ID ANGP2_HUMAN Reviewed; 496 AA. AC O15123; A0AV38; A8K205; B7ZLM7; Q9NRR7; Q9P2Y7; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1998, sequence version 1. DT 27-MAR-2024, entry version 191. DE RecName: Full=Angiopoietin-2; DE Short=ANG-2; DE Flags: Precursor; GN Name=ANGPT2; 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 1), INTERACTION WITH TEK/TIE2, AND RP FUNCTION. RC TISSUE=Lung; 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 [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RX PubMed=9927494; DOI=10.1172/jci4891; RA Tanaka S., Mori M., Sakamoto Y., Makuuchi M., Sugimachi K., Wands J.R.; RT "Biologic significance of angiopoietin-2 expression in human hepatocellular RT carcinoma."; RL J. Clin. Invest. 103:341-345(1999). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). RC TISSUE=Umbilical vein endothelial cell; RX PubMed=10766762; DOI=10.1074/jbc.m910084199; RA Kim I., Kim J.-H., Ryu Y.S., Jung S.H., Nah J.J., Koh G.Y.; RT "Characterization and expression of a novel alternatively spliced human RT angiopoietin-2."; RL J. Biol. Chem. 275:18550-18556(2000). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Substantia nigra; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Colon; 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 INTERACTION WITH TEK/TIE2. 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 [9] 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 [10] RP FUNCTION. RX PubMed=19116766; DOI=10.1007/s10456-008-9126-0; RA Yacyshyn O.K., Lai P.F.H., Forse K., Teichert-Kuliszewska K., Jurasz P., RA Stewart D.J.; RT "Tyrosine phosphatase beta regulates angiopoietin-Tie2 signaling in human RT endothelial cells."; RL Angiogenesis 12:25-33(2009). RN [11] RP FUNCTION, AND INTERACTION WITH TEK/TIE2. RX PubMed=19223473; DOI=10.1128/mcb.01472-08; RA Yuan H.T., Khankin E.V., Karumanchi S.A., Parikh S.M.; RT "Angiopoietin 2 is a partial agonist/antagonist of Tie2 signaling in the RT endothelium."; RL Mol. Cell. Biol. 29:2011-2022(2009). RN [12] 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 [13] RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 281-496 IN COMPLEX WITH CALCIUM RP IONS, DISULFIDE BONDS, AND CALCIUM-BINDING SITES. RX PubMed=15893672; DOI=10.1016/j.str.2005.03.009; RA Barton W.A., Tzvetkova D., Nikolov D.B.; RT "Structure of the angiopoietin-2 receptor binding domain and identification RT of surfaces involved in Tie2 recognition."; RL Structure 13:825-832(2005). RN [14] RP X-RAY CRYSTALLOGRAPHY (3.7 ANGSTROMS) OF 281-495 IN COMPLEX WITH CALCIUM RP IONS AND TEK, DISULFIDE BONDS, AND CALCIUM-BINDING SITES. RX PubMed=16732286; DOI=10.1038/nsmb1101; RA Barton W.A., Tzvetkova-Robev D., Miranda E.P., Kolev M.V., RA Rajashankar K.R., Himanen J.P., Nikolov D.B.; RT "Crystal structures of the Tie2 receptor ectodomain and the angiopoietin-2- RT Tie2 complex."; RL Nat. Struct. Mol. Biol. 13:524-532(2006). RN [15] RP VARIANTS LMPHM10 MET-299; LYS-304; SER-435 AND GLN-492, CHARACTERIZATION OF RP VARIANTS LMPHM10 MET-299; LYS-304; SER-435 AND GLN-492, INVOLVEMENT IN RP LMPHM10, FUNCTION, INTERACTION WITH TEK AND ITGA5, AND SUBCELLULAR RP LOCATION. RX PubMed=32908006; DOI=10.1126/scitranslmed.aax8013; RA Leppaenen V.M., Brouillard P., Korhonen E.A., Sipilae T., Jha S.K., RA Revencu N., Labarque V., Fastre E., Schloegel M., Ravoet M., Singer A., RA Luzzatto C., Angelone D., Crichiutti G., D'Elia A., Kuurne J., Elamaa H., RA Koh G.Y., Saharinen P., Vikkula M., Alitalo K.; RT "Characterization of ANGPT2 mutations associated with primary lymphedema."; RL Sci. Transl. Med. 12:0-0(2020). CC -!- FUNCTION: Binds to TEK/TIE2, competing for the ANGPT1 binding site, and CC modulating ANGPT1 signaling (PubMed:15284220, PubMed:19116766, CC PubMed:19223473, PubMed:9204896). Can induce tyrosine phosphorylation CC of TEK/TIE2 in the absence of ANGPT1 (PubMed:15284220, PubMed:19116766, CC PubMed:19223473, PubMed:9204896). In the absence of angiogenic CC inducers, such as VEGF, ANGPT2-mediated loosening of cell-matrix CC contacts may induce endothelial cell apoptosis with consequent vascular CC regression. In concert with VEGF, it may facilitate endothelial cell CC migration and proliferation, thus serving as a permissive angiogenic CC signal (PubMed:15284220, PubMed:19116766, PubMed:19223473, CC PubMed:9204896). Involved in the regulation of lymphangiogenesis CC (PubMed:32908006). {ECO:0000269|PubMed:15284220, CC ECO:0000269|PubMed:19116766, ECO:0000269|PubMed:19223473, CC ECO:0000269|PubMed:32908006, ECO:0000269|PubMed:9204896}. CC -!- SUBUNIT: Interacts with TEK/TIE2, competing for the same binding site CC as ANGPT1 (PubMed:9204896, PubMed:12427764, PubMed:15284220, CC PubMed:19223473, PubMed:32908006). Interacts with ITGA5 CC (PubMed:32908006). Interacts with SVEP1/polydom (By similarity). CC {ECO:0000250|UniProtKB:O35608, ECO:0000269|PubMed:12427764, CC ECO:0000269|PubMed:15284220, ECO:0000269|PubMed:16732286, CC ECO:0000269|PubMed:19223473, ECO:0000269|PubMed:32908006, CC ECO:0000269|PubMed:9204896}. CC -!- INTERACTION: CC O15123; Q02763: TEK; NbExp=4; IntAct=EBI-2912111, EBI-2257090; CC O15123-1; Q02763: TEK; NbExp=5; IntAct=EBI-15552475, EBI-2257090; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:32908006}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=O15123-1; Sequence=Displayed; CC Name=3; CC IsoId=O15123-2; Sequence=VSP_001540; CC Name=2; CC IsoId=O15123-3; Sequence=VSP_040096; CC -!- DOMAIN: The Fibrinogen C-terminal domain mediates interaction with the CC TEK/TIE2 receptor. CC -!- DISEASE: Lymphatic malformation 10 (LMPHM10) [MIM:619369]: A form of CC primary lymphedema, a disease characterized by swelling of body parts CC due to developmental anomalies and functional defects of the lymphatic CC system. Patients with lymphedema may suffer from recurrent local CC infections. LMPHM10 is an autosomal dominant form characterized by the CC onset of swelling in the lower extremities within the first year of CC life. Lymphedema may also occur in the neck, upper extremities, and CC scrotum or labia majora. Gradual resorption generally occurs, although CC some patients may experience progression complicated by cellulitis. CC Incomplete penetrance has been observed in some families. CC {ECO:0000269|PubMed:32908006}. Note=The disease is caused by variants CC affecting the gene represented in this entry. 