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Protein

Angiopoietin-like protein 8

Gene

ANGPTL8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Hormone that acts as a blood lipid regulator by regulating serum triglyceride levels (PubMed:22569073, PubMed:22809513, PubMed:23150577). 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 (By similarity).By similarity3 Publications

GO - Molecular functioni

GO - Biological processi

  • cell maturation Source: Ensembl
  • cellular lipid metabolic process Source: UniProtKB
  • fat cell differentiation Source: Ensembl
  • positive regulation of protein processing Source: MGI
  • regulation of lipid metabolic process Source: UniProtKB
  • regulation of lipoprotein metabolic process Source: MGI
  • 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:C19orf80, RIFL1 Publication
ORF Names:UNQ599/PRO11851 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:24933. ANGPTL8.

Subcellular locationi

GO - Cellular componenti

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

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Diabetes mellitus, insulin-dependent (IDDM)1 Publication
The gene represented in this entry may be involved in disease pathogenesis. Increased protein levels are observed in the serum of patients. This result should however be reinvestigated in light of recent advances that suggest that this protein is not promoting pancreatic beta cell proliferation.1 Publication
Disease descriptionA multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
See also OMIM:222100
Diabetes mellitus, non-insulin-dependent (NIDDM)4 Publications
The gene represented in this entry may be involved in disease pathogenesis. Increased protein levels are observed in the serum of patients and are associated with insulin resistance (PubMed:25024395, PubMed:25303484, PubMed:24963292, PubMed:24852694). According to another report, protein levels are decreased in the serum of patients (PubMed:25050901). Discrepancies between increased and decreased levels of proteins levels in NIDDM patients may be explained by the use of different kits developed on the market that either use antibodies recognizing the N-terminal or the C-terminal part of the protein (PubMed:25099942). These results should however be reinvestigated in light of recent advances that suggest that this protein is not promoting pancreatic beta cell proliferation.6 Publications
Disease descriptionA multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
See also OMIM:125853

Keywords - Diseasei

Diabetes mellitus

Organism-specific databases

MIMi125853. phenotype.
222100. phenotype.

Polymorphism and mutation databases

BioMutaiC19orf80.
DMDMi74738217.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121Sequence analysisAdd
BLAST
Chaini22 – 198177Angiopoietin-like protein 8PRO_0000319617Add
BLAST

Post-translational modificationi

Proteolytically cleaved at the N-terminus.1 Publication

Proteomic databases

PaxDbiQ6UXH0.
PRIDEiQ6UXH0.

Expressioni

Tissue specificityi

Predominantly expressed in liver. Also expressed in adipose tissues.4 Publications

Developmental stagei

Transcripts are up-regulated by 100 fold during adipogenesis.1 Publication

Inductioni

In response to food intake. Stimulated by insulin.2 Publications

Gene expression databases

BgeeiQ6UXH0.
ExpressionAtlasiQ6UXH0. baseline and differential.
GenevisibleiQ6UXH0. HS.

Interactioni

Subunit structurei

Interacts with ANGPTL3.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
RCHY1Q96PM52EBI-3943039,EBI-947779

GO - Molecular functioni

Protein-protein interaction databases

BioGridi120994. 1 interaction.
IntActiQ6UXH0. 2 interactions.
STRINGi9606.ENSP00000252453.

Structurei

3D structure databases

ProteinModelPortaliQ6UXH0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the ANGPTL8 family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410J1RV. Eukaryota.
ENOG410ZCIU. LUCA.
GeneTreeiENSGT00440000034383.
HOGENOMiHOG000154535.
HOVERGENiHBG097752.
InParanoidiQ6UXH0.
OMAiMPVPALC.
PhylomeDBiQ6UXH0.
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.

Q6UXH0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPVPALCLLW ALAMVTRPAS AAPMGGPELA QHEELTLLFH GTLQLGQALN
60 70 80 90 100
GVYRTTEGRL TKARNSLGLY GRTIELLGQE VSRGRDAAQE LRASLLETQM
110 120 130 140 150
EEDILQLQAE ATAEVLGEVA QAQKVLRDSV QRLEVQLRSA WLGPAYREFE
160 170 180 190
VLKAHADKQS HILWALTGHV QRQRREMVAQ QHRLRQIQER LHTAALPA
Length:198
Mass (Da):22,105
Last modified:July 5, 2004 - v1
Checksum:i90A29DCEBC5E992E
GO

Sequence cautioni

The sequence AAF76204.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence EAW84186.1 differs from that shown. Reason: Erroneous gene model prediction. Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti59 – 591R → W Lover plasma LDL-cholesterol and HDL-cholesterol levels. 1 Publication
Corresponds to variant rs2278426 [ dbSNP | Ensembl ].
VAR_039046
Natural varianti147 – 1471R → Q.
Corresponds to variant rs34056604 [ dbSNP | Ensembl ].
VAR_039047

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF271350 mRNA. Translation: AAF76204.2. Different initiation.
AY358356 mRNA. Translation: AAQ88722.1.
AC011472 Genomic DNA. No translation available.
CH471106 Genomic DNA. Translation: EAW84186.1. Sequence problems.
CCDSiCCDS54220.1.
RefSeqiNP_061157.3. NM_018687.6.
UniGeneiHs.534467.

Genome annotation databases

EnsembliENST00000252453; ENSP00000252453; ENSG00000130173.
ENST00000616433; ENSP00000479969; ENSG00000130173.
GeneIDi55908.
KEGGihsa:55908.
UCSCiuc021upf.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF271350 mRNA. Translation: AAF76204.2. Different initiation.
AY358356 mRNA. Translation: AAQ88722.1.
AC011472 Genomic DNA. No translation available.
CH471106 Genomic DNA. Translation: EAW84186.1. Sequence problems.
CCDSiCCDS54220.1.
RefSeqiNP_061157.3. NM_018687.6.
UniGeneiHs.534467.

