ID ANGL4_HUMAN Reviewed; 406 AA. AC Q9BY76; A8MY84; B4E089; D6W670; F5H0I2; Q53HQ6; Q53HU1; Q6UXN0; Q9HBV4; AC Q9NZU4; Q9Y5B3; DT 08-NOV-2002, integrated into UniProtKB/Swiss-Prot. DT 08-NOV-2002, sequence version 2. DT 02-SEP-2026, entry version 203. DE RecName: Full=Angiopoietin-related protein 4; DE AltName: Full=Angiopoietin-like protein 4; DE AltName: Full=Hepatic fibrinogen/angiopoietin-related protein {ECO:0000303|PubMed:10698685}; DE Short=HFARP {ECO:0000303|PubMed:10698685}; DE Contains: DE RecName: Full=ANGPTL4 N-terminal chain; DE Contains: DE RecName: Full=ANGPTL4 C-terminal chain; DE Flags: Precursor; GN Name=ANGPTL4; GN Synonyms=ARP4, HFARP, PGAR {ECO:0000303|PubMed:10866690}; GN ORFNames=PP1158 {ECO:0000303|PubMed:12015030}, PSEC0166, GN UNQ171/PRO197; 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), TISSUE SPECIFICITY, SUBCELLULAR RP LOCATION, GLYCOSYLATION, AND VARIANT MET-266. RX PubMed=10698685; DOI=10.1042/bj3460603; RA Kim I., Kim H.-G., Kim H., Kim H.-H., Park S.K., Uhm C.-S., Lee Z.H., RA Koh G.Y.; RT "Hepatic expression, synthesis and secretion of a novel RT fibrinogen/angiopoietin-related protein that prevents endothelial-cell RT apoptosis."; RL Biochem. J. 346:603-610(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RC TISSUE=Aortic endothelium; RX PubMed=10866690; DOI=10.1128/mcb.20.14.5343-5349.2000; RA Yoon J.C., Chickering T.W., Rosen E.D., Dussault B., Qin Y., Soukas A., RA Friedman J.M., Holmes W.E., Spiegelman B.M.; RT "Peroxisome proliferator-activated receptor gamma target gene encoding a RT novel angiopoietin-related protein associated with adipose RT differentiation."; RL Mol. Cell. Biol. 20:5343-5349(2000). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Placenta; RX PubMed=11953136; RA Zhu H., Li J., Qin W., Yang Y., He X., Wan D., Gu J.; RT "Cloning of a novel gene, ANGPTL4 and the functional study in RT angiogenesis."; RL Zhonghua Yi Xue Za Zhi 82:94-99(2002). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND SUBCELLULAR LOCATION. RC TISSUE=Placenta; RX PubMed=14583458; RA Ito Y., Oike Y., Yasunaga K., Hamada K., Miyata K., Matsumoto S., RA Sugano S., Tanihara H., Masuho Y., Suda T.; RT "Inhibition of angiogenesis and vascular leakiness by angiopoietin-related RT protein 4."; RL Cancer Res. 63:6651-6657(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Hair follicle dermal papilla; RA Kim M.K., Kim Y.H., Seo J.M., Lee H.M., Chung H.J., Sohn M.Y., Hwang S.Y., RA Im S.U., Jung E.J., Lee J.H., Kim J.C.; RT "A catalogue of genes in the human dermal papilla cells as identified by RT expressed sequence tags."; RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Thymus; 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 [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT MET-266. RC TISSUE=Adipose tissue; RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., RA Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [10] 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 [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Pancreas; 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 [12] RP TISSUE SPECIFICITY. RX PubMed=12015030; RA Zhu H., Li J., Wan D., Yang Y., Qin W., Ge C., Yao M., Gu J.; RT "Expression and function of hepatocellular carcinoma-related gene pp1158."; RL Zhonghua Zhong Liu Za Zhi 24:123-125(2002). RN [13] RP FUNCTION, INDUCTION BY ISCHEMIA, SUBCELLULAR LOCATION, AND PROTEOLYTIC RP CLEAVAGE. RX PubMed=17068295; DOI=10.1161/01.res.0000250758.63358.91; RA Cazes A., Galaup A., Chomel C., Bignon M., Brechot N., Le Jan S., Weber H., RA Corvol P., Muller L., Germain S., Monnot C.; RT "Extracellular matrix-bound angiopoietin-like 4 inhibits endothelial cell RT adhesion, migration, and sprouting and alters actin cytoskeleton."; RL Circ. Res. 99:1207-1215(2006). RN [14] RP SUBCELLULAR LOCATION, SUBUNIT, PROTEOLYTIC CLEAVAGE, CHARACTERIZATION OF RP VARIANT LYS-40, MUTAGENESIS OF GLU-40; CYS-76; CYS-80 AND 161-ARG--ARG-164, RP AND DISULFIDE BONDS. RX PubMed=19270337; DOI=10.1074/jbc.m900553200; RA Yin W., Romeo S., Chang S., Grishin N.V., Hobbs H.H., Cohen J.C.; RT "Genetic variation in ANGPTL4 provides insights into protein processing and RT function."; RL J. Biol. Chem. 284:13213-13222(2009). RN [15] RP SUBCELLULAR LOCATION, PARTIAL PROTEIN SEQUENCE, PROTEOLYTIC CLEAVAGE, AND RP MUTAGENESIS OF ARG-161 AND ARG-164. RX PubMed=21398697; DOI=10.1074/jbc.m110.217638; RA Lei X., Shi F., Basu D., Huq A., Routhier S., Day R., Jin W.; RT "Proteolytic processing of angiopoietin-like protein 4 by proprotein RT convertases modulates its inhibitory effects on lipoprotein lipase RT activity."; RL J. Biol. Chem. 286:15747-15756(2011). RN [16] RP FUNCTION, AND CHARACTERIZATION OF VARIANT LYS-40. RX PubMed=27929370; DOI=10.7554/elife.20958; RA Mysling S., Kristensen K.K., Larsson M., Kovrov O., Bensadouen A., RA Joergensen T.J., Olivecrona G., Young S.G., Ploug M.; RT "The angiopoietin-like protein ANGPTL4 catalyzes unfolding of the hydrolase RT domain in lipoprotein lipase and the endothelial membrane protein GPIHBP1 RT counteracts this unfolding."; RL Elife 5:0-0(2016). RN [17] RP FUNCTION. RX PubMed=29899144; DOI=10.1073/pnas.1806774115; RA Kristensen K.K., Midtgaard S.R., Mysling S., Kovrov O., Hansen L.B., RA Skar-Gislinge N., Beigneux A.P., Kragelund B.B., Olivecrona G., Young S.G., RA Joergensen T.J.D., Fong L.G., Ploug M.; RT "A disordered acidic domain in GPIHBP1 harboring a sulfated tyrosine RT regulates lipoprotein lipase."; RL Proc. Natl. Acad. Sci. U.S.A. 115:E6020-E6029(2018). RN [18] {ECO:0007744|PDB:6EUB} RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 184-406, DISULFIDE BONDS, RP CHARACTERIZATION OF VARIANTS CYS-336; CYS-349 AND SER-361, AND MUTAGENESIS RP OF GLY-223. RX PubMed=29713054; DOI=10.1038/s41598-018-25237-7; RA Biterova E., Esmaeeli M., Alanen H.I., Saaranen M., Ruddock L.W.; RT "Structures of Angptl3 and Angptl4, modulators of triglyceride levels and RT coronary artery disease."; RL Sci. Rep. 8:6752-6752(2018). RN [19] RP ASSOCIATION WITH TGQTL, AND VARIANTS LEU-5; LYS-40; ILE-41; ARG-67; LEU-72; RP ARG-77; LYS-167; SER-174; GLN-190; LYS-196; CYS-230; ARG-233; VAL-237; RP THR-251; MET-266; GLN-278; MET-291; MET-293; VAL-296; SER-307; MET-308; RP CYS-336; GLU-338; CYS-349; SER-361; ARG-361; GLN-371 AND TRP-384. RX PubMed=17322881; DOI=10.1038/ng1984; RA Romeo S., Pennacchio L.A., Fu Y., Boerwinkle E., Tybjaerg-Hansen A., RA Hobbs H.H., Cohen J.C.; RT "Population-based resequencing of ANGPTL4 uncovers variations that reduce RT triglycerides and increase HDL."; RL Nat. Genet. 39:513-516(2007). RN [20] RP VARIANT LYS-40, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=29899519; DOI=10.1038/s41467-018-04611-z; RA Gusarova V., O'Dushlaine C., Teslovich T.M., Benotti P.N., Mirshahi T., RA Gottesman O., Van Hout C.V., Murray M.F., Mahajan A., Nielsen J.B., RA Fritsche L., Wulff A.B., Gudbjartsson D.F., Sjoegren M., Emdin C.A., RA Scott R.A., Lee W.J., Small A., Kwee L.C., Dwivedi O.P., Prasad R.B., RA Bruse S., Lopez A.E., Penn J., Marcketta A., Leader J.B., Still C.D., RA Kirchner H.L., Mirshahi U.L., Wardeh A.H., Hartle C.M., Habegger L., RA Fetterolf S.N., Tusie-Luna T., Morris A.P., Holm H., Steinthorsdottir V., RA Sulem P., Thorsteinsdottir U., Rotter J.I., Chuang L.M., Damrauer S., RA Birtwell D., Brummett C.M., Khera A.V., Natarajan P., Orho-Melander M., RA Flannick J., Lotta L.A., Willer C.J., Holmen O.L., Ritchie M.D., RA Ledbetter D.H., Murphy A.J., Borecki I.B., Reid J.G., Overton J.D., RA Hansson O., Groop L., Shah S.H., Kraus W.E., Rader D.J., Chen Y.I., RA Hveem K., Wareham N.J., Kathiresan S., Melander O., Stefansson K., RA Nordestgaard B.G., Tybjaerg-Hansen A., Abecasis G.R., Altshuler D., RA Florez J.C., Boehnke M., McCarthy M.I., Yancopoulos G.D., Carey D.J., RA Shuldiner A.R., Baras A., Dewey F.E., Gromada J.; RT "Genetic inactivation of ANGPTL4 improves glucose homeostasis and is RT associated with reduced risk of diabetes."; RL Nat. Commun. 9:2252-2252(2018). CC -!- FUNCTION: Mediates inactivation of the lipoprotein lipase LPL, and CC thereby plays a role in the regulation of triglyceride clearance from CC the blood serum and in lipid metabolism (PubMed:19270337, CC PubMed:21398697, PubMed:27929370, PubMed:29899144). May also play a CC role in regulating glucose homeostasis and insulin sensitivity CC (Probable). Inhibits proliferation, migration, and tubule formation of CC endothelial cells and reduces vascular leakage (PubMed:14583458, CC PubMed:17068295). Upon heterologous expression, inhibits the adhesion CC of endothelial cell to the extracellular matrix (ECM), and inhibits the CC reorganization of the actin cytoskeleton, formation of actin stress CC fibers and focal adhesions in endothelial cells that have adhered to CC ANGPTL4-containing ECM (in vitro) (PubMed:17068295). Depending on CC context, may modulate tumor-related angiogenesis (By similarity). CC {ECO:0000250|UniProtKB:Q9Z1P8, ECO:0000269|PubMed:14583458, CC ECO:0000269|PubMed:17068295, ECO:0000269|PubMed:19270337, CC ECO:0000269|PubMed:21398697, ECO:0000269|PubMed:27929370, CC ECO:0000269|PubMed:29899144, ECO:0000305|PubMed:29899519}. CC -!- FUNCTION: [ANGPTL4 N-terminal chain]: Mediates inactivation of the CC lipoprotein lipase LPL, and thereby plays an important role in the CC regulation of triglyceride clearance from the blood serum and in lipid CC metabolism (PubMed:19270337, PubMed:21398697, PubMed:27929370, CC PubMed:29899144). Has higher activity in LPL inactivation than the CC uncleaved protein (PubMed:19270337, PubMed:21398697). CC {ECO:0000269|PubMed:19270337, ECO:0000269|PubMed:21398697, CC ECO:0000269|PubMed:27929370, ECO:0000269|PubMed:29899144}. CC -!- SUBUNIT: Homooligomer; disulfide-linked via Cys residues in the N- CC terminal part of the protein (PubMed:19270337). The homooligomer CC undergoes proteolytic processing to release the ANGPTL4 C-terminal CC chain, which circulates as a monomer (PubMed:19270337). The CC homooligomer unprocessed form is able to interact with the CC extracellular matrix (PubMed:21398697). {ECO:0000250, CC ECO:0000269|PubMed:19270337, ECO:0000269|PubMed:21398697}. CC -!