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Q9NQU5 (PAK6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:PAK6
Synonyms:PAK5
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length681 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.7 Ref.10

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Subunit structure

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. Ref.1 Ref.6 Ref.9

Subcellular location

Cytoplasm. Nucleus. Note: Cotranslocates into nucleus with AR in response to androgen induction. Ref.1 Ref.6

Tissue specificity

Selectively expressed in brain and testis, with lower levels in multiple tissues including prostate and breast. Ref.1 Ref.6

Post-translational modification

Autophosphorylated. Phosphorylated by MAP2K6//MAPKK6, leading to PAK6 activation. Ref.8 Ref.11

Sequence similarities

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

Contains 1 CRIB domain.

Contains 1 protein kinase domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 681681Serine/threonine-protein kinase PAK 6
PRO_0000086476

Regions

Domain12 – 2514CRIB
Domain407 – 658252Protein kinase
Nucleotide binding413 – 4219ATP By similarity
Region26 – 406381Linker

Sites

Active site5261Proton acceptor By similarity
Binding site4361ATP By similarity

Amino acid modifications

Modified residue5601Phosphoserine; by autocatalysis By similarity

Natural variations

Natural variant31R → H in a colorectal cancer sample; somatic mutation. Ref.13
VAR_035631
Natural variant761M → V. Ref.14
Corresponds to variant rs2412504 [ dbSNP | Ensembl ].
VAR_019993
Natural variant1031R → C.
Corresponds to variant rs36081263 [ dbSNP | Ensembl ].
VAR_051655
Natural variant1511T → I.
Corresponds to variant rs35593179 [ dbSNP | Ensembl ].
VAR_051656
Natural variant1841E → K. Ref.14
Corresponds to variant rs56349744 [ dbSNP | Ensembl ].
VAR_040972
Natural variant2051G → E. Ref.14
Corresponds to variant rs55920845 [ dbSNP | Ensembl ].
VAR_040973
Natural variant2081P → T. Ref.14
Corresponds to variant rs35501648 [ dbSNP | Ensembl ].
VAR_040974
Natural variant2101T → M. Ref.14
Corresponds to variant rs34869667 [ dbSNP | Ensembl ].
VAR_040975
Natural variant2151H → R. Ref.14
Corresponds to variant rs3743135 [ dbSNP | Ensembl ].
VAR_019994
Natural variant3371P → L. Ref.14
Corresponds to variant rs3743137 [ dbSNP | Ensembl ].
VAR_019995
Natural variant3761A → V. Ref.14
Corresponds to variant rs55806501 [ dbSNP | Ensembl ].
VAR_040976
Natural variant4751E → K.
Corresponds to variant rs34445577 [ dbSNP | Ensembl ].
VAR_051657
Natural variant5141L → R in a lung small cell carcinoma sample; somatic mutation. Ref.14
VAR_040977

Experimental info

Mutagenesis1651S → A: Almost complete loss of PAK6 activation by MAP2K6/MAPKK6; when associated with F-566. Ref.8
Mutagenesis5601S → A: Complete loss of PAK6 activation by MAP2K6/MAPKK6; when associated with A-165. Ref.8
Mutagenesis5661Y → F: Complete loss of PAK6 activation by MAP2K6/MAPKK6; when associated with A-165. Ref.8

Secondary structure

...................................................... 681
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9NQU5 [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: F20A4FA257649BB9

FASTA68174,869
        10         20         30         40         50         60 
MFRKKKKKRP EISAPQNFQH RVHTSFDPKE GKFVGLPPQW QNILDTLRRP KPVVDPSRIT 

        70         80         90        100        110        120 
RVQLQPMKTV VRGSAMPVDG YISGLLNDIQ KLSVISSNTL RGRSPTSRRR AQSLGLLGDE 

       130        140        150        160        170        180 
HWATDPDMYL QSPQSERTDP HGLYLSCNGG TPAGHKQMPW PEPQSPRVLP NGLAAKAQSL 

       190        200        210        220        230        240 
GPAEFQGASQ RCLQLGACLQ SSPPGASPPT GTNRHGMKAA KHGSEEARPQ SCLVGSATGR 

       250        260        270        280        290        300 
PGGEGSPSPK TRESSLKRRL FRSMFLSTAA TAPPSSSKPG PPPQSKPNSS FRPPQKDNPP 

       310        320        330        340        350        360 
SLVAKAQSLP SDQPVGTFSP LTTSDTSSPQ KSLRTAPATG QLPGRSSPAG SPRTWHAQIS 

       370        380        390        400        410        420 
TSNLYLPQDP TVAKGALAGE DTGVVTHEQF KAALRMVVDQ GDPRLLLDSY VKIGEGSTGI 

       430        440        450        460        470        480 
VCLAREKHSG RQVAVKMMDL RKQQRRELLF NEVVIMRDYQ HFNVVEMYKS YLVGEELWVL 

       490        500        510        520        530        540 
MEFLQGGALT DIVSQVRLNE EQIATVCEAV LQALAYLHAQ GVIHRDIKSD SILLTLDGRV 

       550        560        570        580        590        600 
KLSDFGFCAQ ISKDVPKRKS LVGTPYWMAP EVISRSLYAT EVDIWSLGIM VIEMVDGEPP 

       610        620        630        640        650        660 
YFSDSPVQAM KRLRDSPPPK LKNSHKVSPV LRDFLERMLV RDPQERATAQ ELLDHPFLLQ 

       670        680 
TGLPECLVPL IQLYRKQTST C 

« Hide

References

« Hide 'large scale' references
[1]"Androgen receptor specifically interacts with a novel p21-activated kinase, PAK6."
Yang F., Li X., Sharma M., Zarnegar M., Lim B., Sun Z.
J. Biol. Chem. 276:15345-15353(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INTERACTION WITH AR.
[2]"Pak5, a new member of the p21-activated kinase family, affects Cdc42 signalling to the actin cytoskeleton."
Wagner T., Puls A., Frischauf A.M., Hall A.
Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain and Thalamus.
[4]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[6]"AR and ER interaction with a p21-activated kinase (PAK6)."
Lee S.R., Ramos S.M., Ko A., Masiello D., Swanson K.D., Lu M.L., Balk S.P.
Mol. Endocrinol. 16:85-99(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INTERACTION WITH AR AND ESR1.
[7]"Mechanism of p21-activated kinase 6-mediated inhibition of androgen receptor signaling."
Schrantz N., da Silva Correia J., Fowler B., Ge Q., Sun Z., Bokoch G.M.
J. Biol. Chem. 279:1922-1931(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF AR.
[8]"Activation of p21-activated kinase 6 by MAP kinase kinase 6 and p38 MAP kinase."
Kaur R., Liu X., Gjoerup O., Zhang A., Yuan X., Balk S.P., Schneider M.C., Lu M.L.
J. Biol. Chem. 280:3323-3330(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY MAP2K6, AUTOPHOSPHORYLATION, MUTAGENESIS OF SER-165; SER-560 AND TYR-566.
[9]"Increased PAK6 expression in prostate cancer and identification of PAK6 associated proteins."
Kaur R., Yuan X., Lu M.L., Balk S.P.
Prostate 68:1510-1516(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH IQGAP1 AND PPM1B.
[10]"Inhibition of p21-activated kinase 6 (PAK6) increases radiosensitivity of prostate cancer cells."
Zhang M., Siedow M., Saia G., Chakravarti A.
Prostate 70:807-816(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"Crystal structure of the human p21-activated kinase 6."
Filippakopoulos P., Berridge G., Bray J., Burgess N., Colebrook S., Das S., Eswaran J., Gileadi O., Papagrigoriou E., Savitsky P., Smee C., Turnbull A., Sundstrom M., Arrowsmith C., Weigelt J., Edwards A., Von Delft F., Knapp S.
Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases
Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 383-681, PHOSPHORYLATION AT SER-560.
[12]"The crystal structure of human CDC42 in complex with the CRIB domain of human p21-activated kinase 6 (PAK6)."
Structural genomics consortium (SGC)
Submitted (JAN-2007) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 11-45 IN COMPLEX WITH CDC42.
[13]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] HIS-3.
[14]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] VAL-76; LYS-184; GLU-205; THR-208; MET-210; ARG-215; LEU-337; VAL-376 AND ARG-514.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF276893 mRNA. Translation: AAF82800.1.
AJ236915 mRNA. Translation: CAC18720.1.
AK290227 mRNA. Translation: BAF82916.1.
AK315813 mRNA. Translation: BAF98704.1.
AK315817 mRNA. Translation: BAF98708.1.
CH471125 Genomic DNA. Translation: EAW92395.1.
BC035596 mRNA. Translation: AAH35596.1.
CCDSCCDS10054.1.
RefSeqNP_001122100.1. NM_001128628.2.
NP_001122101.1. NM_001128629.2.
NP_001263646.1. NM_001276717.1.
NP_001263647.1. NM_001276718.1.
NP_064553.1. NM_020168.5.
UniGeneHs.513645.
Hs.732375.
Hs.745440.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2C30X-ray1.60A383-681[»]
2ODBX-ray2.40B11-45[»]
4KS7X-ray1.40A385-674[»]
4KS8X-ray1.95A385-674[»]
ProteinModelPortalQ9NQU5.
SMRQ9NQU5. Positions 11-45, 385-674.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121251. 16 interactions.
IntActQ9NQU5. 8 interactions.
MINTMINT-8247581.
STRING9606.ENSP00000260404.

