O96013 (PAK4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase PAK 4
EC=2.7.11.1

Alternative name(s):
p21-activated kinase 4
Short name=PAK-4

Gene names

Name:	PAK4
Synonyms:	KIAA1142

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	591 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, growth, proliferation or cell survival. Activation by various effectors including growth factor receptors or active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates and inactivates the protein phosphatase SSH1, leading to increased inhibitory phosphorylation of the actin binding/depolymerizing factor cofilin. Decreased cofilin activity may lead to stabilization of actin filaments. Phosphorylates LIMK1, a kinase that also inhibits the activity of cofilin. Phosphorylates integrin beta5/ITGB5 and thus regulates cell motility. Phosphorylates ARHGEF2 and activates the downstream target RHOA that plays a role in the regulation of assembly of focal adhesions and actin stress fibers. Stimulates cell survival by phosphorylating the BCL2 antagonist of cell death BAD. Alternatively, inhibits apoptosis by preventing caspase-8 binding to death domain receptors in a kinase independent manner. Plays a role in cell-cycle progression by controlling levels of the cell-cycle regulatory protein CDKN1A and by phosphorylating RAN. Ref.8 Ref.9 Ref.11 Ref.12 Ref.19 Ref.20 Ref.21
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Subunit structure	Interacts with FGFR2 and GRB2 By similarity. Interacts tightly with GTP-bound but not GDP-bound CDC42/p21 and weakly with RAC1. Ref.13
Subcellular location	Cytoplasm. Note: Seems to shuttle between cytoplasmic compartments depending on the activating effector. For example, can be found on the cell periphery after activation of growth-factor or integrin-mediated signaling pathways. Ref.10
Tissue specificity	Highest expression in prostate, testis and colon.
Post-translational modification	Autophosphorylated on serine residues when activated by CDC42/p21. Ref.27 Phosphorylated on tyrosine residues upon stimulation of FGFR2 By similarity. Ref.27
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 caution	The sequence BAA86456.1 differs from that shown. Reason: Erroneous initiation. The sequence BAC11166.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Apoptosis Cell cycle
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing 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 Ref.23. Source: UniProtKB cell cycle Inferred from electronic annotation. Source: UniProtKB-KW cell growth Traceable author statement Ref.23. Source: UniProtKB cell migration Traceable author statement Ref.23. Source: UniProtKB cell proliferation Traceable author statement Ref.23. Source: UniProtKB cytoskeleton organization Traceable author statement Ref.23. Source: UniProtKB signal transduction Traceable author statement Ref.23. Source: UniProtKB
Cellular_component	Golgi apparatus Traceable author statement Ref.1. Source: ProtInc
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein kinase activity Non-traceable author statement Ref.1. Source: ProtInc protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O96013-1)

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.

Isoform 2 (identifier: O96013-2)

The sequence of this isoform differs from the canonical sequence as follows:
     120-120: E → K
     121-285: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: O96013-3)

The sequence of this isoform differs from the canonical sequence as follows:
     69-221: Missing.

Isoform 4 (identifier: O96013-4)

The sequence of this isoform differs from the canonical sequence as follows:
     132-221: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 591

591

Serine/threonine-protein kinase PAK 4

PRO_0000086474

Regions

Domain

11 – 24

14

CRIB

Domain

321 – 572

252

Protein kinase

Nucleotide binding

327 – 335

9

ATP By similarity

Region

25 – 320

296

Linker

Region

298 – 323

26

GEF-interaction domain (GID)

Compositional bias

105 – 108

4

Poly-Pro

Compositional bias

242 – 247

6

Poly-Ser

Sites

Active site

440

1

Proton acceptor By similarity

Binding site

350

1

ATP By similarity

Amino acid modifications

Modified residue

41

1

Phosphoserine Ref.15 Ref.17

Modified residue

104

1

Phosphoserine Ref.15 Ref.17

Modified residue

148

1

Phosphoserine Ref.15 Ref.17

Modified residue

167

1

Phosphoserine Ref.15 Ref.17

Modified residue

181

1

Phosphoserine Ref.15 Ref.16 Ref.17 Ref.18 Ref.26

Modified residue

187

1

Phosphothreonine Ref.17

Modified residue

195

1

Phosphoserine Ref.17

Modified residue

258

1

Phosphoserine Ref.15 Ref.17

Modified residue

267

1

Phosphoserine Ref.15

Modified residue

291

1

Phosphoserine Ref.15 Ref.17

Modified residue

474

1

Phosphoserine; by autocatalysis Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.24 Ref.26 Ref.27

Natural variations

Alternative sequence

69 – 221

153

Missing in isoform 3.

