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Protein

Integrin-linked protein kinase

Gene

ILK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Receptor-proximal protein kinase regulating integrin-mediated signal transduction. May act as a mediator of inside-out integrin signaling. Focal adhesion protein part of the complex ILK-PINCH. This complex is considered to be one of the convergence points of integrin- and growth factor-signaling pathway. Could be implicated in mediating cell architecture, adhesion to integrin substrates and anchorage-dependent growth in epithelial cells. Phosphorylates beta-1 and beta-3 integrin subunit on serine and threonine residues, but also AKT1 and GSK3B.

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Stimulated rapidly but transiently by both cell fibronectin interactions, as well as by insulin, in a PI3-K-dependent manner, likely via the binding of PtdIns(3,4,5)P3 with a PH-like domain of ILK.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei220ATPPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi199 – 207ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • protein kinase binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB
  • signal transducer activity Source: Ensembl

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS09377-MONOMER.
BRENDAi2.7.10.2. 2681.
ReactomeiR-HSA-446343. Localization of the PINCH-ILK-PARVIN complex to focal adhesions.
R-HSA-446353. Cell-extracellular matrix interactions.
SignaLinkiQ13418.
SIGNORiQ13418.

Names & Taxonomyi

Protein namesi
Recommended name:
Integrin-linked protein kinase (EC:2.7.11.1)
Alternative name(s):
59 kDa serine/threonine-protein kinase
ILK-1
ILK-2
p59ILK
Gene namesi
Name:ILK
Synonyms:ILK1, ILK2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:6040. ILK.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi99H → D: Alters interaction with LIMS1. 1 Publication1
Mutagenesisi359E → K: Inactivation of ILK. 1 Publication1

Organism-specific databases

DisGeNETi3611.
OpenTargetsiENSG00000166333.
PharmGKBiPA29855.

Chemistry databases

ChEMBLiCHEMBL5247.
GuidetoPHARMACOLOGYi2041.

Polymorphism and mutation databases

DMDMi9973397.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000860201 – 452Integrin-linked protein kinaseAdd BLAST452

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei186PhosphoserineCombined sources1
Modified residuei426N6-acetyllysineBy similarity1

Post-translational modificationi

Autophosphorylated on serine residues.

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ13418.
PaxDbiQ13418.
PeptideAtlasiQ13418.
PRIDEiQ13418.

2D gel databases

OGPiQ13418.

PTM databases

iPTMnetiQ13418.
PhosphoSitePlusiQ13418.
SwissPalmiQ13418.

Expressioni

Tissue specificityi

Highly expressed in heart followed by skeletal muscle, pancreas and kidney. Weakly expressed in placenta, lung and liver.

Gene expression databases

BgeeiENSG00000166333.
CleanExiHS_ILK.
ExpressionAtlasiQ13418. baseline and differential.
GenevisibleiQ13418. HS.

Organism-specific databases

HPAiCAB004041.
HPA048437.

Interactioni

Subunit structurei

Interacts with FERMT2 (By similarity). Interacts with the cytoplasmic domain of ITGB1. Could also interact with integrin ITGB2, ITGB3 and/or ITGB5. Interacts (via ANK repeats) with LIMS1 and LIMS2. Interacts with PARVA and PARVB; these compete for the same binding site. Interacts probably also with TGFB1I1. Interacts (via ANK repeats) with EPHA1 (via SAM domain); stimulated by EFNA1 but independent of the kinase activity of EPHA1.By similarity8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CASP8Q147902EBI-747644,EBI-78060
CASP9P552112EBI-747644,EBI-516799
ILKAPQ9H0C83EBI-747644,EBI-2620298
LIMS1P480597EBI-747644,EBI-306928
PARVAQ9NVD714EBI-747644,EBI-747655
PARVGQ9HBI09EBI-747644,EBI-3921217
RICTORQ6R3278EBI-747644,EBI-1387196
SLC4A1APQ9BWU08EBI-747644,EBI-1999704
SYNPO2Q9UMS66EBI-747644,EBI-3453434
TRIM27P143733EBI-747644,EBI-719493

GO - Molecular functioni

  • protein kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi109824. 214 interactors.
DIPiDIP-38657N.
IntActiQ13418. 178 interactors.
MINTiMINT-1465247.
STRINGi9606.ENSP00000299421.

Chemistry databases

BindingDBiQ13418.

Structurei

Secondary structure

1452
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi4 – 10Combined sources7
Helixi13 – 21Combined sources9
Helixi37 – 43Combined sources7
Helixi47 – 55Combined sources9
Helixi70 – 76Combined sources7
Helixi80 – 88Combined sources9
Helixi92 – 94Combined sources3
Helixi103 – 109Combined sources7
Helixi113 – 121Combined sources9
Beta strandi126 – 128Combined sources3
Beta strandi131 – 133Combined sources3
Helixi136 – 139Combined sources4
Helixi142 – 154Combined sources13
Turni167 – 169Combined sources3
Helixi190 – 192Combined sources3
Beta strandi194 – 202Combined sources9
Beta strandi205 – 212Combined sources8
Beta strandi215 – 222Combined sources8
Helixi229 – 238Combined sources10
Helixi239 – 242Combined sources4
Beta strandi255 – 257Combined sources3
Turni259 – 261Combined sources3
Beta strandi262 – 264Combined sources3
Beta strandi266 – 270Combined sources5
Helixi277 – 282Combined sources6
Helixi291 – 308Combined sources18
Beta strandi311 – 313Combined sources3
Beta strandi324 – 327Combined sources4
Beta strandi333 – 336Combined sources4
Helixi337 – 339Combined sources3
Helixi353 – 355Combined sources3
Helixi358 – 362Combined sources5
Helixi365 – 367Combined sources3
Helixi370 – 387Combined sources18
Turni391 – 394Combined sources4
Helixi397 – 406Combined sources10
Helixi419 – 428Combined sources10
Helixi433 – 435Combined sources3
Helixi439 – 449Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2KBXNMR-A1-171[»]
3F6QX-ray1.60A1-170[»]
3IXEX-ray1.90A1-174[»]
3KMUX-ray1.80A183-452[»]
3KMWX-ray2.00A183-452[»]
3REPX-ray1.80A183-452[»]
4HI8X-ray1.20A1-174[»]
4HI9X-ray1.20A1-174[»]
ProteinModelPortaliQ13418.
SMRiQ13418.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13418.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati2 – 30ANK 1Add BLAST29
Repeati31 – 63ANK 2Add BLAST33
Repeati64 – 96ANK 3Add BLAST33
Repeati97 – 129ANK 4Add BLAST33
Repeati130 – 174ANK 5Add BLAST45
Domaini193 – 446Protein kinasePROSITE-ProRule annotationAdd BLAST254

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni33 – 139Interaction with LIMS11 PublicationAdd BLAST107
Regioni180 – 212PH-like; mediates interaction with TGFB1I1Add BLAST33

Domaini

A PH-like domain is involved in phosphatidylinositol phosphate binding.2 Publications

Sequence similaritiesi

Contains 5 ANK repeats.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

ANK repeat, Repeat

Phylogenomic databases

eggNOGiKOG0195. Eukaryota.
COG0666. LUCA.
GeneTreeiENSGT00860000133794.
HOGENOMiHOG000047828.
HOVERGENiHBG002437.
InParanoidiQ13418.
KOiK06272.
PhylomeDBiQ13418.
TreeFamiTF315194.

Family and domain databases

Gene3Di1.25.40.20. 2 hits.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
[Graphical view]
PfamiPF12796. Ank_2. 2 hits.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
SMARTiSM00248. ANK. 3 hits.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 3 hits.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q13418-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MDDIFTQCRE GNAVAVRLWL DNTENDLNQG DDHGFSPLHW ACREGRSAVV
60 70 80 90 100
EMLIMRGARI NVMNRGDDTP LHLAASHGHR DIVQKLLQYK ADINAVNEHG
110 120 130 140 150
NVPLHYACFW GQDQVAEDLV ANGALVSICN KYGEMPVDKA KAPLRELLRE
160 170 180 190 200
RAEKMGQNLN RIPYKDTFWK GTTRTRPRNG TLNKHSGIDF KQLNFLTKLN
210 220 230 240 250
ENHSGELWKG RWQGNDIVVK VLKVRDWSTR KSRDFNEECP RLRIFSHPNV
260 270 280 290 300
LPVLGACQSP PAPHPTLITH WMPYGSLYNV LHEGTNFVVD QSQAVKFALD
310 320 330 340 350
MARGMAFLHT LEPLIPRHAL NSRSVMIDED MTARISMADV KFSFQCPGRM
360 370 380 390 400
YAPAWVAPEA LQKKPEDTNR RSADMWSFAV LLWELVTREV PFADLSNMEI
410 420 430 440 450
GMKVALEGLR PTIPPGISPH VCKLMKICMN EDPAKRPKFD MIVPILEKMQ

DK
Length:452
Mass (Da):51,419
Last modified:August 1, 1998 - v2
Checksum:iE37DC2AD5311A1C2
GO
Isoform 2 (identifier: Q13418-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     118-206: DLVANGALVS...TKLNENHSGE → SGQRRWARISTVFHTRTHSGRGPPALGP

Note: No experimental confirmation available.
Show »
Length:391
Mass (Da):44,349
Checksum:i3290120580572F3C
GO
Isoform 3 (identifier: Q13418-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-134: Missing.

Note: No experimental confirmation available.
Show »
Length:318
Mass (Da):36,467
Checksum:i7516E37CB8353644
GO

Sequence cautioni

The sequence CAB94832 differs from that shown. Probable cloning artifact. Was originally thought to be distinct gene (ILK2) (PubMed:10871859).1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069753262A → V Found in a patient with severe dilated cardiomyopathy; unknown pathological significance. 1 PublicationCorresponds to variant rs387907366dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0559251 – 134Missing in isoform 3. 1 PublicationAdd BLAST134
Alternative sequenceiVSP_054920118 – 206DLVAN…NHSGE → SGQRRWARISTVFHTRTHSG RGPPALGP in isoform 2. 1 PublicationAdd BLAST89

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U40282 mRNA. Translation: AAC16892.1.
AJ277481 mRNA. Translation: CAB94832.1. Sequence problems.
AF244139 Genomic DNA. Translation: AAF74449.1.
AJ404847 Genomic DNA. Translation: CAB99253.1.
AK293474 mRNA. Translation: BAH11516.1.
AK296628 mRNA. Translation: BAH12404.1.
CR407673 mRNA. Translation: CAG28601.1.
CR749220 mRNA. Translation: CAH18077.1.
AC091564 Genomic DNA. No translation available.
CH471064 Genomic DNA. Translation: EAW68688.1.
CH471064 Genomic DNA. Translation: EAW68689.1.
CH471064 Genomic DNA. Translation: EAW68690.1.
BC001554 mRNA. Translation: AAH01554.1.
CCDSiCCDS60712.1. [Q13418-2]
CCDS60713.1. [Q13418-3]
CCDS7768.1. [Q13418-1]
PIRiS68455.
RefSeqiNP_001014794.1. NM_001014794.2. [Q13418-1]
NP_001014795.1. NM_001014795.2. [Q13418-1]
NP_001265370.1. NM_001278441.1. [Q13418-2]
NP_001265371.1. NM_001278442.1. [Q13418-3]
NP_004508.1. NM_004517.3. [Q13418-1]
XP_005252961.1. XM_005252904.4. [Q13418-1]
XP_005252962.1. XM_005252905.2. [Q13418-3]
XP_011518367.1. XM_011520065.1. [Q13418-1]
UniGeneiHs.706355.

Genome annotation databases

EnsembliENST00000299421; ENSP00000299421; ENSG00000166333. [Q13418-1]
ENST00000396751; ENSP00000379975; ENSG00000166333. [Q13418-1]
ENST00000420936; ENSP00000403487; ENSG00000166333. [Q13418-1]
ENST00000528995; ENSP00000435323; ENSG00000166333. [Q13418-2]
ENST00000532063; ENSP00000434492; ENSG00000166333. [Q13418-3]
GeneIDi3611.
KEGGihsa:3611.
UCSCiuc010rap.3. human. [Q13418-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U40282 mRNA. Translation: AAC16892.1.
AJ277481 mRNA. Translation: CAB94832.1. Sequence problems.
AF244139 Genomic DNA. Translation: AAF74449.1.
AJ404847 Genomic DNA. Translation: CAB99253.1.
AK293474 mRNA. Translation: BAH11516.1.
AK296628 mRNA. Translation: BAH12404.1.
CR407673 mRNA. Translation: CAG28601.1.
CR749220 mRNA. Translation: CAH18077.1.
AC091564 Genomic DNA. No translation available.
CH471064 Genomic DNA. Translation: EAW68688.1.
CH471064 Genomic DNA. Translation: EAW68689.1.
CH471064 Genomic DNA. Translation: EAW68690.1.
BC001554 mRNA. Translation: AAH01554.1.
CCDSiCCDS60712.1. [Q13418-2]
CCDS60713.1. [Q13418-3]
CCDS7768.1. [Q13418-1]
PIRiS68455.
RefSeqiNP_001014794.1. NM_001014794.2. [Q13418-1]
NP_001014795.1. NM_001014795.2. [Q13418-1]
NP_001265370.1. NM_001278441.1. [Q13418-2]
NP_001265371.1. NM_001278442.1. [Q13418-3]
NP_004508.1. NM_004517.3. [Q13418-1]
XP_005252961.1. XM_005252904.4. [Q13418-1]
XP_005252962.1. XM_005252905.2. [Q13418-3]
XP_011518367.1. XM_011520065.1. [Q13418-1]
UniGeneiHs.706355.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2KBXNMR-A1-171[»]
3F6QX-ray1.60A1-170[»]
3IXEX-ray1.90A1-174[»]
3KMUX-ray1.80A183-452[»]
3KMWX-ray2.00A183-452[»]
3REPX-ray1.80A183-452[»]
4HI8X-ray1.20A1-174[»]
4HI9X-ray1.20A1-174[»]
ProteinModelPortaliQ13418.
SMRiQ13418.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109824. 214 interactors.
DIPiDIP-38657N.
IntActiQ13418. 178 interactors.
MINTiMINT-1465247.
STRINGi9606.ENSP00000299421.

Chemistry databases

BindingDBiQ13418.
ChEMBLiCHEMBL5247.
GuidetoPHARMACOLOGYi2041.

PTM databases

iPTMnetiQ13418.
PhosphoSitePlusiQ13418.
SwissPalmiQ13418.

Polymorphism and mutation databases

DMDMi9973397.

2D gel databases

OGPiQ13418.

Proteomic databases

EPDiQ13418.
PaxDbiQ13418.
PeptideAtlasiQ13418.
PRIDEiQ13418.

Protocols and materials databases

DNASUi3611.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000299421; ENSP00000299421; ENSG00000166333. [Q13418-1]
ENST00000396751; ENSP00000379975; ENSG00000166333. [Q13418-1]
ENST00000420936; ENSP00000403487; ENSG00000166333. [Q13418-1]
ENST00000528995; ENSP00000435323; ENSG00000166333. [Q13418-2]
ENST00000532063; ENSP00000434492; ENSG00000166333. [Q13418-3]
GeneIDi3611.
KEGGihsa:3611.
UCSCiuc010rap.3. human. [Q13418-1]

Organism-specific databases

CTDi3611.
DisGeNETi3611.
GeneCardsiILK.
HGNCiHGNC:6040. ILK.
HPAiCAB004041.
HPA048437.
MIMi602366. gene.
neXtProtiNX_Q13418.
OpenTargetsiENSG00000166333.
PharmGKBiPA29855.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0195. Eukaryota.
COG0666. LUCA.
GeneTreeiENSGT00860000133794.
HOGENOMiHOG000047828.
HOVERGENiHBG002437.
InParanoidiQ13418.
KOiK06272.
PhylomeDBiQ13418.
TreeFamiTF315194.

Enzyme and pathway databases

BioCyciZFISH:HS09377-MONOMER.
BRENDAi2.7.10.2. 2681.
ReactomeiR-HSA-446343. Localization of the PINCH-ILK-PARVIN complex to focal adhesions.
R-HSA-446353. Cell-extracellular matrix interactions.
SignaLinkiQ13418.
SIGNORiQ13418.

Miscellaneous databases

ChiTaRSiILK. human.
EvolutionaryTraceiQ13418.
GeneWikiiIntegrin-linked_kinase.
GenomeRNAii3611.
PROiQ13418.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000166333.
CleanExiHS_ILK.
ExpressionAtlasiQ13418. baseline and differential.
GenevisibleiQ13418. HS.

Family and domain databases

Gene3Di1.25.40.20. 2 hits.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
[Graphical view]
PfamiPF12796. Ank_2. 2 hits.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
SMARTiSM00248. ANK. 3 hits.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 3 hits.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiILK_HUMAN
AccessioniPrimary (citable) accession number: Q13418
Secondary accession number(s): B7Z1I0
, B7Z418, D3DQU0, P57043, Q68DZ3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: August 1, 1998
Last modified: November 30, 2016
This is version 183 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.