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UniProtKB - O96013 (PAK4_HUMAN)

Protein

Serine/threonine-protein kinase PAK 4

Gene

PAK4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, growth, proliferation or cell survival. Activation by various effectors including growth factor receptors or active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates and inactivates the protein phosphatase SSH1, leading to increased inhibitory phosphorylation of the actin binding/depolymerizing factor cofilin. Decreased cofilin activity may lead to stabilization of actin filaments. Phosphorylates LIMK1, a kinase that also inhibits the activity of cofilin. Phosphorylates integrin beta5/ITGB5 and thus regulates cell motility. Phosphorylates ARHGEF2 and activates the downstream target RHOA that plays a role in the regulation of assembly of focal adhesions and actin stress fibers. Stimulates cell survival by phosphorylating the BCL2 antagonist of cell death BAD. Alternatively, inhibits apoptosis by preventing caspase-8 binding to death domain receptors in a kinase independent manner. Plays a role in cell-cycle progression by controlling levels of the cell-cycle regulatory protein CDKN1A and by phosphorylating RAN.8 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Activity regulationi

Inhibited by INKA1; which inhibits the serine/threonine-protein kinase activity by binding PAK4 in a substrate-like manner (PubMed:26607847).1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei350ATPPROSITE-ProRule annotationCombined sources1 Publication1
Active sitei440Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi327 – 335ATPPROSITE-ProRule annotationCombined sources1 Publication9
Nucleotide bindingi396 – 398ATPCombined sources1 Publication3
Nucleotide bindingi458 – 460ATPCombined sources1 Publication3

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL
  • protein kinase activity Source: ProtInc
  • protein serine/threonine kinase activity Source: UniProtKB
  • Rac GTPase binding Source: GO_Central
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processApoptosis, Cell cycle
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.1 2681
ReactomeiR-HSA-428540 Activation of RAC1
SignaLinkiO96013
SIGNORiO96013

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase PAK 4 (EC:2.7.11.1)
Alternative name(s):
p21-activated kinase 4
Short name:
PAK-4
Gene namesi
Name:PAK4
Synonyms:KIAA1142
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000130669.17
HGNCiHGNC:16059 PAK4
MIMi605451 gene
neXtProtiNX_O96013

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi445S → N: Approximately 30-fold increased autophosphorylation (constitutively active mutant). 1 Publication1
Mutagenesisi474S → E: Approximately 3-fold increased autophosphorylation. 1 Publication1

Organism-specific databases

DisGeNETi10298
OpenTargetsiENSG00000130669
PharmGKBiPA32920

Chemistry databases

ChEMBLiCHEMBL4482
GuidetoPHARMACOLOGYi2136

Polymorphism and mutation databases

BioMutaiPAK4

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000864741 – 591Serine/threonine-protein kinase PAK 4Add BLAST591

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei41PhosphoserineCombined sources1
Modified residuei78N6-methyllysineCombined sources1
Modified residuei104PhosphoserineCombined sources1
Modified residuei148PhosphoserineCombined sources1
Modified residuei167PhosphoserineCombined sources1
Modified residuei181PhosphoserineCombined sources1
Modified residuei187PhosphothreonineCombined sources1
Modified residuei195PhosphoserineCombined sources1
Modified residuei207PhosphothreonineCombined sources1
Modified residuei258PhosphoserineCombined sources1
Modified residuei267PhosphoserineCombined sources1
Modified residuei291PhosphoserineCombined sources1
Modified residuei474Phosphoserine; by autocatalysisCombined sources1 Publication1

Post-translational modificationi

Autophosphorylated on serine residues when activated by CDC42/p21 (Ref. 31). Phosphorylated on tyrosine residues upon stimulation of FGFR2 (By similarity).By similarity1 Publication
Polyubiquitinated, leading to its proteasomal degradation.1 Publication

Keywords - PTMi

Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO96013
MaxQBiO96013
PaxDbiO96013
PeptideAtlasiO96013
PRIDEiO96013
ProteomicsDBi51192
51193 [O96013-2]
51194 [O96013-3]
51195 [O96013-4]

PTM databases

iPTMnetiO96013
PhosphoSitePlusiO96013

Expressioni

Tissue specificityi

Highest expression in prostate, testis and colon.

