ANGP2_MOUSE
ID ANGP2_MOUSE Reviewed; 496 AA.
AC O35608; Q3U1A1; Q9D2D2;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2004, sequence version 2.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Angiopoietin-2;
DE Short=ANG-2;
DE Flags: Precursor;
GN Name=Angpt2; Synonyms=Agpt2;
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].
RC TISSUE=Uterus;
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Head, Ovary, Spleen, and Uterus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [4]
RP FUNCTION.
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. Can induce tyrosine phosphorylation of
CC TEK/TIE2 in the absence of ANGPT1. 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 (By similarity). Involved in the regulation of lymphangiogenesis
CC (PubMed:32908006). {ECO:0000250|UniProtKB:O15123,
CC ECO:0000269|PubMed:32908006}.
CC -!- SUBUNIT: Interacts with TEK/TIE2, competing for the same binding site
CC as ANGPT1. Interacts with ITGA5. {ECO:0000250|UniProtKB:O15123}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:O15123}.
CC -!- TISSUE SPECIFICITY: Expressed only at sites of vascular remodeling.
CC -!- DOMAIN: The Fibrinogen C-terminal domain mediates interaction with the
CC TEK/TIE2 receptor. {ECO:0000250}.
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DR EMBL; AF004326; AAB63189.1; -; mRNA.
DR EMBL; AK019860; BAB31887.1; -; mRNA.
DR EMBL; AK048622; BAC33396.1; -; mRNA.
DR EMBL; AK156132; BAE33599.1; -; mRNA.
DR EMBL; BC027216; AAH27216.1; -; mRNA.
DR CCDS; CCDS22125.1; -.
DR RefSeq; NP_031452.2; NM_007426.4.
DR AlphaFoldDB; O35608; -.
DR SMR; O35608; -.
DR IntAct; O35608; 1.
DR STRING; 10090.ENSMUSP00000033846; -.
DR GlyGen; O35608; 6 sites.
DR iPTMnet; O35608; -.
DR MetOSite; O35608; -.
DR PhosphoSitePlus; O35608; -.
DR MaxQB; O35608; -.
DR PaxDb; O35608; -.
DR PRIDE; O35608; -.
DR ProteomicsDB; 296293; -.
DR Antibodypedia; 4319; 625 antibodies from 41 providers.
DR DNASU; 11601; -.
DR Ensembl; ENSMUST00000033846; ENSMUSP00000033846; ENSMUSG00000031465.
DR GeneID; 11601; -.
DR KEGG; mmu:11601; -.
DR UCSC; uc009kzu.2; mouse.
DR CTD; 285; -.
DR MGI; MGI:1202890; Angpt2.
DR VEuPathDB; HostDB:ENSMUSG00000031465; -.
DR eggNOG; KOG2579; Eukaryota.
DR GeneTree; ENSGT00940000158430; -.
DR HOGENOM; CLU_038628_3_1_1; -.
DR InParanoid; O35608; -.
DR OMA; KIQLKDW; -.
DR OrthoDB; 357340at2759; -.
DR PhylomeDB; O35608; -.
DR TreeFam; TF336658; -.
DR Reactome; R-MMU-210993; Tie2 Signaling.
DR BioGRID-ORCS; 11601; 1 hit in 77 CRISPR screens.
DR PRO; PR:O35608; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; O35608; protein.
DR Bgee; ENSMUSG00000031465; Expressed in gastrula and 177 other tissues.
DR ExpressionAtlas; O35608; baseline and differential.
DR Genevisible; O35608; MM.
DR GO; GO:0042995; C:cell projection; ISO:MGI.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0048019; F:receptor antagonist activity; TAS:MGI.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; ISO:MGI.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0005172; F:vascular endothelial growth factor receptor binding; TAS:MGI.
DR GO; GO:0001525; P:angiogenesis; IGI:MGI.
DR GO; GO:0031100; P:animal organ regeneration; IEA:Ensembl.
DR GO; GO:0048514; P:blood vessel morphogenesis; IMP:MGI.
DR GO; GO:0001974; P:blood vessel remodeling; TAS:DFLAT.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IEA:Ensembl.
DR GO; GO:0007492; P:endoderm development; TAS:MGI.
DR GO; GO:0010467; P:gene expression; ISO:MGI.
DR GO; GO:0007281; P:germ cell development; IEA:Ensembl.
DR GO; GO:0072012; P:glomerulus vasculature development; ISO:MGI.
DR GO; GO:0030097; P:hemopoiesis; TAS:DFLAT.
DR GO; GO:0060135; P:maternal process involved in female pregnancy; IEA:Ensembl.
DR GO; GO:0016525; P:negative regulation of angiogenesis; IDA:MGI.
DR GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; ISO:MGI.
DR GO; GO:0010812; P:negative regulation of cell-substrate adhesion; IDA:MGI.
DR GO; GO:0050928; P:negative regulation of positive chemotaxis; ISO:MGI.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:MGI.
DR GO; GO:0045765; P:regulation of angiogenesis; TAS:DFLAT.
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:0048014; P:Tie signaling pathway; ISO:MGI.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; TAS:MGI.
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 2: Evidence at transcript level;
KW Angiogenesis; Calcium; Coiled coil; Developmental protein; Differentiation;
KW Disulfide bond; Glycoprotein; Metal-binding; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..496
FT /note="Angiopoietin-2"
FT /id="PRO_0000009114"
FT DOMAIN 275..495
FT /note="Fibrinogen C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT COILED 159..256
FT /evidence="ECO:0000255"
FT BINDING 429
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O15123"
FT BINDING 431
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O15123"
FT BINDING 433
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O15123"
FT BINDING 435
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O15123"
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:0000255|PROSITE-ProRule:PRU00739"
FT DISULFID 433..435
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT DISULFID 437..450
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT CONFLICT 348
FT /note="S -> N (in Ref. 1; AAB63189)"
FT /evidence="ECO:0000305"
FT CONFLICT 411
FT /note="G -> A (in Ref. 1; AAB63189)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 496 AA; 56576 MW; E7563B498A0EF331 CRC64;
MWQIIFLTFG WDLVLASAYS NFRKSVDSTG RRQYQVQNGP CSYTFLLPET DSCRSSSSPY
MSNAVQRDAP LDYDDSVQRL QVLENILENN TQWLMKLENY IQDNMKKEMV EIQQNVVQNQ
TAVMIEIGTS LLNQTAAQTR KLTDVEAQVL NQTTRLELQL LQHSISTNKL EKQILDQTSE
INKLQNKNSF LEQKVLDMEG KHSEQLQSMK EQKDELQVLV SKQSSVIDEL EKKLVTATVN
NSLLQKQQHD LMETVNSLLT MMSSPNSKSS VAIRKEEQTT FRDCAEIFKS GLTTSGIYTL
TFPNSTEEIK AYCDMDVGGG GWTVIQHRED GSVDFQRTWK EYKEGFGSPL GEYWLGNEFV
SQLTGQHRYV LKIQLKDWEG NEAHSLYDHF YLAGEESNYR IHLTGLTGTA GKISSISQPG
SDFSTKDSDN DKCICKCSQM LSGGWWFDAC GPSNLNGQYY PQKQNTNKFN GIKWYYWKGS
GYSLKATTMM IRPADF
