O08538 (ANGP1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Gene names

Name:	Angpt1
Synonyms:	Agpt

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

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 transcript 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 By similarity.
Subunit structure	Homooligomer. Interacts with TEK/TIE2 By similarity.
Subcellular location	Secreted.
Developmental stage	Early in development, at E9 to E11, it is found most prominently in the heart myocardium surrounding the endocardium. Later, it becomes more widely distributed, most often in the mesenchyme surrounding developing vessels, in close association with endothelial cells.
Disruption phenotype	Embryonically lethal. Embryos die at about 12.5 dpc, due to important developmental defects of the endocardium and myocardium, plus generalized defects in vascular development. Ref.3
Sequence similarities	Contains 1 fibrinogen C-terminal domain.

Ontologies

Keywords
Biological process	Angiogenesis Differentiation
Cellular component	Secreted
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 Traceable author statement PubMed 20299672. Source: DFLAT activation of transmembrane receptor protein tyrosine kinase activity Inferred from electronic annotation. Source: Compara cardiac muscle tissue morphogenesis Traceable author statement PubMed 20299672. Source: DFLAT cell-substrate adhesion Inferred from direct assay PubMed 9846489. Source: MGI endocardium morphogenesis Traceable author statement PubMed 20299672. Source: DFLAT endoderm development Traceable author statement PubMed 10051567. Source: MGI glomerulus vasculature development Inferred from direct assay PubMed 11507774. Source: MGI hemopoiesis Inferred from direct assay PubMed 15260986. Source: MGI heparin biosynthetic process Inferred from electronic annotation. Source: Compara in utero embryonic development Inferred from mutant phenotype PubMed 11172728. Source: MGI negative regulation of apoptotic process Inferred from direct assay PubMed 19409199. Source: MGI negative regulation of cell adhesion Inferred from electronic annotation. Source: Compara negative regulation of endothelial cell apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of vascular permeability Inferred from direct assay PubMed 10617467PubMed 17562701. Source: MGI patterning of blood vessels Traceable author statement PubMed 20299672. Source: DFLAT positive chemotaxis Inferred from electronic annotation. Source: Compara positive regulation of ERK1 and ERK2 cascade Inferred from electronic annotation. Source: Compara positive regulation of blood vessel endothelial cell migration Inferred from electronic annotation. Source: Compara positive regulation of cell adhesion Inferred from direct assay PubMed 15260986. Source: MGI positive regulation of endothelial cell migration Traceable author statement PubMed 20299672. Source: DFLAT positive regulation of peptidyl-serine phosphorylation Inferred from direct assay PubMed 19409199. Source: MGI positive regulation of peptidyl-tyrosine phosphorylation Inferred from direct assay PubMed 19409199Ref.1. Source: MGI positive regulation of phosphatidylinositol 3-kinase cascade Inferred from direct assay PubMed 19409199. Source: MGI positive regulation of protein kinase B signaling cascade Inferred from electronic annotation. Source: Compara positive regulation of protein ubiquitination Inferred from electronic annotation. Source: Compara positive regulation of receptor internalization Inferred from electronic annotation. Source: Compara positive regulation of vascular endothelial growth factor receptor signaling pathway Traceable author statement PubMed 20406889. Source: DFLAT protein localization to cell surface Inferred from electronic annotation. Source: Compara regulation of satellite cell proliferation Inferred from electronic annotation. Source: Compara sprouting angiogenesis Inferred from electronic annotation. Source: Compara vasculogenesis involved in coronary vascular morphogenesis Traceable author statement PubMed 20299672. Source: DFLAT
Cellular_component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell membrane raft Inferred from electronic annotation. Source: Compara microvillus Inferred from electronic annotation. Source: Compara plasma membrane Inferred from electronic annotation. Source: Compara
Molecular_function	vascular endothelial growth factor receptor binding Traceable author statement PubMed 10051567. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 19	19	Potential
	Chain	20 – 498	479	Angiopoietin-1		PRO_0000009111
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
Experimental info
	Sequence conflict	262	1	I → V in AAB50558. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	O08538 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: FC36F905A9E79074	FASTA	498	57,519
	10 20 30 40 50 60 MTVFLSFAFF AAILTHIGCS NQRRNPENGG RRYNRIQHGQ CAYTFILPEH DGNCRESATE 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 GLVSRQTFII QELEKQLSRA 250 260 270 280 290 300 TNNNSILQKQ QLELMDTVHN LISLCTKEGV LLKGGKREEE KPFRDCADVY QAGFNKSGIY 310 320 330 340 350 360 TIYFNNMPEP 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

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].
[2]	"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]. Strain: C57BL/6J. Tissue: Embryo.
[3]	"Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis." Suri C., Jones P.F., Patan S., Bartunkova S., Maisonpierre P.C., Davis S., Sato T.N., Yancopoulos G.D. Cell 87:1171-1180(1996) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U83509 mRNA. Translation: AAB50558.1. BC067410 mRNA. Translation: AAH67410.1.
IPI	IPI00114350.
RefSeq	NP_033770.2. NM_009640.3.
UniGene	Mm.309336.
3D structure databases
ProteinModelPortal	O08538.
SMR	O08538. Positions 151-497.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-6051N.
STRING	10090.ENSMUSP00000022921.
PTM databases
PhosphoSite	O08538.
Proteomic databases
PaxDb	O08538.
PRIDE	O08538.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000022921; ENSMUSP00000022921; ENSMUSG00000022309.
GeneID	11600.
KEGG	mmu:11600.
Organism-specific databases
CTD	284.
MGI	MGI:108448. Angpt1.
Phylogenomic databases
eggNOG	NOG310490.
GeneTree	ENSGT00700000104380.
HOVERGEN	HBG001644.
InParanoid	Q6NWV7.
KO	K05465.
OMA	WLQKIEN.
OrthoDB	EOG4ZGPC8.
Gene expression databases
ArrayExpress	O08538.
Bgee	O08538.
CleanEx	MM_ANGPT1.
Genevestigator	O08538.
GermOnline	ENSMUSG00000022309. Mus musculus.
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. mouse.
NextBio	279116.
SOURCE	Search...

Entry information

Entry name

ANGP1_MOUSE

Accession

Primary (citable) accession number: O08538
Secondary accession number(s): Q6NWV7

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	July 27, 2011
Last modified:	May 1, 2013
This is version 102 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program