- INTERACTION: CC Q9BY76; Q9BY76: ANGPTL4; NbExp=3; IntAct=EBI-2968146, EBI-2968146; CC Q9BY76; P05556: ITGB1; NbExp=2; IntAct=EBI-2968146, EBI-703066; CC Q9BY76; P18084: ITGB5; NbExp=3; IntAct=EBI-2968146, EBI-1223434; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10698685, CC ECO:0000269|PubMed:14583458, ECO:0000269|PubMed:17068295, CC ECO:0000269|PubMed:19270337, ECO:0000269|PubMed:21398697, CC ECO:0000269|PubMed:29899519}. Secreted, extracellular space, CC extracellular matrix {ECO:0000269|PubMed:17068295, CC ECO:0000269|PubMed:21398697}. Note=The unprocessed form interacts with CC the extracellular matrix (PubMed:17068295, PubMed:21398697). This may CC constitute a dynamic reservoir, a regulatory mechanism of the CC bioavailability of ANGPTL4 (Probable). {ECO:0000269|PubMed:17068295, CC ECO:0000269|PubMed:21398697, ECO:0000305|PubMed:17068295}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q9BY76-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9BY76-2; Sequence=VSP_047045; CC Name=3; CC IsoId=Q9BY76-3; Sequence=VSP_055092; CC -!- TISSUE SPECIFICITY: Detected in blood plasma (at protein level) CC (PubMed:29899519). Detected in liver (PubMed:10698685). Detected in CC white fat tissue and placenta (PubMed:10866690). Expressed at high CC levels in the placenta, heart, liver, muscle, pancreas and lung but CC expressed poorly in the brain and kidney. {ECO:0000269|PubMed:10698685, CC ECO:0000269|PubMed:10866690, ECO:0000269|PubMed:12015030, CC ECO:0000269|PubMed:29899519}. CC -!- INDUCTION: Up-regulated when cells are exposed to severe hypoxia (in CC vitro). {ECO:0000269|PubMed:17068295}. CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:10698685}. CC -!- PTM: [ANGPTL4 N-terminal chain]: Forms disulfide-linked dimers and CC tetramers. {ECO:0000269|PubMed:19270337}. CC -!- PTM: Cleaved into a smaller N-terminal chain and a larger chain that CC contains the fibrinogen C-terminal domain; both cleaved and uncleaved CC forms are detected in the extracellular space. The cleaved form is not CC present within the cell. {ECO:0000269|PubMed:17068295, CC ECO:0000269|PubMed:19270337, ECO:0000269|PubMed:21398697}. CC -!- POLYMORPHISM: Genetic variations in ANGPTL4 are associated with low CC plasma triglyceride levels and define the plasma triglyceride level CC quantitative trait locus (TGQTL) [MIM:615881]. CC {ECO:0000269|PubMed:17322881}. CC -!- SEQUENCE CAUTION: CC Sequence=AAQ88642.1; Type=Erroneous initiation; Evidence={ECO:0000305}; 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; AF169312; AAF62868.1; -; mRNA. DR EMBL; AF202636; AAG22490.1; -; mRNA. DR EMBL; AB056477; BAB40692.1; -; mRNA. DR EMBL; AF153606; AAD41088.1; -; mRNA. DR EMBL; AY358275; AAQ88642.1; ALT_INIT; mRNA. DR EMBL; AK303269; BAG64351.1; -; mRNA. DR EMBL; AK222489; BAD96209.1; -; mRNA. DR EMBL; AK222524; BAD96244.1; -; mRNA. DR EMBL; AC136469; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471139; EAW68930.1; -; Genomic_DNA. DR EMBL; CH471139; EAW68931.1; -; Genomic_DNA. DR EMBL; BC023647; AAH23647.1; -; mRNA. DR CCDS; CCDS12200.1; -. [Q9BY76-1] DR CCDS; CCDS42493.1; -. [Q9BY76-2] DR RefSeq; NP_001034756.1; NM_001039667.3. [Q9BY76-2] DR RefSeq; NP_647475.1; NM_139314.3. [Q9BY76-1] DR PDB; 6EUB; X-ray; 2.30 A; A=184-406. DR PDB; 