VSP_017572

Alternative sequence

120

1

E → K in isoform 2.

VSP_004892

Alternative sequence

121 – 285

165

Missing in isoform 2.

VSP_004893

Alternative sequence

132 – 221

90

Missing in isoform 4.

VSP_017573

Natural variant

135

1

R → Q. Ref.28
Corresponds to variant rs56099436 [ dbSNP | Ensembl ].

VAR_040970

Natural variant

139

1

A → T. Ref.28
Corresponds to variant rs35655056 [ dbSNP | Ensembl ].

VAR_040971

Experimental info

Mutagenesis

445

1

S → N: Approximately 30-fold increased autophosphorylation (constitutively active mutant). Ref.9

Mutagenesis

474

1

S → E: Approximately 3-fold increased autophosphorylation. Ref.9

Secondary structure

1

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591

Helix Strand Turn

Details...

Beta strand

15 – 26

12

Turn

27 – 30

4

Beta strand

31 – 34

4

Helix

37 – 39

3

Turn

40 – 42

3

Helix

301 – 311

11

Helix

317 – 319

3

Beta strand

321 – 329

9

Beta strand

334 – 340

7

Turn

341 – 343

3

Beta strand

346 – 353

8

Helix

354 – 356

3

Helix

360 – 362

3

Helix

363 – 369

7

Turn

370 – 372

3

Beta strand

381 – 387

7

Beta strand

390 – 395

6

Helix

403 – 409

7

Helix

414 – 433

20

Helix

443 – 445

3

Beta strand

446 – 448

3

Beta strand

454 – 456

3

Helix

459 – 461

3

Beta strand

467 – 469

3

Beta strand

475 – 477

3

Helix

479 – 481

3

Helix

484 – 487

4

Helix

495 – 510

16

Turn

514 – 517

4

Helix

520 – 529

10

Helix

538 – 540

3

Helix

543 – 552

10

Turn

557 – 559

3

Helix

563 – 566

4

Helix

570 – 574

5

Helix

578 – 581

4

Helix

582 – 584

3

Turn

586 – 588

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: 04C2A5C0B06427D5	FASTA	591	64,072
	10 20 30 40 50 60 MFGKRKKRVE ISAPSNFEHR VHTGFDQHEQ KFTGLPRQWQ SLIEESARRP KPLVDPACIT 70 80 90 100 110 120 SIQPGAPKTI VRGSKGAKDG ALTLLLDEFE NMSVTRSNSL RRDSPPPPAR ARQENGMPEE 130 140 150 160 170 180 PATTARGGPG KAGSRGRFAG HSEAGGGSGD RRRAGPEKRP KSSREGSGGP QESSRDKRPL 190 200 210 220 230 240 SGPDVGTPQP AGLASGAKLA AGRPFNTYPR ADTDHPSRGA QGEPHDVAPN GPSAGGLAIP 250 260 270 280 290 300 QSSSSSSRPP TRARGAPSPG VLGPHASEPQ LAPPACTPAA PAVPGPPGPR SPQREPQRVS 310 320 330 340 350 360 HEQFRAALQL VVDPGDPRSY LDNFIKIGEG STGIVCIATV RSSGKLVAVK KMDLRKQQRR 370 380 390 400 410 420 ELLFNEVVIM RDYQHENVVE MYNSYLVGDE LWVVMEFLEG GALTDIVTHT RMNEEQIAAV 430 440 450 460 470 480 CLAVLQALSV LHAQGVIHRD IKSDSILLTH DGRVKLSDFG FCAQVSKEVP RRKSLVGTPY 490 500 510 520 530 540 WMAPELISRL PYGPEVDIWS LGIMVIEMVD GEPPYFNEPP LKAMKMIRDN LPPRLKNLHK 550 560 570 580 590 VSPSLKGFLD RLLVRDPAQR ATAAELLKHP FLAKAGPPAS IVPLMRQNRT R
