| IED ID | IndEnz0005000460 |
| Enzyme Type ID | lipase000460 |
| Protein Name |
Angiopoietin-related protein 3 Angiopoietin-5 ANG-5 Angiopoietin-like protein 3 Cleaved into: ANGPTL3 17-221 ; ANGPTL3 17-224 |
| Gene Name | ANGPTL3 ANGPT5 UNQ153/PRO179 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MFTIKLLLFIVPLVISSRIDQDNSSFDSLSPEPKSRFAMLDDVKILANGLLQLGHGLKDFVHKTKGQINDIFQKLNIFDQSFYDLSLQTSEIKEEEKELRRTTYKLQVKNEEVKNMSLELNSKLESLLEEKILLQQKVKYLEEQLTNLIQNQPETPEHPEVTSLKTFVEKQDNSIKDLLQTVEDQYKQLNQQHSQIKEIENQLRRTSIQEPTEISLSSKPRAPRTTPFLQLNEIRNVKHDGIPAECTTIYNRGEHTSGMYAIRPSNSQVFHVYCDVISGSPWTLIQHRIDGSQNFNETWENYKYGFGRLDGEFWLGLEKIYSIVKQSNYVLRIELEDWKDNKHYIEYSFYLGNHETNYTLHLVAITGNVPNAIPENKDLVFSTWDHKAKGHFNCPEGYSGGWWWHDECGENNLNGKYNKPRAKSKPERRRGLSWKSQNGRLYSIKSTKMLIHPTDSESFE |
| Enzyme Length | 460 |
| Uniprot Accession Number | Q9Y5C1 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Acts in part as a hepatokine that is involved in regulation of lipid and glucose metabolism (PubMed:11788823, PubMed:12909640, PubMed:23661675, PubMed:25495645). Proposed to play a role in the trafficking of energy substrates to either storage or oxidative tissues in response to food intake (By similarity). Has a stimulatory effect on plasma triglycerides (TG), which is achieved by suppressing plasma TG clearance via inhibition of LPL activity. The inhibition of LPL activity appears to be an indirect mechanism involving recruitment of proprotein convertases PCSK6 and FURIN to LPL leading to cleavage and dissociation of LPL from the cell surface; the function does not require ANGPTL3 proteolytic cleavage but seems to be mediated by the N-terminal domain, and is not inhibited by GPIHBP1 (PubMed:12097324, PubMed:19318355, PubMed:20581395). Can inhibit endothelial lipase, causing increased plasma levels of high density lipoprotein (HDL) cholesterol and phospholipids (PubMed:17110602, PubMed:19028676). Can bind to adipocytes to activate lipolysis, releasing free fatty acids and glycerol (PubMed:12565906). Suppresses LPL specifically in oxidative tissues which is required to route very low density lipoprotein (VLDL)-TG to white adipose tissue (WAT) for storage in response to food; the function may involve cooperation with circulating, liver-derived ANGPTL8 and ANGPTL4 expression in WAT (By similarity). Contributes to lower plasma levels of low density lipoprotein (LDL)-cholesterol by a mechanism that is independent of the canonical pathway implicating APOE and LDLR. May stimulate hypothalamic LPL activity (By similarity). {ECO:0000250|UniProtKB:Q9R182, ECO:0000269|PubMed:11788823, ECO:0000269|PubMed:12097324, ECO:0000269|PubMed:12565906, ECO:0000269|PubMed:12909640, ECO:0000269|PubMed:17110602, ECO:0000269|PubMed:19028676, ECO:0000269|PubMed:19318355, ECO:0000269|PubMed:20581395, ECO:0000269|PubMed:23661675, ECO:0000269|PubMed:25495645, ECO:0000305|PubMed:20581395}.; FUNCTION: [ANGPTL3(17-221)]: In vitro inhibits LPL activity; not effective on GPIHBP1-stabilized LPL. {ECO:0000269|PubMed:19542565}.; FUNCTION: Involved in angiogenesis. Binds to endothelial cells via integrin alpha-V/beta-3 (ITGAV:ITGB3), activates FAK, MAPK and Akt signaling pathways and induces cell adhesion and cell migration (PubMed:11877390). Secreted from podocytes, may modulate properties of glomerular endothelial cells involving integrin alpha-V/beta-3 and Akt signaling (PubMed:18535744). May increase the motility of podocytes. May induce actin filament rearrangements in podocytes implicating integrin alpha-V/beta-3 and Rac1 activation. Binds to hematopoietic stem cells (HSC) and is involved in the regulation of HSC activity probably implicating down-regulation of IKZF1/IKAROS (By similarity). {ECO:0000250|UniProtKB:Q9R182, ECO:0000269|PubMed:11877390, ECO:0000269|PubMed:18535744}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Beta strand (15); Chain (3); Coiled coil (1); Disulfide bond (2); Domain (1); Glycosylation (4); Helix (5); Mutagenesis (8); Natural variant (13); Region (3); Sequence caution (1); Sequence conflict (1); Signal peptide (1) |
| Keywords | 3D-structure;Angiogenesis;Cell adhesion;Cell projection;Coiled coil;Direct protein sequencing;Disulfide bond;Glycoprotein;Heparin-binding;Lipid metabolism;Reference proteome;Secreted;Signal |
| Interact With | |
| Induction | INDUCTION: Down-regulated by insulin. {ECO:0000269|PubMed:26204133}. |
| Subcellular Location | SUBCELLULAR LOCATION: Secreted {ECO:0000250, ECO:0000305|PubMed:11877390}. Cell projection, lamellipodium {ECO:0000250|UniProtKB:Q9R182}. Note=Colocalized with HSPG2 and activated ITGB3 on podocytes. {ECO:0000250|UniProtKB:Q9R182}. |
| Modified Residue | |
| Post Translational Modification | PTM: O-glycosylated at Thr-226 by GALNT2; blocks processing and activation by proprotein convertases. {ECO:0000269|PubMed:20837471, ECO:0000269|PubMed:22566642}.; PTM: In part proteolytically cleaved by proprotein convertases; proposed to be involved in activation. {ECO:0000269|PubMed:12909640, ECO:0000269|PubMed:20837471}. |
| Signal Peptide | SIGNAL 1..16; /evidence=ECO:0000269|PubMed:15340161 |
| Structure 3D | X-ray crystallography (1) |
| Cross Reference PDB | 6EUA; |
| Mapped Pubmed ID | 10900462; 12518032; 16109723; 16531751; 17088546; 18063851; 18193043; 18193044; 18279878; 18596051; 18804459; 19060906; 19148283; 19282754; 19487539; 19540497; 19656773; 19826106; 19890028; 20160193; 20360639; 20570916; 20571754; 20595410; 20679960; 20714348; 20855565; 20972250; 21691831; 21983347; 22062970; 22155345; 22247256; 22569073; 22659251; 22896670; 23839332; 23978712; 24397894; 24626437; 24768220; 24960069; 25954050; 26639238; 26739706; 26800306; 26933753; 26934567; 26934667; 27040449; 27620179; 27733177; 28371666; 28385496; 28413163; 28538136; 28972399; 29183623; 29334984; 29454388; 29695708; 29989339; 30683883; 30782561; 30827231; 31054480; 31103046; 31223079; 31380419; 31413305; 31923423; 32151767; 32324598; 32332430; 32332431; 32407781; 32440963; 32487544; 32510837; 32646941; 32777482; 33075372; 33273510; 33351885; 33482195; 33588820; 33636293; 33772079; 33927698; 34067751; 34293055; 34360721; 34484467; 34684048; 8020465; |
| Motif | |
| Gene Encoded By | |
| Mass | 53,637 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |