domains on the Byr2 protein kinase.
Tu H et al. Mol Cell Biol 1997 Oct;17(10):5876-87
PMID:8846783 - Fission yeast pak1+ encodes a protein kinase that interacts with Cdc42p and is involved in the control of cell polarity and mating.
Ottilie S et al. EMBO J 1995 Dec 01;14(23):5908-19
PMID:14506270 - The novel Rho GTPase-activating protein family protein, Rga8, provides a potential link between Cdc42/p21-activated kinase and Rho signaling pathways in the fission yeast, Schizosaccharomyces pombe.
Yang P et al. J Biol Chem 2003 Dec 05;278(49):48821-30
PMID:9858584 - Genetic evidence for Pak1 autoinhibition and its release by Cdc42.
Tu H et al. Mol Cell Biol 1999 Jan;19(1):602-11
PMID:20473289 - Analysis of a genome-wide set of gene deletions in the fission yeast Schizosaccharomyces pombe.
Kim DU et al. Nat Biotechnol 2010 Jun;28(6):617-623
PMID:11972773 - The p21-activated kinase, Shk1, is required for proper regulation of microtubule dynamics in the fission yeast, Schizosaccharomyces pombe.
Qyang Y et al. Mol Microbiol 2002 Apr;44(2):325-34
PMID:21511999 - Comparative functional genomics of the fission yeasts.
Rhind N et al. Science 2011 May 20;332(6032):930-6
PMID:23615447 - Compartmentalized nodes control mitotic entry signaling in fission yeast.
Deng L et al. Mol Biol Cell 2013 Jun;24(12):1872-81
PMID:14573463 - Schizosaccharomyces pombe Ras1 effector, Scd1, interacts with Klp5 and Klp6 kinesins to mediate cytokinesis.
Li Y et al. Genetics 2003 Oct;165(2):477-88
PMID:19646873 - The conserved NDR kinase Orb6 controls polarized cell growth by spatial regulation of the small GTPase Cdc42.
Das M et al. Curr Biol 2009 Aug 11;19(15):1314-9
PMID:8943016 - The highly conserved skb1 gene encodes a protein that interacts with Shk1, a fission yeast Ste20/PAK homolog.
Gilbreth M et al. Proc Natl Acad Sci U S A 1996 Nov 26;93(24):13802-7
PMID:11389855 - Genetic and molecular characterization of Skb15, a highly conserved inhibitor of the fission yeast PAK, Shk1.
Kim HW et al. Mol Cell 2001 May;7(5):1095-101
PMID:28808035 - Fission yeast myosin Myo2 is down-regulated in actin affinity by light chain phosphorylation.
Pollard LW et al. Proc Natl Acad Sci U S A 2017 Aug 29;114(35):E7236-E7244
PMID:39705284 - Proteomic and phosphoproteomic analyses reveal that TORC1 is reactivated by pheromone signaling during sexual reproduction in fission yeast.
Bérard M et al. PLoS Biol 2024 Dec 20;22(12):e3002963
PMID:23101633 - Quantitative analysis of fission yeast transcriptomes and proteomes in proliferating and quiescent cells.
Marguerat S et al. Cell 2012 Oct 26;151(3):671-83
PMID:8522609 - Fission yeast cell morphogenesis: identification of new genes and analysis of their role during the cell cycle.
Verde F et al. J Cell Biol 1995 Dec;131(6 Pt 1):1529-38
PMID:24763107 - Absolute proteome and phosphoproteome dynamics during the cell cycle of Schizosaccharomyces pombe (Fission Yeast).
Carpy A et al. Mol Cell Proteomics 2014 Aug;13(8):1925-36
PMID:12007420 - Tea3p is a cell end marker activating polarized growth in Schizosaccharomyces pombe.
Arellano M et al. Curr Biol 2002 Apr 30;12(9):751-6
PMID:10628977 - Isolation and characterization of Nrf1p, a novel negative regulator of the Cdc42p GTPase in Schizosaccharomyces pombe.
Murray JM et al. Genetics 2000 Jan;154(1):155-65
PMID:9200612 - tea1 and the microtubular cytoskeleton are important for generating global spatial order within the fission yeast cell.
Mata J et al. Cell 1997 Jun 13;89(6):939-49
PMID:25837586 - Spontaneous Cdc42 polarization independent of GDI-mediated extraction and actin-based trafficking.
Bendezú FO et al. PLoS Biol 2015 Apr;13(4):e1002097
PMID:19808887 - Ste20-kinase-dependent TEDS-site phosphorylation modulates the dynamic localisation and endocytic function of the fission yeast class I myosin, Myo1.
Attanapola SL et al. J Cell Sci 2009 Nov 01;122(Pt 21):3856-61
PMID:25720772 - Quantitative phosphoproteomics reveals pathways for coordination of cell growth and division by the conserved fission yeast kinase pom1.
Kettenbach AN et al. Mol Cell Proteomics 2015 May;14(5):1275-87
PMID:9679144 - Regulation of cell polarity by microtubules in fission yeast.
Sawin KE et al. J Cell Biol 1998 Jul 27;142(2):457-71
PMID:21652630 - Characterization of Mug33 reveals complementary roles for actin cable-dependent transport and exocyst regulators in fission yeast exocytosis.
