Reviewed, UniProtKB/Swiss-Prot Q9NQU5 (PAK6_HUMAN)

Names and origin

Protein names

Recommended name:
    Serine/threonine-protein kinase PAK 6
    EC=2.7.11.1
Alternative name(s):
    p21-activated kinase 6
      Short name=PAK-6
    PAK-5

Gene names

Name:	PAK6
Synonyms:	PAK5

Organism

Homo sapiens (Human) [Complete proteome]

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	The activated kinase acts on a variety of targets By similarity.
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.
Post-translational modification	Autophosphorylated when activated by CDC42/p21 By similarity. Ref.5
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
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
Gene Ontology (GO)
Biological process	protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
YWHAQ	P27348	1	EBI-1053685,EBI-359854

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 Ref.5

Natural variations

Natural variant

3

1

R → H in a colorectal cancer sample; somatic mutation. Ref.8

VAR_035631

Natural variant

76

1

M → V: dbSNP rs2412504. Ref.9

VAR_019993

Natural variant

103

1

R → C: dbSNP rs36081263.

VAR_051655

Natural variant

151

1

T → I: dbSNP rs35593179.

VAR_051656

Natural variant

184

1

E → K: dbSNP rs56349744. Ref.9

VAR_040972

Natural variant

205

1

G → E: dbSNP rs55920845. Ref.9

VAR_040973

Natural variant

208

1

P → T: dbSNP rs35501648. Ref.9

VAR_040974

Natural variant

210

1

T → M: dbSNP rs34869667. Ref.9

VAR_040975

Natural variant

215

1

H → R: dbSNP rs3743135. Ref.9

VAR_019994

Natural variant

337

1

P → L: dbSNP rs3743137. Ref.9

VAR_019995

Natural variant

376

1

A → V: dbSNP rs55806501. Ref.9

VAR_040976

Natural variant

475

1

E → K: dbSNP rs34445577.

VAR_051657

Natural variant

514

1

L → R in a lung small cell carcinoma sample; somatic mutation. Ref.9

VAR_040977

Secondary structure

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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)
	Q9NQU5-1 [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].
[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]	"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.
[5]	"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: T-cell.
[6]	"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.
[7]	"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.
[8]	"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.
[9]	"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.
NP_001122101.1.
NP_064553.1.

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	[»]

SMR

Q9NQU5. Positions 4-66.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9NQU5. 1 interaction.

STRING

Q9NQU5.

PTM databases

PhosphoSite

Q9NQU5.

Proteomic databases

PRIDE

Q9NQU5.

Genome annotation databases

Ensembl

ENST00000260404; ENSP00000260404; ENSG00000137843; Homo sapiens. [Genome view]
ENST00000441369; ENSP00000406873; ENSG00000137843; Homo sapiens. [Genome view]
ENST00000453867; ENSP00000401153; ENSG00000137843; Homo sapiens. [Genome view]

GeneID

56924.

KEGG

hsa:56924.

UCSC

uc001zlb.2. human.

Organism-specific databases

CTD

56924.

GeneCards

GC15P038319.

H-InvDB

HIX0012122.

HGNC

HGNC:16061. PAK6.

MIM

608110. gene.

PharmGKB

PA32921.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG11420.

HOGENOM

HBG755340.

HOVERGEN

Q9NQU5.

InParanoid

Q9NQU5.

OMA

SPSPKTQ.

OrthoDB

EOG9HX7M4.

PhylomeDB

Q9NQU5.

Enzyme and pathway databases

BRENDA

2.7.11.1. 247.

Reactome

REACT_18266. Axon guidance.

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_prot_kinase-like_dom.
IPR015750. Ser/Thr_kinase_Pak-rel.
IPR002290. Ser/Thr_prot_kinase_dom.
[Graphical view]

PANTHER

PTHR22986:SF84. Pak_like. 1 hit.

Pfam

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

SMART

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

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 Resources

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:	February 9, 2010
This is version 94 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.