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O15123 (ANGP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Angiopoietin-2

Short name=ANG-2
Gene names
Name:ANGPT2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length496 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Binds to TEK/TIE2, competing for the ANGPT1 binding site, and modulating ANGPT1 signaling. Can induce tyrosine phosphorylation of TEK/TIE2 in the absence of ANGPT1. In the absence of angiogenic inducers, such as VEGF, ANGPT2-mediated loosening of cell-matrix contacts may induce endothelial cell apoptosis with consequent vascular regression. In concert with VEGF, it may facilitate endothelial cell migration and proliferation, thus serving as a permissive angiogenic signal. Ref.1 Ref.9 Ref.10 Ref.11

Subunit structure

Interacts with TEK/TIE2, competing for the same binding site as ANGPT1. Ref.1 Ref.8 Ref.9 Ref.11

Subcellular location

Secreted.

Domain

The Fibrinogen C-terminal domain mediates interaction with the TEK/TIE2 receptor.

Sequence similarities

Contains 1 fibrinogen C-terminal domain.

Ontologies

Keywords
   Biological processAngiogenesis
Differentiation
   Cellular componentSecreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainCoiled coil
Signal
   LigandCalcium
Metal-binding
   Molecular functionDevelopmental protein
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processTie signaling pathway

Inferred from direct assay PubMed 19922791. Source: UniProtKB

angiogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

blood coagulation

Traceable author statement. Source: Reactome

cellular response to growth factor stimulus

Inferred from electronic annotation. Source: Ensembl

germ cell development

Inferred from electronic annotation. Source: Ensembl

glomerulus vasculature development

Inferred from sequence or structural similarity. Source: UniProtKB

leukocyte migration

Traceable author statement. Source: Reactome

maternal process involved in female pregnancy

Inferred from electronic annotation. Source: Ensembl

negative regulation of angiogenesis

Inferred from electronic annotation. Source: Ensembl

negative regulation of blood vessel endothelial cell migration

Inferred from direct assay PubMed 9660821. Source: UniProtKB

negative regulation of cell-substrate adhesion

Inferred from electronic annotation. Source: Ensembl

negative regulation of positive chemotaxis

Inferred from direct assay PubMed 9660821. Source: UniProtKB

organ regeneration

Inferred from electronic annotation. Source: Ensembl

positive regulation of angiogenesis

Inferred from electronic annotation. Source: Ensembl

response to activity

Inferred from electronic annotation. Source: Ensembl

response to glucose

Inferred from electronic annotation. Source: Ensembl

response to hypoxia

Inferred from electronic annotation. Source: Ensembl

response to mechanical stimulus

Inferred from electronic annotation. Source: Ensembl

response to organic cyclic compound

Inferred from electronic annotation. Source: Ensembl

response to radiation

Inferred from electronic annotation. Source: Ensembl

signal transduction

Traceable author statement Ref.3. Source: ProtInc

   Cellular_componentcell projection

Inferred from electronic annotation. Source: Ensembl

extracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from direct assay PubMed 9660821. Source: UniProtKB

nucleus

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionmetal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction PubMed 20708158. Source: IntAct

receptor binding

Traceable author statement Ref.3Ref.1. Source: ProtInc

receptor tyrosine kinase binding

Inferred from physical interaction PubMed 19922791. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

TEKQ027634EBI-2912111,EBI-2257090

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O15123-1)

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.
Isoform 3 (identifier: O15123-2)

The sequence of this isoform differs from the canonical sequence as follows:
     97-148: Missing.
Isoform 2 (identifier: O15123-3)

The sequence of this isoform differs from the canonical sequence as follows:
     268-268: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Potential
Chain19 – 496478Angiopoietin-2
PRO_0000009113

Regions

Domain275 – 495221Fibrinogen C-terminal
Coiled coil166 – 24883 Potential

Sites

Metal binding4291Calcium
Metal binding4311Calcium
Metal binding4331Calcium; via carbonyl oxygen
Metal binding4351Calcium; via carbonyl oxygen

Amino acid modifications

Glycosylation891N-linked (GlcNAc...) Potential
Glycosylation1191N-linked (GlcNAc...) Potential
Glycosylation1331N-linked (GlcNAc...) Potential
Glycosylation1511N-linked (GlcNAc...) Potential
Glycosylation2401N-linked (GlcNAc...) Potential
Glycosylation3041N-linked (GlcNAc...) Potential
Disulfide bond284 ↔ 313 Ref.13 Ref.14
Disulfide bond433 ↔ 435 Ref.13 Ref.14
Disulfide bond437 ↔ 450 Ref.13 Ref.14

Natural variations

Alternative sequence97 – 14852Missing in isoform 3.
VSP_001540
Alternative sequence2681Missing in isoform 2.
VSP_040096
Natural variant3331V → I.
Corresponds to variant rs7813215 [ dbSNP | Ensembl ].
VAR_049069