Chemistry

BindingDBQ9NQU5.
ChEMBLCHEMBL4311.
GuidetoPHARMACOLOGY2137.

PTM databases

PhosphoSiteQ9NQU5.

Polymorphism databases

DMDM23396789.

Proteomic databases

MaxQBQ9NQU5.
PaxDbQ9NQU5.
PRIDEQ9NQU5.

Protocols and materials databases

DNASU56924.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000260404; ENSP00000260404; ENSG00000137843.
ENST00000441369; ENSP00000406873; ENSG00000137843.
ENST00000453867; ENSP00000401153; ENSG00000137843.
ENST00000542403; ENSP00000439597; ENSG00000137843.
ENST00000560346; ENSP00000453858; ENSG00000137843.
GeneID56924.
KEGGhsa:56924.
UCSCuc001zlb.3. human.

Organism-specific databases

CTD56924.
GeneCardsGC15P040509.
HGNCHGNC:16061. PAK6.
HPAHPA031124.
MIM608110. gene.
neXtProtNX_Q9NQU5.
PharmGKBPA32921.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000234205.
HOVERGENHBG108518.
InParanoidQ9NQU5.
KOK05735.
OMANRRGMKA.
PhylomeDBQ9NQU5.
TreeFamTF105352.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
SignaLinkQ9NQU5.

Gene expression databases

BgeeQ9NQU5.
CleanExHS_PAK6.
GenevestigatorQ9NQU5.

Family and domain databases

Gene3D3.90.810.10. 1 hit.
InterProIPR000095. CRIB_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
[Graphical view]
PfamPF00786. PBD. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00285. PBD. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS50108. CRIB. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9NQU5.
GeneWikiPAK6.
GenomeRNAi56924.
NextBio62436.
PROQ9NQU5.
SOURCESearch...

Entry information

Entry namePAK6_HUMAN
AccessionPrimary (citable) accession number: Q9NQU5
Secondary accession number(s): A8K2G2
Entry history
Integrated into UniProtKB/Swiss-Prot: September 19, 2002
Last sequence update: October 1, 2000
Last modified: July 9, 2014
This is version 133 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM