Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Tek. (This text reflects annotations as of Wednesday, January 23, 2013.)

---

Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] The TEK receptor tyrosine kinase is expressed almost exclusively in endothelial cells in mice, rats, and humans. This receptor possesses a unique extracellular domain containing 2 immunoglobulin-like loops separated by 3 epidermal growth factor-like repeats that are connected to 3 fibronectin type III-like repeats. The ligand for the receptor is angiopoietin-1. Defects in TEK are associated with inherited venous malformations; the TEK signaling pathway appears to be critical for endothelial cell-smooth muscle cell communication in venous morphogenesis. TEK is closely related to the TIE receptor tyrosine kinase. [provided by RefSeq, Jul 2008]

---

Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Tek
  • participates in the following biological processes:
    • peptidyl-tyrosine phosphorylation ^[4]
    • response to retinoic acid ^[10]
  • performs the following molecular functions:
    • protein tyrosine kinase activity ^[4]
• The gene product of Tek has been shown to bind to the gene products of Angpt2, Ptprb. ^{[5, 7]} Researchers have inferred, based on physical interactions, that the gene product of Tek
  • performs the following molecular functions:
    • receptor activity ^[3]
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Tek
  • participates in the following biological processes:
    • angiogenesis ^{[9, 11]}
    • cell-cell adhesion ^[8]
    • cell-matrix adhesion ^[8]
    • endothelial cell proliferation ^[4]
    • heart development ^[4]
    • heart trabecula formation ^[4]
    • hemopoiesis ^{[1, 11]}
    • negative regulation of endothelial cell apoptotic process ^[6]
    • positive regulation of cell adhesion ^[1]
    • regulation of angiogenesis ^[8]
    • regulation of cell migration ^[8]
    • vasculogenesis ^[4]
• Researchers have inferred, based on genetic interactions, that the gene product of Tek
  • participates in the following biological processes:
    • negative regulation of apoptotic process based on interactions with Angpt1 ^[2]
    • positive regulation of peptidyl-serine phosphorylation based on interactions with Angpt1 ^[2]

---

Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Tek:
  • participates in the following biological processes:
    • intracellular signal transduction
    • negative regulation of angiogenesis
    • peptidyl-tyrosine phosphorylation
    • positive regulation of actin cytoskeleton reorganization
    • positive regulation of angiogenesis
    • positive regulation of endothelial cell migration
    • positive regulation of ERK1 and ERK2 cascade
    • positive regulation of focal adhesion assembly
    • positive regulation of intracellular protein kinase cascade
    • positive regulation of phosphatidylinositol 3-kinase activity
    • positive regulation of phosphatidylinositol 3-kinase cascade
    • positive regulation of protein kinase B signaling cascade
    • positive regulation of protein phosphorylation
    • protein autophosphorylation
    • protein oligomerization
    • regulation of establishment or maintenance of cell polarity
    • response to estrogen stimulus
    • sprouting angiogenesis
    • substrate adhesion-dependent cell spreading
    • Tie receptor signaling pathway
    • transmembrane receptor protein tyrosine kinase signaling pathway
  • performs the following molecular functions:
    • growth factor binding
    • protein tyrosine kinase activity
  • is located in the following cellular components:
    • apical plasma membrane
    • basal plasma membrane
    • basolateral plasma membrane
    • cell surface
    • cell-cell junction
    • integral to membrane
    • integral to plasma membrane
    • intracellular
    • membrane raft
    • microvillus

---

Summary text based on GO annotations supported by structural data

• Tek encodes a protein or proteins that contain the following InterPro domains: EGF-like, conserved site, EGF-like, laminin, Epidermal growth factor-like domain, Fibronectin, type III, Immunoglobulin-like, Immunoglobulin-like fold, Protein kinase, ATP binding site, Protein kinase, catalytic domain, Protein kinase-like domain, Serine-threonine/tyrosine-protein kinase catalytic domain, Tyrosine-protein kinase, active site, Tyrosine-protein kinase, catalytic domain, Tyrosine-protein kinase, receptor Tie-2, Ig-like domain 1, N-terminal, indicating that the gene product:
  • participates in the following biological processes:
    • protein phosphorylation
  • performs the following molecular functions:
    • ATP binding
    • protein kinase activity
    • transferase activity, transferring phosphorus-containing groups
    • transmembrane receptor protein tyrosine kinase activity

---

Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Tek indicates that it:
  • participates in the following biological processes:
    • phosphorylation
  • performs the following molecular functions:
    • ATP binding
    • kinase activity
    • nucleotide binding
    • transferase activity
  • is located in the following cellular components:
    • cell junction
    • cytoplasm
    • cytoskeleton
    • extracellular region
    • membrane
    • plasma membrane
• Tek has been associated with the Enzyme Commission numbers: 2.7.10.1, which implies that the gene product:
  • performs the following molecular functions:
    • transmembrane receptor protein tyrosine kinase activity

---

References

1. Arai F et al. (2004) Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell, 118:149-61. (PubMed:15260986)
2. Bai Y et al. (2009) An Ang1-Tie2-PI3K axis in neural progenitor cells initiates survival responses against oxygen and glucose deprivation. Neuroscience, 160:371-81. (PubMed:19409199)
3. Davis S et al. (1996) Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning [see comments] Cell, 87:1161-9. (PubMed:8980223)
4. Dumont DJ et al. (1994) Dominant-negative and targeted null mutations in the endothelial receptor tyrosine kinase, tek, reveal a critical role in vasculogenesis of the embryo. Genes Dev, 8:1897-909. (PubMed:7958865)
5. Fachinger G et al. (1999) Functional interaction of vascular endothelial-protein-tyrosine phosphatase with the angiopoietin receptor Tie-2. Oncogene, 18:5948-53. (PubMed:10557082)
6. Jones N et al. (2001) Rescue of the early vascular defects in Tek/Tie2 null mice reveals an essential survival function. EMBO Rep, 2:438-45. (PubMed:11375937)
7. Maisonpierre PC et al. (1997) Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis [see comments] Science, 277:55-60. (PubMed:9204896)
8. Patan S. (1998) TIE1 and TIE2 receptor tyrosine kinases inversely regulate embryonic angiogenesis by the mechanism of intussusceptive microvascular growth. Microvasc Res, 56:1-21. (PubMed:9683559)
9. Sato TN et al. (1995) Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation. Nature, 376:70-4. (PubMed:7596437)
10. Su D et al. (2008) Retinoic acid receptor gamma activates receptor tyrosine kinase Tie1 gene transcription through transcription factor GATA4 in F9 stem cells. Exp Hematol, 36:624-41. (PubMed:18439490)
11. Takakura N et al. (1998) Critical role of the TIE2 endothelial cell receptor in the development of definitive hematopoiesis. Immunity, 9:677-86. (PubMed:9846489)

---

---

Gene Ontology Evidence Code Abbreviations:

EXP Inferred from experiment

IC Inferred by curator

IDA Inferred from direct assay

IEA Inferred from electronic annotation

IGI Inferred from genetic interaction

IMP Inferred from mutant phenotype

IPI Inferred from physical interaction

ISS Inferred from sequence or structural similarity

ISO Inferred from sequence orthology

ISA Inferred from sequence alignment

ISM Inferred from sequence model

NAS Non-traceable author statement

ND No biological data available

RCA Reviewed computational analysis

TAS Traceable author statement

---