Angiopoietin-1

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functionⁱ

Miscellaneous

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functionⁱ

• receptor tyrosine kinase binding Source: UniProtKB <p>Inferred from Physical Interaction</p> <p>Covers physical interactions between the gene product of interest and another molecule (or ion, or complex).</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ipi">GO evidence code guide</a></p> Inferred from physical interactionⁱ
  • "Effects of angiopoietins-1 and -2 on the receptor tyrosine kinase Tie2 are differentially regulated at the endothelial cell surface."
    Hansen T.M., Singh H., Tahir T.A., Brindle N.P.
    Cell. Signal. 22:527-532(2010) [PubMed] [Europe PMC] [Abstract]
  • Ref.1

    "Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning."
    Davis S., Aldrich T.H., Jones P.F., Acheson A., Compton D.L., Jain V., Ryan T.E., Bruno J., Radziejewski C., Maisonpierre P.C., Yancopoulos G.D.
    Cell 87:1161-1169(1996) [PubMed] [Europe PMC] [Abstract]

    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).

GO - Biological processⁱ

• activation of transmembrane receptor protein tyrosine kinase activity Source: UniProtKB <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ
  • "Oligomerized Tie2 localizes to clathrin-coated pits in response to angiopoietin-1."
    Bogdanovic E., Coombs N., Dumont D.J.
    Histochem. Cell Biol. 132:225-237(2009) [PubMed] [Europe PMC] [Abstract]
• cell differentiation Source: UniProtKB-KW
• cell-substrate adhesion Source: Ensembl
• glomerulus vasculature development Source: UniProtKB
• hemopoiesis Source: Ensembl
• heparin biosynthetic process Source: UniProtKBInferred from direct assayⁱ
  • "Angiopoietin-1 alters microvascular permeability coefficients in vivo via modification of endothelial glycocalyx."
    Salmon A.H., Neal C.R., Sage L.M., Glass C.A., Harper S.J., Bates D.O.
    Cardiovasc. Res. 83:24-33(2009) [PubMed] [Europe PMC] [Abstract]
• in utero embryonic development Source: Ensembl
• leukocyte migration Source: Reactome
• MAPK cascade Source: Reactome
• negative regulation of apoptotic process Source: UniProtKBInferred from direct assayⁱ
  • "Angiopoietin-1 is an apoptosis survival factor for endothelial cells."
    Kwak H.J., So J.N., Lee S.J., Kim I., Koh G.Y.
    FEBS Lett. 448:249-253(1999) [PubMed] [Europe PMC] [Abstract]
  • "Hypoxia-inducible factor-1 mediates activation of cultured vascular endothelial cells by inducing multiple angiogenic factors."
    Yamakawa M., Liu L.X., Date T., Belanger A.J., Vincent K.A., Akita G.Y., Kuriyama T., Cheng S.H., Gregory R.J., Jiang C.
    Circ. Res. 93:664-673(2003) [PubMed] [Europe PMC] [Abstract]
• negative regulation of cell adhesion Source: UniProtKBInferred from direct assayⁱ
  • "Critical role for GATA3 in mediating Tie2 expression and function in large vessel endothelial cells."
    Song H., Suehiro J., Kanki Y., Kawai Y., Inoue K., Daida H., Yano K., Ohhashi T., Oettgen P., Aird W.C., Kodama T., Minami T.
    J. Biol. Chem. 284:29109-29124(2009) [PubMed] [Europe PMC] [Abstract]
• negative regulation of cytokine secretion involved in immune response Source: Ensembl
• negative regulation of endothelial cell apoptotic process Source: UniProtKBInferred from direct assayⁱ
  • "Critical role for GATA3 in mediating Tie2 expression and function in large vessel endothelial cells."
    Song H., Suehiro J., Kanki Y., Kawai Y., Inoue K., Daida H., Yano K., Ohhashi T., Oettgen P., Aird W.C., Kodama T., Minami T.
    J. Biol. Chem. 284:29109-29124(2009) [PubMed] [Europe PMC] [Abstract]
• negative regulation of neuron apoptotic process Source: Ensembl
• negative regulation of protein import into nucleus Source: Ensembl
• negative regulation of protein phosphorylation Source: Ensembl
• negative regulation of vascular permeability Source: UniProtKBInferred from direct assayⁱ
  • "Angiopoietin 1 and vascular endothelial growth factor modulate human glomerular endothelial cell barrier properties."
    Satchell S.C., Anderson K.L., Mathieson P.W.
    J. Am. Soc. Nephrol. 15:566-574(2004) [PubMed] [Europe PMC] [Abstract]
  • "Angiopoietin-1 alters microvascular permeability coefficients in vivo via modification of endothelial glycocalyx."
    Salmon A.H., Neal C.R., Sage L.M., Glass C.A., Harper S.J., Bates D.O.
    Cardiovasc. Res. 83:24-33(2009) [PubMed] [Europe PMC] [Abstract]
• positive chemotaxis Source: UniProtKBInferred from direct assayⁱ
  • "Chemotactic properties of angiopoietin-1 and -2, ligands for the endothelial-specific receptor tyrosine kinase Tie2."
    Witzenbichler B., Maisonpierre P.C., Jones P., Yancopoulos G.D., Isner J.M.
    J. Biol. Chem. 273:18514-18521(1998) [PubMed] [Europe PMC] [Abstract]
• positive regulation of blood vessel endothelial cell migration Source: UniProtKBInferred from direct assayⁱ
  • "Chemotactic properties of angiopoietin-1 and -2, ligands for the endothelial-specific receptor tyrosine kinase Tie2."
    Witzenbichler B., Maisonpierre P.C., Jones P., Yancopoulos G.D., Isner J.M.
    J. Biol. Chem. 273:18514-18521(1998) [PubMed] [Europe PMC] [Abstract]
• positive regulation of cell adhesion Source: Ensembl
• positive regulation of endothelial cell migration Source: UniProtKBInferred from direct assayⁱ
  • "Hypoxia-inducible factor-1 mediates activation of cultured vascular endothelial cells by inducing multiple angiogenic factors."
    Yamakawa M., Liu L.X., Date T., Belanger A.J., Vincent K.A., Akita G.Y., Kuriyama T., Cheng S.H., Gregory R.J., Jiang C.
    Circ. Res. 93:664-673(2003) [PubMed] [Europe PMC] [Abstract]
• positive regulation of ERK1 and ERK2 cascade Source: UniProtKBInferred from direct assayⁱ
  • Ref.13

