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Angiopoietin-like protein 8 (Betatrophin) (Lipasin) (Refeeding-induced fat and liver protein)

 ANGL8_MOUSE             Reviewed;         198 AA.
Q8R1L8;
26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
26-FEB-2008, sequence version 2.
12-SEP-2018, entry version 82.
RecName: Full=Angiopoietin-like protein 8 {ECO:0000312|MGI:MGI:3643534};
AltName: Full=Betatrophin {ECO:0000303|PubMed:23623304};
AltName: Full=Lipasin {ECO:0000303|PubMed:22809513};
AltName: Full=Refeeding-induced fat and liver protein {ECO:0000303|PubMed:22569073};
Flags: Precursor;
Name=Angptl8 {ECO:0000312|MGI:MGI:3643534};
Synonyms=Gm6484 {ECO:0000312|MGI:MGI:3643534},
Rifl {ECO:0000303|PubMed:22569073};
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
STRAIN=C57BL/6J;
PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S.,
She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W.,
Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T.,
Zhou S., Teague B., Potamousis K., Churas C., Place M., Herschleb J.,
Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z.,
Lindblad-Toh K., Eichler E.E., Ponting C.P.;
"Lineage-specific biology revealed by a finished genome assembly of
the mouse.";
PLoS Biol. 7:E1000112-E1000112(2009).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 18-181.
STRAIN=FVB/N; TISSUE=Liver;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[3]
DISRUPTION PHENOTYPE.
PubMed=20562862; DOI=10.1038/nbt.1644;
Tang T., Li L., Tang J., Li Y., Lin W.Y., Martin F., Grant D.,
Solloway M., Parker L., Ye W., Forrest W., Ghilardi N., Oravecz T.,
Platt K.A., Rice D.S., Hansen G.M., Abuin A., Eberhart D.E.,
Godowski P., Holt K.H., Peterson A., Zambrowicz B.P., de Sauvage F.J.;
"A mouse knockout library for secreted and transmembrane proteins.";
Nat. Biotechnol. 28:749-755(2010).
[4]
FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
STAGE.
PubMed=22569073; DOI=10.1152/ajpendo.00084.2012;
Ren G., Kim J.Y., Smas C.M.;
"Identification of RIFL, a novel adipocyte-enriched insulin target
gene with a role in lipid metabolism.";
Am. J. Physiol. 303:E334-E351(2012).
[5]
FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
PubMed=22809513; DOI=10.1016/j.bbrc.2012.07.038;
Zhang R.;
"Lipasin, a novel nutritionally-regulated liver-enriched factor that
regulates serum triglyceride levels.";
Biochem. Biophys. Res. Commun. 424:786-792(2012).
[6]
INDUCTION.
PubMed=23261442; DOI=10.1016/j.bbrc.2012.12.025;
Fu Z., Yao F., Abou-Samra A.B., Zhang R.;
"Lipasin, thermoregulated in brown fat, is a novel but atypical member
of the angiopoietin-like protein family.";
Biochem. Biophys. Res. Commun. 430:1126-1131(2013).
[7]
FUNCTION, AND INDUCTION.
PubMed=23150577; DOI=10.1073/pnas.1217552109;
Quagliarini F., Wang Y., Kozlitina J., Grishin N.V., Hyde R.,
Boerwinkle E., Valenzuela D.M., Murphy A.J., Cohen J.C., Hobbs H.H.;
"Atypical angiopoietin-like protein that regulates ANGPTL3.";
Proc. Natl. Acad. Sci. U.S.A. 109:19751-19756(2012).
[8]
SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
PubMed=23623304; DOI=10.1016/j.cell.2013.04.008;
Yi P., Park J.S., Melton D.A.;
"Betatrophin: a hormone that controls pancreatic beta cell
proliferation.";
Cell 153:747-758(2013).
[9]
FUNCTION, AND DISRUPTION PHENOTYPE.
PubMed=24043787; DOI=10.1073/pnas.1315292110;
Wang Y., Quagliarini F., Gusarova V., Gromada J., Valenzuela D.M.,
Cohen J.C., Hobbs H.H.;
"Mice lacking ANGPTL8 (Betatrophin) manifest disrupted triglyceride
metabolism without impaired glucose homeostasis.";
Proc. Natl. Acad. Sci. U.S.A. 110:16109-16114(2013).
