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Protein

Serine/threonine-protein kinase PAK 3

Gene

PAK3

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, or cell cycle regulation. Plays a role in dendrite spine morphogenesis as well as synapse formation and plasticity. Acts as downstream effector of the small GTPases CDC42 and RAC1. Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration. Additionally, phosphorylates TNNI3/troponin I to modulate calcium sensitivity and relaxation kinetics of thin myofilaments. May also be involved in early neuronal development.1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Enzyme regulationi

Activated by binding small G proteins. Binding of GTP-bound CDC42 or RAC1 to the autoregulatory region releases monomers from the autoinhibited dimer, enables phosphorylation of Thr-436 and allows the kinase domain to adopt an active structure (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei312ATPPROSITE-ProRule annotation1
Active sitei402Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi289 – 297ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionAllosteric enzyme, Developmental protein, Kinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.1 2681
ReactomeiR-HSA-202433 Generation of second messenger molecules
R-HSA-389359 CD28 dependent Vav1 pathway
R-HSA-3928664 Ephrin signaling
R-HSA-399954 Sema3A PAK dependent Axon repulsion
R-HSA-428540 Activation of RAC1
R-HSA-5218920 VEGFR2 mediated vascular permeability
R-HSA-5621575 CD209 (DC-SIGN) signaling
R-HSA-5627123 RHO GTPases activate PAKs
R-HSA-5687128 MAPK6/MAPK4 signaling
SignaLinkiO75914
SIGNORiO75914

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase PAK 3 (EC:2.7.11.1)
Alternative name(s):
Beta-PAK
Oligophrenin-3
p21-activated kinase 3
Short name:
PAK-3
Gene namesi
Name:PAK3
Synonyms:OPHN3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000077264.14
HGNCiHGNC:8592 PAK3
MIMi300142 gene
neXtProtiNX_O75914

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

Involvement in diseasei

Mental retardation, X-linked 30 (MRX30)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked mental retardation, while syndromic mental retardation presents with associated physical, neurological and/or psychiatric manifestations.
See also OMIM:300558
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02382567R → C in MRX30. 1 PublicationCorresponds to variant dbSNP:rs121434612Ensembl.1
Natural variantiVAR_023826380A → E in MRX30. 1 PublicationCorresponds to variant dbSNP:rs121434613Ensembl.1

Keywords - Diseasei

Disease mutation, Mental retardation

Organism-specific databases

DisGeNETi5063
MalaCardsiPAK3
MIMi300558 phenotype
OpenTargetsiENSG00000077264
Orphaneti777 X-linked non-syndromic intellectual disability
PharmGKBiPA32919

Chemistry databases

ChEMBLiCHEMBL2999
GuidetoPHARMACOLOGYi2135

Polymorphism and mutation databases

BioMutaiPAK3

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000864691 – 559Serine/threonine-protein kinase PAK 3Add BLAST559

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2PhosphoserineBy similarity1
Modified residuei50Phosphoserine; by autocatalysisBy similarity1
Modified residuei154Phosphoserine; by autocatalysisBy similarity1
Modified residuei186PhosphoserineBy similarity1
Modified residuei436Phosphothreonine; by autocatalysisBy similarity1

Post-translational modificationi

Autophosphorylated when activated by CDC42/p21.
Neddylated.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiO75914
PeptideAtlasiO75914
PRIDEiO75914

PTM databases

iPTMnetiO75914
PhosphoSitePlusiO75914

Expressioni

Tissue specificityi

Restricted to the nervous system. Highly expressed in postmitotic neurons of the developing and postnatal cerebral cortex and hippocampus.1 Publication

Gene expression databases

BgeeiENSG00000077264
ExpressionAtlasiO75914 baseline and differential
GenevisibleiO75914 HS

Organism-specific databases

HPAiHPA044791
HPA060219

Interactioni

Subunit structurei

Interacts tightly with GTP-bound but not GDP-bound CDC42/p21 and RAC1. Shows highly specific binding to the SH3 domains of phospholipase C-gamma and of adapter protein NCK. Interacts with the C-terminal of APP (By similarity). Interacts with ARHGEF6 and ARHGEF7.By similarity1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi11109910 interactors.
IntActiO75914 4 interactors.
MINTiO75914
STRINGi9606.ENSP00000353864