	Isoform 2 [UniParc]. Checksum: 505879690593E93A	FASTA	426	47,924
	10 20 30 40 50 60 MFGKRKKRVE ISAPSNFEHR VHTGFDQHEQ KFTGLPRQWQ SLIEESARRP KPLVDPACIT 70 80 90 100 110 120 SIQPGAPKTI VRGSKGAKDG ALTLLLDEFE NMSVTRSNSL RRDSPPPPAR ARQENGMPEK 130 140 150 160 170 180 PPGPRSPQRE PQRVSHEQFR AALQLVVDPG DPRSYLDNFI KIGEGSTGIV CIATVRSSGK 190 200 210 220 230 240 LVAVKKMDLR KQQRRELLFN EVVIMRDYQH ENVVEMYNSY LVGDELWVVM EFLEGGALTD 250 260 270 280 290 300 IVTHTRMNEE QIAAVCLAVL QALSVLHAQG VIHRDIKSDS ILLTHDGRVK LSDFGFCAQV 310 320 330 340 350 360 SKEVPRRKSL VGTPYWMAPE LISRLPYGPE VDIWSLGIMV IEMVDGEPPY FNEPPLKAMK 370 380 390 400 410 420 MIRDNLPPRL KNLHKVSPSL KGFLDRLLVR DPAQRATAAE LLKHPFLAKA GPPASIVPLM RQNRTR
	Isoform 3 [UniParc]. Checksum: 4A596EBBCECE9883	FASTA	438	48,268
	10 20 30 40 50 60 MFGKRKKRVE ISAPSNFEHR VHTGFDQHEQ KFTGLPRQWQ SLIEESARRP KPLVDPACIT 70 80 90 100 110 120 SIQPGAPKGE PHDVAPNGPS AGGLAIPQSS SSSSRPPTRA RGAPSPGVLG PHASEPQLAP 130 140 150 160 170 180 PACTPAAPAV PGPPGPRSPQ REPQRVSHEQ FRAALQLVVD PGDPRSYLDN FIKIGEGSTG 190 200 210 220 230 240 IVCIATVRSS GKLVAVKKMD LRKQQRRELL FNEVVIMRDY QHENVVEMYN SYLVGDELWV 250 260 270 280 290 300 VMEFLEGGAL TDIVTHTRMN EEQIAAVCLA VLQALSVLHA QGVIHRDIKS DSILLTHDGR 310 320 330 340 350 360 VKLSDFGFCA QVSKEVPRRK SLVGTPYWMA PELISRLPYG PEVDIWSLGI MVIEMVDGEP 370 380 390 400 410 420 PYFNEPPLKA MKMIRDNLPP RLKNLHKVSP SLKGFLDRLL VRDPAQRATA AELLKHPFLA 430 KAGPPASIVP LMRQNRTR
	Isoform 4 [UniParc]. Checksum: 6EE6240ECE65E79D	FASTA	501	54,940
	10 20 30 40 50 60 MFGKRKKRVE ISAPSNFEHR VHTGFDQHEQ KFTGLPRQWQ SLIEESARRP KPLVDPACIT 70 80 90 100 110 120 SIQPGAPKTI VRGSKGAKDG ALTLLLDEFE NMSVTRSNSL RRDSPPPPAR ARQENGMPEE 130 140 150 160 170 180 PATTARGGPG KGEPHDVAPN GPSAGGLAIP QSSSSSSRPP TRARGAPSPG VLGPHASEPQ 190 200 210 220 230 240 LAPPACTPAA PAVPGPPGPR SPQREPQRVS HEQFRAALQL VVDPGDPRSY LDNFIKIGEG 250 260 270 280 290 300 STGIVCIATV RSSGKLVAVK KMDLRKQQRR ELLFNEVVIM RDYQHENVVE MYNSYLVGDE 310 320 330 340 350 360 LWVVMEFLEG GALTDIVTHT RMNEEQIAAV CLAVLQALSV LHAQGVIHRD IKSDSILLTH 370 380 390 400 410 420 DGRVKLSDFG FCAQVSKEVP RRKSLVGTPY WMAPELISRL PYGPEVDIWS LGIMVIEMVD 430 440 450 460 470 480 GEPPYFNEPP LKAMKMIRDN LPPRLKNLHK VSPSLKGFLD RLLVRDPAQR ATAAELLKHP 490 500 FLAKAGPPAS IVPLMRQNRT R

