ID ANGP1_HUMAN Reviewed; 498 AA. AC Q15389; Q5HYA0; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1998, sequence version 2. DT 24-JAN-2024, entry version 198. DE RecName: Full=Angiopoietin-1; DE Short=ANG-1; DE Flags: Precursor; GN Name=ANGPT1; Synonyms=KIAA0003; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND SUBCELLULAR LOCATION. RC TISSUE=Fetal lung; 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 [MRNA] (ISOFORM 2). RA Nakatsukasa M., Komai K., Shiozawa S.; RT "Human angiopoietin-1 mRNA variant form."; RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RA Shan Z.X., Yu X.Y., Lin Q.Y., Fu Y.H., Tan H.H., Zheng M., Lin S.G.; RT "Human angiopoietin-1 mRNA variant forms."; RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Bone marrow; RX PubMed=7584026; DOI=10.1093/dnares/1.1.27; RA Nomura N., Miyajima N., Sazuka T., Tanaka A., Kawarabayasi Y., Sato S., RA Nagase T., Seki N., Ishikawa K., Tabata S.; RT "Prediction of the coding sequences of unidentified human genes. I. The RT coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of RT randomly sampled cDNA clones from human immature myeloid cell line KG-1."; RL DNA Res. 1:27-35(1994). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Small intestine; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16421571; DOI=10.1038/nature04406; RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., RA Platzer M., Shimizu N., Lander E.S.; RT "DNA sequence and analysis of human chromosome 8."; RL Nature 439:331-335(2006). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP SEQUENCE REVISION. RX PubMed=12168954; DOI=10.1093/dnares/9.3.99; RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.; RT "Construction of expression-ready cDNA clones for KIAA genes: manual RT curation of 330 KIAA cDNA clones."; RL DNA Res. 9:99-106(2002). RN [10] RP FUNCTION, AND INTERACTION WITH TEK. RX PubMed=9204896; DOI=10.1126/science.277.5322.55; RA Maisonpierre P.C., Suri C., Jones P.F., Bartunkova S., Wiegand S.J., RA Radziejewski C., Compton D.L., McClain J., Aldrich T.H., Papadopoulos N., RA Daly T.J., Davis S., Sato T.N., Yancopoulos G.D.; RT "Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo RT angiogenesis."; RL Science 277:55-60(1997). RN [11] RP INTERACTION WITH TEK. RX PubMed=12427764; DOI=10.1074/jbc.m208550200; RA Fiedler U., Krissl T., Koidl S., Weiss C., Koblizek T., Deutsch U., RA Martiny-Baron G., Marme D., Augustin H.G.; RT "Angiopoietin-1 and angiopoietin-2 share the same binding domains in the RT Tie-2 receptor involving the first Ig-like loop and the epidermal growth RT factor-like repeats."; RL J. Biol. Chem. 278:1721-1727(2003). RN [12] RP FUNCTION IN REGULATION OF ANGIOGENESIS; CELL SURVIVAL; CELL MIGRATION AND RP ACTIVATION OF AKT1, AND INTERACTION WITH TEK/TIE2. RX PubMed=15284220; DOI=10.1096/fj.03-1466com; RA Lee H.J., Cho C.H., Hwang S.J., Choi H.H., Kim K.T., Ahn S.Y., Kim J.H., RA Oh J.L., Lee G.M., Koh G.Y.; RT "Biological characterization of angiopoietin-3 and angiopoietin-4."; RL FASEB J. 18:1200-1208(2004). RN [13] RP FUNCTION IN REGULATION OF ENDOTHELIAL CELL MIGRATION AND CELL SPREADING. RX PubMed=18425120; DOI=10.1038/ncb1714; RA Fukuhara S., Sako K., Minami T., Noda K., Kim H.Z., Kodama T., Shibuya M., RA Takakura N., Koh G.Y., Mochizuki N.; RT "Differential function of Tie2 at cell-cell