Reviewed, UniProtKB/Swiss-Prot O35346 (FAK1_RAT)

Names and origin

Protein names

Recommended name:
    Focal adhesion kinase 1
      Short name=FADK 1
    EC=2.7.10.2
Alternative name(s):
    pp125FAK

Gene names

Name:	Ptk2
Synonyms:	Fak, Fak1

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	1055 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Non-receptor protein-tyrosine kinase implicated in signaling pathways involved in cell motility, proliferation and apoptosis. Activated by tyrosine-phosphorylation in response to either integrin clustering induced by cell adhesion or antibody cross-linking, or via G-protein coupled receptor (GPCR) occupancy by ligands such as bombesin or lysophosphatidic acid, or via LDL receptor occupancy. Plays a potential role in oncogenic transformations resulting in increased kinase activity.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Interacts with CAS family members and with GIT1, SORBS1 and BCAR3. Interacts with SHB By similarity. Interacts with RGNEF and TGFB1I1.
Subcellular location	Cell junction › focal adhesion. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Note: Constituent of focal adhesions.
Domain	The first Pro-rich domain interacts with the SH3 domain of CRK-associated substrate (BCAR1) and CASL By similarity. The carboxy-terminal region is the site of focal adhesion targeting (FAT) sequence which mediates the localization of FAK1 to focal adhesions.
Post-translational modification	Phosphorylated on 6 tyrosine residues upon activation By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. FAK subfamily. Contains 1 FERM domain. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Cell junction Cell membrane Membrane
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Acetylation Phosphoprotein
Gene Ontology (GO)
Biological process	JNK cascade Inferred from mutant phenotype. Source: RGD cellular chloride ion homeostasis Inferred from mutant phenotype. Source: RGD fat cell differentiation Inferred from expression pattern. Source: RGD negative regulation of apoptosis Inferred from mutant phenotype. Source: RGD negative regulation of cell migration Inferred from mutant phenotype. Source: RGD positive regulation of cell adhesion Inferred from mutant phenotype. Source: RGD positive regulation of cell growth Inferred from mutant phenotype. Source: RGD positive regulation of glial cell proliferation Inferred from mutant phenotype. Source: RGD positive regulation of phagocytosis Inferred from mutant phenotype. Source: RGD positive regulation of smooth muscle cell migration Inferred from mutant phenotype. Source: RGD positive regulation of smooth muscle cell proliferation Inferred from mutant phenotype. Source: RGD positive regulation of synaptic transmission Inferred from mutant phenotype. Source: RGD positive regulation of vasodilation Inferred from mutant phenotype. Source: RGD protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro response to arsenic Inferred from expression pattern. Source: RGD response to drug Inferred from expression pattern. Source: RGD response to estradiol stimulus Inferred from expression pattern. Source: RGD response to glucose stimulus Inferred from expression pattern. Source: RGD response to mechanical stimulus Inferred from expression pattern. Source: RGD response to organic cyclic substance Inferred from expression pattern. Source: RGD response to organic nitrogen Inferred from expression pattern. Source: RGD signal complex assembly Inferred from electronic annotation. Source: InterPro
Cellular component	apical plasma membrane Inferred from direct assay. Source: RGD cytoskeleton Inferred from electronic annotation. Source: InterPro focal adhesion Ref.1 Inferred from direct assay. Source: RGD intercalated disc Inferred from direct assay. Source: RGD internal side of plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell nuclear body Inferred from direct assay. Source: RGD nucleolus Inferred from direct assay. Source: RGD sarcolemma Inferred from direct assay. Source: RGD
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC protein complex binding Inferred from physical interaction. Source: RGD signal transducer activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 1055	1054	Focal adhesion kinase 1		PRO_0000088079
Regions
	Domain	35 – 355	321	FERM
	Domain	422 – 680	259	Protein kinase
	Nucleotide binding	428 – 436	9	ATP By similarity
	Region	707 – 1055	349	Interaction with TGFB1I1 By similarity
	Region	915 – 1055	141	Interaction with RGNEF By similarity
	Compositional bias	712 – 733	22	Pro-rich
	Compositional bias	863 – 916	54	Pro-rich
Sites
	Active site	546	1	Proton acceptor By similarity
	Binding site	454	1	ATP By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylalanine By similarity
	Modified residue	13	1	Phosphothreonine By similarity
	Modified residue	29	1	Phosphoserine By similarity
	Modified residue	397	1	Phosphotyrosine By similarity
	Modified residue	407	1	Phosphotyrosine By similarity
	Modified residue	568	1	Phosphoserine By similarity
	Modified residue	570	1	Phosphotyrosine By similarity
	Modified residue	576	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	577	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	722	1	Phosphoserine By similarity
	Modified residue	840	1	Phosphoserine By similarity
	Modified residue	843	1	Phosphoserine By similarity
	Modified residue	861	1	Phosphotyrosine By similarity
	Modified residue	913	1	Phosphoserine By similarity
	Modified residue	928	1	Phosphotyrosine By similarity

Sequences

	Sequence		Length	Mass (Da)
	O35346-1 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 3AFB4ED682D14A33	FASTA	1,055	119,717
	10 20 30 40 50 60 MAAAYLDPNL NHTPSSSTKT HLGTGTERSP GAMERVLKVF HYFESSNEPT TWASIIRHGD 70 80 90 100 110 120 ATDVRGIIQK IVDSHKVKHV ACYGFRLSHL RSEEVHWLHV DMGVSSVREK YELAHPPEEW 130 140 150 160 170 180 KYELRIRYLP KGFLNQFTED KPTLNFFYQQ VKSDYMLEIA DQVDQDIALK LGCLEIRRSY 190 200 210 220 230 240 WEMRGNALEK KSNYEVLEKD VGLKRFFPKS LLDSVKAKTL RKLIQQTFRQ FANLNREESI 250 260 270 280 290 300 LKFFEILSPV YRFDKECFKC ALGSSWIISV ELAIGPEEGI SYLTDKGCNP THLADFNQVQ 310 320 330 340 350 360 TIQYSNSEDK DRKGMLQLKI AGAPEPLTVT APSLTIAENM ADLIDGYCRL VNGATQSFII 370 380 390 400 410 420 RPQKEGERAL PSIPKLANNE KQGMRTHAVS VSETDDYAEI IDEEDTYTMP STRDYEIQRE 430 440 450 460 470 480 RIELGRCIGE GQFGDVHQGV YLSPENPALA VAIKTCKNCT SDSVREKFLQ EALTMRQFDH 490 500 510 520 530 540 PHIVKLIGVI TENPVWIIME LCTLGELRSF LQVRKYSLDL ASLILYAYQL STALAYLESK 550 560 570 580 590 600 RFVHRDIAAR NVLVSSNDCV KLGDFGLSRY MEDSTYYKAS KGKLPIKWMA PESINFRRFT 610 620 630 640 650 660 SASDVWMFGV CMWEILMHGV KPFQGVKNND VIGRIENGER LPMPPNCPPT LYSLMTKCWA 670 680 690 700 710 720 YDPSRRPRFT ELKAQLSTIL EEEKVQQEER MRMESRRQAT VSWDSGGSDE APPKPSRPGY 730 740 750 760 770 780 PSPRSSEGFY PSPQHMVQTN HYQISGYPGS HGIPAMAGSI YPGQASLLDQ TELWNHRPQE 790 800 810 820 830 840 MSMWQPSVED SAALDLRGMG QVLPPHLMEE RLIRQQQEME EDQRWLEKEE RFLKPDVRLS 850 860 870 880 890 900 RGSIDREDGS FQGPTGNQHI YQPVGKPDPA APPKKPPRPG APGHLSNLSS ISSPAESYNE 910 920 930 940 950 960 GVKPWRLQPQ EISPPPTANL DRSNDKVYEN VTGLVKAVIE MSSKIQPAPP EEYVPMVKEV 970 980 990 1000 1010 1020 GLALRTLLAT VDETIPILPA STHREIEMAQ KLLNSDLGEL ISKMKLAQQY VMTSLQQEYK 1030 1040 1050 KQMLTAAHAL AVDAKNLLDV IDQARLKMLG QTRPH

