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Protein

Integrin-linked protein kinase

Gene

Ilk

Organism
Mus musculus (Mouse)
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 (By similarity).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei220 – 2201ATPPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi199 – 2079ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. protein kinase binding Source: MGI
  3. protein serine/threonine kinase activity Source: MGI
  4. signal transducer activity Source: Ensembl

GO - Biological processi

  1. branching involved in ureteric bud morphogenesis Source: MGI
  2. cell aging Source: Ensembl
  3. cell cycle arrest Source: Ensembl
  4. cell projection organization Source: MGI
  5. establishment or maintenance of epithelial cell apical/basal polarity Source: MGI
  6. extracellular fibril organization Source: Ensembl
  7. fibroblast migration Source: MGI
  8. integrin-mediated signaling pathway Source: MGI
  9. myelin assembly Source: Ensembl
  10. myelination in peripheral nervous system Source: MGI
  11. negative regulation of cardiac muscle cell apoptotic process Source: Ensembl
  12. negative regulation of neural precursor cell proliferation Source: MGI
  13. negative regulation of neuron apoptotic process Source: Ensembl
  14. negative regulation of protein kinase activity Source: Ensembl
  15. negative regulation of smooth muscle cell migration Source: Ensembl
  16. negative regulation of smooth muscle cell proliferation Source: Ensembl
  17. nerve development Source: MGI
  18. neuron projection morphogenesis Source: Ensembl
  19. peptidyl-serine phosphorylation Source: MGI
  20. platelet aggregation Source: MGI
  21. positive regulation of axon extension Source: Ensembl
  22. positive regulation of BMP signaling pathway Source: BHF-UCL
  23. positive regulation of canonical Wnt signaling pathway Source: MGI
  24. positive regulation of cell-matrix adhesion Source: Ensembl
  25. positive regulation of cell migration Source: Ensembl
  26. positive regulation of cell proliferation Source: MGI
  27. positive regulation of dendrite morphogenesis Source: Ensembl
  28. positive regulation of MAP kinase activity Source: Ensembl
  29. positive regulation of myoblast differentiation Source: Ensembl
  30. positive regulation of osteoblast differentiation Source: BHF-UCL
  31. positive regulation of phosphorylation Source: MGI
  32. positive regulation of protein kinase B signaling Source: Ensembl
  33. positive regulation of transcription, DNA-templated Source: MGI
  34. protein heterooligomerization Source: Ensembl
  35. protein kinase B signaling Source: MGI
  36. protein phosphorylation Source: MGI
  37. regulation of actin cytoskeleton organization Source: Ensembl
  38. Schwann cell development Source: MGI
  39. substrate adhesion-dependent cell spreading Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.2. 3474.
ReactomeiREACT_242946. Localization of the PINCH-ILK-PARVIN complex to focal adhesions.

Names & Taxonomyi

Protein namesi
Recommended name:
Integrin-linked protein kinase (EC:2.7.11.1)
Gene namesi
Name:Ilk
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 7

Organism-specific databases

MGIiMGI:1195267. Ilk.

Subcellular locationi

GO - Cellular componenti

  1. cell-cell junction Source: Ensembl
  2. cell junction Source: MGI
  3. costamere Source: Ensembl
  4. cytoplasm Source: MGI
  5. dendritic shaft Source: Ensembl
  6. focal adhesion Source: MGI
  7. lamellipodium Source: UniProtKB
  8. membrane Source: MGI
  9. neuronal cell body Source: Ensembl
  10. nucleoplasm Source: MGI
  11. plasma membrane Source: UniProtKB-SubCell
  12. protein complex Source: Ensembl
  13. sarcomere Source: UniProtKB-SubCell
  14. stress fiber Source: Ensembl
  15. terminal bouton Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 452452Integrin-linked protein kinasePRO_0000086022Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineBy similarity
Modified residuei186 – 1861PhosphoserineBy similarity
Modified residuei426 – 4261N6-acetyllysine1 Publication

Post-translational modificationi

Autophosphorylated on serine residues.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiO55222.
PaxDbiO55222.
PRIDEiO55222.

PTM databases

PhosphoSiteiO55222.

Expressioni

Tissue specificityi

Highly expressed in lung, heart, kidney, liver, brain, spleen and skeletal muscle. Weakly expressed in testis.

Gene expression databases

BgeeiO55222.
CleanExiMM_ILK.
ExpressionAtlasiO55222. baseline and differential.
GenevestigatoriO55222.

Interactioni

Subunit structurei

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. Interacts (via ANK repeats) with EPHA1 (via SAM domain); stimulated by EFNA1 but independent of the kinase activity of EPHA1 (By similarity). Interacts with TGFB1I1. Interacts with FERMT2.By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
LIMS1P480593EBI-6690138,EBI-306928From a different organism.
ParvaQ9EPC14EBI-6690138,EBI-6690233
ParvbQ9ES462EBI-6690138,EBI-6914996
Stub1Q9WUD17EBI-6690138,EBI-773027

Protein-protein interaction databases

BioGridi200649. 6 interactions.
DIPiDIP-41971N.
IntActiO55222. 44 interactions.
MINTiMINT-150552.
STRINGi10090.ENSMUSP00000033182.