    "Differential function of Tie2 at cell-cell contacts and cell-substratum contacts regulated by angiopoietin-1."
    Fukuhara S., Sako K., Minami T., Noda K., Kim H.Z., Kodama T., Shibuya M., Takakura N., Koh G.Y., Mochizuki N.
    Nat. Cell Biol. 10:513-526(2008) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION IN REGULATION OF ENDOTHELIAL CELL MIGRATION AND CELL SPREADING.
  • "Lipid rafts serve as signaling platforms for Tie2 receptor tyrosine kinase in vascular endothelial cells."
    Katoh S.Y., Kamimoto T., Yamakawa D., Takakura N.
    Exp. Cell Res. 315:2818-2823(2009) [PubMed] [Europe PMC] [Abstract]
• positive regulation of peptidyl-serine phosphorylation Source: Ensembl
• positive regulation of peptidyl-tyrosine phosphorylation Source: UniProtKBInferred from direct assayⁱ
  • "Multiple angiopoietin recombinant proteins activate the Tie1 receptor tyrosine kinase and promote its interaction with Tie2."
    Saharinen P., Kerkela K., Ekman N., Marron M., Brindle N., Lee G.M., Augustin H., Koh G.Y., Alitalo K.
    J. Cell Biol. 169:239-243(2005) [PubMed] [Europe PMC] [Abstract]
  • "Angiopoietin-1-induced ubiquitylation of Tie2 by c-Cbl is required for internalization and degradation."
    Wehrle C., Van Slyke P., Dumont D.J.
    Biochem. J. 423:375-380(2009) [PubMed] [Europe PMC] [Abstract]
• positive regulation of phosphatidylinositol 3-kinase signaling Source: Ensembl
• positive regulation of protein kinase B signaling Source: UniProtKBInferred from direct assayⁱ
  • Ref.13

