Q9NQU5 (PAK6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	PAK6
Synonyms:	PAK5

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	681 AA.
Sequence status	Complete.
Protein existence	Evidence 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.5 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.4 Ref.7
Subcellular location	Cytoplasm. Nucleus. Note: Cotranslocates into nucleus with AR in response to androgen induction. Ref.1 Ref.4
Tissue specificity	Selectively expressed in brain and testis, with lower levels in multiple tissues including prostate and breast. Ref.1 Ref.4
Post-translational modification	Autophosphorylated. Phosphorylated by MAP2K6//MAPKK6, leading to PAK6 activation. Ref.5 Ref.6 Ref.8 Ref.9 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.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	apoptotic process Traceable author statement. Source: UniProtKB cytoskeleton organization Traceable author statement. Source: UniProtKB regulation of transcription, DNA-dependent Traceable author statement. Source: UniProtKB
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 681

681

Serine/threonine-protein kinase PAK 6

PRO_0000086476

Regions

Domain

12 – 25

14

CRIB

Domain

407 – 658

252

Protein kinase

Nucleotide binding

413 – 421

9

ATP By similarity

Region

26 – 406

381

Linker

Sites

Active site

526

1

Proton acceptor By similarity

Binding site

436

1

ATP By similarity

Amino acid modifications

Modified residue

560

1

Phosphoserine; by autocatalysis By similarity

Natural variations

Natural variant

3

1

R → H in a colorectal cancer sample; somatic mutation. Ref.13

VAR_035631

Natural variant

76

1

M → V. Ref.14
Corresponds to variant rs2412504 [ dbSNP | Ensembl ].

VAR_019993

Natural variant

103

1

R → C.
Corresponds to variant rs36081263 [ dbSNP | Ensembl ].

VAR_051655

Natural variant

151

1

T → I.
Corresponds to variant rs35593179 [ dbSNP | Ensembl ].

VAR_051656

Natural variant

184

1

E → K. Ref.14
Corresponds to variant rs56349744 [ dbSNP | Ensembl ].

VAR_040972

Natural variant

205

1

G → E. Ref.14
Corresponds to variant rs55920845 [ dbSNP | Ensembl ].

VAR_040973

Natural variant

208

1

P → T. Ref.14
Corresponds to variant rs35501648 [ dbSNP | Ensembl ].

VAR_040974

Natural variant

210

1

T → M. Ref.14
Corresponds to variant rs34869667 [ dbSNP | Ensembl ].

VAR_040975

Natural variant

215

1

H → R. Ref.14
Corresponds to variant rs3743135 [ dbSNP | Ensembl ].

VAR_019994

Natural variant

337

1

P → L. Ref.14
Corresponds to variant rs3743137 [ dbSNP | Ensembl ].

VAR_019995

Natural variant

376

1

A → V. Ref.14
Corresponds to variant rs55806501 [ dbSNP | Ensembl ].

VAR_040976

Natural variant

475

1

E → K.
Corresponds to variant rs34445577 [ dbSNP | Ensembl ].

VAR_051657

Natural variant

514

1

L → R in a lung small cell carcinoma sample; somatic mutation. Ref.14

VAR_040977

Experimental info

Mutagenesis

165

1

S → A: Almost complete loss of PAK6 activation by MAP2K6/MAPKK6; when associated with F-566. Ref.6

Mutagenesis

560

1

S → A: Complete loss of PAK6 activation by MAP2K6/MAPKK6; when associated with A-165. Ref.6

Mutagenesis

566

1

Y → F: Complete loss of PAK6 activation by MAP2K6/MAPKK6; when associated with A-165. Ref.6

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

681

Helix Strand Turn

Details...

