ID ANGP4_HUMAN Reviewed; 503 AA. AC Q9Y264; B4E3J9; Q5TFF4; Q9H4Z4; DT 29-AUG-2001, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1999, sequence version 1. DT 16-SEP-2015, entry version 119. DE RecName: Full=Angiopoietin-4; DE Short=ANG-4; DE AltName: Full=Angiopoietin-3; DE Short=ANG-3; DE Flags: Precursor; GN Name=ANGPT4; Synonyms=ANG3, ANG4; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Aorta; RX PubMed=10218486; DOI=10.1016/S0014-5793(99)00381-6; RA Nishimura M., Miki T., Yashima R., Yokoi N., Yano H., Sato Y., RA Seino S.; RT "Angiopoietin-3, a novel member of the angiopoietin family."; RL FEBS Lett. 448:254-256(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Ovary; RX PubMed=10051567; DOI=10.1073/pnas.96.5.1904; RA Valenzuela D.M., Griffiths J.A., Rojas J., Aldrich T.H., Jones P.F., RA Zhou H., McClain J., Copeland N.G., Gilbert D.J., Jenkins N.A., RA Huang T., Papadopoulos N., Maisonpierre P.C., Davis S., RA Yancopoulos G.D.; RT "Angiopoietins 3 and 4: diverging gene counterparts in mice and RT humans."; RL Proc. Natl. Acad. Sci. U.S.A. 96:1904-1909(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Uterus; 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=11780052; DOI=10.1038/414865a; RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., RA Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., RA Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 20."; RL Nature 414:865-871(2001). RN [5] 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP FUNCTION IN REGULATION OF ANGIOGENESIS; CELL SURVIVAL; CELL MIGRATION RP AND ACTIVATION OF AKT1, SUBUNIT, 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., RA Kim J.H., 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 [7] 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). CC -!- FUNCTION: Binds to TEK/TIE2, modulating ANGPT1 signaling. Can CC induce tyrosine phosphorylation of TEK/TIE2. Promotes endothelial CC cell survival, migration and angiogenesis. CC {ECO:0000269|PubMed:15284220}. CC -!- SUBUNIT: Homodimer; disulfide-linked. Interacts with TEK/TIE2. CC {ECO:0000269|PubMed:15284220}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9Y264-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9Y264-2; Sequence=VSP_055091; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Highly expressed in the lung with much lower CC levels found in other tissues. CC -!- SIMILARITY: Contains 1 fibrinogen C-terminal domain. CC {ECO:0000255|PROSITE-ProRule:PRU00739}. 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; AF074332; AAD31728.1; -; mRNA. DR EMBL; AF113708; AAD21587.1; -; mRNA. DR EMBL; AK304756; BAG65511.1; -; mRNA. DR EMBL; AL161939; CAC09933.2; -; Genomic_DNA. DR EMBL; AL050325; CAC09933.2; JOINED; Genomic_DNA. DR EMBL; AL050325; CAI22922.1; -; Genomic_DNA. DR EMBL; AL161939; CAI22922.1; JOINED; Genomic_DNA. DR EMBL; BC111976; AAI11977.1; -; mRNA. DR EMBL; BC111978; AAI11979.1; -; mRNA. DR CCDS; CCDS13009.1; -. [Q9Y264-1] DR RefSeq; NP_057069.1; NM_015985.2. [Q9Y264-1] DR RefSeq; XP_005260777.1; XM_005260720.2. [Q9Y264-2] DR UniGene; Hs.278973; -. DR ProteinModelPortal; Q9Y264; -. DR SMR; Q9Y264; 171-502. DR BioGrid; 119510; 2. DR IntAct; Q9Y264; 1. DR STRING; 9606.ENSP00000371347; -. DR PhosphoSite; Q9Y264; -. DR BioMuta; ANGPT4; -. DR DMDM; 17433288; -. DR PaxDb; Q9Y264; -. DR PRIDE; Q9Y264; -. DR DNASU; 51378; -. DR Ensembl; ENST00000381922; ENSP00000371347; ENSG00000101280. [Q9Y264-1] DR GeneID; 51378; -. DR KEGG; hsa:51378; -. DR UCSC; uc002wei.3; human. [Q9Y264-1] DR UCSC; uc010zpn.2; human. DR CTD; 51378; -. DR GeneCards; GC20M000869; -. DR HGNC; HGNC:487; ANGPT4. DR HPA; CAB013260; -. DR HPA; CAB013305; -. DR MIM; 603705; gene. DR neXtProt; NX_Q9Y264; -. DR PharmGKB; PA24793; -. DR eggNOG; NOG273522; -. DR GeneTree; ENSGT00760000118809; -. DR HOGENOM; HOG000037128; -. DR HOVERGEN; HBG001644; -. DR InParanoid; Q9Y264; -. DR KO; K05467; -. DR OMA; YYPARHH; -. DR OrthoDB; EOG7X9G60; -. DR PhylomeDB; Q9Y264; -. DR TreeFam; TF336658; -. DR Reactome; R-HSA-210993; Tie2 Signaling. DR SignaLink; Q9Y264; -. DR GeneWiki; ANGPT4; -. DR GenomeRNAi; 51378; -. DR NextBio; 35477558; -. DR PRO; PR:Q9Y264; -. DR Proteomes; UP000005640; Chromosome 20. DR Bgee; Q9Y264; -. DR CleanEx; HS_ANGPT4; -. DR Genevisible; Q9Y264; HS. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0030971; F:receptor tyrosine kinase binding; IDA:UniProtKB. DR GO; GO:0030297; F:transmembrane receptor protein tyrosine kinase activator activity; IDA:UniProtKB. DR GO; GO:0007171; P:activation of transmembrane receptor protein tyrosine kinase activity; IDA:GOC. DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW. DR GO; GO:0007596; P:blood coagulation; TAS:Reactome. DR GO; GO:0071456; P:cellular response to hypoxia; IEP:UniProtKB. DR GO; GO:0050900; P:leukocyte migration; TAS:Reactome. DR GO; GO:0016525; P:negative regulation of angiogenesis; IDA:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; IDA:UniProtKB. DR GO; GO:0045766; P:positive regulation of angiogenesis; IDA:UniProtKB. DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IDA:UniProtKB. DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IDA:UniProtKB. DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:UniProtKB. DR Gene3D; 3.90.215.10; -; 1. DR Gene3D; 4.10.530.10; -; 1. DR InterPro; IPR028845; Ang-4. DR InterPro; IPR014716; Fibrinogen_a/b/g_C_1. DR InterPro; IPR014715; Fibrinogen_a/b/g_C_2. DR InterPro; IPR002181; Fibrinogen_a/b/g_C_dom. DR InterPro; IPR020837; Fibrinogen_CS. DR PANTHER; PTHR19143:SF31; PTHR19143:SF31; 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 Alternative splicing; Angiogenesis; Coiled coil; Complete proteome; KW Disulfide bond; Glycoprotein; Polymorphism; Reference proteome; KW Secreted; Signal. FT SIGNAL 1 24 {ECO:0000255}. FT CHAIN 25 503 Angiopoietin-4. FT /FTId=PRO_0000009116. FT DOMAIN 282 502 Fibrinogen C-terminal. FT {ECO:0000255|PROSITE-ProRule:PRU00739}. FT COILED 84 238 {ECO:0000255}. FT CARBOHYD 96 96 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 126 126 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 140 140 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 158 158 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 247 247 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 274 274 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 311 311 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 337 337 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 427 427 N-linked (GlcNAc...). {ECO:0000255}. FT DISULFID 291 320 {ECO:0000255|PROSITE-ProRule:PRU00739}. FT DISULFID 444 457 {ECO:0000255|PROSITE-ProRule:PRU00739}. FT VAR_SEQ 408 503 LSVVGYSGSAGRQSSLVLQNTSFSTLDSDNDHCLCKCAQVM FT SGGWWFDACGLSNLNGVYYHAPDNKYKMDGIRWHYFKGPSY FT SLRASRMMIRPLDI -> VVV (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_055091. FT VARIANT 395 395 E -> K (in dbSNP:rs869171). FT /FTId=VAR_049070. SQ SEQUENCE 503 AA; 56849 MW; 79CE52F66B532340 CRC64; MLSQLAMLQG SLLLVVATMS VAQQTRQEAD RGCETLVVQH GHCSYTFLLP KSEPCPPGPE VSRDSNTLQR ESLANPLHLG KLPTQQVKQL EQALQNNTQW LKKLERAIKT ILRSKLEQVQ QQMAQNQTAP MLELGTSLLN QTTAQIRKLT DMEAQLLNQT SRMDAQMPET FLSTNKLENQ LLLQRQKLQQ LQGQNSALEK RLQALETKQQ EELASILSKK AKLLNTLSRQ SAALTNIERG LRGVRHNSSL LQDQQHSLRQ LLVLLRHLVQ ERANASAPAF IMAGEQVFQD CAEIQRSGAS ASGVYTIQVS NATKPRKVFC DLQSSGGRWT LIQRRENGTV NFQRNWKDYK QGFGDPAGEH WLGNEVVHQL TRRAAYSLRV ELQDWEGHEA YAQYEHFHLG SENQLYRLSV VGYSGSAGRQ SSLVLQNTSF STLDSDNDHC LCKCAQVMSG GWWFDACGLS NLNGVYYHAP DNKYKMDGIR WHYFKGPSYS LRASRMMIRP LDI //