References

[1]	"Cloning of focal adhesion kinase, pp125FAK, from rat brain reveals multiple transcripts with different patterns of expression." Burgaya F., Girault J.A. Brain Res. Mol. Brain Res. 37:63-73(1996) [PubMed: 8738136] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Corpus striatum.
[2]	Sasaki T., Nagura K., Sasaki H. Submitted (DEC-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 350-528. Strain: Wistar.
[3]	"Cell adhesion kinase beta forms a complex with a new member, Hic-5, of proteins localized at focal adhesions." Matsuya M., Sasaki H., Aoto H., Mitaka T., Nagura K., Ohba T., Ishino M., Takahashi S., Suzuki R., Sasaki T. J. Biol. Chem. 273:1003-1014(1998) [PubMed: 9422762] [Abstract] Cited for: INTERACTION WITH TGFB1I1.
[4]	"Direct interaction of focal adhesion kinase with p190RhoGEF." Zhai J., Lin H., Nie Z., Wu J., Canete-Soler R., Schlaepfer W.W., Schlaepfer D.D. J. Biol. Chem. 278:24865-24873(2003) [PubMed: 12702722] [Abstract] Cited for: INTERACTION WITH RGNEF.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF020777 mRNA. Translation: AAB72203.1. U43942 mRNA. Translation: AAA86280.1.
IPI	IPI00476238.
RefSeq	NP_037213.1.
UniGene	Rn.2809
3D structure databases
HSSP	HSSP built from PDB template 1K04 based on UniProtKB Q05397.
SMR	O35346. Positions 33-383, 415-686, 911-1052.
ModBase	Search...
Protein-protein interaction databases
STRING	O35346.
PTM databases
PhosphoSite	O35346.
Genome annotation databases
Ensembl	ENSRNOT00000011219; ENSRNOP00000011219; ENSRNOG00000007916; Rattus norvegicus. [Genome view] ENSRNOT00000046362; ENSRNOP00000044307; ENSRNOG00000007916; Rattus norvegicus. [Genome view]
GeneID	25614.
KEGG	rno:25614.
UCSC	NM_013081. rat.
Organism-specific databases
CTD	25614.
RGD	3443. Ptk2.
Phylogenomic databases
HOVERGEN	O35346.
Enzyme and pathway databases
BRENDA	2.7.10.2. 248.
Gene expression databases
ArrayExpress	O35346.
Genevestigator	O35346.
GermOnline	ENSRNOG00000007916. Rattus norvegicus.
Family and domain databases
InterPro	IPR019749. Band_41_domain. IPR019748. FERM_central. IPR019747. FERM_CS. IPR000299. FERM_domain. IPR005189. Focal_adhesion_target_reg. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR001245. Tyr_pkinase. IPR008266. Tyr_pkinase_AS. [Graphical view]
Pfam	PF00373. FERM_M. 1 hit. PF03623. Focal_AT. 1 hit. PF07714. Pkinase_Tyr. 1 hit. [Graphical view]
PRINTS	PR00109. TYRKINASE.
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00295. B41. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
PROSITE	PS00660. FERM_1. False negative. PS00661. FERM_2. 1 hit. PS50057. FERM_3. 1 hit. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00109. PROTEIN_KINASE_TYR. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	607363.

Entry information

Entry name

FAK1_RAT

Accession

Primary (citable) accession number: O35346
Secondary accession number(s): Q62900

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	January 1, 1998
Last modified:	October 13, 2009
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)