contacts and cell-substratum RT contacts regulated by angiopoietin-1."; RL Nat. Cell Biol. 10:513-526(2008). RN [14] RP FUNCTION IN REGULATION OF ENDOTHELIAL CELL MIGRATION. RX PubMed=18425119; DOI=10.1038/ncb1715; RA Saharinen P., Eklund L., Miettinen J., Wirkkala R., Anisimov A., RA Winderlich M., Nottebaum A., Vestweber D., Deutsch U., Koh G.Y., RA Olsen B.R., Alitalo K.; RT "Angiopoietins assemble distinct Tie2 signalling complexes in endothelial RT cell-cell and cell-matrix contacts."; RL Nat. Cell Biol. 10:527-537(2008). RN [15] RP REVIEW. RX PubMed=19234476; DOI=10.1038/nrm2639; RA Augustin H.G., Koh G.Y., Thurston G., Alitalo K.; RT "Control of vascular morphogenesis and homeostasis through the RT angiopoietin-Tie system."; RL Nat. Rev. Mol. Cell Biol. 10:165-177(2009). RN [16] RP REVIEW. RX PubMed=20054809; DOI=10.14670/hh-25.387; RA Fukuhara S., Sako K., Noda K., Zhang J., Minami M., Mochizuki N.; RT "Angiopoietin-1/Tie2 receptor signaling in vascular quiescence and RT angiogenesis."; RL Histol. Histopathol. 25:387-396(2010). RN [17] RP REVIEW. RX PubMed=20651738; DOI=10.1038/nrc2894; RA Huang H., Bhat A., Woodnutt G., Lappe R.; RT "Targeting the ANGPT-TIE2 pathway in malignancy."; RL Nat. Rev. Cancer 10:575-585(2010). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [19] RP VARIANTS HAE5 SER-119; CYS-225 AND GLN-494, INVOLVEMENT IN HAE5, SUBUNIT, RP INTERACTION WITH TEK, AND CHARACTERIZATION OF VARIANTS HAE5 SER-119; RP CYS-225 AND GLN-494. RX PubMed=28601681; DOI=10.1016/j.jaci.2017.05.020; RA Bafunno V., Firinu D., D'Apolito M., Cordisco G., Loffredo S., Leccese A., RA Bova M., Barca M.P., Santacroce R., Cicardi M., Del Giacco S., RA Margaglione M.; RT "Mutation of the angiopoietin-1 gene (ANGPT1) associates with a new type of RT hereditary angioedema."; RL J. Allergy Clin. Immunol. 141:1009-1017(2018). RN [20] RP VARIANT HAE5 SER-119, FUNCTION, INTERACTION WITH TEK, AND CHARACTERIZATION RP OF VARIANT HAE5 SER-119. RX PubMed=30689269; DOI=10.1111/cea.13349; RA d'Apolito M., Santacroce R., Colia A.L., Cordisco G., Maffione A.B., RA Margaglione M.; RT "Angiopoietin-1 haploinsufficiency affects the endothelial barrier and RT causes hereditary angioedema."; RL Clin. Exp. Allergy 49:626-635(2019). 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. {ECO:0000269|PubMed:15284220, CC ECO:0000269|PubMed:18425119, ECO:0000269|PubMed:18425120, CC ECO:0000269|PubMed:30689269, ECO:0000269|PubMed:9204896}. CC -!- SUBUNIT: Homooligomer (PubMed:28601681). Interacts with TEK/TIE2 CC (PubMed:28601681, PubMed:30689269). Interacts with SVEP1/polydom (By CC similarity). {ECO:0000250|UniProtKB:O08538, CC ECO:0000269|PubMed:12427764, ECO:0000269|PubMed:15284220, CC ECO:0000269|PubMed:28601681, ECO:0000269|PubMed:30689269, CC ECO:0000269|PubMed:9204896}. CC -!- INTERACTION: CC Q15389; Q15389: ANGPT1; NbExp=3; IntAct=EBI-2922365, EBI-2922365; CC Q15389; Q02763: TEK; NbExp=2; IntAct=EBI-2922365, EBI-2257090; CC Q15389-2; Q13387: MAPK8IP2; NbExp=3; IntAct=EBI-10692491, EBI-722813; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:8980223}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q15389-1; Sequence=Displayed; CC Name=2; Synonyms=Gly-269 del; CC IsoId=Q15389-2; Sequence=VSP_046324; CC -!- PTM: Glycosylated. CC -!- DISEASE: Angioedema, hereditary, 5 (HAE5) [MIM:619361]: A form of CC angioedema, a disorder characterized by episodic local swelling CC involving subcutaneous or submucous tissue of the upper respiratory and CC gastrointestinal tracts, face, extremities, and genitalia. HAE5 is an CC autosomal dominant form characterized by onset of episodic swelling of CC the face, lips, hands, and abdomen in the second decade of life. CC {ECO:0000269|PubMed:28601681, ECO:0000269|PubMed:30689269}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- MISCELLANEOUS: It may have a potential therapeutic utility since it can CC be used for specifically targeting tumor vasculature or for promoting CC angiogenic processes in certain organs such as an ischemic heart. CC -!- SEQUENCE CAUTION: CC Sequence=BAA02793.2; Type=Erroneous initiation; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Angiopoietin entry; CC URL="https://en.wikipedia.org/wiki/Angiopoietin"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U83508; AAB50557.1; -; mRNA. DR EMBL; AB084454; BAB91325.1; -; mRNA. DR EMBL; AY121504; AAM81745.1; -; mRNA. DR EMBL; AY124380; AAM92271.1; -; mRNA. DR EMBL; D13628; BAA02793.2; ALT_INIT; mRNA. DR EMBL; BX648814; CAI45984.1; -; mRNA. DR EMBL; AC091010; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP000428; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP003480; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471060; EAW91909.1; -; Genomic_DNA. DR EMBL; BC152411; AAI52412.1; -; mRNA. DR EMBL; BC152419; AAI52420.1; -; mRNA. DR CCDS; CCDS56551.1; -. [Q15389-2] DR CCDS; CCDS6306.1; -. [Q15389-1] DR RefSeq; NP_001137.2; NM_001146.4. [Q15389-1] DR RefSeq; NP_001186788.1; NM_001199859.2. [Q15389-2] DR RefSeq; NP_001300980.1; NM_001314051.1. DR PDB; 4EPU; X-ray; 2.10 A; A/B=282-497. DR PDB; 4JYO; X-ray; 2.50 A; X=280-498. DR PDB; 4K0V; X-ray; 4.51 A; B=280-498. DR PDBsum; 4EPU; -. DR PDBsum; 4JYO; -. DR PDBsum; 4K0V; -. DR AlphaFoldDB; Q15389; -. DR SMR; Q15389; -. DR BioGRID; 106781; 14. DR IntAct; Q15389; 3. DR MINT; Q15389; -. DR STRING; 9606.ENSP00000428340; -. DR ChEMBL; CHEMBL3217395; -. DR UniLectin; Q15389; -. DR GlyCosmos; Q15389; 5 sites, No reported glycans. DR GlyGen; Q15389; 6 sites, 1 O-linked glycan (1 site). DR iPTMnet; Q15389; -. DR PhosphoSitePlus; Q15389; -. DR BioMuta; ANGPT1; -. DR DMDM; 12229574; -. DR EPD; Q15389; -. DR jPOST; Q15389; -. DR MassIVE; Q15389; -. DR PaxDb; 9606-ENSP00000428340; -. DR PeptideAtlas; Q15389; -. DR ProteomicsDB; 60559; -. [Q15389-1] DR ABCD; Q15389; 3 sequenced antibodies. DR Antibodypedia; 4501; 768 antibodies from 40 providers. DR DNASU; 284; -. DR Ensembl; ENST00000297450.7; ENSP00000297450.3; ENSG00000154188.10. [Q15389-2] DR Ensembl; ENST00000517746.6; ENSP00000428340.1; ENSG00000154188.10. [Q15389-1] DR GeneID; 284; -. DR KEGG; hsa:284; -. DR MANE-Select; ENST00000517746.6; ENSP00000428340.1; NM_001146.5; NP_001137.2. DR UCSC; uc003ymn.4; human. [Q15389-1] DR AGR; HGNC:484; -. DR CTD; 284; -. DR DisGeNET; 284; -. DR GeneCards; ANGPT1; -. DR HGNC; HGNC:484; ANGPT1. DR HPA; ENSG00000154188; Tissue enhanced (seminal). DR MalaCards; ANGPT1; -. DR MIM; 601667; gene. DR MIM; 619361; phenotype. DR neXtProt; NX_Q15389; -. DR OpenTargets; ENSG00000154188; -. DR Orphanet; 599418; Hereditary angioedema with normal C1Inh not related to F12 or PLG variant. DR PharmGKB; PA24791; -. DR VEuPathDB; HostDB:ENSG00000154188; -. DR eggNOG; KOG2579; Eukaryota. DR GeneTree; ENSGT00940000158117; -. DR HOGENOM; CLU_038628_3_1_1; -. DR InParanoid; Q15389; -. DR OMA; HIGCNNQ; -. DR OrthoDB; 3134470at2759; -. DR PhylomeDB; Q15389; -. DR TreeFam; TF336658; -. DR PathwayCommons; Q15389; -. DR Reactome; R-HSA-210993; Tie2 Signaling. DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade. DR SignaLink; Q15389; -. DR SIGNOR; Q15389; -. DR BioGRID-ORCS; 284; 8 hits in 1123 CRISPR screens. DR ChiTaRS; ANGPT1; human. DR GeneWiki; Angiopoietin_1; -. DR GenomeRNAi; 284; -. DR Pharos; Q15389; Tbio. DR PRO; PR:Q15389; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; Q15389; Protein. DR Bgee; ENSG00000154188; Expressed in lower lobe of lung and 173 other cell types or tissues. DR ExpressionAtlas; Q15389; baseline and differential. DR GO; GO:0062023; C:collagen-containing extracellular matrix; IBA:GO_Central. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB. DR GO; GO:0005902; C:microvillus; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0030971; F:receptor tyrosine kinase binding; IPI:UniProtKB. DR GO; GO:0007171; P:activation of transmembrane receptor protein tyrosine kinase activity; IDA:UniProtKB. DR GO; GO:0001525; P:angiogenesis; IBA:GO_Central. DR GO; GO:0031589; P:cell-substrate adhesion; IEA:Ensembl. DR GO; GO:0072012; P:glomerulus vasculature development; ISS:UniProtKB. DR GO; GO:0030097; P:hemopoiesis; IEA:Ensembl. DR GO; GO:0030210; P:heparin biosynthetic process; IDA:UniProtKB. DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl. DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0007162; P:negative regulation of cell adhesion; IDA:UniProtKB. DR GO; GO:0002719; P:negative regulation of cytokine production involved in immune response; IEA:Ensembl. DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; IDA:UniProtKB. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl. DR GO; GO:0042308; P:negative regulation of protein import into nucleus; IEA:Ensembl. DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IEA:Ensembl. DR GO; GO:0043116; P:negative regulation of vascular permeability; IDA:UniProtKB. DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl. DR GO; GO:0050918; P:positive chemotaxis; IDA:UniProtKB. DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IDA:UniProtKB. DR GO; GO:1905605; P:positive regulation of blood-brain barrier permeability; IMP:ARUK-UCL. DR GO; GO:0045785; P:positive regulation of cell adhesion; IEA:Ensembl. DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IDA:UniProtKB. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:ARUK-UCL. DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IEA:Ensembl. DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:UniProtKB. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:UniProtKB. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:ARUK-UCL. DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:UniProtKB. DR GO; GO:0002092; P:positive regulation of receptor internalization; IDA:UniProtKB. DR GO; GO:0034394; P:protein localization to cell surface; IDA:UniProtKB. DR GO; GO:0043122; P:regulation of canonical NF-kappaB signal transduction; IEA:Ensembl. DR GO; GO:2000446; P:regulation of macrophage migration inhibitory factor signaling pathway; IEA:Ensembl. DR GO; GO:0014842; P:regulation of skeletal muscle satellite cell proliferation; IDA:UniProtKB. DR GO; GO:0032680; P:regulation of tumor necrosis factor production; IEA:Ensembl. DR GO; GO:0002040; P:sprouting angiogenesis; IDA:UniProtKB. DR GO; GO:0048014; P:Tie signaling pathway; IDA:UniProtKB. 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; Q15389; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Angiogenesis; Coiled coil; KW Developmental protein; Differentiation; Disease variant; Disulfide bond; KW Glycoprotein; Reference proteome; Secreted; Signal. FT SIGNAL 1..15 FT /evidence="ECO:0000255" FT CHAIN 16..498 FT /note="Angiopoietin-1" FT /id="PRO_0000009110" 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 VAR_SEQ 269 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:8980223, ECO:0000303|Ref.2, FT ECO:0000303|Ref.3" FT /id="VSP_046324" FT VARIANT 119 FT /note="A -> S (in HAE5; decreased oligomerization; FT decreased interaction with TEK; fails to form proper FT cell-cell adhesions in an in vitro model of endothelial FT cell barrier; dbSNP:rs764987358)" FT /evidence="ECO:0000269|PubMed:28601681, FT ECO:0000269|PubMed:30689269" FT /id="VAR_085814" FT VARIANT 225 FT /note="R -> C (in HAE5; uncertain significance; does not FT affect oligomerization; does not affect interaction with FT TEK; dbSNP:rs777414772)" FT /evidence="ECO:0000269|PubMed:28601681" FT /id="VAR_085815" FT VARIANT 247 FT /note="L -> P (in dbSNP:rs73701083)" FT /id="VAR_069165" FT VARIANT 494 FT /note="R -> Q (in HAE5; uncertain significance; does not FT affect oligomerization; does not affect interaction with FT TEK; dbSNP:rs377442517)" FT /evidence="ECO:0000269|PubMed:28601681" FT /id="VAR_085816" FT HELIX 286..291 FT /evidence="ECO:0007829|PDB:4EPU" FT STRAND 298..302 FT /evidence="ECO:0007829|PDB:4EPU" FT STRAND 311..316 FT /evidence="ECO:0007829|PDB:4EPU" FT HELIX 319..321 FT /evidence="ECO:0007829|PDB:4EPU" FT STRAND 324..333 FT /evidence="ECO:0007829|PDB:4EPU" FT HELIX 341..346 FT /evidence="ECO:0007829|PDB:4EPU" FT STRAND 353..356 FT /evidence="ECO:0007829|PDB:4EPU" FT HELIX 359..366 FT /evidence="ECO:0007829|PDB:4EPU" FT STRAND 371..378 FT /evidence="ECO:0007829|PDB:4EPU" FT STRAND 384..394 FT /evidence="ECO:0007829|PDB:4EPU" FT HELIX 397..399 FT /evidence="ECO:0007829|PDB:4EPU" FT STRAND 403..412 FT /evidence="ECO:0007829|PDB:4EPU" FT STRAND 433..437 FT /evidence="ECO:0007829|PDB:4EPU" FT HELIX 439..443 FT /evidence="ECO:0007829|PDB:4EPU" FT STRAND 450..452 FT /evidence="ECO:0007829|PDB:4EPU" FT STRAND 454..456 FT /evidence="ECO:0007829|PDB:4EPU" FT TURN 463..467 FT /evidence="ECO:0007829|PDB:4EPU" FT STRAND 473..476 FT /evidence="ECO:0007829|PDB:4EPU" FT TURN 477..479 FT /evidence="ECO:0007829|PDB:4EPU" FT STRAND 487..495 FT /evidence="ECO:0007829|PDB:4EPU" SQ SEQUENCE 498 AA; 57513 MW; 5D5FA63AEF6BE920 CRC64; MTVFLSFAFL AAILTHIGCS NQRRSPENSG RRYNRIQHGQ CAYTFILPEH DGNCRESTTD QYNTNALQRD APHVEPDFSS QKLQHLEHVM ENYTQWLQKL ENYIVENMKS EMAQIQQNAV QNHTATMLEI GTSLLSQTAE QTRKLTDVET QVLNQTSRLE IQLLENSLST YKLEKQLLQQ TNEILKIHEK NSLLEHKILE MEGKHKEELD TLKEEKENLQ GLVTRQTYII QELEKQLNRA TTNNSVLQKQ QLELMDTVHN LVNLCTKEGV LLKGGKREEE KPFRDCADVY QAGFNKSGIY TIYINNMPEP KKVFCNMDVN GGGWTVIQHR EDGSLDFQRG WKEYKMGFGN PSGEYWLGNE FIFAITSQRQ YMLRIELMDW EGNRAYSQYD RFHIGNEKQN YRLYLKGHTG TAGKQSSLIL HGADFSTKDA DNDNCMCKCA LMLTGGWWFD ACGPSNLNGM FYTAGQNHGK LNGIKWHYFK GPSYSLRSTT MMIRPLDF //