6U0A; X-ray; 2.11 A; A=185-400. DR PDB; 6U1U; X-ray; 1.75 A; A=185-400. DR PDB; 6U73; X-ray; 2.38 A; A=185-400. DR AlphaFoldDB; Q9BY76; -. DR SASBDB; Q9BY76; -. DR SMR; Q9BY76; -. DR BioGRID; 119316; 37. DR CORUM; Q9BY76; -. DR FunCoup; Q9BY76; 277. DR IntAct; Q9BY76; 31. DR MINT; Q9BY76; -. DR NDEx; IQUERY-CP-ANGPTL4; 4 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000301455; -. DR UniLectin; Q9BY76; -. DR GlyConnect; Q9BY76; 11 N-Linked glycans (1 site). DR GlyCosmos; Q9BY76; 4 sites, 16 glycans. DR GlyGen; Q9BY76; 4 sites, 22 N-linked glycans (1 site), 3 O-linked glycans (3 sites). DR iPTMnet; Q9BY76; -. DR PhosphoSitePlus; Q9BY76; -. DR BioMuta; ANGPTL4; -. DR DMDM; 25008123; -. DR jPOST; Q9BY76; -. DR MassIVE; Q9BY76; -. DR PaxDb; 9606-ENSP00000301455; -. DR PeptideAtlas; Q9BY76; -. DR ProteomicsDB; 2383; -. DR ProteomicsDB; 25349; -. DR ProteomicsDB; 79597; -. [Q9BY76-1] DR ABCD; Q9BY76; 17 sequenced antibodies. DR Antibodypedia; 1649; 587 antibodies from 41 providers. DR DNASU; 51129; -. DR Ensembl; ENST00000301455.7; ENSP00000301455.1; ENSG00000167772.13. [Q9BY76-1] DR Ensembl; ENST00000393962.6; ENSP00000377534.1; ENSG00000167772.13. [Q9BY76-2] DR Ensembl; ENST00000593998.5; ENSP00000472551.1; ENSG00000167772.13. [Q9BY76-1] DR Ensembl; ENST00000955922.1; ENSP00000625981.1; ENSG00000167772.13. [Q9BY76-2] DR Ensembl; ENST00000955923.1; ENSP00000625982.1; ENSG00000167772.13. [Q9BY76-1] DR GeneID; 51129; -. DR KEGG; hsa:51129; -. DR MANE-Select; ENST00000301455.7; ENSP00000301455.1; NM_139314.3; NP_647475.1. DR UCSC; uc002mjq.3; human. [Q9BY76-1] DR AGR; HGNC:16039; -. DR ClinPGx; PA24797; -. DR CTD; 51129; -. DR DisGeNET; 51129; -. DR GeneCards; ANGPTL4; -. DR HGNC; HGNC:16039; ANGPTL4. DR HPA; ENSG00000167772; Tissue enhanced (adipose tissue, breast, liver). DR MalaCards; ANGPTL4; -. DR MIM; 605910; gene. DR MIM; 615881; phenotype. DR OpenTargets; ENSG00000167772; -. DR VEuPathDB; HostDB:ENSG00000167772; -. DR eggNOG; KOG2579; Eukaryota. DR GeneTree; ENSGT00940000159478; -. DR HOGENOM; CLU_038628_2_1_1; -. DR InParanoid; Q9BY76; -. DR OMA; MATGFPF; -. DR OrthoDB; 6145874at2759; -. DR PAN-GO; Q9BY76; 4 GO annotations based on evolutionary models. DR PhylomeDB; Q9BY76; -. DR PathwayCommons; Q9BY76; -. DR Reactome; R-HSA-1989781; PPARA activates gene expression. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR Reactome; R-HSA-8963889; Assembly of active LPL and LIPC lipase complexes. DR Reactome; R-HSA-9762292; Regulation of CDH11 function. DR Reactome; R-HSA-9841922; MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis. DR SignaLink; Q9BY76; -. DR Agora; ENSG00000167772; -. DR BioGRID-ORCS; 51129; 16 hits in 1153 CRISPR screens. DR ChiTaRS; ANGPTL4; human. DR GeneWiki; ANGPTL4; -. DR GenomeRNAi; 51129; -. DR Pharos; Q9BY76; Tbio. DR PRO; PR:Q9BY76; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q9BY76; protein. DR Bgee; ENSG00000167772; Expressed in pericardium and 160 other cell types or tissues. DR ExpressionAtlas; Q9BY76; baseline and differential. DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB. DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central. DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB. DR GO; GO:0004857; F:enzyme inhibitor activity; ISS:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0035473; F:lipase binding; IPI:BHF-UCL. DR