3D structure databases

ProteinModelPortaliQ6UXH0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120994. 1 interaction.
IntActiQ6UXH0. 2 interactions.
STRINGi9606.ENSP00000252453.

Polymorphism and mutation databases

BioMutaiC19orf80.
DMDMi74738217.

Proteomic databases

PaxDbiQ6UXH0.
PRIDEiQ6UXH0.

Protocols and materials databases

DNASUi55908.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000252453; ENSP00000252453; ENSG00000130173.
ENST00000616433; ENSP00000479969; ENSG00000130173.
GeneIDi55908.
KEGGihsa:55908.
UCSCiuc021upf.2. human.

Organism-specific databases

CTDi55908.
GeneCardsiC19orf80.
HGNCiHGNC:24933. ANGPTL8.
MIMi125853. phenotype.
222100. phenotype.
616223. gene.
neXtProtiNX_Q6UXH0.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J1RV. Eukaryota.
ENOG410ZCIU. LUCA.
GeneTreeiENSGT00440000034383.
HOGENOMiHOG000154535.
HOVERGENiHBG097752.
InParanoidiQ6UXH0.
OMAiMPVPALC.
PhylomeDBiQ6UXH0.
TreeFamiTF337951.

Miscellaneous databases

GenomeRNAii55908.
PROiQ6UXH0.
SOURCEiSearch...

Gene expression databases

BgeeiQ6UXH0.
ExpressionAtlasiQ6UXH0. baseline and differential.
GenevisibleiQ6UXH0. HS.

Family and domain databases

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

Publicationsi

« Hide 'large scale' publications
  1. "Identification of genes differentially expressed in human hepatocellular carcinoma by a modified suppression subtractive hybridization method."
    Dong X.Y., Pang X.W., Yu S.T., Su Y.R., Wang H.C., Yin Y.H., Wang Y.D., Chen W.F.
    Int. J. Cancer 112:239-248(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  3. "The DNA sequence and biology of human chromosome 19."
    Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V.
    , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
    Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "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, TISSUE SPECIFICITY, INDUCTION, DEVELOPMENTAL STAGE.
  6. "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: TISSUE SPECIFICITY.
  7. Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION, INTERACTION WITH ANGPTL3, VARIANT TRP-59, CHARACTERIZATION OF VARIANT TRP-59.
  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. "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.
  10. Cited for: ROLE IN PANCREATIC BETA-CELLS PROLIFERATION.
  11. "Increased circulating levels of betatrophin in newly diagnosed type 2 diabetic patients."
    Hu H., Sun W., Yu S., Hong X., Qian W., Tang B., Wang D., Yang L., Wang J., Mao C., Zhou L., Yuan G.
    Diabetes Care 37:2718-2722(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: POSSIBLE INVOLVEMENT IN NIDDM.
  12. "Increased circulating levels of betatrophin in individuals with long-standing type 1 diabetes."
    Espes D., Lau J., Carlsson P.O.
    Diabetologia 57:50-53(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: POSSIBLE INVOLVEMENT IN IDDM.
  13. "An explanation for recent discrepancies in levels of human circulating betatrophin."
    Fu Z., Abou-Samra A.B., Zhang R.
    Diabetologia 57:2232-2234(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEOLYTIC PROCESSING.
  14. "Increased circulating betatrophin concentrations in patients with type 2 diabetes."
    Espes D., Martinell M., Carlsson P.O.
    Int. J. Endocrinol. 2014:323407-323407(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: POSSIBLE INVOLVEMENT IN NIDDM.
  15. "Circulating betatrophin concentrations are decreased in human obesity and type 2 diabetes."
    Gomez-Ambrosi J., Pascual E., Catalan V., Rodriguez A., Ramirez B., Silva C., Gil M.J., Salvador J., Fruehbeck G.
    J. Clin. Endocrinol. Metab. 99:E2004-E2004(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: POSSIBLE INVOLVEMENT IN NIDDM.
  16. "Circulating betatrophin levels are increased in patients with type 2 diabetes and associated with insulin resistance."
    Chen X., Lu P., He W., Zhang J., Liu L., Yang Y., Liu Z., Xie J., Shao S., Du T., Su X., Zhou X., Hu S., Yuan G., Zhang M., Zhang H., Liu L., Wang D., Yu X.
    J. Clin. Endocrinol. Metab. 100:E96-E100(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: POSSIBLE INVOLVEMENT IN NIDDM.
  17. "Elevated circulating lipasin/betatrophin in human type 2 diabetes and obesity."
    Fu Z., Berhane F., Fite A., Seyoum B., Abou-Samra A.B., Zhang R.
    Sci. Rep. 4:5013-5013(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: POSSIBLE INVOLVEMENT IN NIDDM.

Entry informationi

Entry nameiANGL8_HUMAN
AccessioniPrimary (citable) accession number: Q6UXH0
Secondary accession number(s): Q9NQZ1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 26, 2008
Last sequence update: July 5, 2004
Last modified: June 8, 2016
This is version 81 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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). Overexpression of ANGPTL8 in mouse liver leads to elevated serum triglyceride levels but not significant pancreatic beta cell proliferation (PubMed:25417115). Knockout experiments in mouse also support a role of ANGPTL8 in regulating serum triglyceride levels without affecting glucose homeostasis. The authors of the original study agree with these conclusions (PubMed:25417096).2 Publications1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.