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 24-JAN-2024, entry version 169.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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., 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., Huang T.,
RA Papadopoulos N., Maisonpierre P.C., Davis S., Yancopoulos G.D.;
RT "Angiopoietins 3 and 4: diverging gene counterparts in mice and 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., 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 [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., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., 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., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., 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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION IN REGULATION OF ANGIOGENESIS; CELL SURVIVAL; CELL MIGRATION AND
RP 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., 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 [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 induce
CC tyrosine phosphorylation of TEK/TIE2. Promotes endothelial cell
CC survival, migration and angiogenesis. {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 -!- TISSUE SPECIFICITY: Highly expressed in the lung with much lower levels
CC found in other tissues.
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DR EMBL; AF074332; AAD31728.1; -; mRNA.
DR EMBL; AF113708; AAD21587.1; -; mRNA.
DR EMBL; AK304756; BAG65511.1; -; mRNA.
DR EMBL; AL050325; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL161939; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC111976; AAI11977.1; -; mRNA.
DR EMBL; BC111978; AAI11979.1; -; mRNA.
DR CCDS; CCDS13009.1; -. [Q9Y264-1]
DR RefSeq; NP_001309738.1; NM_001322809.1. [Q9Y264-2]
DR RefSeq; NP_057069.1; NM_015985.3. [Q9Y264-1]
DR AlphaFoldDB; Q9Y264; -.
DR SMR; Q9Y264; -.
DR BioGRID; 119510; 46.
DR IntAct; Q9Y264; 3.
DR STRING; 9606.ENSP00000371347; -.
DR GlyCosmos; Q9Y264; 9 sites, No reported glycans.
DR GlyGen; Q9Y264; 9 sites.
DR iPTMnet; Q9Y264; -.
DR PhosphoSitePlus; Q9Y264; -.
DR BioMuta; ANGPT4; -.
DR DMDM; 17433288; -.
DR EPD; Q9Y264; -.
DR MassIVE; Q9Y264; -.
DR PaxDb; 9606-ENSP00000371347; -.
DR PeptideAtlas; Q9Y264; -.
DR ABCD; Q9Y264; 10 sequenced antibodies.
DR Antibodypedia; 23019; 303 antibodies from 27 providers.
DR DNASU; 51378; -.
DR Ensembl; ENST00000381922.5; ENSP00000371347.3; ENSG00000101280.8. [Q9Y264-1]
DR GeneID; 51378; -.
DR KEGG; hsa:51378; -.
DR MANE-Select; ENST00000381922.5; ENSP00000371347.3; NM_015985.4; NP_057069.1.
DR UCSC; uc002wei.4; human. [Q9Y264-1]
DR AGR; HGNC:487; -.
DR CTD; 51378; -.
DR DisGeNET; 51378; -.
DR GeneCards; ANGPT4; -.
DR HGNC; HGNC:487; ANGPT4.
DR HPA; ENSG00000101280; Tissue enhanced (adipose tissue, breast).
DR MIM; 603705; gene.
DR neXtProt; NX_Q9Y264; -.
DR OpenTargets; ENSG00000101280; -.
DR PharmGKB; PA24793; -.
DR VEuPathDB; HostDB:ENSG00000101280; -.
DR eggNOG; KOG2579; Eukaryota.
DR GeneTree; ENSGT00940000160129; -.
DR HOGENOM; CLU_038628_3_1_1; -.
DR InParanoid; Q9Y264; -.
DR OMA; HAPDNKY; -.
DR OrthoDB; 3134470at2759; -.
DR PhylomeDB; Q9Y264; -.
DR TreeFam; TF336658; -.
DR PathwayCommons; Q9Y264; -.
DR Reactome; R-HSA-210993; Tie2 Signaling.
DR SignaLink; Q9Y264; -.
DR SIGNOR; Q9Y264; -.
DR BioGRID-ORCS; 51378; 13 hits in 1144 CRISPR screens.
DR ChiTaRS; ANGPT4; human.
DR GeneWiki; ANGPT4; -.
DR GenomeRNAi; 51378; -.
DR Pharos; Q9Y264; Tbio.
DR PRO; PR:Q9Y264; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9Y264; Protein.
DR Bgee; ENSG00000101280; Expressed in subcutaneous adipose tissue and 90 other cell types or tissues.
DR Genevisible; Q9Y264; HS.
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: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:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0071456; P:cellular response to hypoxia; IEP:UniProtKB.
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:0007219; P:Notch signaling pathway; IEA:Ensembl.
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 GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR CDD; cd00087; FReD; 1.
DR Gene3D; 3.90.215.10; Gamma Fibrinogen, chain A, domain 1; 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:SF31; ANGIOPOIETIN-4; 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.
PE 1: Evidence at protein level;
KW Alternative splicing; Angiogenesis; Coiled coil; Disulfide bond;
KW Glycoprotein; Reference proteome; Secreted; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..503
FT /note="Angiopoietin-4"
FT /id="PRO_0000009116"
FT DOMAIN 282..502
FT /note="Fibrinogen C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT COILED 84..238
FT /evidence="ECO:0000255"
FT CARBOHYD 96
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 126
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 140
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 158
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 247
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 274
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 311
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 337
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 427
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 291..320
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT DISULFID 444..457
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT VAR_SEQ 408..503
FT /note="LSVVGYSGSAGRQSSLVLQNTSFSTLDSDNDHCLCKCAQVMSGGWWFDACGL
FT SNLNGVYYHAPDNKYKMDGIRWHYFKGPSYSLRASRMMIRPLDI -> VVV (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055091"
FT VARIANT 395
FT /note="E -> K (in dbSNP:rs869171)"
FT /id="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
//