Snaith HA et al. J Cell Sci 2011 Jul 01;124(Pt 13):2187-99
PB_REF:0000003 - Disease Association Curation
PMID:39367033 - Quantitative proteomics and phosphoproteomics profiling of meiotic divisions in the fission yeast Schizosaccharomyces pombe.
Sivakova B et al. Sci Rep 2024 Oct 04;14(1):23105
PMID:10574765 - Mis-specification of cortical identity in a fission yeast PAK mutant.
Sawin KE et al. Curr Biol 1999 Nov 18;9(22):1335-8
PMID:9636183 - Fission yeast orb6, a ser/thr protein kinase related to mammalian rho kinase and myotonic dystrophy kinase, is required for maintenance of cell polarity and coordinates cell morphogenesis with the cell cycle.
Verde F et al. Proc Natl Acad Sci U S A 1998 Jun 23;95(13):7526-31
PMID:16537923 - Sterol regulatory element binding protein is a principal regulator of anaerobic gene expression in fission yeast.
Todd BL et al. Mol Cell Biol 2006 Apr;26(7):2817-31
PMID:31719163 - A novel interplay between GEFs orchestrates Cdc42 activity during cell polarity and cytokinesis in fission yeast.
Hercyk BS et al. J Cell Sci 2019 Dec 03;132(23)
PMID:9660817 - Cloning and characterization of shk2, a gene encoding a novel p21-activated protein kinase from fission yeast.
Yang P et al. J Biol Chem 1998 Jul 17;273(29):18481-9
PMID:9660818 - Characterization of Pak2p, a pleckstrin homology domain-containing, p21-activated protein kinase from fission yeast.
Sells MA et al. J Biol Chem 1998 Jul 17;273(29):18490-8
PMID:28218250 - Chromatin remodeller Fun30 Fft3 induces nucleosome disassembly to facilitate RNA polymerase II elongation.
Lee J et al. Nat Commun 2017 Feb 20;8:14527
PMID:23297348 - Comprehensive proteomics analysis reveals new substrates and regulators of the fission yeast clp1/cdc14 phosphatase.
Chen JS et al. Mol Cell Proteomics 2013 May;12(5):1074-86
PMID:30726745 - Fission Yeast NDR/LATS Kinase Orb6 Regulates Exocytosis via Phosphorylation of the Exocyst Complex.
Tay YD et al. Cell Rep 2019 Feb 05;26(6):1654-1667.e7
PMID:12529446 - Gef1p, a new guanine nucleotide exchange factor for Cdc42p, regulates polarity in Schizosaccharomyces pombe.
Coll PM et al. Mol Biol Cell 2003 Jan;14(1):313-23
PMID:7597098 - Shk1, a homolog of the Saccharomyces cerevisiae Ste20 and mammalian p65PAK protein kinases, is a component of a Ras/Cdc42 signaling module in the fission yeast Schizosaccharomyces pombe.
Marcus S et al. Proc Natl Acad Sci U S A 1995 Jun 20;92(13):6180-4
PMID:19474789 - A spatial gradient coordinates cell size and mitotic entry in fission yeast.
Moseley JB et al. Nature 2009 Jun 11;459(7248):857-60
PMID:10567532 - Direct binding and In vivo regulation of the fission yeast p21-activated kinase shk1 by the SH3 domain protein scd2.
Chang E et al. Mol Cell Biol 1999 Dec;19(12):8066-74
PMID:23051734 - Myosin Vs organize actin cables in fission yeast.
Lo Presti L et al. Mol Biol Cell 2012 Dec;23(23):4579-91
PMID:29930085 - Local and global Cdc42 guanine nucleotide exchange factors for fission yeast cell polarity are coordinated by microtubules and the Tea1-Tea4-Pom1 axis.
Tay YD et al. J Cell Sci 2018 Jul 19;131(14)
PMID:37970674 - SUMOylation regulates Lem2 function in centromere clustering and silencing.
Strachan J et al. J Cell Sci 2023 Dec 01;136(23)
PMID:39110593 - VAP-mediated membrane-tethering mechanisms implicate ER-PM contact function in pH homeostasis.
Hoh KL et al. Cell Rep 2024 Aug 05;43(8):114592
PMID:19547744 - Evolution of phosphoregulation: comparison of phosphorylation patterns across yeast species.
Beltrao P et al. PLoS Biol 2009 Jun 16;7(6):e1000134
PMID:21712547 - Mitotic substrates of the kinase aurora with roles in chromatin regulation identified through quantitative phosphoproteomics of fission yeast.
Koch A et al. Sci Signal 2011 Jun 28;4(179):rs6
PB_REF:0000006 - Disease associations from Monarch via human-pombe orthologs
PMID:37746062 - Polarity kinases that phosphorylate F-BAR protein Cdc15 have unique localization patterns during cytokinesis and contributions to preventing tip septation in Schizosaccharomyces pombe .
Igarashi MG et al. MicroPubl Biol 2023;2023
PMID:9843966 - Negative regulation of mitosis in fission yeast by the shk1 interacting protein skb1 and its human homolog, Skb1Hs.
Gilbreth M et al. Proc Natl Acad Sci U S A 1998 Dec 08;95(25):14781-6
PMID:24013502 - Epe1 recruits BET family bromodomain protein Bdf2 to establish heterochromatin boundaries.
Wang J et al. Genes Dev 2013 Sep 01;27(17):1886-902