    "Differential function of Tie2 at cell-cell contacts and cell-substratum contacts regulated by angiopoietin-1."
    Fukuhara S., Sako K., Minami T., Noda K., Kim H.Z., Kodama T., Shibuya M., Takakura N., Koh G.Y., Mochizuki N.
    Nat. Cell Biol. 10:513-526(2008) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION IN REGULATION OF ENDOTHELIAL CELL MIGRATION AND CELL SPREADING.
  • "Lipid rafts serve as signaling platforms for Tie2 receptor tyrosine kinase in vascular endothelial cells."
    Katoh S.Y., Kamimoto T., Yamakawa D., Takakura N.
    Exp. Cell Res. 315:2818-2823(2009) [PubMed] [Europe PMC] [Abstract]
• positive regulation of protein ubiquitination Source: UniProtKBInferred from direct assayⁱ
  • "Angiopoietin-1-induced ubiquitylation of Tie2 by c-Cbl is required for internalization and degradation."
    Wehrle C., Van Slyke P., Dumont D.J.
    Biochem. J. 423:375-380(2009) [PubMed] [Europe PMC] [Abstract]
• positive regulation of receptor internalization Source: UniProtKBInferred from direct assayⁱ
  • "Oligomerized Tie2 localizes to clathrin-coated pits in response to angiopoietin-1."
    Bogdanovic E., Coombs N., Dumont D.J.
    Histochem. Cell Biol. 132:225-237(2009) [PubMed] [Europe PMC] [Abstract]
• protein localization to cell surface Source: UniProtKBInferred from direct assayⁱ
  • "Lipid rafts serve as signaling platforms for Tie2 receptor tyrosine kinase in vascular endothelial cells."
    Katoh S.Y., Kamimoto T., Yamakawa D., Takakura N.
    Exp. Cell Res. 315:2818-2823(2009) [PubMed] [Europe PMC] [Abstract]
• regulation of I-kappaB kinase/NF-kappaB signaling Source: Ensembl
• regulation of macrophage migration inhibitory factor signaling pathway Source: Ensembl
• regulation of protein binding Source: Ensembl
• regulation of skeletal muscle satellite cell proliferation Source: UniProtKBInferred from direct assayⁱ
  • "Autocrine and paracrine angiopoietin 1/Tie-2 signaling promotes muscle satellite cell self-renewal."
    Abou-Khalil R., Le Grand F., Pallafacchina G., Valable S., Authier F.J., Rudnicki M.A., Gherardi R.K., Germain S., Chretien F., Sotiropoulos A., Lafuste P., Montarras D., Chazaud B.
    Cell Stem Cell 5:298-309(2009) [PubMed] [Europe PMC] [Abstract]
• regulation of tumor necrosis factor production Source: Ensembl
• sprouting angiogenesis Source: UniProtKBInferred from direct assayⁱ
  • "Angiopoietin-1 is an apoptosis survival factor for endothelial cells."
    Kwak H.J., So J.N., Lee S.J., Kim I., Koh G.Y.
    FEBS Lett. 448:249-253(1999) [PubMed] [Europe PMC] [Abstract]
  • "Angiopoietin-1 induces sprouting angiogenesis in vitro."
    Koblizek T.I., Weiss C., Yancopoulos G.D., Deutsch U., Risau W.
    Curr. Biol. 8:529-532(1998) [PubMed] [Europe PMC] [Abstract]
• Tie signaling pathway Source: UniProtKBInferred from direct assayⁱ
  • "Angiopoietin-1-induced ubiquitylation of Tie2 by c-Cbl is required for internalization and degradation."
    Wehrle C., Van Slyke P., Dumont D.J.
    Biochem. J. 423:375-380(2009) [PubMed] [Europe PMC] [Abstract]
  • "Effects of angiopoietins-1 and -2 on the receptor tyrosine kinase Tie2 are differentially regulated at the endothelial cell surface."
    Hansen T.M., Singh H., Tahir T.A., Brindle N.P.
    Cell. Signal. 22:527-532(2010) [PubMed] [Europe PMC] [Abstract]

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsⁱ

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyⁱ

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationⁱ

Keywords - Cellular componentⁱ

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechⁱ

Organism-specific databases

Chemistry databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingⁱ

Molecule processing

Amino acid modifications

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationⁱ

Keywords - PTMⁱ

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressionⁱ

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactionⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structureⁱ

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsⁱ

GO - Molecular functionⁱ

• receptor tyrosine kinase binding Source: UniProtKBInferred from physical interactionⁱ
  • "Effects of angiopoietins-1 and -2 on the receptor tyrosine kinase Tie2 are differentially regulated at the endothelial cell surface."
    Hansen T.M., Singh H., Tahir T.A., Brindle N.P.
    Cell. Signal. 22:527-532(2010) [PubMed] [Europe PMC] [Abstract]
  • Ref.1

    "Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning."
    Davis S., Aldrich T.H., Jones P.F., Acheson A., Compton D.L., Jain V., Ryan T.E., Bruno J., Radziejewski C., Maisonpierre P.C., Yancopoulos G.D.
    Cell 87:1161-1169(1996) [PubMed] [Europe PMC] [Abstract]

    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structureⁱ

Secondary structure

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsⁱ

Domains and Repeats

Coiled coil

Keywords - Domainⁱ

Phylogenomic databases

Family and domain databases

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2+)ⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusⁱ: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingⁱ: The displayed sequence is further processed into a mature form.

