Q15389 (ANGP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Angiopoietin-1
Short name=ANG-1

Gene names

Name:	ANGPT1
Synonyms:	KIAA0003

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	498 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 process	Angiogenesis Differentiation
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil Signal
Molecular function	Developmental protein
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Tie receptor 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: Compara glomerulus vasculature development Inferred from sequence or structural similarity. Source: UniProtKB hemopoiesis Inferred from electronic annotation. Source: Compara heparin biosynthetic process Inferred from direct assay PubMed 19297368. Source: UniProtKB in utero embryonic development Inferred from electronic annotation. Source: Compara leukocyte migration Traceable author statement. Source: Reactome 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 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: Compara positive regulation of peptidyl-serine phosphorylation Inferred from electronic annotation. Source: Compara positive regulation of peptidyl-tyrosine phosphorylation Inferred from direct assay PubMed 15851516PubMed 19689429. Source: UniProtKB positive regulation of phosphatidylinositol 3-kinase cascade Inferred from electronic annotation. Source: Compara positive regulation of protein kinase B signaling cascade 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_component	extracellular space Inferred from direct assay PubMed 10218485Ref.1. Source: UniProtKB 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
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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 15	15	Potential
	Chain	16 – 498	483	Angiopoietin-1		PRO_0000009110
Regions
	Domain	277 – 497	221	Fibrinogen C-terminal
	Coiled coil	81 – 119	39	Potential
	Coiled coil	153 – 261	109	Potential
Amino acid modifications
	Glycosylation	92	1	N-linked (GlcNAc...) Potential
	Glycosylation	122	1	N-linked (GlcNAc...) Potential
	Glycosylation	154	1	N-linked (GlcNAc...) Potential
	Glycosylation	243	1	N-linked (GlcNAc...) Potential
	Glycosylation	295	1	N-linked (GlcNAc...) Potential
	Disulfide bond	286 ↔ 315		By similarity
	Disulfide bond	439 ↔ 452		By similarity
Natural variations
	Alternative sequence	269	1	Missing in isoform 2.		VSP_046324
	Natural variant	247	1	L → P. Corresponds to variant rs73701083 [ dbSNP | Ensembl ].		VAR_069165

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 1, 1998. Version 2. Checksum: 5D5FA63AEF6BE920	FASTA	498	57,513
	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
	Isoform 2 (Gly-269 del) [UniParc]. Checksum: 3055148F097AC6AF	FASTA	497	57,456
	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 LVNLCTKEVL LKGGKREEEK PFRDCADVYQ AGFNKSGIYT 310 320 330 340 350 360 IYINNMPEPK KVFCNMDVNG GGWTVIQHRE DGSLDFQRGW KEYKMGFGNP SGEYWLGNEF 370 380 390 400 410 420 IFAITSQRQY MLRIELMDWE GNRAYSQYDR FHIGNEKQNY RLYLKGHTGT AGKQSSLILH 430 440 450 460 470 480 GADFSTKDAD NDNCMCKCAL MLTGGWWFDA CGPSNLNGMF YTAGQNHGKL NGIKWHYFKG 490 PSYSLRSTTM MIRPLDF

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
IPI	IPI00016677.
RefSeq	NP_001137.2. NM_001146.3. NP_001186788.1. NM_001199859.1.
UniGene	Hs.369675.
3D structure databases
ProteinModelPortal	Q15389.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-6046N.
IntAct	Q15389. 1 interaction.
STRING	9606.ENSP00000297450.
PTM databases
PhosphoSite	Q15389.
Polymorphism databases
DMDM	12229574.
Proteomic databases
PaxDb	Q15389.
PRIDE	Q15389.
Protocols and materials databases
DNASU	284.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000297450; ENSP00000297450; ENSG00000154188. ENST00000517746; ENSP00000428340; ENSG00000154188.
GeneID	284.
KEGG	hsa:284.
UCSC	uc003ymn.3. human.
Organism-specific databases
CTD	284.
GeneCards	GC08M108330.
HGNC	HGNC:484. ANGPT1.
HPA	CAB017815. HPA018793. HPA018816.
MIM	601667. gene.
neXtProt	NX_Q15389.
PharmGKB	PA24791.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG310490.
HOGENOM	HOG000037128.
HOVERGEN	HBG001644.
InParanoid	Q15389.
KO	K05465.
OMA	WLQKIEN.
OrthoDB	EOG4ZGPC8.
PhylomeDB	Q15389.
Enzyme and pathway databases
Pathway_Interaction_DB	angiopoietinreceptor_pathway. Angiopoietin receptor Tie2-mediated signaling.
Reactome	REACT_604. Hemostasis.
Gene expression databases
ArrayExpress	Q15389.
Bgee	Q15389.
CleanEx	HS_ANGPT1.
Genevestigator	Q15389.
GermOnline	ENSG00000154188. Homo sapiens.
Family and domain databases
Gene3D	3.90.215.10. 1 hit. 4.10.530.10. 1 hit.
InterPro	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]
Pfam	PF00147. Fibrinogen_C. 1 hit. [Graphical view]
SMART	SM00186. FBG. 1 hit. [Graphical view]
SUPFAM	SSF56496. Fibrinogen_a/b/g_C. 1 hit.
PROSITE	PS00514. FIBRINOGEN_C_1. 1 hit. PS51406. FIBRINOGEN_C_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	ANGPT1. human.
GenomeRNAi	284.
NextBio	1147.
SOURCE	Search...

Entry information

Entry name

ANGP1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 119 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.