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"PAK4, a novel effector for Cdc42Hs, is implicated in the reorganization of the actin cytoskeleton and in the formation of filopodia." Abo A., Qu J., Cammarano M.S., Dan C., Fritsch A., Baud V., Belisle B., Minden A. EMBO J. 17:6527-6540(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Lymphoma.
[2]	Melnick M.B. Submitted (MAY-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Neuroblastoma.
[3]	"Characterization of cDNA clones selected by the GeneMark analysis from size-fractionated cDNA libraries from human brain." Hirosawa M., Nagase T., Ishikawa K., Kikuno R., Nomura N., Ohara O. DNA Res. 6:329-336(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Brain.
[4]	"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. , 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] (ISOFORM 3), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 264-591 (ISOFORM 1). Tissue: Brain and Teratocarcinoma.
[5]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Brain.
[6]	Mural R.J., Istrail S., Sutton G.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. , 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].
[7]	"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] (ISOFORMS 1; 2 AND 4). Tissue: Eye, Pancreas and Placenta.
[8]	"The serine/threonine kinase PAK4 prevents caspase activation and protects cells from apoptosis." Gnesutta N., Qu J., Minden A. J. Biol. Chem. 276:14414-14419(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF BAD.
[9]	"Activated PAK4 regulates cell adhesion and anchorage-independent growth." Qu J., Cammarano M.S., Shi Q., Ha K.C., de Lanerolle P., Minden A. Mol. Cell. Biol. 21:3523-3533(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF SER-445 AND SER-474.
[10]	"P21-activated kinase 4 interacts with integrin alpha v beta 5 and regulates alpha v beta 5-mediated cell migration." Zhang H., Li Z., Viklund E.K., Stromblad S. J. Cell Biol. 158:1287-1297(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[11]	"Death receptor-induced activation of initiator caspase 8 is antagonized by serine/threonine kinase PAK4." Gnesutta N., Minden A. Mol. Cell. Biol. 23:7838-7848(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[12]	"Interplay between components of a novel LIM kinase-slingshot phosphatase complex regulates cofilin." Soosairajah J., Maiti S., Wiggan O., Sarmiere P., Moussi N., Sarcevic B., Sampath R., Bamburg J.R., Bernard O. EMBO J. 24:473-486(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[13]	"PAK4 mediates morphological changes through the regulation of GEF-H1." Callow M.G., Zozulya S., Gishizky M.L., Jallal B., Smeal T. J. Cell Sci. 118:1861-1872(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ARHGEF2.
[14]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-474, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[15]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-41; SER-104; SER-148; SER-167; SER-181; SER-258; SER-267; SER-291 AND SER-474, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[16]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181 AND SER-474, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[17]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-41; SER-104; SER-148; SER-167; SER-181; THR-187; SER-195; SER-258; SER-291 AND SER-474, MASS SPECTROMETRY.
[18]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181 AND SER-474, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[19]	"p21-activated kinase 4 phosphorylation of integrin beta5 Ser-759 and Ser-762 regulates cell migration." Li Z., Zhang H., Lundin L., Thullberg M., Liu Y., Wang Y., Claesson-Welsh L., Stromblad S. J. Biol. Chem. 285:23699-23710(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF ITGB5.
[20]	"Subgroup II PAK-mediated phosphorylation regulates Ran activity during mitosis." Bompard G., Rabeharivelo G., Frank M., Cau J., Delsert C., Morin N. J. Cell Biol. 190:807-822(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF RAN.
[21]	"Cdc42 regulates apical junction formation in human bronchial epithelial cells through PAK4 and Par6B." Wallace S.W., Durgan J., Jin D., Hall A. Mol. Biol. Cell 21:2996-3006(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[22]	"p21-activated kinases: three more join the Pak." Jaffer Z.M., Chernoff J. Int. J. Biochem. Cell Biol. 34:713-717(2002) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[23]	"The emerging importance of group II PAKs." Wells C.M., Jones G.E. Biochem. J. 425:465-473(2010) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[24]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-474, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[25]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[26]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181 AND SER-474, MASS SPECTROMETRY.
[27]	"Crystal structure of the human p21-activated kinase 4." Eswaran J., Debreczeni J.E., Bunkoczi G., Filippakopoulos P., Das S., Fedorov O., Sundstrom M., Arrowsmith C., Edwards A., von Delft F., Knapp S. Submitted (JUL-2005) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 300-591, PHOSPHORYLATION AT SER-474.
[28]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLN-135 AND THR-139.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AJ011855 mRNA. Translation: CAA09820.1.
AF005046 mRNA. Translation: AAD01210.1.
AB032968 mRNA. Translation: BAA86456.1. Different initiation.
AK074728 mRNA. Translation: BAC11166.1. Different initiation.
AK294586 mRNA. Translation: BAG57777.1.
AL834236 mRNA. Translation: CAD38914.2.
CH471126 Genomic DNA. Translation: EAW56861.1.
BC002921 mRNA. Translation: AAH02921.1.
BC011368 mRNA. Translation: AAH11368.1.
BC025282 mRNA. Translation: AAH25282.1.
BC034511 mRNA. Translation: AAH34511.1.

IPI

IPI00014068.
IPI00178714.
IPI00384231.
IPI00556065.

RefSeq

NP_001014831.1. NM_001014831.2.
NP_001014832.1. NM_001014832.1.
NP_001014834.1. NM_001014834.2.
NP_001014835.1. NM_001014835.1.
NP_005875.1. NM_005884.3.

UniGene

Hs.20447.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2BVA	X-ray	2.30	A/B	300-591	[»]
2CDZ	X-ray	2.30	A	291-591	[»]
2J0I	X-ray	1.60	A	291-591	[»]
2OV2	X-ray	2.10	I/J/K/L/M/N/O/P	10-44	[»]
2Q0N	X-ray	1.75	A	291-591	[»]
2X4Z	X-ray	2.10	A	300-591	[»]
4APP	X-ray	2.20	A	300-591	[»]
4FIE	X-ray	3.11	A/B	5-591	[»]
4FIF	X-ray	2.60	A/B	109-591	[»]
			C/D	49-56	[»]
4FIG	X-ray	3.01	A/B	109-591	[»]
4FIH	X-ray	1.97	A	109-591	[»]
4FII	X-ray	2.00	A	109-591	[»]
			B	49-56	[»]
4FIJ	X-ray	2.30	A	109-591	[»]

ProteinModelPortal

O96013.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-39742N.

IntAct

O96013. 4 interactions.

MINT

MINT-1387795.

STRING

9606.ENSP00000351049.

PTM databases

PhosphoSite

O96013.

Proteomic databases

PaxDb

O96013.

PRIDE

O96013.

Protocols and materials databases

DNASU

10298.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000321944; ENSP00000326864; ENSG00000130669.
ENST00000358301; ENSP00000351049; ENSG00000130669.
ENST00000360442; ENSP00000353625; ENSG00000130669.
ENST00000435673; ENSP00000392753; ENSG00000130669.
ENST00000593690; ENSP00000469413; ENSG00000130669.
ENST00000599386; ENSP00000471157; ENSG00000130669.
ENST00000599470; ENSP00000470284; ENSG00000130669.

GeneID

10298.

KEGG

hsa:10298.

UCSC

uc002okj.1. human.
uc002okm.1. human.
uc002okp.1. human.

Organism-specific databases

CTD

10298.

GeneCards

GC19P039616.

HGNC

HGNC:16059. PAK4.

HPA

CAB025747.

MIM

605451. gene.

neXtProt

NX_O96013.

PharmGKB

PA32920.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOVERGEN

HBG108518.

InParanoid

O96013.

KO

K05734.

OMA

GFDQHEQ.

OrthoDB

EOG4RNB7X.

PhylomeDB

O96013.

Enzyme and pathway databases

BRENDA

2.7.11.1. 2681.

Pathway_Interaction_DB

fgf_pathway. FGF signaling pathway.

Reactome

REACT_111045. Developmental Biology.

Gene expression databases

ArrayExpress

O96013.

Bgee

O96013.

CleanEx

HS_PAK4.

Genevestigator

O96013.

GermOnline

ENSG00000130669. Homo sapiens.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR000095. PAK_box_Rho-bd.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
[Graphical view]

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

BindingDB

O96013.

ChEMBL

CHEMBL4482.

ChiTaRS

PAK4. human.

EvolutionaryTrace

O96013.

GenomeRNAi

10298.

NextBio

39028.

SOURCE

Search...

Entry information

Entry name

PAK4_HUMAN

Accession

Primary (citable) accession number: O96013
Secondary accession number(s): B4DGG6 , Q8N4E1, Q8NCH5, Q8NDE3, Q9BU33, Q9ULS8

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 24, 2001
Last sequence update:	May 1, 1999
Last modified:	May 1, 2013
This is version 139 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.