Gene expression databases

BgeeiENSG00000130669 Expressed in 233 organ(s), highest expression level in type B pancreatic cell
CleanExiHS_PAK4
ExpressionAtlasiO96013 baseline and differential
GenevisibleiO96013 HS

Organism-specific databases

HPAiCAB025747
CAB044670
HPA070175
HPA072220

Interactioni

Subunit structurei

Interacts with FGFR2 and GRB2 (By similarity). Interacts tightly with GTP-bound but not GDP-bound CDC42/p21 and weakly with RAC1 (PubMed:15827085). Interacts with INKA1 (PubMed:26607847). Interacts with SH3RF2 (PubMed:24130170).By similarity3 Publications

Binary interactionsi

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi115586, 63 interactors
DIPiDIP-39742N
IntActiO96013, 24 interactors
MINTiO96013
STRINGi9606.ENSP00000351049

Chemistry databases

BindingDBiO96013

Structurei

Secondary structure

1591
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO96013
SMRiO96013
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO96013

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini11 – 24CRIBPROSITE-ProRule annotationAdd BLAST14
Domaini321 – 572Protein kinasePROSITE-ProRule annotationAdd BLAST252

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni25 – 320LinkerAdd BLAST296
Regioni298 – 323GEF-interaction domain (GID)Add BLAST26

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi105 – 108Poly-Pro4
Compositional biasi242 – 247Poly-Ser6

Sequence similaritiesi

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.Curated

Phylogenomic databases

eggNOGiKOG0578 Eukaryota
ENOG410XP4K LUCA
GeneTreeiENSGT00920000148968
HOVERGENiHBG108518
InParanoidiO96013
KOiK05734
OMAiRQENGMP
OrthoDBiEOG091G0OT5
PhylomeDBiO96013
TreeFamiTF105352

Family and domain databases

CDDicd01093 CRIB_PAK_like, 1 hit
Gene3Di3.90.810.10, 1 hit
InterProiView protein in InterPro
IPR000095 CRIB_dom
IPR036936 CRIB_dom_sf
IPR011009 Kinase-like_dom_sf
IPR033923 PAK_BD
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
PfamiView protein in Pfam
PF00786 PBD, 1 hit
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00285 PBD, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50108 CRIB, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 4 potential isoforms that are computationally mapped.iShow all

Isoform 1 (identifier: O96013-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MFGKRKKRVE ISAPSNFEHR VHTGFDQHEQ KFTGLPRQWQ SLIEESARRP 
        60         70         80         90        100
KPLVDPACIT SIQPGAPKTI VRGSKGAKDG ALTLLLDEFE NMSVTRSNSL 
       110        120        130        140        150
RRDSPPPPAR ARQENGMPEE PATTARGGPG KAGSRGRFAG HSEAGGGSGD 
       160        170        180        190        200
RRRAGPEKRP KSSREGSGGP QESSRDKRPL SGPDVGTPQP AGLASGAKLA 
       210        220        230        240        250
AGRPFNTYPR ADTDHPSRGA QGEPHDVAPN GPSAGGLAIP QSSSSSSRPP 
       260        270        280        290        300
TRARGAPSPG VLGPHASEPQ LAPPACTPAA PAVPGPPGPR SPQREPQRVS 
       310        320        330        340        350
HEQFRAALQL VVDPGDPRSY LDNFIKIGEG STGIVCIATV RSSGKLVAVK 
       360        370        380        390        400
KMDLRKQQRR ELLFNEVVIM RDYQHENVVE MYNSYLVGDE LWVVMEFLEG 
       410        420        430        440        450
GALTDIVTHT RMNEEQIAAV CLAVLQALSV LHAQGVIHRD IKSDSILLTH 
       460        470        480        490        500
DGRVKLSDFG FCAQVSKEVP RRKSLVGTPY WMAPELISRL PYGPEVDIWS 
       510        520        530        540        550
LGIMVIEMVD GEPPYFNEPP LKAMKMIRDN LPPRLKNLHK VSPSLKGFLD 
       560        570        580        590 
RLLVRDPAQR ATAAELLKHP FLAKAGPPAS IVPLMRQNRT R
Length:591
Mass (Da):64,072
Last modified:May 1, 1999 - v1
Checksum:i04C2A5C0B06427D5
GO
Isoform 2 (identifier: O96013-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     120-120: E → K
     121-285: Missing.

Note: No experimental confirmation available.
Show »
Length:426
Mass (Da):47,924
Checksum:i505879690593E93A
GO
Isoform 3 (identifier: O96013-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     69-221: Missing.

Show »
Length:438
Mass (Da):48,268
Checksum:i4A596EBBCECE9883
GO
Isoform 4 (identifier: O96013-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     132-221: Missing.

Note: No experimental confirmation available.
Show »
Length:501
Mass (Da):54,940
Checksum:i6EE6240ECE65E79D
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
M0R1R1M0R1R1_HUMAN
Serine/threonine-protein kinase PAK...
PAK4
149Annotation score:
M0R0L9M0R0L9_HUMAN
Serine/threonine-protein kinase PAK...
PAK4
182Annotation score:
M0R2X4M0R2X4_HUMAN
Serine/threonine-protein kinase PAK...
PAK4
131Annotation score:
M0R3G6M0R3G6_HUMAN
Serine/threonine-protein kinase PAK...
PAK4
93Annotation score:

Sequence cautioni

The sequence BAA86456 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAC11166 differs from that shown. Reason: Erroneous initiation.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_040970135R → Q1 PublicationCorresponds to variant dbSNP:rs56099436Ensembl.1
Natural variantiVAR_040971139A → T1 PublicationCorresponds to variant dbSNP:rs35655056Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_01757269 – 221Missing in isoform 3. 3 PublicationsAdd BLAST153
Alternative sequenceiVSP_004892120E → K in isoform 2. 1 Publication1
Alternative sequenceiVSP_004893121 – 285Missing in isoform 2. 1 PublicationAdd BLAST165
Alternative sequenceiVSP_017573132 – 221Missing in isoform 4. 1 PublicationAdd BLAST90

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ011855 mRNA Translation: CAA09820.1
AF005046 mRNA Translation: AAD01210.1
AB032968 mRNA Translation: BAA86456.1 Different initiation.
AK074728 mRNA Translation: BAC11166.1 Different initiation.
AK294586 mRNA Translation: BAG57777.1
AL834236 mRNA Translation: CAD38914.2
CH471126 Genomic DNA Translation: EAW56861.1
BC002921 mRNA Translation: AAH02921.1
BC011368 mRNA Translation: AAH11368.1
BC025282 mRNA Translation: AAH25282.1
BC034511 mRNA Translation: AAH34511.1
CCDSiCCDS12528.1 [O96013-1]
CCDS33019.1 [O96013-3]
RefSeqiNP_001014831.1, NM_001014831.2 [O96013-1]
NP_001014832.1, NM_001014832.1 [O96013-1]
NP_001014834.1, NM_001014834.2 [O96013-3]
NP_001014835.1, NM_001014835.1 [O96013-3]
NP_005875.1, NM_005884.3 [O96013-1]
XP_011524618.1, XM_011526316.1 [O96013-1]
XP_011524619.1, XM_011526317.2 [O96013-1]
XP_011524620.1, XM_011526318.2 [O96013-1]
XP_011524621.1, XM_011526319.2 [O96013-1]
XP_011524622.1, XM_011526320.1 [O96013-3]
UniGeneiHs.20447

Genome annotation databases

EnsembliENST00000321944; ENSP00000326864; ENSG00000130669 [O96013-4]
ENST00000358301; ENSP00000351049; ENSG00000130669 [O96013-1]
ENST00000360442; ENSP00000353625; ENSG00000130669 [O96013-1]
ENST00000593690; ENSP00000469413; ENSG00000130669 [O96013-1]
ENST00000599386; ENSP00000471157; ENSG00000130669 [O96013-3]
ENST00000599470; ENSP00000470284; ENSG00000130669 [O96013-3]
GeneIDi10298
KEGGihsa:10298
UCSCiuc002okj.2 human [O96013-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPAK4_HUMAN
AccessioniPrimary (citable) accession number: O96013
Secondary accession number(s): B4DGG6
, Q8N4E1, Q8NCH5, Q8NDE3, Q9BU33, Q9ULS8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: May 1, 1999
Last modified: September 12, 2018
This is version 197 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health

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