Secondary structure

...................................... 496
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: 5642A58847A7385C

FASTA49656,919
        10         20         30         40         50         60 
MWQIVFFTLS CDLVLAAAYN NFRKSMDSIG KKQYQVQHGS CSYTFLLPEM DNCRSSSSPY 

        70         80         90        100        110        120 
VSNAVQRDAP LEYDDSVQRL QVLENIMENN TQWLMKLENY IQDNMKKEMV EIQQNAVQNQ 

       130        140        150        160        170        180 
TAVMIEIGTN LLNQTAEQTR KLTDVEAQVL NQTTRLELQL LEHSLSTNKL EKQILDQTSE 

       190        200        210        220        230        240 
INKLQDKNSF LEKKVLAMED KHIIQLQSIK EEKDQLQVLV SKQNSIIEEL EKKIVTATVN 

       250        260        270        280        290        300 
NSVLQKQQHD LMETVNNLLT MMSTSNSAKD PTVAKEEQIS FRDCAEVFKS GHTTNGIYTL 

       310        320        330        340        350        360 
TFPNSTEEIK AYCDMEAGGG GWTIIQRRED GSVDFQRTWK EYKVGFGNPS GEYWLGNEFV 

       370        380        390        400        410        420 
SQLTNQQRYV LKIHLKDWEG NEAYSLYEHF YLSSEELNYR IHLKGLTGTA GKISSISQPG 

       430        440        450        460        470        480 
NDFSTKDGDN DKCICKCSQM LTGGWWFDAC GPSNLNGMYY PQRQNTNKFN GIKWYYWKGS 

       490 
GYSLKATTMM IRPADF 

« Hide

Isoform 3 [UniParc].

Checksum: E512409CE73987A1
Show »

FASTA44450,958
Isoform 2 [UniParc].

Checksum: EBFAC35ABF1F08F6
Show »

FASTA49556,848

References

« Hide 'large scale' references
[1]"Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis."
Maisonpierre P.C., Suri C., Jones P.F., Bartunkova S., Wiegand S.J., Radziejewski C., Compton D.L., McClain J., Aldrich T.H., Papadopoulos N., Daly T.J., Davis S., Sato T.N., Yancopoulos G.D.
Science 277:55-60(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH TEK/TIE2, FUNCTION.
Tissue: Lung.
[2]"Biologic significance of angiopoietin-2 expression in human hepatocellular carcinoma."
Tanaka S., Mori M., Sakamoto Y., Makuuchi M., Sugimachi K., Wands J.R.
J. Clin. Invest. 103:341-345(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]"Characterization and expression of a novel alternatively spliced human angiopoietin-2."
Kim I., Kim J.-H., Ryu Y.S., Jung S.H., Nah J.J., Koh G.Y.
J. Biol. Chem. 275:18550-18556(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
Tissue: Umbilical vein endothelial cell.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Substantia nigra.
[5]"DNA sequence and analysis of human chromosome 8."
Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. expand/collapse author list , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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] (ISOFORMS 1 AND 2).
Tissue: Colon.
[8]"Angiopoietin-1 and angiopoietin-2 share the same binding domains in the Tie-2 receptor involving the first Ig-like loop and the epidermal growth factor-like repeats."
Fiedler U., Krissl T., Koidl S., Weiss C., Koblizek T., Deutsch U., Martiny-Baron G., Marme D., Augustin H.G.
J. Biol. Chem. 278:1721-1727(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TEK/TIE2.
[9]"Biological characterization of angiopoietin-3 and angiopoietin-4."
Lee H.J., Cho C.H., Hwang S.J., Choi H.H., Kim K.T., Ahn S.Y., Kim J.H., Oh J.L., Lee G.M., Koh G.Y.
FASEB J. 18:1200-1208(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN REGULATION OF ANGIOGENESIS; CELL SURVIVAL; CELL MIGRATION AND ACTIVATION OF AKT1, INTERACTION WITH TEK/TIE2.
[10]"Tyrosine phosphatase beta regulates angiopoietin-Tie2 signaling in human endothelial cells."
Yacyshyn O.K., Lai P.F.H., Forse K., Teichert-Kuliszewska K., Jurasz P., Stewart D.J.
Angiogenesis 12:25-33(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"Angiopoietin 2 is a partial agonist/antagonist of Tie2 signaling in the endothelium."
Yuan H.T., Khankin E.V., Karumanchi S.A., Parikh S.M.
Mol. Cell. Biol. 29:2011-2022(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH TEK/TIE2.
[12]"Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system."
Augustin H.G., Koh G.Y., Thurston G., Alitalo K.
Nat. Rev. Mol. Cell Biol. 10:165-177(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[13]"Structure of the angiopoietin-2 receptor binding domain and identification of surfaces involved in Tie2 recognition."
Barton W.A., Tzvetkova D., Nikolov D.B.
Structure 13:825-832(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 281-496, DISULFIDE BONDS, CALCIUM-BINDING SITES.
[14]"Crystal structures of the Tie2 receptor ectodomain and the angiopoietin-2-Tie2 complex."
Barton W.A., Tzvetkova-Robev D., Miranda E.P., Kolev M.V., Rajashankar K.R., Himanen J.P., Nikolov D.B.
Nat. Struct. Mol. Biol. 13:524-532(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.7 ANGSTROMS) OF 281-495 IN COMPLEX WITH TEK, DISULFIDE BONDS, CALCIUM-BINDING SITES.
+Additional computationally mapped references.

