ANGP1_MOUSE
ID ANGP1_MOUSE Reviewed; 498 AA.
AC O08538; Q6NWV7;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Angiopoietin-1;
DE Short=ANG-1;
DE Flags: Precursor;
GN Name=Angpt1; Synonyms=Agpt;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8980223; DOI=10.1016/s0092-8674(00)81812-7;
RA Davis S., Aldrich T.H., Jones P.F., Acheson A., Compton D.L., Jain V.,
RA Ryan T.E., Bruno J., Radziejewski C., Maisonpierre P.C., Yancopoulos G.D.;
RT "Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-
RT trap expression cloning.";
RL Cell 87:1161-1169(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP DISRUPTION PHENOTYPE.
RX PubMed=8980224; DOI=10.1016/s0092-8674(00)81813-9;
RA Suri C., Jones P.F., Patan S., Bartunkova S., Maisonpierre P.C., Davis S.,
RA Sato T.N., Yancopoulos G.D.;
RT "Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during
RT embryonic angiogenesis.";
RL Cell 87:1171-1180(1996).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
CC -!- FUNCTION: Binds and activates TEK/TIE2 receptor by inducing its
CC dimerization and tyrosine phosphorylation. Plays an important role in
CC the regulation of angiogenesis, endothelial cell survival,
CC proliferation, migration, adhesion and cell spreading, reorganization
CC of the actin cytoskeleton, but also maintenance of vascular quiescence.
CC Required for normal angiogenesis and heart development during
CC embryogenesis. After birth, activates or inhibits angiogenesis,
CC depending on the context. Inhibits angiogenesis and promotes vascular
CC stability in quiescent vessels, where endothelial cells have tight
CC contacts. In quiescent vessels, ANGPT1 oligomers recruit TEK to cell-
CC cell contacts, forming complexes with TEK molecules from adjoining
CC cells, and this leads to preferential activation of
CC phosphatidylinositol 3-kinase and the AKT1 signaling cascades. In
CC migrating endothelial cells that lack cell-cell adhesions, ANGT1
CC recruits TEK to contacts with the extracellular matrix, leading to the
CC formation of focal adhesion complexes, activation of PTK2/FAK and of
CC the downstream kinases MAPK1/ERK2 and MAPK3/ERK1, and ultimately to the
CC stimulation of sprouting angiogenesis. Mediates blood vessel
CC maturation/stability. Implicated in endothelial developmental processes
CC later and distinct from that of VEGF. Appears to play a crucial role in
CC mediating reciprocal interactions between the endothelium and
CC surrounding matrix and mesenchyme (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homooligomer. Interacts with TEK/TIE2 (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- DEVELOPMENTAL STAGE: Early in development, at 9 dpc to 11 dpc, it is
CC found most prominently in the heart myocardium surrounding the
CC endocardium. Later, it becomes more widely distributed, most often in
CC the mesenchyme surrounding developing vessels, in close association
CC with endothelial cells.
CC -!- DISRUPTION PHENOTYPE: Embryonically lethal. Embryos die at about 12.5
CC dpc, due to important developmental defects of the endocardium and
CC myocardium, plus generalized defects in vascular development.
CC {ECO:0000269|PubMed:8980224}.
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DR EMBL; U83509; AAB50558.1; -; mRNA.
DR EMBL; BC067410; AAH67410.1; -; mRNA.
DR CCDS; CCDS27450.1; -.
DR RefSeq; NP_033770.2; NM_009640.4.
DR AlphaFoldDB; O08538; -.
DR SMR; O08538; -.
DR DIP; DIP-6051N; -.
DR IntAct; O08538; 1.
DR STRING; 10090.ENSMUSP00000022921; -.
DR GlyGen; O08538; 5 sites.
DR iPTMnet; O08538; -.
DR PhosphoSitePlus; O08538; -.
DR MaxQB; O08538; -.
DR PaxDb; O08538; -.
DR PRIDE; O08538; -.
DR ProteomicsDB; 296037; -.
DR Antibodypedia; 4501; 694 antibodies from 40 providers.
DR DNASU; 11600; -.
DR Ensembl; ENSMUST00000022921; ENSMUSP00000022921; ENSMUSG00000022309.
DR GeneID; 11600; -.
DR KEGG; mmu:11600; -.
DR UCSC; uc007vpc.2; mouse.
DR CTD; 284; -.
DR MGI; MGI:108448; Angpt1.
DR VEuPathDB; HostDB:ENSMUSG00000022309; -.
DR eggNOG; KOG2579; Eukaryota.
DR GeneTree; ENSGT00940000158117; -.
DR HOGENOM; CLU_038628_3_1_1; -.
DR InParanoid; O08538; -.
DR OMA; QAFSQYD; -.
DR OrthoDB; 357340at2759; -.
DR PhylomeDB; O08538; -.
DR TreeFam; TF336658; -.
DR Reactome; R-MMU-210993; Tie2 Signaling.
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR BioGRID-ORCS; 11600; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Angpt1; mouse.
DR PRO; PR:O08538; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; O08538; protein.
DR Bgee; ENSMUSG00000022309; Expressed in cardiac atrium and 164 other tissues.
DR Genevisible; O08538; MM.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0005902; C:microvillus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; ISO:MGI.
DR GO; GO:0005102; F:signaling receptor binding; IPI:MGI.
DR GO; GO:0005172; F:vascular endothelial growth factor receptor binding; TAS:MGI.
DR GO; GO:0007171; P:activation of transmembrane receptor protein tyrosine kinase activity; ISO:MGI.
DR GO; GO:0001525; P:angiogenesis; IDA:MGI.
DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; TAS:DFLAT.
DR GO; GO:0055008; P:cardiac muscle tissue morphogenesis; TAS:DFLAT.
DR GO; GO:0031589; P:cell-substrate adhesion; IDA:MGI.
DR GO; GO:0003160; P:endocardium morphogenesis; TAS:DFLAT.
DR GO; GO:0007492; P:endoderm development; TAS:MGI.
DR GO; GO:0072012; P:glomerulus vasculature development; IDA:MGI.
DR GO; GO:0030097; P:hemopoiesis; IDA:MGI.
DR GO; GO:0030210; P:heparin biosynthetic process; ISO:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0007162; P:negative regulation of cell adhesion; ISO:MGI.
DR GO; GO:0002719; P:negative regulation of cytokine production involved in immune response; IDA:MGI.
DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; ISO:MGI.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IDA:MGI.
DR GO; GO:0042308; P:negative regulation of protein import into nucleus; IDA:MGI.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IDA:MGI.
DR GO; GO:0043116; P:negative regulation of vascular permeability; IDA:MGI.
DR GO; GO:0051402; P:neuron apoptotic process; IDA:MGI.
DR GO; GO:0001541; P:ovarian follicle development; ISO:MGI.
DR GO; GO:0050918; P:positive chemotaxis; ISO:MGI.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISO:MGI.
DR GO; GO:1905605; P:positive regulation of blood-brain barrier permeability; ISO:MGI.
DR GO; GO:0045785; P:positive regulation of cell adhesion; IDA:MGI.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; ISO:MGI.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:MGI.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:MGI.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IDA:MGI.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; ISO:MGI.
DR GO; GO:0002092; P:positive regulation of receptor internalization; ISO:MGI.
DR GO; GO:0030949; P:positive regulation of vascular endothelial growth factor receptor signaling pathway; TAS:DFLAT.
DR GO; GO:0034394; P:protein localization to cell surface; ISO:MGI.
DR GO; GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; IGI:MGI.
DR GO; GO:2000446; P:regulation of macrophage migration inhibitory factor signaling pathway; IDA:MGI.
DR GO; GO:0043393; P:regulation of protein binding; IDA:MGI.
DR GO; GO:0014842; P:regulation of skeletal muscle satellite cell proliferation; ISO:MGI.
DR GO; GO:0032680; P:regulation of tumor necrosis factor production; IDA:MGI.
DR GO; GO:0002040; P:sprouting angiogenesis; ISO:MGI.
DR GO; GO:0048014; P:Tie signaling pathway; ISO:MGI.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IDA:MGI.
DR GO; GO:0001570; P:vasculogenesis; TAS:DFLAT.
DR GO; GO:0060979; P:vasculogenesis involved in coronary vascular morphogenesis; TAS:DFLAT.
DR CDD; cd00087; FReD; 1.
DR Gene3D; 3.90.215.10; -; 1.
DR InterPro; IPR028843; Ang-1.
DR InterPro; IPR036056; Fibrinogen-like_C.
DR InterPro; IPR014716; Fibrinogen_a/b/g_C_1.
DR InterPro; IPR002181; Fibrinogen_a/b/g_C_dom.
DR InterPro; IPR020837; Fibrinogen_CS.
DR PANTHER; PTHR19143:SF156; PTHR19143:SF156; 1.
DR Pfam; PF00147; Fibrinogen_C; 1.
DR SMART; SM00186; FBG; 1.
DR SUPFAM; SSF56496; SSF56496; 1.
DR PROSITE; PS00514; FIBRINOGEN_C_1; 1.
DR PROSITE; PS51406; FIBRINOGEN_C_2; 1.
PE 1: Evidence at protein level;
KW Angiogenesis; Coiled coil; Developmental protein; Differentiation;
KW Disulfide bond; Glycoprotein; Reference proteome; Secreted; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..498
FT /note="Angiopoietin-1"
FT /id="PRO_0000009111"
FT DOMAIN 277..497
FT /note="Fibrinogen C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT COILED 81..119
FT /evidence="ECO:0000255"
FT COILED 153..261
FT /evidence="ECO:0000255"
FT CARBOHYD 92
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 122
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 154
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 243
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 295
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 286..315
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT DISULFID 439..452
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT CONFLICT 262
FT /note="I -> V (in Ref. 1; AAB50558)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 498 AA; 57519 MW; FC36F905A9E79074 CRC64;
MTVFLSFAFF AAILTHIGCS NQRRNPENGG RRYNRIQHGQ CAYTFILPEH DGNCRESATE
QYNTNALQRD APHVEPDFSS QKLQHLEHVM ENYTQWLQKL ENYIVENMKS EMAQIQQNAV
QNHTATMLEI GTSLLSQTAE QTRKLTDVET QVLNQTSRLE IQLLENSLST YKLEKQLLQQ
TNEILKIHEK NSLLEHKILE MEGKHKEELD TLKEEKENLQ GLVSRQTFII QELEKQLSRA
TNNNSILQKQ QLELMDTVHN LISLCTKEGV LLKGGKREEE KPFRDCADVY QAGFNKSGIY
TIYFNNMPEP KKVFCNMDVN GGGWTVIQHR EDGSLDFQRG WKEYKMGFGN PSGEYWLGNE
FIFAITSQRQ YMLRIELMDW EGNRAYSQYD RFHIGNEKQN YRLYLKGHTG TAGKQSSLIL
HGADFSTKDA DNDNCMCKCA LMLTGGWWFD ACGPSNLNGM FYTAGQNHGK LNGIKWHYFK
GPSYSLRSTT MMIRPLDF
