ANGL8_MOUSE
ID ANGL8_MOUSE Reviewed; 198 AA.
AC Q8R1L8;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 2.
DT 03-AUG-2022, entry version 99.
DE RecName: Full=Angiopoietin-like protein 8 {ECO:0000312|MGI:MGI:3643534};
DE AltName: Full=Betatrophin {ECO:0000303|PubMed:24043787};
DE AltName: Full=Lipasin {ECO:0000303|PubMed:22809513};
DE AltName: Full=Refeeding-induced fat and liver protein {ECO:0000303|PubMed:22569073};
DE Flags: Precursor;
GN Name=Angptl8 {ECO:0000312|MGI:MGI:3643534};
GN Synonyms=Gm6484 {ECO:0000312|MGI:MGI:3643534},
GN Rifl {ECO:0000303|PubMed:22569073};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 18-181.
RC STRAIN=FVB/N; TISSUE=Liver;
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 [3]
RP DISRUPTION PHENOTYPE.
RX PubMed=20562862; DOI=10.1038/nbt.1644;
RA Tang T., Li L., Tang J., Li Y., Lin W.Y., Martin F., Grant D., Solloway M.,
RA Parker L., Ye W., Forrest W., Ghilardi N., Oravecz T., Platt K.A.,
RA Rice D.S., Hansen G.M., Abuin A., Eberhart D.E., Godowski P., Holt K.H.,
RA Peterson A., Zambrowicz B.P., de Sauvage F.J.;
RT "A mouse knockout library for secreted and transmembrane proteins.";
RL Nat. Biotechnol. 28:749-755(2010).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=22569073; DOI=10.1152/ajpendo.00084.2012;
RA Ren G., Kim J.Y., Smas C.M.;
RT "Identification of RIFL, a novel adipocyte-enriched insulin target gene
RT with a role in lipid metabolism.";
RL Am. J. Physiol. 303:E334-E351(2012).
RN [5]
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=22809513; DOI=10.1016/j.bbrc.2012.07.038;
RA Zhang R.;
RT "Lipasin, a novel nutritionally-regulated liver-enriched factor that
RT regulates serum triglyceride levels.";
RL Biochem. Biophys. Res. Commun. 424:786-792(2012).
RN [6]
RP INDUCTION.
RX PubMed=23261442; DOI=10.1016/j.bbrc.2012.12.025;
RA Fu Z., Yao F., Abou-Samra A.B., Zhang R.;
RT "Lipasin, thermoregulated in brown fat, is a novel but atypical member of
RT the angiopoietin-like protein family.";
RL Biochem. Biophys. Res. Commun. 430:1126-1131(2013).
RN [7]
RP FUNCTION, AND INDUCTION.
RX PubMed=23150577; DOI=10.1073/pnas.1217552109;
RA Quagliarini F., Wang Y., Kozlitina J., Grishin N.V., Hyde R.,
RA Boerwinkle E., Valenzuela D.M., Murphy A.J., Cohen J.C., Hobbs H.H.;
RT "Atypical angiopoietin-like protein that regulates ANGPTL3.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:19751-19756(2012).
RN [8]
RP RETRACTED PAPER.
RX PubMed=23623304; DOI=10.1016/j.cell.2013.04.008;
RA Yi P., Park J.S., Melton D.A.;
RT "Betatrophin: a hormone that controls pancreatic beta cell proliferation.";
RL Cell 153:747-758(2013).
RN [9]
RP RETRACTION NOTICE OF PUBMED:23623304.
RX PubMed=28038792; DOI=10.1016/j.cell.2016.12.017;
RA Yi P., Park J.S., Melton D.A.;
RL Cell 168:326-326(2017).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24043787; DOI=10.1073/pnas.1315292110;
RA Wang Y., Quagliarini F., Gusarova V., Gromada J., Valenzuela D.M.,
RA Cohen J.C., Hobbs H.H.;
RT "Mice lacking ANGPTL8 (Betatrophin) manifest disrupted triglyceride
RT metabolism without impaired glucose homeostasis.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:16109-16114(2013).
RN [11]
RP EXPRESSION IN HUMAN PANCREATIC BETA-CELLS.
RX PubMed=24353178; DOI=10.2337/db13-1435;
RA Jiao Y., Le Lay J., Yu M., Naji A., Kaestner K.H.;
RT "Elevated mouse hepatic betatrophin expression does not increase human
RT beta-cell replication in the transplant setting.";
RL Diabetes 63:1283-1288(2014).
RN [12]
RP DISRUPTION PHENOTYPE.
RX PubMed=25417115; DOI=10.1016/j.cell.2014.09.027;
RA Gusarova V., Alexa C.A., Na A., Stevis P.E., Xin Y., Bonner-Weir S.,
RA Cohen J.C., Hobbs H.H., Murphy A.J., Yancopoulos G.D., Gromada J.;
RT "ANGPTL8/betatrophin does not control pancreatic beta cell expansion.";
RL Cell 159:691-696(2014).
CC -!- FUNCTION: Hormone that acts as a blood lipid regulator by regulating
CC serum triglyceride levels (PubMed:22569073, PubMed:22809513,
CC PubMed:23150577, PubMed:24043787). May be involved in the metabolic
CC transition between fasting and refeeding: required to direct fatty
CC acids to adipose tissue for storage in the fed state (PubMed:24043787).
CC According to a report, may act by promoting ANGPTL3 cleavage
CC (PubMed:23150577). According to another study, not required for
CC cleavage of ANGPTL3 (PubMed:24043787). {ECO:0000269|PubMed:22569073,
CC ECO:0000269|PubMed:22809513, ECO:0000269|PubMed:23150577,
CC ECO:0000269|PubMed:24043787}.
CC -!- SUBUNIT: Interacts with ANGPTL3. {ECO:0000250|UniProtKB:Q6UXH0}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:22569073}.
CC -!- TISSUE SPECIFICITY: Expressed in liver and fat. Enriched in white and
CC brown adipose tissues. {ECO:0000269|PubMed:22569073,
CC ECO:0000269|PubMed:22809513}.
CC -!- DEVELOPMENTAL STAGE: Expressed during adipogenesis.
CC {ECO:0000269|PubMed:22569073}.
CC -!- INDUCTION: Highly up-regulated following high-fat diet treatment. Down-
CC regulated upon fasting. Strongly induced in the cold environment (4
CC Degrees Celsius for 4 hours). {ECO:0000269|PubMed:22809513,
CC ECO:0000269|PubMed:23150577, ECO:0000269|PubMed:23261442}.
CC -!- PTM: Proteolytically cleaved at the N-terminus.
CC {ECO:0000250|UniProtKB:Q6UXH0}.
CC -!- DISRUPTION PHENOTYPE: Reduced levels of serum triglyceride
CC (PubMed:20562862, PubMed:24043787). Mice gain weight more slowly than
CC wild-type littermates due to a reduction in adipose tissue accretion.
CC Plasma levels of triglycerides are similar to wild-type animals in the
CC fasted state but decreased after refeeding. The lower triglyceride
CC levels are associated with a reduction in very low density lipoprotein
CC secretion and an increase in lipoprotein lipase (LPL) activity
CC (PubMed:24043787). Glucose and insulin tolerance are not affected and
CC no alterations in glucose homeostasis are observed in mice fed either a
CC chow or high fat diet (PubMed:24043787). Moreover, deletion does not
CC affect the compensatory proliferation of pancreatic beta cells in
CC response to insulin resistance induced by a high-fat diet or treatment
CC with the insulin antagonist S961 (PubMed:25417115).
CC {ECO:0000269|PubMed:20562862, ECO:0000269|PubMed:24043787,
CC ECO:0000269|PubMed:25417115}.
CC -!- SIMILARITY: Belongs to the ANGPTL8 family. {ECO:0000305}.
CC -!- CAUTION: Initially reported to specifically promote pancreatic beta
CC cell proliferation without insulin resistance and to promote beta cell
CC mass expansion, thereby improving glucose tolerance (PubMed:23623304).
CC However, this result could not be confirmed by further studies and the
CC original paper was later retracted (PubMed:28038792). The lack of a
CC role in beta cell proliferation was also confirmed in another study
CC (PubMed:25417115). {ECO:0000269|PubMed:25417115,
CC ECO:0000305|PubMed:23623304, ECO:0000305|PubMed:28038792}.
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DR EMBL; AC166992; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC024408; AAH24408.1; -; mRNA.
DR CCDS; CCDS40556.1; -.
DR RefSeq; NP_001074409.1; NM_001080940.1.
DR AlphaFoldDB; Q8R1L8; -.
DR SMR; Q8R1L8; -.
DR BioGRID; 550761; 2.
DR STRING; 10090.ENSMUSP00000058951; -.
DR PhosphoSitePlus; Q8R1L8; -.
DR PaxDb; Q8R1L8; -.
DR PRIDE; Q8R1L8; -.
DR ProteomicsDB; 296231; -.
DR Antibodypedia; 25764; 217 antibodies from 25 providers.
DR Ensembl; ENSMUST00000058777; ENSMUSP00000058951; ENSMUSG00000047822.
DR GeneID; 624219; -.
DR KEGG; mmu:624219; -.
DR UCSC; uc009omr.1; mouse.
DR CTD; 55908; -.
DR MGI; MGI:3643534; Angptl8.
DR VEuPathDB; HostDB:ENSMUSG00000047822; -.
DR eggNOG; ENOG502SF52; Eukaryota.
DR GeneTree; ENSGT00440000034383; -.
DR HOGENOM; CLU_097765_0_0_1; -.
DR InParanoid; Q8R1L8; -.
DR OMA; GAWLGHA; -.
DR OrthoDB; 1420384at2759; -.
DR PhylomeDB; Q8R1L8; -.
DR TreeFam; TF337951; -.
DR Reactome; R-MMU-8963889; Assembly of active LPL and LIPC lipase complexes.
DR BioGRID-ORCS; 624219; 1 hit in 34 CRISPR screens.
DR ChiTaRS; Angptl8; mouse.
DR PRO; PR:Q8R1L8; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q8R1L8; protein.
DR Bgee; ENSMUSG00000047822; Expressed in left lobe of liver and 56 other tissues.
DR ExpressionAtlas; Q8R1L8; baseline and differential.
DR Genevisible; Q8R1L8; MM.
DR GO; GO:0005576; C:extracellular region; ISO:MGI.
DR GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW.
DR GO; GO:0048469; P:cell maturation; IMP:MGI.
DR GO; GO:0044255; P:cellular lipid metabolic process; IMP:UniProtKB.
DR GO; GO:0045444; P:fat cell differentiation; IMP:UniProtKB.
DR GO; GO:0051005; P:negative regulation of lipoprotein lipase activity; TAS:UniProtKB.
DR GO; GO:0010954; P:positive regulation of protein processing; ISO:MGI.
DR GO; GO:0019216; P:regulation of lipid metabolic process; IMP:UniProtKB.
DR GO; GO:0050746; P:regulation of lipoprotein metabolic process; IMP:UniProtKB.
DR GO; GO:0070328; P:triglyceride homeostasis; IMP:UniProtKB.
DR InterPro; IPR026614; ANGPTL8.
DR PANTHER; PTHR21463; PTHR21463; 1.
PE 2: Evidence at transcript level;
KW Hormone; Lipid metabolism; Reference proteome; Secreted; Signal.
FT SIGNAL 1..15
FT /evidence="ECO:0000255"
FT CHAIN 16..198
FT /note="Angiopoietin-like protein 8"
FT /id="PRO_0000319618"
FT CONFLICT 19
FT /note="A -> T (in Ref. 2; AAH24408)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 198 AA; 22063 MW; ADA35D41CFECDD11 CRC64;
MAVLALCLLW TLASAVRPAP VAPLGGPEPA QYEELTLLFH GALQLGQALN GVYRATEARL
TEAGHSLGLY DRALEFLGTE VRQGQDATQE LRTSLSEIQV EEDALHLRAE ATARSLGEVA
RAQQALRDTV RRLQVQLRGA WLGQAHQEFE TLKARADKQS HLLWALTGHV QRQQREMAEQ
QQWLRQIQQR LHTAALPA