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; AF004327; AAB63190.1; -; mRNA. DR EMBL; AB009865; BAA95590.1; -; mRNA. DR EMBL; AF187858; AAF76526.1; -; mRNA. DR EMBL; AK290070; BAF82759.1; -; mRNA. DR EMBL; AC018398; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471153; EAW80474.1; -; Genomic_DNA. DR EMBL; BC126200; AAI26201.1; -; mRNA. DR EMBL; BC126202; AAI26203.1; -; mRNA. DR EMBL; BC143902; AAI43903.1; -; mRNA. DR CCDS; CCDS47761.1; -. [O15123-2] DR CCDS; CCDS47762.1; -. [O15123-3] DR CCDS; CCDS5958.1; -. [O15123-1] DR RefSeq; NP_001112359.1; NM_001118887.1. [O15123-3] DR RefSeq; NP_001112360.1; NM_001118888.1. [O15123-2] DR RefSeq; NP_001138.1; NM_001147.2. [O15123-1] DR PDB; 1Z3S; X-ray; 2.35 A; A/B=281-496. DR PDB; 1Z3U; X-ray; 2.25 A; A/B/C/D=281-496. DR PDB; 2GY7; X-ray; 3.70 A; A=281-495. DR PDB; 4JZC; X-ray; 1.90 A; A=279-496. DR PDB; 4ZFG; X-ray; 2.27 A; A=277-496. DR PDBsum; 1Z3S; -. DR PDBsum; 1Z3U; -. DR PDBsum; 2GY7; -. DR PDBsum; 4JZC; -. DR PDBsum; 4ZFG; -. DR AlphaFoldDB; O15123; -. DR SMR; O15123; -. DR BioGRID; 106782; 19. DR DIP; DIP-6048N; -. DR IntAct; O15123; 10. DR MINT; O15123; -. DR STRING; 9606.ENSP00000314897; -. DR ChEMBL; CHEMBL3580489; -. DR DrugBank; DB15303; Faricimab. DR DrugBank; DB12317; Vanucizumab. DR UniLectin; O15123; -. DR GlyConnect; 664; 2 N-Linked glycans (2 sites). DR GlyCosmos; O15123; 6 sites, 4 glycans. DR GlyGen; O15123; 7 sites, 4 N-linked glycans (2 sites), 1 O-linked glycan (1 site). DR iPTMnet; O15123; -. DR PhosphoSitePlus; O15123; -. DR SwissPalm; O15123; -. DR BioMuta; ANGPT2; -. DR EPD; O15123; -. DR jPOST; O15123; -. DR MassIVE; O15123; -. DR PaxDb; 9606-ENSP00000314897; -. DR PeptideAtlas; O15123; -. DR ProteomicsDB; 48460; -. [O15123-1] DR ProteomicsDB; 48461; -. [O15123-2] DR ProteomicsDB; 48462; -. [O15123-3] DR ABCD; O15123; 119 sequenced antibodies. DR Antibodypedia; 4319; 934 antibodies from 41 providers. DR DNASU; 285; -. DR Ensembl; ENST00000325203.9; ENSP00000314897.5; ENSG00000091879.14. [O15123-1] DR Ensembl; ENST00000338312.10; ENSP00000343517.6; ENSG00000091879.14. [O15123-2] DR Ensembl; ENST00000629816.3; ENSP00000486858.2; ENSG00000091879.14. [O15123-3] DR GeneID; 285; -. DR KEGG; hsa:285; -. DR MANE-Select; ENST00000629816.3; ENSP00000486858.2; NM_001118887.2; NP_001112359.1. [O15123-3] DR UCSC; uc003wqj.6; human. [O15123-1] DR AGR; HGNC:485; -. DR CTD; 285; -. DR DisGeNET; 285; -. DR GeneCards; ANGPT2; -. DR HGNC; HGNC:485; ANGPT2. DR HPA; ENSG00000091879; Low tissue specificity. DR MalaCards; ANGPT2; -. DR MIM; 601922; gene. DR MIM; 619369; phenotype. DR neXtProt; NX_O15123; -. DR OpenTargets; ENSG00000091879; -. DR Orphanet; 79452; Milroy disease. DR Orphanet; 363999; Non-immune hydrops fetalis. DR PharmGKB; PA24792; -. DR VEuPathDB; HostDB:ENSG00000091879; -. DR eggNOG; KOG2579; Eukaryota. DR GeneTree; ENSGT00940000158430; -. DR InParanoid; O15123; -. DR OMA; EQKYRIY; -. DR OrthoDB; 3134470at2759; -. DR PhylomeDB; O15123; -. DR TreeFam; TF336658; -. DR PathwayCommons; O15123; -. DR Reactome; R-HSA-210993; Tie2 Signaling. DR SignaLink; O15123; -. DR SIGNOR; O15123; -. DR BioGRID-ORCS; 285; 13 hits in 1154 CRISPR screens. DR ChiTaRS; ANGPT2; human. DR EvolutionaryTrace; O15123; -. DR GeneWiki; ANGPT2; -. DR GenomeRNAi; 285; -. DR Pharos; O15123; Tclin. DR PRO; PR:O15123; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; O15123; Protein. DR Bgee; ENSG00000091879; Expressed in tendon of biceps brachii and 153 other cell types or tissues. DR ExpressionAtlas; O15123; baseline and differential. DR GO; GO:0042995; C:cell projection; IEA:Ensembl. DR GO; GO:0062023; C:collagen-containing extracellular matrix; IBA:GO_Central. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0030971; F:receptor tyrosine kinase binding; IPI:UniProtKB. DR GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc. DR GO; GO:0001525; P:angiogenesis; IBA:GO_Central. DR GO; GO:0031100; P:animal organ regeneration; IEA:Ensembl. DR GO; GO:0071363; P:cellular response to growth factor stimulus; IEA:Ensembl. DR GO; GO:0010467; P:gene expression; IDA:MGI. DR GO; GO:0007281; P:germ cell development; IEA:Ensembl. DR GO; GO:0072012; P:glomerulus vasculature development; ISS:UniProtKB. DR GO; GO:0060135; P:maternal process involved in female pregnancy; IEA:Ensembl. DR GO; GO:0016525; P:negative regulation of angiogenesis; IEA:Ensembl. DR GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; IDA:UniProtKB. DR GO; GO:0010812; P:negative regulation of cell-substrate adhesion; IEA:Ensembl. DR GO; GO:0050928; P:negative regulation of positive chemotaxis; IDA:UniProtKB. DR GO; GO:0045766; P:positive regulation of angiogenesis; IEA:Ensembl. DR GO; GO:0014823; P:response to activity; IEA:Ensembl. DR GO; GO:0009749; P:response to glucose; IEA:Ensembl. DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl. DR GO; GO:0009612; P:response to mechanical stimulus; IEA:Ensembl. DR GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. 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:SF199; ANGIOPOIETIN-2; 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; O15123; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Angiogenesis; Calcium; Coiled coil; KW Developmental protein; Differentiation; Disease variant; Disulfide bond; KW Glycoprotein; Metal-binding; Reference proteome; Secreted; Signal. FT SIGNAL 1..18 FT /evidence="ECO:0000255" FT CHAIN 19..496 FT /note="Angiopoietin-2" FT /id="PRO_0000009113" FT DOMAIN 275..495 FT /note="Fibrinogen C-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739" FT COILED 166..248 FT /evidence="ECO:0000255" FT BINDING 429 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:15893672, FT ECO:0000269|PubMed:16732286, ECO:0007744|PDB:1Z3U" FT BINDING 431 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:15893672, FT ECO:0000269|PubMed:16732286, ECO:0007744|PDB:1Z3U" FT BINDING 433 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:15893672, FT ECO:0000269|PubMed:16732286, ECO:0007744|PDB:1Z3U" FT BINDING 435 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:15893672, FT ECO:0000269|PubMed:16732286, ECO:0007744|PDB:1Z3U" FT CARBOHYD 89 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 119 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 133 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 151 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 240 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 304 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 284..313 FT /evidence="ECO:0000269|PubMed:15893672, FT ECO:0000269|PubMed:16732286, ECO:0007744|PDB:1Z3U" FT DISULFID 433..435 