Beta strand

16 – 27

12

Turn

28 – 31

4

Beta strand

32 – 35

4

Helix

38 – 44

7

Helix

387 – 395

9

Helix

403 – 406

4

Beta strand

407 – 416

10

Beta strand

419 – 426

8

Turn

427 – 429

3

Beta strand

432 – 439

8

Turn

440 – 442

3

Helix

446 – 456

11

Beta strand

467 – 473

7

Beta strand

476 – 481

6

Helix

489 – 493

5

Helix

500 – 519

20

Helix

529 – 531

3

Beta strand

532 – 534

3

Beta strand

540 – 542

3

Beta strand

553 – 555

3

Helix

565 – 567

3

Helix

570 – 573

4

Helix

581 – 596

16

Turn

600 – 603

4

Helix

606 – 615

10

Helix

624 – 626

3

Helix

629 – 638

10

Turn

643 – 645

3

Helix

649 – 653

5

Helix

656 – 660

5

Helix

664 – 667

4

Helix

668 – 673

6

Sequences

	Sequence		Length	Mass (Da)
	Q9NQU5 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: F20A4FA257649BB9	FASTA	681	74,869
	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

References

	« Hide 'large scale' referencesShow '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: 11278661] [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]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[4]	"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: 11773441] [Abstract] Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INTERACTION WITH AR AND ESR1.
[5]	"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: 14573606] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF AR.
[6]	"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: 15550393] [Abstract] Cited for: PHOSPHORYLATION BY MAP2K6, AUTOPHOSPHORYLATION, MUTAGENESIS OF SER-165; SER-560 AND TYR-566.
[7]	"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: 18642328] [Abstract] Cited for: INTERACTION WITH IQGAP1 AND PPM1B.
[8]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-560, MASS SPECTROMETRY.
[9]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-560, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[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: 20054820] [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. , 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: 16959974] [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. , 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: 17344846] [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.
BC035596 mRNA. Translation: AAH35596.1.

IPI

IPI00024584.

RefSeq

NP_001122100.1. NM_001128628.1.
NP_001122101.1. NM_001128629.1.
NP_064553.1. NM_020168.4.

UniGene

Hs.513645.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2C30	X-ray	1.60	A	383-681	[»]
2ODB	X-ray	2.40	B	11-45	[»]

ProteinModelPortal

Q9NQU5.

SMR

Q9NQU5. Positions 11-71, 385-674.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9NQU5. 6 interactions.

STRING

Q9NQU5.

PTM databases

PhosphoSite

Q9NQU5.

Polymorphism databases

DMDM

23396789.

Proteomic databases

PRIDE

Q9NQU5.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000260404; ENSP00000260404; ENSG00000137843.
ENST00000441369; ENSP00000406873; ENSG00000137843.
ENST00000453867; ENSP00000401153; ENSG00000137843.

GeneID

56924.

KEGG

hsa:56924.

UCSC

uc001zlb.2. human.

Organism-specific databases

CTD

56924.

GeneCards

GC15P040509.

HGNC

HGNC:16061. PAK6.

HPA

HPA031124.

MIM

608110. gene.

neXtProt

NX_Q9NQU5.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG11420.

GeneTree

ENSGT00580000081260.

HOGENOM

HBG755340.

HOVERGEN

HBG108518.

InParanoid

Q9NQU5.

OMA

PSPKTQE.

OrthoDB

EOG4QNMVX.

PhylomeDB

Q9NQU5.

Enzyme and pathway databases

Reactome

REACT_111045. Developmental Biology.

Gene expression databases

ArrayExpress

Q9NQU5.

Bgee

Q9NQU5.

CleanEx

HS_PAK6.

Genevestigator

Q9NQU5.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR000095. PAK_box_Rho-bd.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_kinase-like_dom.
IPR002290. Ser/Thr_kinase_dom.
[Graphical view]

KO

K05735.

Pfam

PF00786. PBD. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]

SMART

SM00285. PBD. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS50108. CRIB. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. False negative.
[Graphical view]

ProtoNet

Search...

Other

NextBio

62436.

SOURCE

Search...

Entry information

Entry name

PAK6_HUMAN

Accession

Primary (citable) accession number: Q9NQU5

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 19, 2002
Last sequence update:	October 1, 2000
Last modified:	January 25, 2012
This is version 111 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.