GO; GO:0055102; F:lipase inhibitor activity; IDA:BHF-UCL. DR GO; GO:0007596; P:blood coagulation; IEA:InterPro. DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0045717; P:negative regulation of fatty acid biosynthetic process; IDA:ARUK-UCL. DR GO; GO:0010903; P:negative regulation of very-low-density lipoprotein particle remodeling; IDA:BHF-UCL. DR GO; GO:0045766; P:positive regulation of angiogenesis; TAS:UniProtKB. DR GO; GO:0043335; P:protein unfolding; IDA:ARUK-UCL. DR GO; GO:0090318; P:regulation of chylomicron remodeling; IDA:BHF-UCL. DR GO; GO:1905883; P:regulation of triglyceride transport; IDA:BHF-UCL. DR GO; GO:0001666; P:response to hypoxia; NAS:UniProtKB. DR GO; GO:0070328; P:triglyceride homeostasis; ISS:BHF-UCL. DR CDD; cd00087; FReD; 1. DR FunFam; 3.90.215.10:FF:000003; angiopoietin-2 isoform X1; 1. DR FunFam; 4.10.530.10:FF:000001; angiopoietin-2 isoform X1; 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; IPR037579; FIB_ANG-like. 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; PTHR47221; FIBRINOGEN ALPHA CHAIN; 1. DR PANTHER; PTHR47221:SF6; FIBRINOGEN ALPHA CHAIN; 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 PDBsum; 6EUB; -. DR PDBsum; 6U0A; -. DR PDBsum; 6U1U; -. DR PDBsum; 6U73; -. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Angiogenesis; Coiled coil; KW Direct protein sequencing; Disulfide bond; Extracellular matrix; KW Glycoprotein; Lipid metabolism; Proteomics identification; KW Reference proteome; Secreted; Signal. FT SIGNAL 1..25 FT /evidence="ECO:0000255" FT CHAIN 26..406 FT /note="Angiopoietin-related protein 4" FT /id="PRO_0000009124" FT CHAIN 26..163 FT /note="ANGPTL4 N-terminal chain" FT /evidence="ECO:0000305" FT /id="PRO_0000446859" FT CHAIN 164..406 FT /note="ANGPTL4 C-terminal chain" FT /evidence="ECO:0000305" FT /id="PRO_0000446860" FT DOMAIN 179..401 FT /note="Fibrinogen C-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739" FT COILED 100..143 FT /evidence="ECO:0000255" FT SITE 164..165 FT /note="Cleavage" FT /evidence="ECO:0000269|PubMed:21398697" FT CARBOHYD 177 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 188..216 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739, FT ECO:0000269|PubMed:29713054, ECO:0007744|PDB:6EUB" FT DISULFID 341..354 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739, FT ECO:0000269|PubMed:29713054, ECO:0007744|PDB:6EUB" FT VAR_SEQ 1..167 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055092" FT VAR_SEQ 183..221 FT /note="RLPRDCQELFQVGERQSGLFEIQPQGSPPFLVNCKMTSD -> H (in FT isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_047045" FT VARIANT 5 FT /note="P -> L (in dbSNP:rs761583091)" FT /evidence="ECO:0000269|PubMed:17322881" FT /id="VAR_032642" FT VARIANT 40 FT /note="E -> K (associated with lower plasma levels of FT triglyceride and higher levels of HDL cholesterol; strongly FT reduced inactivation of lipoprotein lipase LPL; no effect FT on protein secretion and stability of monomers; abolishes FT accumulation of oligomers; dbSNP:rs116843064)" FT /evidence="ECO:0000269|PubMed:17322881, FT ECO:0000269|PubMed:19270337, ECO:0000269|PubMed:27929370, FT ECO:0000269|PubMed:29899519" FT /id="VAR_032643" FT VARIANT 41 FT /note="M -> I (in dbSNP:rs186754194)" FT /evidence="ECO:0000269|PubMed:17322881" FT /id="VAR_032644" FT VARIANT 67 FT /note="S -> R (in dbSNP:rs538554190)" FT /evidence="ECO:0000269|PubMed:17322881" FT /id="VAR_032645" FT VARIANT 72 FT /note="R -> L (in dbSNP:rs141831018)" FT /evidence="ECO:0000269|PubMed:17322881" FT /id="VAR_032646" FT VARIANT 77 FT /note="G -> R (in dbSNP:rs568624939)" FT /evidence="ECO:0000269|PubMed:17322881" FT /id="VAR_032647" FT VARIANT 167 FT /note="E -> K (in dbSNP:rs140640857)" FT /evidence="ECO:0000269|PubMed:17322881" FT /id="VAR_032648" FT VARIANT 174 FT /note="P -> S (in dbSNP:rs1008363865)" FT /evidence="ECO:0000269|PubMed:17322881" FT /id="VAR_032649" FT VARIANT 190 FT /note="E -> Q (in dbSNP:rs77938377)" FT /evidence="ECO:0000269|PubMed:17322881" FT /id="VAR_032650" FT VARIANT 196 FT /note="E -> K (in dbSNP:rs1192364228)" FT /evidence="ECO:0000269|PubMed:17322881" FT /id="VAR_032651" FT VARIANT 230 FT /note="R -> C (in dbSNP:rs201026877)" FT /evidence="ECO:0000269|PubMed:17322881" FT /id="VAR_032652" FT VARIANT 233 FT /note="G -> R" FT /evidence="ECO:0000269|PubMed:17322881" FT /id="VAR_032653" FT VARIANT 237 FT /note="F -> V (in dbSNP:rs768374046)" FT /evidence="ECO:0000269|PubMed:17322881" FT /id="VAR_032654" FT VARIANT 251 FT /note="P -> T (in dbSNP:rs376328756)" FT /evidence="ECO:0000269|PubMed:17322881" FT /id="VAR_032655" FT VARIANT 266 FT /note="T -> M (in dbSNP:rs1044250)" FT /evidence="ECO:0000269|PubMed:10698685, FT ECO:0000269|PubMed:17322881, ECO:0000269|Ref.8" FT /id="VAR_020428" FT VARIANT 278 FT /note="R -> Q (in dbSNP:rs35061979)" FT /evidence="ECO:0000269|PubMed:17322881" FT /id="VAR_032656" FT VARIANT 291 FT /note="V -> M (in dbSNP:rs150000287)" FT /evidence="ECO:0000269|PubMed:17322881" FT /id="VAR_032657" FT VARIANT 293 FT /note="L -> M (in dbSNP:rs775667046)" FT /evidence="ECO:0000269|PubMed:17322881" FT /id="VAR_032658" FT VARIANT 296 FT /note="E -> V" FT /evidence="ECO:0000269|PubMed:17322881" FT /id="VAR_032659" FT VARIANT 307 FT /note="P -> S (in dbSNP:rs751249880)" FT /evidence="ECO:0000269|PubMed:17322881" FT /id="VAR_032660" FT VARIANT 308 FT /note="V -> M (in dbSNP:rs139998264)" FT /evidence="ECO:0000269|PubMed:17322881" FT /id="VAR_032661" FT VARIANT 336 FT /note="R -> C (no effect on protein folding; FT dbSNP:rs140744493)" FT /evidence="ECO:0000269|PubMed:17322881, FT ECO:0000269|PubMed:29713054" FT /id="VAR_032662" FT VARIANT 338 FT /note="D -> E (in dbSNP:rs780121474)" FT /evidence="ECO:0000269|PubMed:17322881" FT /id="VAR_032663" FT VARIANT 349 FT /note="W -> C (impaired protein folding; FT dbSNP:rs1033145581)" FT /evidence="ECO:0000269|PubMed:17322881, FT ECO:0000269|PubMed:29713054" FT /id="VAR_032664" FT VARIANT 361 FT /note="G -> R (in dbSNP:rs755737249)" FT /evidence="ECO:0000269|PubMed:17322881" FT /id="VAR_032665" FT VARIANT 361 FT /note="G -> S (impaired protein folding; FT dbSNP:rs755737249)" FT /evidence="ECO:0000269|PubMed:17322881, FT ECO:0000269|PubMed:29713054" FT /id="VAR_032666" FT VARIANT 371 FT /note="R -> Q (in dbSNP:rs779488814)" FT /evidence="ECO:0000269|PubMed:17322881" FT /id="VAR_032667" FT VARIANT 384 FT /note="R -> W (impaired protein folding; FT dbSNP:rs146942305)" FT /evidence="ECO:0000269|PubMed:17322881, FT ECO:0000269|PubMed:29713054" FT /id="VAR_032668" FT MUTAGEN 40 FT /note="E->A: Loss of inactivation of lipoprotein lipase FT LPL." FT /evidence="ECO:0000269|PubMed:19270337" FT MUTAGEN 40 FT /note="E->D: Decreased inactivation of lipoprotein lipase FT LPL." FT /evidence="ECO:0000269|PubMed:19270337" FT MUTAGEN 76 FT /note="C->A: No effect on secretion and proteolytic FT cleavage. Loss of oligomerization; when associated with FT A-80." FT /evidence="ECO:0000269|PubMed:19270337" FT MUTAGEN 80 FT /note="C->A: No effect on secretion and proteolytic FT cleavage. Loss of oligomerization; when associated with FT A-76." FT /evidence="ECO:0000269|PubMed:19270337" FT MUTAGEN 161..164 FT /note="RRKR->GSGS: Loss of proteolytic cleavage. No effect FT on the ability to inactivate lipoprotein lipase LPL." FT /evidence="ECO:0000269|PubMed:19270337" FT MUTAGEN 161 FT /note="R->A: Loss of proteolytic cleavage. Decreased FT ability to inactivate lipoprotein lipase LPL." FT /evidence="ECO:0000269|PubMed:21398697" FT MUTAGEN 164 FT /note="R->A: Loss of proteolytic cleavage." FT /evidence="ECO:0000269|PubMed:21398697" FT MUTAGEN 223 FT /note="G->R: Impaired protein folding." FT /evidence="ECO:0000269|PubMed:29713054" FT CONFLICT 55..71 FT /note="LREHAERTRSQLSALER -> CANTGAHPQSAERAGA (in Ref. 5; FT AAD41088)" FT /evidence="ECO:0000305" FT CONFLICT 60 FT /note="E -> G (in Ref. 4; BAB40692)" FT /evidence="ECO:0000305" FT CONFLICT 175 FT /note="A -> P (in Ref. 1; AAF62868)" FT /evidence="ECO:0000305" FT CONFLICT 237 FT /note="F -> S (in Ref. 7; BAG64351)" FT /evidence="ECO:0000305" FT CONFLICT 251 FT /note="P -> S (in Ref. 8; BAD96209)" FT /evidence="ECO:0000305" FT CONFLICT 270 FT /note="N -> D (in Ref. 7; BAG64351 and 8; BAD96209)" FT /evidence="ECO:0000305" FT CONFLICT 277 FT /note="L -> R (in Ref. 8; BAD96244)" FT /evidence="ECO:0000305" FT CONFLICT 304 FT /note="L -> F (in Ref. 1; AAF62868)" FT /evidence="ECO:0000305" FT CONFLICT 363 FT /note="Y -> H (in Ref. 8; BAD96209)" FT /evidence="ECO:0000305" FT CONFLICT 389 FT /note="P -> S (in Ref. 1; AAF62868)" FT /evidence="ECO:0000305" FT HELIX 188..193 FT /evidence="ECO:0007829|PDB:6U1U" FT STRAND 200..204 FT /evidence="ECO:0007829|PDB:6U1U" FT STRAND 212..219 FT /evidence="ECO:0007829|PDB:6U1U" FT STRAND 222..233 FT /evidence="ECO:0007829|PDB:6U1U" FT HELIX 241..246 FT /evidence="ECO:0007829|PDB:6U1U" FT STRAND 253..256 FT /evidence="ECO:0007829|PDB:6U1U" FT HELIX 259..266 FT /evidence="ECO:0007829|PDB:6U1U" FT STRAND 271..278 FT /evidence="ECO:0007829|PDB:6U1U" FT STRAND 284..293 FT /evidence="ECO:0007829|PDB:6U1U" FT HELIX 296..298 FT /evidence="ECO:0007829|PDB:6U1U" FT STRAND 302..304 FT /evidence="ECO:0007829|PDB:6U1U" FT HELIX 306..311 FT /evidence="ECO:0007829|PDB:6U1U" FT STRAND 322..324 FT /evidence="ECO:0007829|PDB:6U1U" FT HELIX 341..344 FT /evidence="ECO:0007829|PDB:6U1U" FT STRAND 352..358 FT /evidence="ECO:0007829|PDB:6U1U" FT HELIX 371..374 FT /evidence="ECO:0007829|PDB:6U1U" FT HELIX 381..384 FT /evidence="ECO:0007829|PDB:6U1U" FT HELIX 388..390 FT /evidence="ECO:0007829|PDB:6U1U" FT STRAND 391..399 FT /evidence="ECO:0007829|PDB:6U1U" SQ SEQUENCE 406 AA; 45214 MW; 219E56FEB3F602AF CRC64; MSGAPTAGAA LMLCAATAVL LSAQGGPVQS KSPRFASWDE MNVLAHGLLQ LGQGLREHAE RTRSQLSALE RRLSACGSAC QGTEGSTDLP LAPESRVDPE VLHSLQTQLK AQNSRIQQLF HKVAQQQRHL EKQHLRIQHL QSQFGLLDHK HLDHEVAKPA RRKRLPEMAQ PVDPAHNVSR LHRLPRDCQE LFQVGERQSG LFEIQPQGSP PFLVNCKMTS DGGWTVIQRR HDGSVDFNRP WEAYKAGFGD PHGEFWLGLE KVHSITGDRN SRLAVQLRDW DGNAELLQFS VHLGGEDTAY SLQLTAPVAG QLGATTVPPS GLSVPFSTWD QDHDLRRDKN CAKSLSGGWW FGTCSHSNLN GQYFRSIPQQ RQKLKKGIFW KTWRGRYYPL QATTMLIQPM AAEAAS //