Structurei

3D structure databases

ProteinModelPortaliO55222.
SMRiO55222. Positions 2-171, 185-452.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati2 – 3029ANK 1Add
BLAST
Repeati31 – 6333ANK 2Add
BLAST
Repeati64 – 9633ANK 3Add
BLAST
Repeati97 – 12933ANK 4Add
BLAST
Repeati130 – 17445ANK 5Add
BLAST
Domaini193 – 446254Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni33 – 139107Interaction with LIMS1By similarityAdd
BLAST
Regioni180 – 21233PH-like; mediates interaction with TGFB1I1Add
BLAST

Domaini

A PH-like domain is involved in phosphatidylinositol phosphate binding.By similarity

Sequence similaritiesi

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

Keywords - Domaini

ANK repeat, Repeat

Phylogenomic databases

eggNOGiCOG0666.
GeneTreeiENSGT00780000121938.
HOGENOMiHOG000047828.
HOVERGENiHBG002437.
InParanoidiO55222.
KOiK06272.
OMAiARINENQ.
OrthoDBiEOG7T1RB0.
PhylomeDBiO55222.
TreeFamiTF315194.

Family and domain databases

Gene3Di1.25.40.20. 2 hits.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR016253. Integrin-linked_kinase.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
[Graphical view]
PfamiPF00023. Ank. 3 hits.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFiPIRSF000654. Integrin-linked_kinase. 1 hit.
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]

Sequencei

Sequence statusi: Complete.

O55222-1 [UniParc]FASTAAdd to basket

« 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 KQLNFLAKLN
210 220 230 240 250
ENHSGELWKG RWQGNDIVVK VLKVRDWSTR KSRDFNEECP RLRIFSHPNV
260 270 280 290 300
LPVLGACQAP 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):51,373
Last modified:October 31, 2006 - v2
Checksum:iF41960CF8EC503A7
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti93 – 931I → T in AAB94646 (PubMed:9366252).Curated
Sequence conflicti413 – 4131I → V in AAB94646 (PubMed:9366252).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U94479 mRNA. Translation: AAB94646.1.
BC003737 mRNA. Translation: AAH03737.1.
CCDSiCCDS21659.1.
RefSeqiNP_001155196.1. NM_001161724.1.
NP_034692.2. NM_010562.2.
UniGeneiMm.274846.

Genome annotation databases

EnsembliENSMUST00000033182; ENSMUSP00000033182; ENSMUSG00000030890.
ENSMUST00000163389; ENSMUSP00000130341; ENSMUSG00000030890.
GeneIDi16202.
KEGGimmu:16202.
UCSCiuc009izb.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U94479 mRNA. Translation: AAB94646.1.
BC003737 mRNA. Translation: AAH03737.1.
CCDSiCCDS21659.1.
RefSeqiNP_001155196.1. NM_001161724.1.
NP_034692.2. NM_010562.2.
UniGeneiMm.274846.

3D structure databases

ProteinModelPortaliO55222.
SMRiO55222. Positions 2-171, 185-452.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200649. 6 interactions.
DIPiDIP-41971N.
IntActiO55222. 44 interactions.
MINTiMINT-150552.
STRINGi10090.ENSMUSP00000033182.

PTM databases

PhosphoSiteiO55222.

Proteomic databases

MaxQBiO55222.
PaxDbiO55222.
PRIDEiO55222.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000033182; ENSMUSP00000033182; ENSMUSG00000030890.
ENSMUST00000163389; ENSMUSP00000130341; ENSMUSG00000030890.
GeneIDi16202.
KEGGimmu:16202.
UCSCiuc009izb.2. mouse.

Organism-specific databases

CTDi3611.
MGIiMGI:1195267. Ilk.

Phylogenomic databases

eggNOGiCOG0666.
GeneTreeiENSGT00780000121938.
HOGENOMiHOG000047828.
HOVERGENiHBG002437.
InParanoidiO55222.
KOiK06272.
OMAiARINENQ.
OrthoDBiEOG7T1RB0.
PhylomeDBiO55222.
TreeFamiTF315194.

Enzyme and pathway databases

BRENDAi2.7.10.2. 3474.
ReactomeiREACT_242946. Localization of the PINCH-ILK-PARVIN complex to focal adhesions.

Miscellaneous databases

NextBioi289147.
PROiO55222.
SOURCEiSearch...

Gene expression databases

BgeeiO55222.
CleanExiMM_ILK.
ExpressionAtlasiO55222. baseline and differential.
GenevestigatoriO55222.

Family and domain databases

Gene3Di1.25.40.20. 2 hits.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR016253. Integrin-linked_kinase.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
[Graphical view]
PfamiPF00023. Ank. 3 hits.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFiPIRSF000654. Integrin-linked_kinase. 1 hit.
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...

Publicationsi

« Hide 'large scale' publications
  1. "Identification and characterization of a mouse protein kinase that is highly homologous to human integrin-linked kinase."
    Li F., Liu J., Mayne R., Wu C.
    Biochim. Biophys. Acta 1358:215-220(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: BALB/c.
    Tissue: Heart.
  2. "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].
    Strain: FVB/N.
    Tissue: Mammary tumor.
  3. "Oligomerizing potential of a focal adhesion LIM protein Hic-5 organizing a nuclear-cytoplasmic shuttling complex."
    Mori K., Asakawa M., Hayashi M., Imura M., Ohki T., Hirao E., Kim-Kaneyama J.-R., Nose K., Shibanuma M.
    J. Biol. Chem. 281:22048-22061(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TGFB1I1.
  4. Cited for: SUBCELLULAR LOCATION.
  5. "Kindlin-2 controls bidirectional signaling of integrins."
    Montanez E., Ussar S., Schifferer M., Bosl M., Zent R., Moser M., Fassler R.
    Genes Dev. 22:1325-1330(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, INTERACTION WITH FERMT2.
  6. "SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
    Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
    Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-426, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Embryonic fibroblast.

Entry informationi

Entry nameiILK_MOUSE
AccessioniPrimary (citable) accession number: O55222
Secondary accession number(s): Q78KK2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: October 31, 2006
Last modified: March 4, 2015
This is version 144 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.