PAK4
Serine/threonine-protein kinase PAK 4
Also known as: PAK4_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- O96013
- Gene
- PAK4
- Ensembl
- ENSG00000130669
- Chromosome
- 19
- Canonical length
- 591 aa
- Protein class
- Enzymes, Predicted intracellular proteins, RAS pathway related proteins
- Subcellular location
- Plasma membrane,Cell Junctions
OverviewNCBI Gene
PAK proteins, a family of serine/threonine p21-activating kinases, include PAK1, PAK2, PAK3 and PAK4. PAK proteins are critical effectors that link Rho GTPases to cytoskeleton reorganization and nuclear signaling. They serve as targets for the small GTP binding proteins Cdc42 and Rac and have been implicated in a wide range of biological activities. PAK4 interacts specifically with the GTP-bound form of Cdc42Hs and weakly activates the JNK family of MAP kinases. PAK4 is a mediator of filopodia formation and may play a role in the reorganization of the actin cytoskeleton. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Canonical amino-acid sequenceUniProt
591 residues, UniProt reviewed canonical sequence.
>O96013|PAK4
1 MFGKRKKRVE ISAPSNFEHR VHTGFDQHEQ KFTGLPRQWQ SLIEESARRP KPLVDPACIT
61 SIQPGAPKTI VRGSKGAKDG ALTLLLDEFE NMSVTRSNSL RRDSPPPPAR ARQENGMPEE
121 PATTARGGPG KAGSRGRFAG HSEAGGGSGD RRRAGPEKRP KSSREGSGGP QESSRDKRPL
181 SGPDVGTPQP AGLASGAKLA AGRPFNTYPR ADTDHPSRGA QGEPHDVAPN GPSAGGLAIP
241 QSSSSSSRPP TRARGAPSPG VLGPHASEPQ LAPPACTPAA PAVPGPPGPR SPQREPQRVS
301 HEQFRAALQL VVDPGDPRSY LDNFIKIGEG STGIVCIATV RSSGKLVAVK KMDLRKQQRR
361 ELLFNEVVIM RDYQHENVVE MYNSYLVGDE LWVVMEFLEG GALTDIVTHT RMNEEQIAAV
421 CLAVLQALSV LHAQGVIHRD IKSDSILLTH DGRVKLSDFG FCAQVSKEVP RRKSLVGTPY
481 WMAPELISRL PYGPEVDIWS LGIMVIEMVD GEPPYFNEPP LKAMKMIRDN LPPRLKNLHK
541 VSPSLKGFLD RLLVRDPAQR ATAAELLKHP FLAKAGPPAS IVPLMRQNRT RLocalizationUniProt · AlphaFold · HPA
Whether an antibody against PAK4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.47
- Highest tissue expression
- 42 nTPM
Expression across tissuesHPA
Tissue
- esophagus: 42 nTPM
- salivary gland: 40 nTPM
- prostate: 39 nTPM
- skin: 39 nTPM
- lung: 37 nTPM
- kidney: 37 nTPM
Single-cell type
- esophageal apical cells: 106 nCPM
- extravillous trophoblasts: 96 nCPM
- syncytiotrophoblasts: 92 nCPM
- distal convoluted tubule cells: 82 nCPM
- renal connecting tubule cells: 80 nCPM
- renal collecting duct intercalated cells: 78 nCPM
Immune cell
- eosinophil: 1.2 nTPM
- memory CD8 T-cell: 1.1 nTPM
- myeloid DC: 0.9 nTPM
- NK-cell: 0.9 nTPM
- T-reg: 0.9 nTPM
- MAIT T-cell: 0.8 nTPM
Brain region
- basal ganglia: 39 nTPM
- medulla oblongata: 38 nTPM
- midbrain: 37 nTPM
- cerebral cortex: 37 nTPM
- amygdala: 36 nTPM
- white matter: 36 nTPM
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.78
- gnomAD pLI
- 0
- gnomAD missense Z
- 0.59
- DepMap mean gene effect
- -0.05
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 10% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- apoptotic process
- cell migration
- cellular response to starvation
- cytoskeleton organization
- dendritic spine development
- intracellular signal transduction
- negative regulation of endothelial cell apoptotic process
- positive regulation of angiogenesis
- positive regulation of focal adhesion disassembly
- protein stabilization
- regulation of cell growth
- regulation of MAPK cascade
- signal transduction
Molecular functions
- ATP binding
- cadherin binding involved in cell-cell adhesion
- protein kinase activity
- protein serine kinase activity
- protein serine/threonine kinase activity
- protein-macromolecule adaptor activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of PAK4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads PAK4 as an antibody target. Whether an autoantibody or antibody against PAK4 could matter depends on whether native PAK4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
PAK4 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label PAK4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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