Web resources

Wikipedia

Angiopoietin entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF004327 mRNA. Translation: AAB63190.1.
AB009865 mRNA. Translation: BAA95590.1.
AF187858 mRNA. Translation: AAF76526.1.
AK290070 mRNA. Translation: BAF82759.1.
AC018398 Genomic DNA. No translation available.
CH471153 Genomic DNA. Translation: EAW80474.1.
BC126200 mRNA. Translation: AAI26201.1.
BC126202 mRNA. Translation: AAI26203.1.
BC143902 mRNA. Translation: AAI43903.1.
CCDSCCDS47761.1. [O15123-2]
CCDS47762.1. [O15123-3]
CCDS5958.1. [O15123-1]
RefSeqNP_001112359.1. NM_001118887.1. [O15123-3]
NP_001112360.1. NM_001118888.1. [O15123-2]
NP_001138.1. NM_001147.2. [O15123-1]
UniGeneHs.583870.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1Z3SX-ray2.35A/B281-496[»]
1Z3UX-ray2.25A/B/C/D281-496[»]
2GY7X-ray3.70A281-495[»]
4JZCX-ray1.90A279-496[»]
ProteinModelPortalO15123.
SMRO15123. Positions 165-495.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106782. 7 interactions.
DIPDIP-6048N.
IntActO15123. 6 interactions.
MINTMINT-8247351.
STRING9606.ENSP00000314897.

PTM databases

PhosphoSiteO15123.

Proteomic databases

PaxDbO15123.
PRIDEO15123.

Protocols and materials databases

DNASU285.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000325203; ENSP00000314897; ENSG00000091879. [O15123-1]
ENST00000338312; ENSP00000343517; ENSG00000091879. [O15123-2]
ENST00000415216; ENSP00000400782; ENSG00000091879. [O15123-3]
GeneID285.
KEGGhsa:285.
UCSCuc003wqj.4. human. [O15123-1]
uc003wqk.4. human. [O15123-3]
uc010lri.3. human. [O15123-2]

Organism-specific databases

CTD285.
GeneCardsGC08M006347.
HGNCHGNC:485. ANGPT2.
HPACAB011437.
CAB017626.
MIM601922. gene.
neXtProtNX_O15123.
PharmGKBPA24792.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG298026.
HOGENOMHOG000037128.
HOVERGENHBG001644.
InParanoidO15123.
KOK05466.
OMAIKAYCDM.
OrthoDBEOG7X9G60.
PhylomeDBO15123.
TreeFamTF336658.

Enzyme and pathway databases

ReactomeREACT_604. Hemostasis.
SignaLinkO15123.

Gene expression databases

ArrayExpressO15123.
BgeeO15123.
CleanExHS_ANGPT2.
GenevestigatorO15123.

Family and domain databases

Gene3D3.90.215.10. 1 hit.
4.10.530.10. 1 hit.
InterProIPR028844. Ang-2.
IPR014716. Fibrinogen_a/b/g_C_1.
IPR014715. Fibrinogen_a/b/g_C_2.
IPR002181. Fibrinogen_a/b/g_C_dom.
IPR020837. Fibrinogen_CS.
[Graphical view]
PANTHERPTHR19143:SF199. PTHR19143:SF199. 1 hit.
PfamPF00147. Fibrinogen_C. 1 hit.
[Graphical view]
SMARTSM00186. FBG. 1 hit.
[Graphical view]
SUPFAMSSF56496. SSF56496. 1 hit.
PROSITEPS00514. FIBRINOGEN_C_1. 1 hit.
PS51406. FIBRINOGEN_C_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO15123.
GeneWikiANGPT2.
GenomeRNAi285.
NextBio1151.
PROO15123.
SOURCESearch...

Entry information

Entry nameANGP2_HUMAN
AccessionPrimary (citable) accession number: O15123
Secondary accession number(s): A0AV38 expand/collapse secondary AC list , A8K205, B7ZLM7, Q9NRR7, Q9P2Y7
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: January 1, 1998
Last modified: July 9, 2014
This is version 127 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM