Angiopoietin Like Protein 8 Regulatory Pathway (Homo sapiens)

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Revision as of 05:44, 17 November 2016 by Siddiqa (talk | contribs) (Modified title)
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Transport of GLUT4 Transporters to Plasma Membrane Ampk isoforms Insulin Receptor Substrates Erk Signal Transduction Pathway Hepatocyte Inhibition Glucose Uptake Pancreatic Beta-cell proliferation T3 Activation PI 3-Kinase isoforms Legend mTORC1 Raptor mlst8 mTOR p70 S6 Kinases RPS6KB2 RPS6KB1 PI(3,4,5)P3 PTP GLUT1 PPARalpha AMPK Pathway GS X-5-P RHEB PI(4,5)P2 CD45+ hematopoietic- derived cell proliferation Glycolysis-Gluconeogenesis Insulin Signaling Pathway Glucose Autophagy Signaling INSR Chrebp GLUT4 glycogen Glycogenesis LPL GCK Insulin Triacylglyceride Synthesis RAS RAF1 Protein synthesis and Translation Regulation SEST3 SREBP Pathway PP2A Cell Growth Differentiation amino acids CIP42 Exo70 TSC2 TSC1 SIN1 Rictor mTOR mlst8 mTORC2 SREBP1a-c SREBP2 Transcription factors LXR target genes IRS1 IRS2 IRS4 SOS1 SOS2 GRB2 PIK3CD PIK3C3 PIK3R3 PIK3R1 PIK3C2G PIK3R2 PIK3CG PIK3CB PIK3R4 PIK3C2A PIK3CA FBP G6PC PEPCK LXR RXRA G-6-P F-2,6-P2 DIO2 RXRA THRA THRB RXRA SLC16A2 SLCO1C1 T3 T4 ANGPTL8 T3 and T4 intracelullar uptake SHC2 SHC3 SHC1 GSK3A GSK3B PDK PKB/Akt isoforms pT308 AKT1 pT308 AKT2 EIF4E EIF4EBP1 mTOR p SIN1 Rictor mlst8 mTORC2 FOXO1A FOXO3A INSR CAP1 CBL FLOT1 FLOT2 CBLC CBLB CRK RAPGEF1 RHOQ Rictor ABCG8 FASN ABCG5 CYP3A4 CYP7A1 CYP2B6 LXR target genes Drug and steroid metabolism Multi-drug resistance lipogenesis SCD MEK/MAP Kinases MAP2K1 MAP3K7 MAPK14 MAPK1 MAP2K2 MAP3K2 MAP3K6 MAPK8 MAP4K1 MAP3K11 MAP4K3 MAPK10 MAP2K7 MAP3K4 MAP3K1 MAP3K12 MAPK4 MAPK11 MAP4K5 MAPK6 MAP4K4 MAPK3 MAP3K14 MAPK12 MAP2K5 MAP2K4 MAPK13 MAP3K5 MAPK9 MAPK7 MAP3K3 MAP3K9 MAP3K8 MAP2K6 MAP3K13 MAP4K2 MAP2K3 MAP3K10 MINK1 p90 Rsk Kinases RPS6KA5 RPS6KA6 RPS6KA4 RPS6KA1 RPS6KA2 RPS6KA3 PI(3,4,5)P3 PKB/Akt isoforms pS473 pT308 AKT1 pS473 pT308 AKT2 FOXO1A FOXO3A Insulin INSR Catalysis Insulin Signaling Pathway Undefined Mechanism T4 Activation from within the Pathway AMPKy3 AMPKa1 AMPKy2 AMPKy1 AMPKb2 AMPKb1 AMPKa2 Ampk isoforms Name: Angiopoietin Like Protein 8 Regulatory Pathway Last Modified: 1/08/2016 Organism: Homo sapiens


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Ontology Terms



  1. Saltiel AR, Kahn CR; ''Insulin signalling and the regulation of glucose and lipid metabolism.''; Nature, 2001 PubMed
  2. Chen CC, Jeon SM, Bhaskar PT, Nogueira V, Sundararajan D, Tonic I, Park Y, Hay N; ''FoxOs inhibit mTORC1 and activate Akt by inducing the expression of Sestrin3 and Rictor.''; Dev Cell, 2010 PubMed
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  7. Cox AR, Barrandon O, Cai EP, Rios JS, Chavez J, Bonnyman CW, Lam CJ, Yi P, Melton DA, Kushner JA; ''Resolving Discrepant Findings on ANGPTL8 in β-Cell Proliferation: A Collaborative Approach to Resolving the Betatrophin Controversy.''; PLoS One, 2016 PubMed
  8. Fu Z, Yao F, Abou-Samra AB, Zhang R; ''Lipasin, thermoregulated in brown fat, is a novel but atypical member of the angiopoietin-like protein family.''; Biochem Biophys Res Commun, 2013 PubMed
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  11. Rong Guo X, Li Wang X, Chen Y, Hong Yuan Y, Mei Chen Y, Ding Y, Fang J, Jiao Bian L, Sheng Li D; ''ANGPTL8/betatrophin alleviates insulin resistance via the Akt-GSK3β or Akt-FoxO1 pathway in HepG2 cells.''; Exp Cell Res, 2016 PubMed
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  23. Tanti JF, Jager J; ''Cellular mechanisms of insulin resistance: role of stress-regulated serine kinases and insulin receptor substrates (IRS) serine phosphorylation.''; Curr Opin Pharmacol, 2009 PubMed
  24. Raghow R; ''Betatrophin: A liver-derived hormone for the pancreatic β-cell proliferation.''; World J Diabetes, 2013 PubMed
  25. Fu Z, Berhane F, Fite A, Seyoum B, Abou-Samra AB, Zhang R; ''Elevated circulating lipasin/betatrophin in human type 2 diabetes and obesity.''; Sci Rep, 2014 PubMed
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  27. Zhang Y, Li S, Donelan W, Xie C, Wang H, Wu Q, Purich DL, Reeves WH, Tang D, Yang LJ; ''Angiopoietin-like protein 8 (betatrophin) is a stress-response protein that down-regulates expression of adipocyte triglyceride lipase.''; Biochim Biophys Acta, 2016 PubMed
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  36. Lee J, Hong SW, Park SE, Rhee EJ, Park CY, Oh KW, Park SW, Lee WY; ''AMP-activated protein kinase suppresses the expression of LXR/SREBP-1 signaling-induced ANGPTL8 in HepG2 cells.''; Mol Cell Endocrinol, 2015 PubMed
  37. Quagliarini F, Wang Y, Kozlitina J, Grishin NV, Hyde R, Boerwinkle E, Valenzuela DM, Murphy AJ, Cohen JC, Hobbs HH; ''Atypical angiopoietin-like protein that regulates ANGPTL3.''; Proc Natl Acad Sci U S A, 2012 PubMed
  38. Kenner KA, Anyanwu E, Olefsky JM, Kusari J; ''Protein-tyrosine phosphatase 1B is a negative regulator of insulin- and insulin-like growth factor-I-stimulated signaling.''; J Biol Chem, 1996 PubMed
  39. Vadlakonda L, Dash A, Pasupuleti M, Anil Kumar K, Reddanna P; ''The Paradox of Akt-mTOR Interactions.''; Front Oncol, 2013 PubMed
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  43. Xu RX, Lambert MH, Wisely BB, Warren EN, Weinert EE, Waitt GM, Williams JD, Collins JL, Moore LB, Willson TM, Moore JT; ''A structural basis for constitutive activity in the human CAR/RXRalpha heterodimer.''; Mol Cell, 2004 PubMed
  44. Kwiatkowski DJ, Manning BD; ''Tuberous sclerosis: a GAP at the crossroads of multiple signaling pathways.''; Hum Mol Genet, 2005 PubMed
View all...


View all...
94801view 16:35, 5 October 2017AlexanderPicoConverted lines, removed nested groups and connected interactions
93137view 08:19, 31 July 2017SiddiqaANGPTL8 role in CD45+ hematopoietic-derived cell proliferation
92444view 23:37, 5 June 2017SiddiqaInteractions present exclusively in rat/mouse updated.
92359view 01:00, 30 May 2017SusanLegend adapted
90629view 07:45, 2 December 2016EgonwNo mim-conversion on gene-gene interactions.
90628view 07:41, 2 December 2016EgonwRemoved type info from Entrez Gene ID.
90627view 07:09, 2 December 2016EgonwUppercased c in KEGG identifier.
90610view 15:11, 1 December 2016KhanspersModified description
90604view 03:18, 1 December 2016Elisasolved unconnected lines
90499view 07:52, 18 November 2016SusanOntology Term : 'insulin signaling pathway' added !
90498view 07:51, 18 November 2016SusanModified description
90497view 07:48, 18 November 2016SusanOntology Term : 'regulatory pathway' added !
90463view 05:44, 17 November 2016SiddiqaModified title
90461view 05:40, 17 November 2016SiddiqaAdded AUthor List
90460view 04:58, 17 November 2016SiddiqaNew pathway

External references


View all...
NameTypeDatabase referenceComment
AMPK PathwayPathwayWP1403 (WikiPathways)
ABCG5GeneProductENSG00000138075 (Ensembl)
ABCG8GeneProductENSG00000143921 (Ensembl)
AKT1GeneProduct207 (Entrez Gene)
AKT2GeneProduct208 (Entrez Gene)
AMPKa1GeneProduct5562 (Entrez Gene)
AMPKa2GeneProduct5563 (Entrez Gene)
AMPKb1GeneProduct5564 (Entrez Gene)
AMPKb2GeneProduct5565 (Entrez Gene)
AMPKy1GeneProduct5571 (Entrez Gene)
AMPKy2GeneProduct51422 (Entrez Gene)
AMPKy3GeneProduct53632 (Entrez Gene)
ANGPTL8GeneProduct55908 (Entrez Gene)
  • synonyms: RIFL; TD26; PRO1185; PVPA599; C19orf80
  • Type your comment here
Autophagy SignalingPathway
CAP1GeneProduct10487 (Entrez Gene)
CBLGeneProduct867 (Entrez Gene)
CBLBGeneProduct868 (Entrez Gene)
CBLCGeneProduct23624 (Entrez Gene)
CD45+ hematopoietic-
  derived cell 
PathwayWP2849 (WikiPathways)
CIP42GeneProduct9322 (Entrez Gene)
CRKGeneProduct1398 (Entrez Gene)
CYP2B6GeneProductENSG00000197408 (Ensembl)
CYP3A4GeneProductENSG00000160868 (Ensembl)
CYP7A1GeneProductENSG00000167910 (Ensembl)is not affected in human
Cell Growth DifferentiationPathwayWP2029 (WikiPathways)
ChrebpGeneProduct51085 (Entrez Gene)
DIO2GeneProduct1734 (Entrez Gene)
Drug and steroid metabolismPathway
EIF4EGeneProduct1977 (Entrez Gene)
EIF4EBP1GeneProduct1978 (Entrez Gene)
Exo70GeneProduct23265 (Entrez Gene)
F-2,6-P2MetaboliteC00665 (KEGG Compound)
FASNGeneProductENSG00000169710 (Ensembl)
FBPGeneProduct2203 (Entrez Gene)
FLOT1GeneProduct10211 (Entrez Gene)
FLOT2GeneProduct2319 (Entrez Gene)
FOXO1AGeneProduct2308 (Entrez Gene)
FOXO3AGeneProduct2309 (Entrez Gene)
G-6-PMetaboliteC00092 (KEGG Compound)
G6PCGeneProduct2538 (Entrez Gene)
GCKGeneProduct2645 (KEGG Genes)
GLUT1GeneProduct6513 (Entrez Gene)
GLUT4GeneProduct6517 (Entrez Gene)
GSGeneProduct2997 (Entrez Gene)
GSK3AGeneProduct2931 (Entrez Gene)
GSK3BGeneProduct2932 (Entrez Gene)
GlucoseMetaboliteC00031 (KEGG Compound)
Glycolysis-GluconeogenesisPathwayWP534 (WikiPathways)
INSRGeneProduct3643 (Entrez Gene)
IRS1GeneProduct3667 (Entrez Gene)
IRS2GeneProduct8660 (Entrez Gene)
IRS4GeneProduct8471 (Entrez Gene)
Insulin Signaling Pathway Pathway
Insulin Signaling Pathway PathwayWP1982 (WikiPathways)
InsulinProteinA6XGL2 (Uniprot-TrEMBL)
LPLGeneProduct4023 (Entrez Gene)
LXRGeneProduct10062 (Entrez Gene)
MAP2K1GeneProduct5604 (Entrez Gene)
MAP2K2GeneProduct5605 (Entrez Gene)
MAP2K3GeneProduct5606 (Entrez Gene)
MAP2K4GeneProduct6416 (Entrez Gene)
MAP2K5GeneProduct5607 (Entrez Gene)
MAP2K6GeneProduct5608 (Entrez Gene)
MAP2K7GeneProduct5609 (Entrez Gene)
MAP3K10GeneProduct4294 (Entrez Gene)
MAP3K11GeneProduct4296 (Entrez Gene)
MAP3K12GeneProduct7786 (Entrez Gene)
MAP3K13GeneProduct9175 (Entrez Gene)
MAP3K1GeneProduct4214 (Entrez Gene)
MAP3K14GeneProduct9020 (Entrez Gene)
MAP3K2GeneProduct10746 (Entrez Gene)
MAP3K3GeneProduct4215 (Entrez Gene)
MAP3K4GeneProduct4216 (Entrez Gene)
MAP3K5GeneProduct4217 (Entrez Gene)
MAP3K6GeneProduct9064 (Entrez Gene)
MAP3K7GeneProduct6885 (Entrez Gene)
MAP3K8GeneProduct1326 (Entrez Gene)
MAP3K9GeneProduct4293 (Entrez Gene)
MAP4K1GeneProduct11184 (Entrez Gene)
MAP4K2GeneProduct5871 (Entrez Gene)
MAP4K3GeneProduct8491 (Entrez Gene)
MAP4K4GeneProduct9448 (Entrez Gene)
MAP4K5GeneProduct11183 (Entrez Gene)
MAPK10GeneProduct5602 (Entrez Gene)
MAPK11GeneProduct5600 (Entrez Gene)
MAPK12GeneProduct6300 (Entrez Gene)
MAPK13GeneProduct5603 (Entrez Gene)
MAPK14GeneProduct1432 (Entrez Gene)
MAPK1GeneProduct5594 (Entrez Gene)
MAPK3GeneProduct5595 (Entrez Gene)
MAPK4GeneProduct5596 (Entrez Gene)
MAPK6GeneProduct5597 (Entrez Gene)
MAPK7GeneProduct5598 (Entrez Gene)
MAPK8GeneProduct5599 (Entrez Gene)
MAPK9GeneProduct5601 (Entrez Gene)
MINK1GeneProduct50488 (Entrez Gene)
Multi-drug resistancePathway
PDKGeneProduct5170 (Entrez Gene)
PEPCKGeneProduct5105 (Entrez Gene)
PI(3,4,5)P3MetaboliteC05981 (KEGG Compound)Type your comment herePhosphatidylinositol-3,4,5-trisphosphate(PIP3)
PI(4,5)P2MetaboliteC04637 (KEGG Compound)
PIK3C2AGeneProduct5286 (Entrez Gene)
PIK3C2GGeneProduct5288 (Entrez Gene)
PIK3C3GeneProduct5289 (Entrez Gene)
PIK3CAGeneProduct5290 (Entrez Gene)
PIK3CBGeneProduct5291 (Entrez Gene)
PIK3CDGeneProduct5293 (Entrez Gene)
PIK3CGGeneProduct5294 (Entrez Gene)
PIK3R1GeneProduct5295 (Entrez Gene)
PIK3R2GeneProduct5296 (Entrez Gene)
PIK3R3GeneProduct8503 (Entrez Gene)
PIK3R4GeneProduct30849 (Entrez Gene)
PTPGeneProduct5770 (Entrez Gene)PTPs catalyze the hydrolysis of the phosphate monoesters specifically on tyrosine residues. Members of the PTP family share a highly conserved catalytic motif, which is essential for the catalytic activity. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP has been shown to act as a negative regulator of insulin signaling by dephosphorylating the phosphotryosine residues of insulin receptor kinase
Protein synthesis and Translation RegulationPathway
RAF1GeneProduct5894 (Entrez Gene)
RAPGEF1GeneProduct2889 (Entrez Gene)
RASGeneProduct3265 (Entrez Gene)
RHEBGeneProduct6009 (Entrez Gene)
RHOQGeneProduct23433 (Entrez Gene)
RPS6KA1GeneProduct6195 (Entrez Gene)
RPS6KA2GeneProduct6196 (Entrez Gene)
RPS6KA3GeneProduct6197 (Entrez Gene)
RPS6KA4GeneProduct8986 (Entrez Gene)
RPS6KA5GeneProduct9252 (Entrez Gene)
RPS6KA6GeneProduct27330 (Entrez Gene)
RPS6KB1GeneProduct6198 (Entrez Gene)
RPS6KB2GeneProduct6199 (Entrez Gene)
RXRAGeneProduct6256 (Entrez Gene)
RXRAGeneProductENSG00000186350 (Ensembl)
RaptorGeneProduct57521 (Entrez Gene)
RictorGeneProduct253260 (Entrez Gene)
SCDGeneProductENSG00000099194 (Ensembl)
SEST3GeneProduct143686 (Entrez Gene)
SHC1GeneProduct6464 (Entrez Gene)
SHC2GeneProduct25759 (Entrez Gene)
SHC3GeneProduct53358 (Entrez Gene)
SIN1GeneProduct79109 (Entrez Gene)
SLC16A2GeneProduct6567 (Entrez Gene)
SLCO1C1GeneProduct53919 (Entrez Gene)
SOS1GeneProduct6654 (Entrez Gene)
SOS2GeneProduct6655 (Entrez Gene)
SREBP PathwayPathwayWP1982 (WikiPathways)
SREBP1a-cGeneProductENSG00000072310 (Ensembl)
SREBP2GeneProductENSG00000198911 (Ensembl)
T3Metabolite5707 (Chemspider)
T4MetaboliteHMDB00248 (HMDB)
THRAGeneProduct7067 (Entrez Gene)
THRBGeneProduct7068 (Entrez Gene)
TSC1GeneProduct7248 (Entrez Gene)
TSC2GeneProduct7249 (Entrez Gene)
Transcription factorsPathway
Triacylglyceride SynthesisPathwayWP325 (KEGG Pathway)
X-5-PMetaboliteC00231 (KEGG Compound)
amino acids
glycogenMetaboliteC00369 (KEGG Compound)
mTOR GeneProduct2475 (Entrez Gene)
mTORGeneProduct2475 (Entrez Gene)
mlst8GeneProduct64223 (Entrez Gene)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
ArrowWP1982 (WikiPathways)
ArrowWP2882 (WikiPathways)
Arrowhsa04910 (KEGG Pathway)
Cell Growth DifferentiationArrowhsa04910 (KEGG Pathway)
DIO2mim-catalysisR03734 (KEGG Reaction)
GSTBarhsa04910 (KEGG Pathway)
GlucoseArrowhsa04911 (KEGG Pathway)
INSRArrowhsa04910 (KEGG Pathway)
PTPINSRTBarhsa04910 (KEGG Pathway)
PTPTBarhsa04910 (KEGG Pathway)
RAF1Arrowhsa04910 (KEGG Pathway)
RASArrowhsa04910 (KEGG Pathway)
RASRAF1Arrowhsa04910 (KEGG Pathway)
RHOQArrowhsa04910 (KEGG Pathway)
SLC16A2T3Arrowhsa04919 (KEGG Pathway)
SLCO1C1T4Arrowhsa04919 (KEGG Pathway)
SLCO1C1hsa04919 (KEGG Pathway)
T4T3Arrowhsa04919 (KEGG Pathway)
  • In humans 80 percent T3 is contributed via regulation from deiodinases especially DIO2.
  • The local thyroid hormone signaling is coupled with nutritional availaibility via insulin signaling.
  • Type your comment here
TBarhsa04910 (KEGG Pathway)
mim-catalysisR04545 (KEGG Reaction)