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Q15389 (ANGP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 129. 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·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Angiopoietin-1

Short name=ANG-1
Gene names
Name:ANGPT1
Synonyms:KIAA0003
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length498 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Binds and activates TEK/TIE2 receptor by inducing its dimerization and tyrosine phosphorylation. Plays an important role in the regulation of angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskeleton, but also maintenance of vascular quiescence. Required for normal angiogenesis and heart development during embryogenesis. After birth, activates or inhibits angiogenesis, depending on the context. Inhibits angiogenesis and promotes vascular stability in quiescent vessels, where endothelial cells have tight contacts. In quiescent vessels, ANGPT1 oligomers recruit TEK to cell-cell contacts, forming complexes with TEK molecules from adjoining cells, and this leads to preferential activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascades. In migrating endothelial cells that lack cell-cell adhesions, ANGT1 recruits TEK to contacts with the extracellular matrix, leading to the formation of focal adhesion complexes, activation of PTK2/FAK and of the downstream kinases MAPK1/ERK2 and MAPK3/ERK1, and ultimately to the stimulation of sprouting angiogenesis. Mediates blood vessel maturation/stability. Implicated in endothelial developmental processes later and distinct from that of VEGF. Appears to play a crucial role in mediating reciprocal interactions between the endothelium and surrounding matrix and mesenchyme. Ref.10 Ref.12 Ref.13 Ref.14

Subunit structure

Homooligomer. Interacts with TEK/TIE2. Ref.10 Ref.11 Ref.12

Subcellular location

Secreted.

Post-translational modification

Glycosylated.

Miscellaneous

It may have a potential therapeutic utility since it can be used for specifically targeting tumor vasculature or for promoting angiogenic processes in certain organs such as an ischemic heart.

Sequence similarities

Contains 1 fibrinogen C-terminal domain.

Sequence caution

The sequence BAA02793.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processAngiogenesis
Differentiation
   Cellular componentSecreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainCoiled coil
Signal
   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 19689429PubMed 19922791. Source: UniProtKB

activation of transmembrane receptor protein tyrosine kinase activity

Inferred from direct assay PubMed 19424712. Source: UniProtKB

blood coagulation

Traceable author statement. Source: Reactome

cell differentiation

Inferred from electronic annotation. Source: UniProtKB-KW

cell-substrate adhesion

Inferred from electronic annotation. Source: Ensembl

glomerulus vasculature development

Inferred from sequence or structural similarity. Source: UniProtKB

hemopoiesis

Inferred from electronic annotation. Source: Ensembl

heparin biosynthetic process

Inferred from direct assay PubMed 19297368. Source: UniProtKB

in utero embryonic development

Inferred from electronic annotation. Source: Ensembl

leukocyte migration

Traceable author statement. Source: Reactome

negative regulation of apoptotic process

Inferred from direct assay PubMed 10218485PubMed 12958144. Source: UniProtKB

negative regulation of cell adhesion

Inferred from direct assay PubMed 19674970. Source: UniProtKB

negative regulation of endothelial cell apoptotic process

Inferred from direct assay PubMed 19674970. Source: UniProtKB

negative regulation of neuron apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of vascular permeability

Inferred from direct assay PubMed 14978158PubMed 19297368. Source: UniProtKB

positive chemotaxis

Inferred from direct assay PubMed 9660821. Source: UniProtKB

positive regulation of ERK1 and ERK2 cascade

Inferred from direct assay Ref.13PubMed 19615361. Source: UniProtKB

positive regulation of blood vessel endothelial cell migration

Inferred from direct assay PubMed 9660821. Source: UniProtKB

positive regulation of cell adhesion

Inferred from electronic annotation. Source: Ensembl

positive regulation of endothelial cell migration

Inferred from direct assay PubMed 12958144. Source: UniProtKB

positive regulation of peptidyl-serine phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of peptidyl-tyrosine phosphorylation

Inferred from direct assay PubMed 15851516PubMed 19689429. Source: UniProtKB

positive regulation of phosphatidylinositol 3-kinase signaling

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein kinase B signaling

Inferred from direct assay Ref.13PubMed 19615361. Source: UniProtKB

positive regulation of protein ubiquitination

Inferred from direct assay PubMed 19689429. Source: UniProtKB

positive regulation of receptor internalization

Inferred from direct assay PubMed 19424712. Source: UniProtKB

protein localization to cell surface

Inferred from direct assay PubMed 19615361. Source: UniProtKB

regulation of satellite cell proliferation

Inferred from direct assay PubMed 19733541. Source: UniProtKB

sprouting angiogenesis

Inferred from direct assay PubMed 10218485PubMed 9560344. Source: UniProtKB

   Cellular_componentextracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from direct assay PubMed 10218485Ref.1. Source: UniProtKB

extracellular vesicular exosome

Inferred from direct assay PubMed 19199708. Source: UniProt

membrane raft

Inferred from direct assay PubMed 19615361. Source: UniProtKB

microvillus

Inferred from direct assay PubMed 19424712. Source: UniProtKB

plasma membrane

Inferred from direct assay PubMed 19424712. Source: UniProtKB

   Molecular_functionreceptor tyrosine kinase binding

Inferred from physical interaction PubMed 19922791Ref.1. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q15389-1)

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 2 (identifier: Q15389-2)

Also known as: Gly-269 del;

The sequence of this isoform differs from the canonical sequence as follows:
     269-269: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1515 Potential
Chain16 – 498483Angiopoietin-1
PRO_0000009110

Regions

Domain277 – 497221Fibrinogen C-terminal
Coiled coil81 – 11939 Potential
Coiled coil153 – 261109 Potential

Amino acid modifications

Glycosylation921N-linked (GlcNAc...) Potential
Glycosylation1221N-linked (GlcNAc...) Potential
Glycosylation1541N-linked (GlcNAc...) Potential
Glycosylation2431N-linked (GlcNAc...) Potential
Glycosylation2951N-linked (GlcNAc...) Potential
Disulfide bond286 ↔ 315 By similarity
Disulfide bond439 ↔ 452 By similarity

Natural variations

Alternative sequence2691Missing in isoform 2.
VSP_046324
Natural variant2471L → P.
Corresponds to variant rs73701083 [ dbSNP | Ensembl ].
VAR_069165

Secondary structure

........................................ 498
Helix Strand Turn

Details...

Sequences

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

Last modified January 1, 1998. Version 2.
Checksum: 5D5FA63AEF6BE920

FASTA49857,513
        10         20         30         40         50         60 
MTVFLSFAFL AAILTHIGCS NQRRSPENSG RRYNRIQHGQ CAYTFILPEH DGNCRESTTD 

        70         80         90        100        110        120 
QYNTNALQRD APHVEPDFSS QKLQHLEHVM ENYTQWLQKL ENYIVENMKS EMAQIQQNAV 

       130        140        150        160        170        180 
QNHTATMLEI GTSLLSQTAE QTRKLTDVET QVLNQTSRLE IQLLENSLST YKLEKQLLQQ 

       190        200        210        220        230        240 
TNEILKIHEK NSLLEHKILE MEGKHKEELD TLKEEKENLQ GLVTRQTYII QELEKQLNRA 

       250        260        270        280        290        300 
TTNNSVLQKQ QLELMDTVHN LVNLCTKEGV LLKGGKREEE KPFRDCADVY QAGFNKSGIY 

       310        320        330        340        350        360 
TIYINNMPEP KKVFCNMDVN GGGWTVIQHR EDGSLDFQRG WKEYKMGFGN PSGEYWLGNE 

       370        380        390        400        410        420 
FIFAITSQRQ YMLRIELMDW EGNRAYSQYD RFHIGNEKQN YRLYLKGHTG TAGKQSSLIL 

       430        440        450        460        470        480 
HGADFSTKDA DNDNCMCKCA LMLTGGWWFD ACGPSNLNGM FYTAGQNHGK LNGIKWHYFK 

       490 
GPSYSLRSTT MMIRPLDF 

« Hide

Isoform 2 (Gly-269 del) [UniParc].

Checksum: 3055148F097AC6AF
Show »

FASTA49757,456

References

« Hide 'large scale' references
[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).
Tissue: Fetal lung.
[2]"Human angiopoietin-1 mRNA variant form."
Nakatsukasa M., Komai K., Shiozawa S.
Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]"Human angiopoietin-1 mRNA variant forms."
Shan Z.X., Yu X.Y., Lin Q.Y., Fu Y.H., Tan H.H., Zheng M., Lin S.G.
Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[4]"Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1."
Nomura N., Miyajima N., Sazuka T., Tanaka A., Kawarabayasi Y., Sato S., Nagase T., Seki N., Ishikawa K., Tabata S.
DNA Res. 1:27-35(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Bone marrow.
[5]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Small intestine.
[6]"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].
[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] (ISOFORM 1).
[8]Mural R.J., Istrail S., Sutton 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones."
Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.
DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SEQUENCE REVISION.
[10]"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: FUNCTION, INTERACTION WITH TEK.
[11]"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.
[12]"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.
[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.
[14]"Angiopoietins assemble distinct Tie2 signalling complexes in endothelial cell-cell and cell-matrix contacts."
Saharinen P., Eklund L., Miettinen J., Wirkkala R., Anisimov A., Winderlich M., Nottebaum A., Vestweber D., Deutsch U., Koh G.Y., Olsen B.R., Alitalo K.
Nat. Cell Biol. 10:527-537(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN REGULATION OF ENDOTHELIAL CELL MIGRATION.
[15]"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.
[16]"Angiopoietin-1/Tie2 receptor signaling in vascular quiescence and angiogenesis."
Fukuhara S., Sako K., Noda K., Zhang J., Minami M., Mochizuki N.
Histol. Histopathol. 25:387-396(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[17]"Targeting the ANGPT-TIE2 pathway in malignancy."
Huang H., Bhat A., Woodnutt G., Lappe R.
Nat. Rev. Cancer 10:575-585(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
+Additional computationally mapped references.

Web resources

Wikipedia

Angiopoietin entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U83508 mRNA. Translation: AAB50557.1.
AB084454 mRNA. Translation: BAB91325.1.
AY121504 mRNA. Translation: AAM81745.1.
AY124380 mRNA. Translation: AAM92271.1.
D13628 mRNA. Translation: BAA02793.2. Different initiation.
BX648814 mRNA. Translation: CAI45984.1.
AC091010 Genomic DNA. No translation available.
AP000428 Genomic DNA. No translation available.
AP003480 Genomic DNA. No translation available.
CH471060 Genomic DNA. Translation: EAW91909.1.
BC152411 mRNA. Translation: AAI52412.1.
BC152419 mRNA. Translation: AAI52420.1.
RefSeqNP_001137.2. NM_001146.3.
NP_001186788.1. NM_001199859.1.
UniGeneHs.369675.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4EPUX-ray2.10A/B282-497[»]
4JYOX-ray2.50X280-498[»]
4K0VX-ray4.51B280-498[»]
ProteinModelPortalQ15389.
SMRQ15389. Positions 172-497.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106781. 2 interactions.
DIPDIP-6046N.
IntActQ15389. 1 interaction.
STRING9606.ENSP00000297450.

PTM databases

PhosphoSiteQ15389.

Polymorphism databases

DMDM12229574.

Proteomic databases

PaxDbQ15389.
PRIDEQ15389.

Protocols and materials databases

DNASU284.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000297450; ENSP00000297450; ENSG00000154188. [Q15389-2]
ENST00000517746; ENSP00000428340; ENSG00000154188. [Q15389-1]
GeneID284.
KEGGhsa:284.
UCSCuc003ymn.3. human. [Q15389-1]

Organism-specific databases

CTD284.
GeneCardsGC08M108330.
HGNCHGNC:484. ANGPT1.
HPACAB017815.
HPA018793.
HPA018816.
MIM601667. gene.
neXtProtNX_Q15389.
PharmGKBPA24791.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG310490.
HOGENOMHOG000037128.
HOVERGENHBG001644.
InParanoidQ15389.
KOK05465.
OMAWLQKIEN.
OrthoDBEOG7X9G60.
PhylomeDBQ15389.
TreeFamTF336658.

Enzyme and pathway databases

ReactomeREACT_604. Hemostasis.
SignaLinkQ15389.

Gene expression databases

ArrayExpressQ15389.
BgeeQ15389.
CleanExHS_ANGPT1.
GenevestigatorQ15389.

Family and domain databases

Gene3D3.90.215.10. 1 hit.
4.10.530.10. 1 hit.
InterProIPR028843. Ang-1.
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:SF156. PTHR19143:SF156. 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

ChiTaRSANGPT1. human.
GeneWikiAngiopoietin_1.
GenomeRNAi284.
NextBio1147.
PROQ15389.
SOURCESearch...

Entry information

Entry nameANGP1_HUMAN
AccessionPrimary (citable) accession number: Q15389
Secondary accession number(s): Q5HYA0
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: January 1, 1998
Last modified: April 16, 2014
This is version 129 of the entry and version 2 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