FT /evidence="ECO:0000269|PubMed:15893672, FT ECO:0000269|PubMed:16732286, ECO:0007744|PDB:1Z3U" FT DISULFID 437..450 FT /evidence="ECO:0000269|PubMed:15893672, FT ECO:0000269|PubMed:16732286, ECO:0007744|PDB:1Z3U" FT VAR_SEQ 97..148 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:10766762" FT /id="VSP_001540" FT VAR_SEQ 268 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:9927494" FT /id="VSP_040096" FT VARIANT 299 FT /note="T -> M (in LMPHM10; uncertain significance; results FT in increased lymphangiogenesis; decreased interaction with FT ITGA5; no effect on protein abundance; no effect on FT secretion; no effect on interaction with TEK; FT dbSNP:rs61733318)" FT /evidence="ECO:0000269|PubMed:32908006" FT /id="VAR_085861" FT VARIANT 304 FT /note="N -> K (in LMPHM10; uncertain significance; no FT effect on protein abundance; reduced secretion; reduced FT glycosylation; no effect on interaction with TEK; FT dbSNP:rs767462360)" FT /evidence="ECO:0000269|PubMed:32908006" FT /id="VAR_085862" FT VARIANT 333 FT /note="V -> I (in dbSNP:rs7813215)" FT /id="VAR_049069" FT VARIANT 435 FT /note="C -> S (in LMPHM10; no effect on protein abundance; FT mutant protein is not secreted; loss of interaction with FT TEK)" FT /evidence="ECO:0000269|PubMed:32908006" FT /id="VAR_085863" FT VARIANT 492 FT /note="R -> Q (in LMPHM10; uncertain significance; no FT effect on protein abundance; severely decreased secretion)" FT /evidence="ECO:0000269|PubMed:32908006" FT /id="VAR_085864" FT STRAND 281..283 FT /evidence="ECO:0007829|PDB:4JZC" FT HELIX 284..289 FT /evidence="ECO:0007829|PDB:4JZC" FT STRAND 296..301 FT /evidence="ECO:0007829|PDB:4JZC" FT STRAND 308..314 FT /evidence="ECO:0007829|PDB:4JZC" FT HELIX 317..319 FT /evidence="ECO:0007829|PDB:4ZFG" FT STRAND 322..331 FT /evidence="ECO:0007829|PDB:4JZC" FT HELIX 339..344 FT /evidence="ECO:0007829|PDB:4JZC" FT STRAND 351..354 FT /evidence="ECO:0007829|PDB:4JZC" FT HELIX 357..364 FT /evidence="ECO:0007829|PDB:4JZC" FT STRAND 369..376 FT /evidence="ECO:0007829|PDB:4JZC" FT STRAND 378..380 FT /evidence="ECO:0007829|PDB:1Z3U" FT STRAND 382..392 FT /evidence="ECO:0007829|PDB:4JZC" FT HELIX 395..397 FT /evidence="ECO:0007829|PDB:4JZC" FT STRAND 401..410 FT /evidence="ECO:0007829|PDB:4JZC" FT STRAND 431..435 FT /evidence="ECO:0007829|PDB:4JZC" FT HELIX 437..441 FT /evidence="ECO:0007829|PDB:4JZC" FT STRAND 448..450 FT /evidence="ECO:0007829|PDB:4JZC" FT STRAND 452..454 FT /evidence="ECO:0007829|PDB:4JZC" FT STRAND 471..474 FT /evidence="ECO:0007829|PDB:4ZFG" FT HELIX 475..478 FT /evidence="ECO:0007829|PDB:4JZC" FT STRAND 485..493 FT /evidence="ECO:0007829|PDB:4JZC" SQ SEQUENCE 496 AA; 56919 MW; 5642A58847A7385C CRC64; MWQIVFFTLS CDLVLAAAYN NFRKSMDSIG KKQYQVQHGS CSYTFLLPEM DNCRSSSSPY VSNAVQRDAP LEYDDSVQRL QVLENIMENN TQWLMKLENY IQDNMKKEMV EIQQNAVQNQ TAVMIEIGTN LLNQTAEQTR KLTDVEAQVL NQTTRLELQL LEHSLSTNKL EKQILDQTSE INKLQDKNSF LEKKVLAMED KHIIQLQSIK EEKDQLQVLV SKQNSIIEEL EKKIVTATVN NSVLQKQQHD LMETVNNLLT MMSTSNSAKD PTVAKEEQIS FRDCAEVFKS GHTTNGIYTL TFPNSTEEIK AYCDMEAGGG GWTIIQRRED GSVDFQRTWK EYKVGFGNPS GEYWLGNEFV SQLTNQQRYV LKIHLKDWEG NEAYSLYEHF YLSSEELNYR IHLKGLTGTA GKISSISQPG NDFSTKDGDN DKCICKCSQM LTGGWWFDAC GPSNLNGMYY PQRQNTNKFN GIKWYYWKGS GYSLKATTMM IRPADF //