Angiopoietin-related protein 3 (Angiopoietin-5) (ANG-5) (Angiopoietin-like protein 3) [Cleaved into: ANGPTL3(17-221); ANGPTL3(17-224)]
1_MFTIK 6_ LLLFI 11_ VPLVI 16_ SSRID 21_ QDNSS 26_ FDSLS 31_ PEPKS 36_ RFAML 41_ DDVKI 46_ LANGL 51_ LQLGH 56_ GLKDF 61_ VHKTK 66_ GQIND 71_ IFQKL 76_ NIFDQ 81_ SFYDL 86_ SLQTS 91_ EIKEE 96_ EKELR 101_ RTTYK 106_ LQVKN 111_ EEVKN 116_ MSLEL 121_ NSKLE 126_ SLLEE 131_ KILLQ 136_ QKVKY 141_ LEEQL 146_ TNLIQ 151_ NQPET 156_ PEHPE 161_ VTSLK 166_ TFVEK 171_ QDNSI 176_ KDLLQ 181_ TVEDQ 186_ YKQLN 191_ QQHSQ 196_ IKEIE 201_ NQLRR 206_ TSIQE 211_ PTEIS 216_ LSSKP 221_ RAPRT 226_ TPFLQ 231_ LNEIR 236_ NVKHD 241_ GIPAE 246_ CTTIY 251_ NRGEH 256_ TSGMY 261_ AIRPS 266_ NSQVF 271_ HVYCD 276_ VISGS 281_ PWTLI 286_ QHRID 291_ GSQNF 296_ NETWE 301_ NYKYG 306_ FGRLD 311_ GEFWL 316_ GLEKI 321_ YSIVK 326_ QSNYV 331_ LRIEL 336_ EDWKD 341_ NKHYI 346_ EYSFY 351_ LGNHE 356_ TNYTL 361_ HLVAI 366_ TGNVP 371_ NAIPE 376_ NKDLV 381_ FSTWD 386_ HKAKG 391_ HFNCP 396_ EGYSG 401_ GWWWH 406_ DECGE 411_ NNLNG 416_ KYNKP 421_ RAKSK 426_ PERRR 431_ GLSWK 436_ SQNGR 441_ LYSIK 446_ STKML 451_IHPTD
1: 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)
2: In vitro inhibits LPL activity; not effective on GPIHBP1-stabilized LPL
3: 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)