[10]
EXPRESSION IN HUMAN PANCREATIC BETA-CELLS.
PubMed=24353178; DOI=10.2337/db13-1435;
Jiao Y., Le Lay J., Yu M., Naji A., Kaestner K.H.;
"Elevated mouse hepatic betatrophin expression does not increase human
beta-cell replication in the transplant setting.";
Diabetes 63:1283-1288(2014).
[11]
ROLE IN PANCREATIC BETA-CELLS PROLIFERATION.
PubMed=25417096; DOI=10.1016/j.cell.2014.09.028;
Yi P., Park J.S., Melton D.A.;
"Perspectives on the activities of ANGPTL8/betatrophin.";
Cell 159:467-468(2014).
[12]
DISRUPTION PHENOTYPE.
PubMed=25417115; DOI=10.1016/j.cell.2014.09.027;
Gusarova V., Alexa C.A., Na A., Stevis P.E., Xin Y., Bonner-Weir S.,
Cohen J.C., Hobbs H.H., Murphy A.J., Yancopoulos G.D., Gromada J.;
"ANGPTL8/betatrophin does not control pancreatic beta cell
expansion.";
Cell 159:691-696(2014).
-!- FUNCTION: Hormone that acts as a blood lipid regulator by
regulating serum triglyceride levels (PubMed:22569073,
PubMed:22809513, PubMed:23150577, PubMed:24043787). May be
involved in the metabolic transition between fasting and
refeeding: required to direct fatty acids to adipose tissue for
storage in the fed state (PubMed:24043787). According to a report,
may act by promoting ANGPTL3 cleavage (PubMed:23150577). According
to another study, not required for cleavage of ANGPTL3
(PubMed:24043787). {ECO:0000269|PubMed:22569073,
ECO:0000269|PubMed:22809513, ECO:0000269|PubMed:23150577,
ECO:0000269|PubMed:24043787}.
-!- SUBUNIT: Interacts with ANGPTL3. {ECO:0000250|UniProtKB:Q6UXH0}.
-!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:22569073,
ECO:0000269|PubMed:23623304}.
-!- TISSUE SPECIFICITY: Expressed in liver and fat. Enriched in white
and brown adipose tissues. {ECO:0000269|PubMed:22569073,
ECO:0000269|PubMed:22809513, ECO:0000269|PubMed:23623304}.
-!- DEVELOPMENTAL STAGE: Expressed during adipogenesis.
{ECO:0000269|PubMed:22569073}.
-!- INDUCTION: Highly up-regulated following high-fat diet treatment.
Down-regulated upon fasting. Strongly induced in the cold
environment (4 Degrees Celsius for 4 hours).
{ECO:0000269|PubMed:22809513, ECO:0000269|PubMed:23150577,
ECO:0000269|PubMed:23261442}.
-!- PTM: Proteolytically cleaved at the N-terminus.
{ECO:0000250|UniProtKB:Q6UXH0}.
-!- DISRUPTION PHENOTYPE: Reduced levels of serum triglyceride
(PubMed:20562862, PubMed:24043787). Mice gain weight more slowly
than wild-type littermates due to a reduction in adipose tissue
accretion. Plasma levels of triglycerides are similar to wild-type
animals in the fasted state but decreased after refeeding. The
lower triglyceride levels are associated with a reduction in very
low density lipoprotein secretion and an increase in lipoprotein
lipase (LPL) activity (PubMed:24043787). Glucose and insulin
tolerance are not affected and no alterations in glucose
homeostasis are observed in mice fed either a chow or high fat
diet (PubMed:24043787). Moreover, deletion does not affect the
compensatory proliferation of pancreatic beta cells in response to
insulin resistance induced by a high-fat diet or treatment with
the insulin antagonist S961 (PubMed:25417115).
{ECO:0000269|PubMed:20562862, ECO:0000269|PubMed:24043787,
ECO:0000269|PubMed:25417115}.
-!- SIMILARITY: Belongs to the ANGPTL8 family. {ECO:0000305}.
-!- CAUTION: Initially reported to specifically promote pancreatic
beta cell proliferation without insulin resistance and promote
beta cell mass expansion, thereby improving glucose tolerance
(PubMed:23623304). The ability to induce pancreatic beta cell
proliferation was promising in diabetes therapy; however, this
result could not be confirmed by further studies
(PubMed:23623304). Knockout experiments showed that glucose and
insulin tolerance were not affected and no alterations in glucose
homeostasis were observed in mice fed either a chow or high fat
diet (PubMed:24043787). High expression of mouse protein does not
promote any increase of human pancreatic beta-cell replication
(PubMed:24353178). Knockout experiments show that the absence of
the protein does not affect the compensatory proliferation of
pancreatic beta cells in response to insulin resistance induced by
a high-fat diet or treatment with the insulin antagonist S961
(PubMed:25417115). The authors of the original study agree with
these conclusions (PubMed:25417096). {ECO:0000269|PubMed:24043787,
ECO:0000269|PubMed:24353178, ECO:0000269|PubMed:25417115,
ECO:0000305|PubMed:23623304, ECO:0000305|PubMed:25417096}.
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EMBL; AC166992; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; BC024408; AAH24408.1; -; mRNA.
CCDS; CCDS40556.1; -.
RefSeq; NP_001074409.1; NM_001080940.1.
UniGene; Mm.440264; -.
ProteinModelPortal; Q8R1L8; -.
SMR; Q8R1L8; -.
STRING; 10090.ENSMUSP00000058951; -.
PaxDb; Q8R1L8; -.
PRIDE; Q8R1L8; -.
Ensembl; ENSMUST00000058777; ENSMUSP00000058951; ENSMUSG00000047822.
GeneID; 624219; -.
KEGG; mmu:624219; -.
UCSC; uc009omr.1; mouse.
CTD; 55908; -.
MGI; MGI:3643534; Angptl8.
eggNOG; ENOG410J1RV; Eukaryota.
eggNOG; ENOG410ZCIU; LUCA.
GeneTree; ENSGT00440000034383; -.
HOGENOM; HOG000154535; -.
HOVERGEN; HBG097752; -.
InParanoid; Q8R1L8; -.
KO; K22289; -.
OMA; MVTRPAS; -.
OrthoDB; EOG091G0QW6; -.
PhylomeDB; Q8R1L8; -.
TreeFam; TF337951; -.
Reactome; R-MMU-8963889; Assembly of active LPL and LIPC lipase complexes.
PRO; PR:Q8R1L8; -.
Proteomes; UP000000589; Chromosome 9.
Bgee; ENSMUSG00000047822; Expressed in 51 organ(s), highest expression level in brown adipose tissue.
CleanEx; MM_EG624219; -.
ExpressionAtlas; Q8R1L8; baseline and differential.
Genevisible; Q8R1L8; MM.
GO; GO:0005576; C:extracellular region; ISO:MGI.
GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW.
GO; GO:0048469; P:cell maturation; IMP:MGI.
GO; GO:0044255; P:cellular lipid metabolic process; IMP:UniProtKB.
GO; GO:0045444; P:fat cell differentiation; IMP:UniProtKB.
GO; GO:0051005; P:negative regulation of lipoprotein lipase activity; TAS:UniProtKB.
GO; GO:0010954; P:positive regulation of protein processing; ISO:MGI.
GO; GO:0019216; P:regulation of lipid metabolic process; IMP:UniProtKB.
GO; GO:0050746; P:regulation of lipoprotein metabolic process; IMP:UniProtKB.
GO; GO:0070328; P:triglyceride homeostasis; IMP:UniProtKB.
InterPro; IPR026614; ANGPTL8.
PANTHER; PTHR21463; PTHR21463; 1.
2: Evidence at transcript level;
Complete proteome; Hormone; Lipid metabolism; Reference proteome;
Secreted; Signal.
SIGNAL 1 15 {ECO:0000255}.
CHAIN 16 198 Angiopoietin-like protein 8.
/FTId=PRO_0000319618.
CONFLICT 19 19 A -> T (in Ref. 2; AAH24408).
{ECO:0000305}.
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


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