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Protein

Angiopoietin-like protein 8

Gene

Angptl8

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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).4 Publications

GO - Molecular functioni

  • hormone activity Source: UniProtKB

GO - Biological processi

  • cell maturation Source: MGI
  • cellular lipid metabolic process Source: UniProtKB
  • fat cell differentiation Source: UniProtKB
  • glucose metabolic process Source: UniProtKB
  • negative regulation of lipoprotein lipase activity Source: UniProtKB
  • positive regulation of protein processing Source: MGI
  • regulation of lipid metabolic process Source: UniProtKB
  • regulation of lipoprotein metabolic process Source: UniProtKB
  • triglyceride homeostasis Source: UniProtKB
  • type B pancreatic cell proliferation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hormone

Keywords - Biological processi

Lipid metabolism

Names & Taxonomyi

Protein namesi
Recommended name:
Angiopoietin-like protein 8Imported
Alternative name(s):
Betatrophin1 Publication
Lipasin1 Publication
Refeeding-induced fat and liver protein1 Publication
Gene namesi
Name:Angptl8Imported
Synonyms:Gm6484Imported, Rifl1 Publication
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:3643534. Angptl8.

Subcellular locationi

GO - Cellular componenti

  • extracellular region Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Disruption phenotypei

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).3 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1515Sequence analysisAdd
BLAST
Chaini16 – 198183Angiopoietin-like protein 8PRO_0000319618Add
BLAST

Post-translational modificationi

Proteolytically cleaved at the N-terminus.By similarity

Proteomic databases

PaxDbiQ8R1L8.
PRIDEiQ8R1L8.

Expressioni

Tissue specificityi

Expressed in liver and fat. Enriched in white and brown adipose tissues.3 Publications

Developmental stagei

Expressed during adipogenesis.1 Publication

Inductioni

Highly up-regulated following high-fat diet treatment. Down-regulated upon fasting. Strongly induced in the cold environment (4 Degrees Celsius for 4 hours).3 Publications

Gene expression databases

BgeeiQ8R1L8.
CleanExiMM_EG624219.
ExpressionAtlasiQ8R1L8. baseline and differential.
GenevisibleiQ8R1L8. MM.

Interactioni

Subunit structurei

Interacts with ANGPTL3.By similarity

GO - Molecular functioni

  • hormone activity Source: UniProtKB

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000058951.

Structurei

3D structure databases

ProteinModelPortaliQ8R1L8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the ANGPTL8 family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410J1RV. Eukaryota.
ENOG410ZCIU. LUCA.
GeneTreeiENSGT00440000034383.
HOGENOMiHOG000154535.
HOVERGENiHBG097752.
InParanoidiQ8R1L8.
OMAiMPVPALC.
OrthoDBiEOG71CFQ0.
PhylomeDBiQ8R1L8.
TreeFamiTF337951.

Family and domain databases

InterProiIPR026614. TD26.
[Graphical view]
PANTHERiPTHR21463. PTHR21463. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q8R1L8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAVLALCLLW TLASAVRPAP VAPLGGPEPA QYEELTLLFH GALQLGQALN
60 70 80 90 100
GVYRATEARL TEAGHSLGLY DRALEFLGTE VRQGQDATQE LRTSLSEIQV
110 120 130 140 150
EEDALHLRAE ATARSLGEVA RAQQALRDTV RRLQVQLRGA WLGQAHQEFE
160 170 180 190
TLKARADKQS HLLWALTGHV QRQQREMAEQ QQWLRQIQQR LHTAALPA
Length:198
Mass (Da):22,063
Last modified:February 26, 2008 - v2
Checksum:iADA35D41CFECDD11
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti19 – 191A → T in AAH24408 (PubMed:15489334).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC166992 Genomic DNA. No translation available.
BC024408 mRNA. Translation: AAH24408.1.
CCDSiCCDS40556.1.
RefSeqiNP_001074409.1. NM_001080940.1.
UniGeneiMm.440264.

Genome annotation databases

EnsembliENSMUST00000058777; ENSMUSP00000058951; ENSMUSG00000047822.
GeneIDi624219.
KEGGimmu:624219.
UCSCiuc009omr.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC166992 Genomic DNA. No translation available.
BC024408 mRNA. Translation: AAH24408.1.
CCDSiCCDS40556.1.
RefSeqiNP_001074409.1. NM_001080940.1.
UniGeneiMm.440264.

3D structure databases

ProteinModelPortaliQ8R1L8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000058951.

Proteomic databases

PaxDbiQ8R1L8.
PRIDEiQ8R1L8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000058777; ENSMUSP00000058951; ENSMUSG00000047822.
GeneIDi624219.
KEGGimmu:624219.
UCSCiuc009omr.1. mouse.

Organism-specific databases

CTDi55908.
MGIiMGI:3643534. Angptl8.

Phylogenomic databases

eggNOGiENOG410J1RV. Eukaryota.
ENOG410ZCIU. LUCA.
GeneTreeiENSGT00440000034383.
HOGENOMiHOG000154535.
HOVERGENiHBG097752.
InParanoidiQ8R1L8.
OMAiMPVPALC.
OrthoDBiEOG71CFQ0.
PhylomeDBiQ8R1L8.
TreeFamiTF337951.

Miscellaneous databases

PROiQ8R1L8.
SOURCEiSearch...

Gene expression databases

BgeeiQ8R1L8.
CleanExiMM_EG624219.
ExpressionAtlasiQ8R1L8. baseline and differential.
GenevisibleiQ8R1L8. MM.

Family and domain databases

InterProiIPR026614. TD26.
[Graphical view]
PANTHERiPTHR21463. PTHR21463. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 18-181.
    Strain: FVB/N.
    Tissue: Liver.
  3. Cited for: DISRUPTION PHENOTYPE.
  4. "Identification of RIFL, a novel adipocyte-enriched insulin target gene with a role in lipid metabolism."
    Ren G., Kim J.Y., Smas C.M.
    Am. J. Physiol. 303:E334-E351(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
  5. "Lipasin, a novel nutritionally-regulated liver-enriched factor that regulates serum triglyceride levels."
    Zhang R.
    Biochem. Biophys. Res. Commun. 424:786-792(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY, INDUCTION.
  6. "Lipasin, thermoregulated in brown fat, is a novel but atypical member of the angiopoietin-like protein family."
    Fu Z., Yao F., Abou-Samra A.B., Zhang R.
    Biochem. Biophys. Res. Commun. 430:1126-1131(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  7. Cited for: FUNCTION, INDUCTION.
  8. "Betatrophin: a hormone that controls pancreatic beta cell proliferation."
    Yi P., Park J.S., Melton D.A.
    Cell 153:747-758(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  9. "Mice lacking ANGPTL8 (Betatrophin) manifest disrupted triglyceride metabolism without impaired glucose homeostasis."
    Wang Y., Quagliarini F., Gusarova V., Gromada J., Valenzuela D.M., Cohen J.C., Hobbs H.H.
    Proc. Natl. Acad. Sci. U.S.A. 110:16109-16114(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  10. "Elevated mouse hepatic betatrophin expression does not increase human beta-cell replication in the transplant setting."
    Jiao Y., Le Lay J., Yu M., Naji A., Kaestner K.H.
    Diabetes 63:1283-1288(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: EXPRESSION IN HUMAN PANCREATIC BETA-CELLS.
  11. "Perspectives on the activities of ANGPTL8/betatrophin."
    Yi P., Park J.S., Melton D.A.
    Cell 159:467-468(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: ROLE IN PANCREATIC BETA-CELLS PROLIFERATION.
  12. Cited for: DISRUPTION PHENOTYPE.

Entry informationi

Entry nameiANGL8_MOUSE
AccessioniPrimary (citable) accession number: Q8R1L8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 26, 2008
Last sequence update: February 26, 2008
Last modified: June 8, 2016
This is version 72 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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).2 Publications3 Publications

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.