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   24-JAN-2024, entry version 171.
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], AND SUBCELLULAR LOCATION.
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).
RN   [5]
RP   INTERACTION WITH SVEP1.
RX   PubMed=28179430; DOI=10.1161/circresaha.116.308825;
RA   Morooka N., Futaki S., Sato-Nishiuchi R., Nishino M., Totani Y.,
RA   Shimono C., Nakano I., Nakajima H., Mochizuki N., Sekiguchi K.;
RT   "Polydom Is an Extracellular Matrix Protein Involved in Lymphatic Vessel
RT   Remodeling.";
RL   Circ. Res. 120:1276-1288(2017).
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 (By similarity). Interacts with TEK/TIE2 (By
CC       similarity). Interacts with SVEP1/polydom (PubMed:28179430).
CC       {ECO:0000250|UniProtKB:Q15389, ECO:0000269|PubMed:28179430}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:8980223}.
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   GlyCosmos; O08538; 5 sites, No reported glycans.
DR   GlyGen; O08538; 5 sites.
DR   iPTMnet; O08538; -.
DR   PhosphoSitePlus; O08538; -.
DR   MaxQB; O08538; -.
DR   PaxDb; 10090-ENSMUSP00000022921; -.
DR   ProteomicsDB; 296037; -.
DR   Antibodypedia; 4501; 768 antibodies from 40 providers.
DR   DNASU; 11600; -.
DR   Ensembl; ENSMUST00000022921.7; ENSMUSP00000022921.6; ENSMUSG00000022309.10.
DR   GeneID; 11600; -.
DR   KEGG; mmu:11600; -.
DR   UCSC; uc007vpc.2; mouse.
DR   AGR; MGI:108448; -.
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; HIGCNNQ; -.
DR   OrthoDB; 3134470at2759; -.
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 76 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 165 other cell types or tissues.
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: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:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA: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 canonical NF-kappaB signal transduction; IGI:MGI.
DR   GO; GO:2000446; P:regulation of macrophage migration inhibitory factor signaling pathway; 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; Gamma Fibrinogen, chain A, domain 1; 1.
DR   Gene3D; 4.10.530.10; Gamma-fibrinogen Carboxyl Terminal Fragment, domain 2; 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   NCBIfam; NF040941; GGGWT_bact; 1.
DR   PANTHER; PTHR19143:SF156; ANGIOPOIETIN-1; 1.
DR   PANTHER; PTHR19143; FIBRINOGEN/TENASCIN/ANGIOPOEITIN; 1.
DR   Pfam; PF00147; Fibrinogen_C; 1.
DR   SMART; SM00186; FBG; 1.
DR   SUPFAM; SSF56496; Fibrinogen C-terminal domain-like; 1.
DR   PROSITE; PS00514; FIBRINOGEN_C_1; 1.
DR   PROSITE; PS51406; FIBRINOGEN_C_2; 1.
DR   Genevisible; O08538; MM.
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
//