ANGP2_HUMAN
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 03-AUG-2022, entry version 182.
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 of
CC TEK/TIE2 in the absence of ANGPT1 (PubMed:15284220, PubMed:19116766,
CC PubMed:19223473,PubMed:9204896). In the absence of angiogenic inducers,
CC such as VEGF, ANGPT2-mediated loosening of cell-matrix contacts may
CC induce endothelial cell apoptosis with consequent vascular regression.
CC In concert with VEGF, it may facilitate endothelial cell migration and
CC proliferation, thus serving as a permissive angiogenic signal
CC (PubMed:15284220, PubMed:19116766, PubMed:19223473,PubMed:9204896).
CC Involved in the regulation of lymphangiogenesis (PubMed:32908006).
CC {ECO:0000269|PubMed:15284220, ECO:0000269|PubMed:19116766,
CC ECO:0000269|PubMed:19223473, ECO:0000269|PubMed:32908006,
CC 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). {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";
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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 GlyConnect; 664; 2 N-Linked glycans (2 sites).
DR GlyGen; O15123; 6 sites, 4 N-linked glycans (2 sites).
DR iPTMnet; O15123; -.
DR PhosphoSitePlus; O15123; -.
DR SwissPalm; O15123; -.
DR BioMuta; ANGPT2; -.
DR EPD; O15123; -.
DR jPOST; O15123; -.
DR MassIVE; O15123; -.
DR PaxDb; O15123; -.
DR PeptideAtlas; O15123; -.
DR PRIDE; 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; 625 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 CTD; 285; -.
DR DisGeNET; 285; -.
DR GeneCards; ANGPT2; -.
DR HGNC; HGNC:485; ANGPT2.
DR HPA; ENSG00000091879; Tissue enhanced (brain).
DR MIM; 601922; gene.
DR MIM; 619369; phenotype.
DR neXtProt; NX_O15123; -.
DR OpenTargets; ENSG00000091879; -.
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; KIQLKDW; -.
DR OrthoDB; 357340at2759; -.
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; 12 hits in 1076 CRISPR screens.
DR ChiTaRS; ANGPT2; human.
DR EvolutionaryTrace; O15123; -.
DR GeneWiki; ANGPT2; -.
DR GenomeRNAi; 285; -.
DR Pharos; O15123; Tbio.
DR PRO; PR:O15123; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; O15123; protein.
DR Bgee; ENSG00000091879; Expressed in tendon of biceps brachii and 151 other tissues.
DR ExpressionAtlas; O15123; baseline and differential.
DR Genevisible; O15123; HS.
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:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
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; IBA:GO_Central.
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:0009314; P:response to radiation; 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; -; 1.
DR InterPro; IPR028844; Ang-2.
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:SF199; PTHR19143:SF199; 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 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; unknown pathological
FT significance; results in increased lymphangiogenesis;
FT decreased interaction with ITGA5; no effect on protein
FT abundance; no effect on secretion; no effect on interaction
FT with TEK)"
FT /evidence="ECO:0000269|PubMed:32908006"
FT /id="VAR_085861"
FT VARIANT 304
FT /note="N -> K (in LMPHM10; unknown pathological
FT significance; no effect on protein abundance; reduced
FT secretion; reduced glycosylation; no effect on interaction
FT with TEK)"
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; unknown pathological
FT significance; no effect on protein abundance; severely
FT 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