Chemistry databases

BindingDBiO75914

Structurei

Secondary structure

1559
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi263 – 273Combined sources11
Beta strandi274 – 277Combined sources4
Helixi279 – 281Combined sources3
Beta strandi283 – 291Combined sources9
Beta strandi293 – 302Combined sources10
Turni303 – 305Combined sources3
Beta strandi308 – 315Combined sources8
Helixi316 – 318Combined sources3
Helixi324 – 334Combined sources11
Beta strandi343 – 349Combined sources7
Beta strandi352 – 358Combined sources7
Helixi365 – 371Combined sources7
Helixi376 – 395Combined sources20
Helixi405 – 407Combined sources3
Beta strandi408 – 410Combined sources3
Beta strandi416 – 418Combined sources3
Helixi441 – 443Combined sources3
Helixi446 – 449Combined sources4
Helixi458 – 472Combined sources15
Turni476 – 479Combined sources4
Helixi482 – 492Combined sources11
Helixi500 – 502Combined sources3
Helixi505 – 514Combined sources10
Turni519 – 521Combined sources3
Helixi525 – 528Combined sources4
Helixi532 – 536Combined sources5
Helixi540 – 543Combined sources4
Helixi544 – 555Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
6FD3X-ray1.52A261-559[»]
ProteinModelPortaliO75914
SMRiO75914
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini70 – 83CRIBPROSITE-ProRule annotationAdd BLAST14
Domaini283 – 534Protein kinasePROSITE-ProRule annotationAdd BLAST252

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni65 – 150Autoregulatory regionBy similarityAdd BLAST86
Regioni65 – 123GTPase-bindingBy similarityAdd BLAST59
Regioni84 – 282LinkerAdd BLAST199

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi187 – 201Poly-GluAdd BLAST15

Sequence similaritiesi

Keywords - Domaini

SH3-binding

Phylogenomic databases

eggNOGiKOG0578 Eukaryota
ENOG410XP4K LUCA
GeneTreeiENSGT00910000143994
HOGENOMiHOG000234202
HOVERGENiHBG108518
InParanoidiO75914
KOiK05733
OMAiEFTPDLY
OrthoDBiEOG091G04H8
PhylomeDBiO75914
TreeFamiTF105351

Family and domain databases

CDDicd01093 CRIB_PAK_like, 1 hit
cd06656 STKc_PAK3, 1 hit
Gene3Di3.90.810.101 hit
InterProiView protein in InterPro
IPR000095 CRIB_dom
IPR036936 CRIB_dom_sf
IPR011009 Kinase-like_dom_sf
IPR035065 PAK2/3
IPR033923 PAK_BD
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
IPR035063 STK_PAK3
PANTHERiPTHR24361:SF250 PTHR24361:SF250, 1 hit
PfamiView protein in Pfam
PF00786 PBD, 1 hit
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00285 PBD, 1 hit
SM00220 S_TKc, 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
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (4)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: O75914-1) [UniParc]FASTAAdd to basket
Also known as: PAK3b

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
MSDGLDNEEK PPAPPLRMNS NNRDSSALNH SSKPLPMAPE EKNKKARLRS
60 70 80 90 100
IFPGGGDKTN KKKEKERPEI SLPSDFEHTI HVGFDAVTGE FTPDLYGSQM
110 120 130 140 150
CPGKLPEGIP EQWARLLQTS NITKLEQKKN PQAVLDVLKF YDSKETVNNQ
160 170 180 190 200
KYMSFTSGDK SAHGYIAAHP SSTKTASEPP LAPPVSEEED EEEEEEEDEN
210 220 230 240 250
EPPPVIAPRP EHTKSIYTRS VVESIASPAV PNKEVTPPSA ENANSSTLYR
260 270 280 290 300
NTDRQRKKSK MTDEEILEKL RSIVSVGDPK KKYTRFEKIG QGASGTVYTA
310 320 330 340 350
LDIATGQEVA IKQMNLQQQP KKELIINEIL VMRENKNPNI VNYLDSYLVG
360 370 380 390 400
DELWVVMEYL AGGSLTDVVT ETCMDEGQIA AVCRECLQAL DFLHSNQVIH
410 420 430 440 450
RDIKSDNILL GMDGSVKLTD FGFCAQITPE QSKRSTMVGT PYWMAPEVVT
460 470 480 490 500
RKAYGPKVDI WSLGIMAIEM VEGEPPYLNE NPLRALYLIA TNGTPELQNP
510 520 530 540 550
ERLSAVFRDF LNRCLEMDVD RRGSAKELLQ HPFLKLAKPL SSLTPLIIAA

KEAIKNSSR
Length:559
Mass (Da):62,310
Last modified:May 10, 2004 - v2
Checksum:iBC39AEC6F0A5478B
GO
Isoform 2 (identifier: O75914-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     93-107: Missing.

Show »
Length:544
Mass (Da):60,693
Checksum:i230AF6952CB049E2
GO
Isoform 3 (identifier: O75914-3) [UniParc]FASTAAdd to basket
Also known as: PAK3cb

The sequence of this isoform differs from the canonical sequence as follows:
     92-92: T → TNSPFQTSRPVTVASSQSEGKM

Show »
Length:580
Mass (Da):64,530
Checksum:i9646E127F2F007A2
GO
Isoform 4 (identifier: O75914-4) [UniParc]FASTAAdd to basket
Also known as: PAK3c

The sequence of this isoform differs from the canonical sequence as follows:
     92-107: TPDLYGSQMCPGKLPE → TNSPFQTSRPVTVASSQSEGKM

Show »
Length:565
Mass (Da):62,913
Checksum:i6A0C2190BBBBDC1F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti32S → F in AAF67008 (Ref. 2) Curated1
Sequence conflicti36P → S in AAF67008 (Ref. 2) Curated1
Sequence conflicti73P → S in AAF67008 (Ref. 2) Curated1
Sequence conflicti106 – 107PE → SL in AAF67008 (Ref. 2) Curated2
Sequence conflicti123T → P in AAF67008 (Ref. 2) Curated1
Sequence conflicti127 – 130QKKN → PEEE in AAF67008 (Ref. 2) Curated4
Sequence conflicti134 – 137VLDV → CSRC in AAF67008 (Ref. 2) Curated4
Sequence conflicti146 – 148TVN → PVT in AAF67008 (Ref. 2) Curated3
Sequence conflicti175T → P in AAF67008 (Ref. 2) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02382567R → C in MRX30. 1 PublicationCorresponds to variant dbSNP:rs121434612Ensembl.1
Natural variantiVAR_023826380A → E in MRX30. 1 PublicationCorresponds to variant dbSNP:rs121434613Ensembl.1
Natural variantiVAR_046764440T → S in a colorectal adenocarcinoma sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04184092 – 107TPDLY…GKLPE → TNSPFQTSRPVTVASSQSEG KM in isoform 4. 1 PublicationAdd BLAST16
Alternative sequenceiVSP_04183992T → TNSPFQTSRPVTVASSQSEG KM in isoform 3. 1 Publication1
Alternative sequenceiVSP_01024293 – 107Missing in isoform 2. 3 PublicationsAdd BLAST15

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF068864 mRNA Translation: AAC36097.1
AF155651 mRNA Translation: AAF67008.1
AB102659 mRNA Translation: BAC81128.1
AB102251 Genomic DNA Translation: BAC80750.1
AB102252 Genomic DNA Translation: BAC80751.1
AB102253 Genomic DNA Translation: BAC80752.1
AB102254 Genomic DNA Translation: BAC80753.1
AB102255 Genomic DNA Translation: BAC80754.1
AB102256 Genomic DNA Translation: BAC80755.1
AB102257 Genomic DNA Translation: BAC80756.1
AB102258 Genomic DNA Translation: BAC80757.1
AB102259 Genomic DNA Translation: BAC80758.1
AB102260 Genomic DNA Translation: BAC80759.1
AB102261 Genomic DNA Translation: BAC80760.1
AB102262 Genomic DNA Translation: BAC80761.1
AB102263 Genomic DNA Translation: BAC80762.1
AB102264 Genomic DNA Translation: BAC80763.1
AB102265 Genomic DNA Translation: BAC80764.1
AB102266 Genomic DNA Translation: BAC80765.1
AB102267 Genomic DNA Translation: BAC80766.1
AB102268 Genomic DNA Translation: BAC80767.1
AB102269 Genomic DNA Translation: BAC80768.1
AB102270 Genomic DNA Translation: BAC80769.1
AB102281 Genomic DNA Translation: BAC80780.1
AB102282 Genomic DNA Translation: BAC80781.1
AB102283 Genomic DNA Translation: BAC80782.1
AB102284 Genomic DNA Translation: BAC80783.1
AB102285 Genomic DNA Translation: BAC80784.1
AB102286 Genomic DNA Translation: BAC80785.1
AB102287 Genomic DNA Translation: BAC80786.1
AB102288 Genomic DNA Translation: BAC80787.1
AB102289 Genomic DNA Translation: BAC80788.1
AB102290 Genomic DNA Translation: BAC80789.1
AB102291 Genomic DNA Translation: BAC80790.1
AB102292 Genomic DNA Translation: BAC80791.1
AB102293 Genomic DNA Translation: BAC80792.1
AB102294 Genomic DNA Translation: BAC80793.1
AB102295 Genomic DNA Translation: BAC80794.1
AB102296 Genomic DNA Translation: BAC80795.1
AB102297 Genomic DNA Translation: BAC80796.1
AB102298 Genomic DNA Translation: BAC80797.1
AB102299 Genomic DNA Translation: BAC80798.1
AB102300 Genomic DNA Translation: BAC80799.1
AM943850 mRNA Translation: CAQ16016.1
AM943851 mRNA Translation: CAQ16017.1
AM943852 mRNA Translation: CAQ16018.1
AK290504 mRNA Translation: BAF83193.1
AL356578 Genomic DNA No translation available.
AL357774 Genomic DNA No translation available.
AL031117 Genomic DNA No translation available.
AL117326 Genomic DNA No translation available.
CH471120 Genomic DNA Translation: EAX02654.1
CCDSiCCDS14554.1 [O75914-2]
CCDS48151.1 [O75914-3]
CCDS48152.1 [O75914-4]
CCDS48153.1 [O75914-1]
RefSeqiNP_001121638.1, NM_001128166.2 [O75914-2]
NP_001121639.1, NM_001128167.2 [O75914-2]
NP_001121640.1, NM_001128168.2 [O75914-3]
NP_001121644.1, NM_001128172.2 [O75914-4]
NP_001121645.1, NM_001128173.2 [O75914-1]
NP_001311254.1, NM_001324325.1 [O75914-2]
NP_001311255.1, NM_001324326.1 [O75914-2]
NP_001311256.1, NM_001324327.1 [O75914-1]
NP_001311257.1, NM_001324328.1 [O75914-1]
NP_001311258.1, NM_001324329.1 [O75914-1]
NP_001311259.1, NM_001324330.1 [O75914-2]
NP_001311260.1, NM_001324331.1 [O75914-2]
NP_001311261.1, NM_001324332.1 [O75914-2]
NP_001311262.1, NM_001324333.1 [O75914-1]
NP_001311263.1, NM_001324334.1 [O75914-2]
NP_002569.1, NM_002578.4 [O75914-2]
XP_016885046.1, XM_017029557.1 [O75914-1]
XP_016885050.1, XM_017029561.1 [O75914-2]
XP_016885052.1, XM_017029563.1 [O75914-3]
UniGeneiHs.593599
Hs.655757
Hs.656789

Genome annotation databases

EnsembliENST00000262836; ENSP00000262836; ENSG00000077264 [O75914-1]
ENST00000360648; ENSP00000353864; ENSG00000077264 [O75914-3]
ENST00000372007; ENSP00000361077; ENSG00000077264 [O75914-2]
ENST00000372010; ENSP00000361080; ENSG00000077264 [O75914-1]
ENST00000417227; ENSP00000389172; ENSG00000077264 [O75914-4]
ENST00000425146; ENSP00000401982; ENSG00000077264 [O75914-2]
ENST00000446737; ENSP00000410853; ENSG00000077264 [O75914-2]
ENST00000518291; ENSP00000428921; ENSG00000077264 [O75914-3]
ENST00000519681; ENSP00000429113; ENSG00000077264 [O75914-4]
GeneIDi5063
KEGGihsa:5063
UCSCiuc004eoz.3 human [O75914-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPAK3_HUMAN
AccessioniPrimary (citable) accession number: O75914
Secondary accession number(s): A8K389
, B1GX77, B1GX78, B1GX79, Q5JWX1, Q5JWX2, Q7Z2D6, Q7Z2E4, Q7Z3Z8, Q8WWK5, Q8WX23, Q9P0J8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: May 10, 2004
Last modified: March 28, 2018
This is version 186 of the entry and version 2 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