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Protein

Serine/threonine-protein kinase PAK 6

Gene

PAK6

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

Functioni

Serine/threonine protein kinase that plays a role in the regulation of gene transcription. The kinase activity is induced by various effectors including AR or MAP2K6/MAPKK6. Phosphorylates the DNA-binding domain of androgen receptor/AR and thereby inhibits AR-mediated transcription. Inhibits also ESR1-mediated transcription. May play a role in cytoskeleton regulation by interacting with IQGAP1. May protect cells from apoptosis through phosphorylation of BAD.2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei436ATPPROSITE-ProRule annotation1
Active sitei526Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi413 – 421ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • cadherin binding Source: BHF-UCL
  • protein serine/threonine kinase activity Source: GO_Central
  • Rac GTPase binding Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-428540 Activation of RAC1
SignaLinkiQ9NQU5
SIGNORiQ9NQU5

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase PAK 6 (EC:2.7.11.1)
Alternative name(s):
PAK-5
p21-activated kinase 6
Short name:
PAK-6
Gene namesi
Name:PAK6
Synonyms:PAK5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

EuPathDBiHostDB:ENSG00000137843.11
HGNCiHGNC:16061 PAK6
MIMi608110 gene
neXtProtiNX_Q9NQU5

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, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi165S → A: Almost complete loss of PAK6 activation by MAP2K6/MAPKK6; when associated with F-566. 1 Publication1
Mutagenesisi560S → A: Complete loss of PAK6 activation by MAP2K6/MAPKK6; when associated with A-165. 1 Publication1
Mutagenesisi566Y → F: Complete loss of PAK6 activation by MAP2K6/MAPKK6; when associated with A-165. 1 Publication1

Organism-specific databases

DisGeNETi106821730
56924
OpenTargetsiENSG00000137843
ENSG00000259288
PharmGKBiPA32921

Chemistry databases

ChEMBLiCHEMBL4311
GuidetoPHARMACOLOGYi2137

Polymorphism and mutation databases

DMDMi23396789

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000864761 – 681Serine/threonine-protein kinase PAK 6Add BLAST681

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei560Phosphoserine; by autocatalysisBy similarity1

Post-translational modificationi

Autophosphorylated. Phosphorylated by MAP2K6//MAPKK6, leading to PAK6 activation.2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9NQU5
MaxQBiQ9NQU5
PaxDbiQ9NQU5
PeptideAtlasiQ9NQU5
PRIDEiQ9NQU5
ProteomicsDBi82189

PTM databases

iPTMnetiQ9NQU5
PhosphoSitePlusiQ9NQU5

Expressioni

Tissue specificityi

Selectively expressed in brain and testis, with lower levels in multiple tissues including prostate and breast.2 Publications

Gene expression databases

BgeeiENSG00000137843 Expressed in 91 organ(s), highest expression level in prefrontal cortex
CleanExiHS_PAK6
ExpressionAtlasiQ9NQU5 baseline and differential
GenevisibleiQ9NQU5 HS

Organism-specific databases

HPAiHPA031124

Interactioni

Subunit structurei

Interacts tightly with GTP-bound but not GDP-bound CDC42/p21 and RAC1 (By similarity). Interacts with the androgen receptor AR and the estrogen receptor ESR1. Interacts with IQGAP1 and PPM1B.By similarity4 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi121251, 24 interactors
IntActiQ9NQU5, 16 interactors
MINTiQ9NQU5
STRINGi9606.ENSP00000260404

Chemistry databases

BindingDBiQ9NQU5

Structurei

Secondary structure

1681
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9NQU5
SMRiQ9NQU5
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9NQU5

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini12 – 25CRIBPROSITE-ProRule annotationAdd BLAST14
Domaini407 – 658Protein kinasePROSITE-ProRule annotationAdd BLAST252

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni26 – 406LinkerAdd BLAST381

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0578 Eukaryota
ENOG410XP4K LUCA
GeneTreeiENSGT00930000150829
HOGENOMiHOG000234205
HOVERGENiHBG108518
InParanoidiQ9NQU5
KOiK05735
OMAiRPPQKDS
OrthoDBiEOG091G0OT5
PhylomeDBiQ9NQU5
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
IPR035066 PAK6
IPR033923 PAK_BD
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
PANTHERiPTHR24361:SF182 PTHR24361:SF182, 1 hit
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 (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 10 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9NQU5-1) [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
MFRKKKKKRP EISAPQNFQH RVHTSFDPKE GKFVGLPPQW QNILDTLRRP
60 70 80 90 100
KPVVDPSRIT RVQLQPMKTV VRGSAMPVDG YISGLLNDIQ KLSVISSNTL
110 120 130 140 150
RGRSPTSRRR AQSLGLLGDE HWATDPDMYL QSPQSERTDP HGLYLSCNGG
160 170 180 190 200
TPAGHKQMPW PEPQSPRVLP NGLAAKAQSL GPAEFQGASQ RCLQLGACLQ
210 220 230 240 250
SSPPGASPPT GTNRHGMKAA KHGSEEARPQ SCLVGSATGR PGGEGSPSPK
260 270 280 290 300
TRESSLKRRL FRSMFLSTAA TAPPSSSKPG PPPQSKPNSS FRPPQKDNPP
310 320 330 340 350
SLVAKAQSLP SDQPVGTFSP LTTSDTSSPQ KSLRTAPATG QLPGRSSPAG
360 370 380 390 400
SPRTWHAQIS TSNLYLPQDP TVAKGALAGE DTGVVTHEQF KAALRMVVDQ
410 420 430 440 450
GDPRLLLDSY VKIGEGSTGI VCLAREKHSG RQVAVKMMDL RKQQRRELLF
460 470 480 490 500
NEVVIMRDYQ HFNVVEMYKS YLVGEELWVL MEFLQGGALT DIVSQVRLNE
510 520 530 540 550
EQIATVCEAV LQALAYLHAQ GVIHRDIKSD SILLTLDGRV KLSDFGFCAQ
560 570 580 590 600
ISKDVPKRKS LVGTPYWMAP EVISRSLYAT EVDIWSLGIM VIEMVDGEPP
610 620 630 640 650
YFSDSPVQAM KRLRDSPPPK LKNSHKVSPV LRDFLERMLV RDPQERATAQ
660 670 680
ELLDHPFLLQ TGLPECLVPL IQLYRKQTST C
Length:681
Mass (Da):74,869
Last modified:October 1, 2000 - v1
Checksum:iF20A4FA257649BB9
GO
Isoform 2 (identifier: Q9NQU5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     583-627: Missing.

Show »
Length:636
Mass (Da):69,777
Checksum:i3CA588AAB5B8E522
GO

Computationally mapped potential isoform sequencesi

There are 10 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YL16H0YL16_HUMAN
Serine/threonine-protein kinase PAK...
PAK6
284Annotation score:
H0YK38H0YK38_HUMAN
Serine/threonine-protein kinase PAK...
PAK6
74Annotation score:
H0YK91H0YK91_HUMAN
Serine/threonine-protein kinase PAK...
PAK6
112Annotation score:
H0YM99H0YM99_HUMAN
Serine/threonine-protein kinase PAK...
PAK6
104Annotation score:
H0YL47H0YL47_HUMAN
Serine/threonine-protein kinase PAK...
PAK6
71Annotation score:
H0YMS4H0YMS4_HUMAN
Serine/threonine-protein kinase PAK...
PAK6
123Annotation score:
H0YLZ9H0YLZ9_HUMAN
Serine/threonine-protein kinase PAK...
PAK6
122Annotation score:
H0YKB6H0YKB6_HUMAN
Serine/threonine-protein kinase PAK...
PAK6
57Annotation score:
H0YK74H0YK74_HUMAN
Serine/threonine-protein kinase PAK...
PAK6
109Annotation score:
H0YL02H0YL02_HUMAN
Serine/threonine-protein kinase PAK...
PAK6
20Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti60T → A in BAG54772 (PubMed:14702039).Curated1
Sequence conflicti381D → G in BAG54772 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0356313R → H in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs201346085Ensembl.1
Natural variantiVAR_01999376M → V1 PublicationCorresponds to variant dbSNP:rs2412504Ensembl.1
Natural variantiVAR_051655103R → C. Corresponds to variant dbSNP:rs36081263Ensembl.1
Natural variantiVAR_051656151T → I. Corresponds to variant dbSNP:rs35593179Ensembl.1
Natural variantiVAR_040972184E → K1 PublicationCorresponds to variant dbSNP:rs56349744Ensembl.1
Natural variantiVAR_040973205G → E1 PublicationCorresponds to variant dbSNP:rs55920845Ensembl.1
Natural variantiVAR_040974208P → T1 PublicationCorresponds to variant dbSNP:rs35501648Ensembl.1
Natural variantiVAR_040975210T → M1 PublicationCorresponds to variant dbSNP:rs34869667Ensembl.1
Natural variantiVAR_019994215H → R1 PublicationCorresponds to variant dbSNP:rs3743135Ensembl.1
Natural variantiVAR_019995337P → L1 PublicationCorresponds to variant dbSNP:rs3743137Ensembl.1
Natural variantiVAR_040976376A → V1 PublicationCorresponds to variant dbSNP:rs55806501Ensembl.1
Natural variantiVAR_051657475E → K. Corresponds to variant dbSNP:rs34445577Ensembl.1
Natural variantiVAR_040977514L → R in a lung small cell carcinoma sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_056733583 – 627Missing in isoform 2. 1 PublicationAdd BLAST45

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF276893 mRNA Translation: AAF82800.1
AJ236915 mRNA Translation: CAC18720.1
AK131522 mRNA Translation: BAG54772.1
AK290227 mRNA Translation: BAF82916.1
AK315813 mRNA Translation: BAF98704.1
AK315817 mRNA Translation: BAF98708.1
AC020658 Genomic DNA No translation available.
AC025429 Genomic DNA No translation available.
CH471125 Genomic DNA Translation: EAW92395.1
CH471125 Genomic DNA Translation: EAW92401.1
BC035596 mRNA Translation: AAH35596.1
CCDSiCCDS10054.1 [Q9NQU5-1]
CCDS61590.1 [Q9NQU5-2]
RefSeqiNP_001122100.1, NM_001128628.2 [Q9NQU5-1]
NP_001122101.1, NM_001128629.2 [Q9NQU5-1]
NP_001263646.1, NM_001276717.1 [Q9NQU5-1]
NP_001263647.1, NM_001276718.1 [Q9NQU5-2]
NP_064553.1, NM_020168.5 [Q9NQU5-1]
UniGeneiHs.732375
Hs.745440

Genome annotation databases

EnsembliENST00000260404; ENSP00000260404; ENSG00000137843 [Q9NQU5-1]
ENST00000455577; ENSP00000409465; ENSG00000137843 [Q9NQU5-2]
ENST00000542403; ENSP00000439597; ENSG00000137843 [Q9NQU5-1]
ENST00000560346; ENSP00000453858; ENSG00000137843 [Q9NQU5-1]
GeneIDi106821730
56924
KEGGihsa:106821730
hsa:56924
UCSCiuc001zky.5 human [Q9NQU5-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF276893 mRNA Translation: AAF82800.1
AJ236915 mRNA Translation: CAC18720.1
AK131522 mRNA Translation: BAG54772.1
AK290227 mRNA Translation: BAF82916.1
AK315813 mRNA Translation: BAF98704.1
AK315817 mRNA Translation: BAF98708.1
AC020658 Genomic DNA No translation available.
AC025429 Genomic DNA No translation available.
CH471125 Genomic DNA Translation: EAW92395.1
CH471125 Genomic DNA Translation: EAW92401.1
BC035596 mRNA Translation: AAH35596.1
CCDSiCCDS10054.1 [Q9NQU5-1]
CCDS61590.1 [Q9NQU5-2]
RefSeqiNP_001122100.1, NM_001128628.2 [Q9NQU5-1]
NP_001122101.1, NM_001128629.2 [Q9NQU5-1]
NP_001263646.1, NM_001276717.1 [Q9NQU5-1]
NP_001263647.1, NM_001276718.1 [Q9NQU5-2]
NP_064553.1, NM_020168.5 [Q9NQU5-1]
UniGeneiHs.732375
Hs.745440

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2C30X-ray1.60A383-681[»]
2ODBX-ray2.40B11-45[»]
4KS7X-ray1.40A385-674[»]
4KS8X-ray1.95A385-674[»]
ProteinModelPortaliQ9NQU5
SMRiQ9NQU5
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121251, 24 interactors
IntActiQ9NQU5, 16 interactors
MINTiQ9NQU5
STRINGi9606.ENSP00000260404

Chemistry databases

BindingDBiQ9NQU5
ChEMBLiCHEMBL4311
GuidetoPHARMACOLOGYi2137

PTM databases

iPTMnetiQ9NQU5
PhosphoSitePlusiQ9NQU5

Polymorphism and mutation databases

DMDMi23396789

Proteomic databases

EPDiQ9NQU5
MaxQBiQ9NQU5
PaxDbiQ9NQU5
PeptideAtlasiQ9NQU5
PRIDEiQ9NQU5
ProteomicsDBi82189

Protocols and materials databases

DNASUi56924
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000260404; ENSP00000260404; ENSG00000137843 [Q9NQU5-1]
ENST00000455577; ENSP00000409465; ENSG00000137843 [Q9NQU5-2]
ENST00000542403; ENSP00000439597; ENSG00000137843 [Q9NQU5-1]
ENST00000560346; ENSP00000453858; ENSG00000137843 [Q9NQU5-1]
GeneIDi106821730
56924
KEGGihsa:106821730
hsa:56924
UCSCiuc001zky.5 human [Q9NQU5-1]

Organism-specific databases

CTDi106821730
56924
DisGeNETi106821730
56924
EuPathDBiHostDB:ENSG00000137843.11
GeneCardsiPAK6
HGNCiHGNC:16061 PAK6
HPAiHPA031124
MIMi608110 gene
neXtProtiNX_Q9NQU5
OpenTargetsiENSG00000137843
ENSG00000259288
PharmGKBiPA32921
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0578 Eukaryota
ENOG410XP4K LUCA
GeneTreeiENSGT00930000150829
HOGENOMiHOG000234205
HOVERGENiHBG108518
InParanoidiQ9NQU5
KOiK05735
OMAiRPPQKDS
OrthoDBiEOG091G0OT5
PhylomeDBiQ9NQU5
TreeFamiTF105352

Enzyme and pathway databases

ReactomeiR-HSA-428540 Activation of RAC1
SignaLinkiQ9NQU5
SIGNORiQ9NQU5

Miscellaneous databases

EvolutionaryTraceiQ9NQU5
GeneWikiiPAK6
GenomeRNAii56924
PROiPR:Q9NQU5
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000137843 Expressed in 91 organ(s), highest expression level in prefrontal cortex
CleanExiHS_PAK6
ExpressionAtlasiQ9NQU5 baseline and differential
GenevisibleiQ9NQU5 HS

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
IPR035066 PAK6
IPR033923 PAK_BD
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
PANTHERiPTHR24361:SF182 PTHR24361:SF182, 1 hit
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
ProtoNetiSearch...

Entry informationi

Entry nameiPAK6_HUMAN
AccessioniPrimary (citable) accession number: Q9NQU5
Secondary accession number(s): A8K2G2, B3KYB0, G5E9R2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 19, 2002
Last sequence update: October 1, 2000
Last modified: November 7, 2018
This is version 174 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

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  7. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
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