This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

        10         20         30         40         50
MTVFLSFAFL AAILTHIGCS NQRRSPENSG RRYNRIQHGQ CAYTFILPEH 
        60         70         80         90        100
DGNCRESTTD QYNTNALQRD APHVEPDFSS QKLQHLEHVM ENYTQWLQKL 
       110        120        130        140        150
ENYIVENMKS EMAQIQQNAV QNHTATMLEI GTSLLSQTAE QTRKLTDVET 
       160        170        180        190        200
QVLNQTSRLE IQLLENSLST YKLEKQLLQQ TNEILKIHEK NSLLEHKILE 
       210        220        230        240        250
MEGKHKEELD TLKEEKENLQ GLVTRQTYII QELEKQLNRA TTNNSVLQKQ 
       260        270        280        290        300
QLELMDTVHN LVNLCTKEGV LLKGGKREEE KPFRDCADVY QAGFNKSGIY 
       310        320        330        340        350
TIYINNMPEP KKVFCNMDVN GGGWTVIQHR EDGSLDFQRG WKEYKMGFGN 
       360        370        380        390        400
PSGEYWLGNE FIFAITSQRQ YMLRIELMDW EGNRAYSQYD RFHIGNEKQN 
       410        420        430        440        450
YRLYLKGHTG TAGKQSSLIL HGADFSTKDA DNDNCMCKCA LMLTGGWWFD 
       460        470        480        490 
ACGPSNLNGM FYTAGQNHGK LNGIKWHYFK GPSYSLRSTT MMIRPLDF   

        10         20         30         40         50
MTVFLSFAFL AAILTHIGCS NQRRSPENSG RRYNRIQHGQ CAYTFILPEH 
        60         70         80         90        100
DGNCRESTTD QYNTNALQRD APHVEPDFSS QKLQHLEHVM ENYTQWLQKL 
       110        120        130        140        150
ENYIVENMKS EMAQIQQNAV QNHTATMLEI GTSLLSQTAE QTRKLTDVET 
       160        170        180        190        200
QVLNQTSRLE IQLLENSLST YKLEKQLLQQ TNEILKIHEK NSLLEHKILE 
       210        220        230        240        250
MEGKHKEELD TLKEEKENLQ GLVTRQTYII QELEKQLNRA TTNNSVLQKQ 
       260        270        280        290        300
QLELMDTVHN LVNLCTKEVL LKGGKREEEK PFRDCADVYQ AGFNKSGIYT 
       310        320        330        340        350
IYINNMPEPK KVFCNMDVNG GGWTVIQHRE DGSLDFQRGW KEYKMGFGNP 
       360        370        380        390        400
SGEYWLGNEF IFAITSQRQY MLRIELMDWE GNRAYSQYDR FHIGNEKQNY 
       410        420        430        440        450
RLYLKGHTGT AGKQSSLILH GADFSTKDAD NDNCMCKCAL MLTGGWWFDA 
       460        470        480        490 
CGPSNLNGMF YTAGQNHGKL NGIKWHYFKG PSYSLRSTTM MIRPLDF    

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautionⁱ

Natural variant

Alternative sequence

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityⁱ

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsⁱ

• 100% Identity
• 90% Identity
• 50% Identity

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesⁱ

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesⁱ

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationⁱ

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousⁱ

Keywords - Technical termⁱ

Documents

1. PDB cross-references
   Index of Protein Data Bank (PDB) cross-references
2. Human chromosome 8
   Human chromosome 8: entries, gene names and cross-references to MIM
3. Human entries with polymorphisms or disease mutations
   List of human entries with polymorphisms or disease mutations
4. Human polymorphisms and disease mutations
   Index of human polymorphisms and disease mutations
5. MIM cross-references
   Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot