ANGPTL3
entrez
27329
canonical
uniprot
Q9Y5C1
canonical
ensembl
ENSG00000132855
resolver
ensp
ENSP00000360170
resolver
enst
ENST00000371129
resolver
genesymbol
ANGPTL3
resolver
genesymbol_syn
ANGPT5
resolver
hgnc
HGNC:491
resolver
uniprot
A0JLS0
resolver
uniprot
B1ALJ0
resolver
uniprot
B2RCW1
resolver
uniprot_entry
ANGL3_HUMAN
resolver
uniprot_sec
A0JLS0
resolver
uniprot_sec
B1ALJ0
resolver
uniprot_sec
B2RCW1
resolver
amino_acid_sequence
MFTIKLLLFIVPLVISSRIDQDNSSFDSLSPEPKSRFAMLDDVKILANGLLQLGHGLKDFVHKTKGQINDIFQKLNIFDQSFYDLSLQTSEIKEEEKELRRTTYKLQVKNEEVKNMSLELNSKLESLLEEKILLQQKVKYLEEQLTNLIQNQPETPEHPEVTSLKTFVEKQDNSIKDLLQTVEDQYKQLNQQHSQIKEIENQLRRTSIQEPTEISLSSKPRAPRTTPFLQLNEIRNVKHDGIPAECTTIYNRGEHTSGMYAIRPSNSQVFHVYCDVISGSPWTLIQHRIDGSQNFNETWENYKYGFGRLDGEFWLGLEKIYSIVKQSNYVLRIELEDWKDNKHYIEYSFYLGNHETNYTLHLVAITGNVPNAIPENKDLVFSTWDHKAKGHFNCPEGYSGGWWWHDECGENNLNGKYNKPRAKSKPERRRGLSWKSQNGRLYSIKSTKMLIHPTDSESFE
uniprot
proteins
disease_involvement
DISEASE: Hypobetalipoproteinemia, familial, 2 (FHBL2) [MIM:605019]: A disorder of lipid metabolism characterized by less than 5th percentile age- and sex-specific levels of low density lipoproteins, and dietary fat malabsorption. Affected individuals present with combined hypolipidemia, consisting of extremely low plasma levels of LDL cholesterol, HDL cholesterol, and triglycerides. {ECO:0000269|PubMed:20942659}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Note=May be involved in atherosclerosis. Plasma levels are closely associated with arterial wall thickness. {ECO:0000305|PubMed:17191020}.; DISEASE: Note=May be involved in nephrotic syndrome. {ECO:0000305|PubMed:25710887}.
uniprot
proteins
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}.
uniprot
proteins
mass_dalton
53637
uniprot
proteins
mutagenesis
MUTAGEN 62..63; /note="HK->IN: Abolishes effect on plasma triglyceride level; when associated with N-65."; /evidence="ECO:0000269|PubMed:12909640"; MUTAGEN 63; /note="K->N: Abolishes inhibitory effect on LIPG/EL phospholipase activity; when associated with N-65."; /evidence="ECO:0000269|PubMed:17110602"; MUTAGEN 65; /note="K->N: Abolishes effect on plasma triglyceride level; when associated with 62-I-N-63."; /evidence="ECO:0000269|PubMed:12909640"; MUTAGEN 65; /note="K->N: Abolishes inhibitory effect on LIPG/EL phospholipase activity; when associated with N-63."; /evidence="ECO:0000269|PubMed:17110602"; MUTAGEN 204..205; /note="RR->TT: Abolishes proteolytical cleavage and effect on plasma triglyceride levels, keeps in vitro inactivation of LPL activity; when associated with S-221; S-224 and S-235."; /evidence="ECO:0000269|PubMed:12909640"; MUTAGEN 221; /note="R->ST: Abolishes proteolytical cleavage and effect on plasma triglyceride levels, keeps in vitro inactivation of LPL activity; when associated with 204-T-T-205; S-224 and S-235."; /evidence="ECO:0000269|PubMed:12909640"; MUTAGEN 224; /note="R->S: Abolishes proteolytical cleavage and effect on plasma triglyceride levels, keeps in vitro inactivation of LPL activity; when associated with 204-T-T-205; S-221 and S-235."; /evidence="ECO:0000269|PubMed:12909640"; MUTAGEN 235; /note="R->T: Abolishes proteolytical cleavage and effect on plasma triglyceride levels, keeps in vitro inactivation of LPL activity; when associated with 204-T-T-205; S-221 and S-224."; /evidence="ECO:0000269|PubMed:12909640
uniprot
proteins
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}.
uniprot
proteins
pubmed
10644446
uniprot
proteins
pubmed
11788823
uniprot
proteins
pubmed
11877390
uniprot
proteins
pubmed
12097324
uniprot
proteins
pubmed
12565906
uniprot
proteins
pubmed
12909640
uniprot
proteins
pubmed
12975309
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15340161
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16335952
uniprot
proteins
pubmed
17110602
uniprot
proteins
pubmed
17191020
uniprot
proteins
pubmed
18535744
uniprot
proteins
pubmed
19028676
uniprot
proteins
pubmed
19075393
uniprot
proteins
pubmed
19159218
uniprot
proteins
pubmed
19318355
uniprot
proteins
pubmed
19542565
uniprot
proteins
pubmed
20581395
uniprot
proteins
pubmed
20837471
uniprot
proteins
pubmed
20942659
uniprot
proteins
pubmed
22095935
uniprot
proteins
pubmed
22566642
uniprot
proteins
pubmed
23150577
uniprot
proteins
pubmed
23661675
uniprot
proteins
pubmed
25495645
uniprot
proteins
pubmed
25710887
uniprot
proteins
pubmed
25733326
uniprot
proteins
pubmed
26204133
uniprot
proteins
pubmed
29713054
uniprot
proteins
sequence_length
460
uniprot
proteins
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}.
uniprot
proteins