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Protein

Serine/threonine-protein kinase PAK 6

Gene

PAK6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

GO - Biological processi

  • apoptotic process Source: UniProtKB
  • cytoskeleton organization Source: UniProtKB
  • regulation of transcription, DNA-templated Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS06409-MONOMER.
ReactomeiR-HSA-428540. Activation of Rac.
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

HGNCiHGNC:16061. PAK6.

Subcellular locationi

  • Cytoplasm
  • Nucleus

  • Note: Cotranslocates into nucleus with AR in response to androgen induction.

GO - Cellular componenti

  • cell-cell adherens junction Source: BHF-UCL
  • cytoplasm Source: GO_Central
  • nucleus Source: UniProtKB-SubCell
Complete GO annotation...

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

DisGeNETi56924.
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.

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.
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

WithEntry#Exp.IntActNotes
LRRK2Q5S0072EBI-1053685,EBI-5323863
RHOJQ9H4E53EBI-1053685,EBI-6285694

GO - Molecular functioni

  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL

Protein-protein interaction databases

BioGridi121251. 21 interactors.
IntActiQ9NQU5. 14 interactors.
MINTiMINT-8247581.
STRINGi9606.ENSP00000260404.

Chemistry databases

BindingDBiQ9NQU5.

Structurei

Secondary structure

1681
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi16 – 27Combined sources12
Turni28 – 31Combined sources4
Beta strandi32 – 35Combined sources4
Helixi38 – 44Combined sources7
Helixi387 – 395Combined sources9
Helixi404 – 406Combined sources3
Beta strandi407 – 416Combined sources10
Beta strandi419 – 426Combined sources8
Turni427 – 429Combined sources3
Beta strandi432 – 439Combined sources8
Turni440 – 442Combined sources3
Helixi446 – 448Combined sources3
Helixi449 – 458Combined sources10
Beta strandi467 – 473Combined sources7
Beta strandi476 – 481Combined sources6
Helixi489 – 493Combined sources5
Helixi500 – 519Combined sources20
Helixi529 – 531Combined sources3
Beta strandi532 – 534Combined sources3
Beta strandi540 – 542Combined sources3
Helixi545 – 547Combined sources3
Beta strandi553 – 555Combined sources3
Helixi565 – 567Combined sources3
Helixi570 – 573Combined sources4
Helixi581 – 596Combined sources16
Turni600 – 603Combined sources4
Helixi606 – 615Combined sources10
Helixi624 – 626Combined sources3
Helixi629 – 638Combined sources10
Turni643 – 645Combined sources3
Helixi649 – 653Combined sources5
Helixi656 – 660Combined sources5
Helixi664 – 670Combined sources7

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...

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

Contains 1 CRIB domain.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0578. Eukaryota.
ENOG410XP4K. LUCA.
GeneTreeiENSGT00860000133680.
HOGENOMiHOG000234205.
HOVERGENiHBG108518.
InParanoidiQ9NQU5.
KOiK05735.
OMAiHSGRHVA.
OrthoDBiEOG091G0OT5.
PhylomeDBiQ9NQU5.
TreeFamiTF105352.

Family and domain databases

CDDicd01093. CRIB_PAK_like. 1 hit.
Gene3Di3.90.810.10. 1 hit.
InterProiIPR000095. CRIB_dom.
IPR011009. Kinase-like_dom.
IPR033923. PAK_BD.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
[Graphical view]
PfamiPF00786. PBD. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00285. PBD. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50108. CRIB. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

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

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 rs201346085dbSNPEnsembl.1
Natural variantiVAR_01999376M → V.1 PublicationCorresponds to variant rs2412504dbSNPEnsembl.1
Natural variantiVAR_051655103R → C.Corresponds to variant rs36081263dbSNPEnsembl.1
Natural variantiVAR_051656151T → I.Corresponds to variant rs35593179dbSNPEnsembl.1
Natural variantiVAR_040972184E → K.1 PublicationCorresponds to variant rs56349744dbSNPEnsembl.1
Natural variantiVAR_040973205G → E.1 PublicationCorresponds to variant rs55920845dbSNPEnsembl.1
Natural variantiVAR_040974208P → T.1 PublicationCorresponds to variant rs35501648dbSNPEnsembl.1
Natural variantiVAR_040975210T → M.1 PublicationCorresponds to variant rs34869667dbSNPEnsembl.1
Natural variantiVAR_019994215H → R.1 PublicationCorresponds to variant rs3743135dbSNPEnsembl.1
Natural variantiVAR_019995337P → L.1 PublicationCorresponds to variant rs3743137dbSNPEnsembl.1
Natural variantiVAR_040976376A → V.1 PublicationCorresponds to variant rs55806501dbSNPEnsembl.1
Natural variantiVAR_051657475E → K.Corresponds to variant rs34445577dbSNPEnsembl.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

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. 21 interactors.
IntActiQ9NQU5. 14 interactors.
MINTiMINT-8247581.
STRINGi9606.ENSP00000260404.

Chemistry databases

BindingDBiQ9NQU5.
ChEMBLiCHEMBL4311.
GuidetoPHARMACOLOGYi2137.

PTM databases

iPTMnetiQ9NQU5.
PhosphoSitePlusiQ9NQU5.

Polymorphism and mutation databases

DMDMi23396789.

Proteomic databases

EPDiQ9NQU5.
MaxQBiQ9NQU5.
PaxDbiQ9NQU5.
PeptideAtlasiQ9NQU5.
PRIDEiQ9NQU5.

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.
DisGeNETi56924.
GeneCardsiPAK6.
HGNCiHGNC:16061. PAK6.
HPAiHPA031124.
MIMi608110. gene.
neXtProtiNX_Q9NQU5.
OpenTargetsiENSG00000137843.
ENSG00000259288.
PharmGKBiPA32921.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0578. Eukaryota.
ENOG410XP4K. LUCA.
GeneTreeiENSGT00860000133680.
HOGENOMiHOG000234205.
HOVERGENiHBG108518.
InParanoidiQ9NQU5.
KOiK05735.
OMAiHSGRHVA.
OrthoDBiEOG091G0OT5.
PhylomeDBiQ9NQU5.
TreeFamiTF105352.

Enzyme and pathway databases

BioCyciZFISH:HS06409-MONOMER.
ReactomeiR-HSA-428540. Activation of Rac.
SignaLinkiQ9NQU5.
SIGNORiQ9NQU5.

Miscellaneous databases

EvolutionaryTraceiQ9NQU5.
GeneWikiiPAK6.
GenomeRNAii56924.
PROiQ9NQU5.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000137843.
CleanExiHS_PAK6.
ExpressionAtlasiQ9NQU5. baseline and differential.
GenevisibleiQ9NQU5. HS.

Family and domain databases

CDDicd01093. CRIB_PAK_like. 1 hit.
Gene3Di3.90.810.10. 1 hit.
InterProiIPR000095. CRIB_dom.
IPR011009. Kinase-like_dom.
IPR033923. PAK_BD.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
[Graphical view]
PfamiPF00786. PBD. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00285. PBD. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50108. CRIB. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPAK6_HUMAN
AccessioniPrimary (citable) accession number: Q9NQU5
Secondary accession number(s): A8K2G2, B3KYB0, G5E9R2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 19, 2002
Last sequence update: October 1, 2000
Last modified: November 30, 2016
This is version 158 of the entry and version 1 of the sequence. [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. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  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 and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.