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Protein

Angiopoietin-related protein 3

Gene

Angptl3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Acts in part as a hepatokine that is involved in regulation of lipid and glucose metabolism (PubMed:11788823, PubMed:12671033). Proposed to play a role in the trafficking of energy substrates to either storage or oxidative tissues in response to food intake (PubMed:26305978). Has a stimulatory effect on plasma triglycerides (TG), which is achieved by suppressing plasma TG clearance via inhibition of LPL activity; the function seems to be specific for the feeding conditions. The inhibition of LPL activity appears to be an indirect mechanism involving recruitment of proprotein convertases PCSK6 and FURIN to LPL leading to cleavage and dissociation of LPL from the cell surface; the function does not require ANGPTL3 proteolytic cleavage but seems to be mediated by the N-terminal domain, and is not inhibited by GPIHBP1 (PubMed:12909640, PubMed:16081640, PubMed:20581395). Can inhibit endothelial lipase, causing increased plasma levels of high density lipoprotein (HDL) cholesterol and phospholipids; the cleaved N-terminal domain is more efficient than the uncleaved proprotein (PubMed:17681148). Can bind to adipocytes to activate lipolysis, releasing free fatty acids and glycerol (By similarity). Suppresses LPL specifically in oxidative tissues which is required to route very low density lipoprotein (VLDL)-TG to white adipose tissue (WAT) for storage in response to food; the function may involve cooperation with circulating, liver-derived ANGPTL8 and ANGPTL4 expression in WAT (PubMed:26305978). Contributes to lower plasma levels of low density lipoprotein (LDL)-cholesterol by a mechanism that is independent of the canonical pathway implicating APOE and LDLR (PubMed:25954050). May stimulate hypothalamic LPL activity (PubMed:25338813).By similarity8 Publications
Involved in angiogenesis (PubMed:11877390). Binds to endothelial cells via integrin alpha-V/beta-3 (ITGAV:ITGB3), activates FAK, MAPK and Akt signaling pathways and induces cell adhesion and cell migration (By similarity). May increase the motility of podocytes. Secreted from podocytes, may modulate properties of glomerular endothelial cells involving integrin alpha-V/beta-3 and Akt signaling (By similarity). May induce actin filament rearrangements in podocytes implicating integrin alpha-V/beta-3 and Rac1 activation (PubMed:20633534, PubMed:24294595, PubMed:25710887). Binds to hematopoietic stem cells (HSC) and is involved in the regulation of HSC activity probably implicating down-regulation of IKZF1/IKAROS (PubMed:20959605).By similarity5 Publications

Miscellaneous

Was suggested to inhibit LPL through a direct mechanism; however, the necessary concentrations to achieve the in vitro inhibition are at least 30-fold higher than ANGPTL3 plasma concentrations.1 Publication

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHeparin-binding
Biological processAngiogenesis, Cell adhesion, Lipid metabolism

Enzyme and pathway databases

ReactomeiR-MMU-8963889 Assembly of active LPL and LIPC lipase complexes

Names & Taxonomyi

Protein namesi
Recommended name:
Angiopoietin-related protein 3
Alternative name(s):
Angiopoietin-like protein 3
Cleaved into the following chain:
Gene namesi
Name:Angptl3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:1353627 Angptl3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell projection, Secreted

Pathology & Biotechi

Disruption phenotypei

Low plasma levels of triglyceride, HDL cholesterol and HDL phospholipids, and non-esterified fatty acids (NEFA). Animals fed on high-fat, high-calorie (HFC) diet show reduced epididymal adipose tissue weight with no difference in adipocyte size. Hypotriglyceridemia with elevated postheparin plasma LPL activity is specifically observed in the fed state. Mice deficient in both Angptl3 and Angptl4 show an additive effect on plasma triglycerides and did not survive past 2 months of age.4 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi221R → A: Abolishes proteolytical cleavage. 2 Publications1
Mutagenesisi224R → A: Abolishes proteolytical cleavage. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 16Sequence analysisAdd BLAST16
ChainiPRO_000000912317 – 455Angiopoietin-related protein 3Add BLAST439
ChainiPRO_000043590517 – 224ANGPTL3(17-224)2 PublicationsAdd BLAST208

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi115N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi226O-linked (GlcNAc) threonineBy similarity1
Glycosylationi232N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi246 ↔ 274PROSITE-ProRule annotation
Glycosylationi296N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi357N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi394 ↔ 408PROSITE-ProRule annotation

Post-translational modificationi

In part proteolytically cleaved by proprotein convertases; proposed to be involved in activation. In primary hepatocytes is intracellularily predominantly processed by FURIN and extracellularily by FURIN and PCSK6/PACE4. In E18.5 embryos 75% of protein is found to be processed compared to 25 % in adults.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ9R182
PaxDbiQ9R182
PRIDEiQ9R182

PTM databases

iPTMnetiQ9R182
PhosphoSitePlusiQ9R182

Expressioni

Tissue specificityi

Predominantly expressed in liver, weakly expressed in kidney and lung. Expressed in podocytes (at protein level). Expressed in hypothalamic neurons (at protein level). Expressed in bone marrow sinusoidal endothelial cells (at protein level).4 Publications

Inductioni

Down-regulated by insulin and leptin. Not regulated by nutritional status (fed/fasting) Up-regulated in podocytes by puromycin. Up-regulated after feeding in the hypothalamus.4 Publications

Gene expression databases

BgeeiENSMUSG00000028553 Expressed in 68 organ(s), highest expression level in liver
CleanExiMM_ANGPTL3
ExpressionAtlasiQ9R182 baseline and differential
GenevisibleiQ9R182 MM

Interactioni

Subunit structurei

Interacts with ANGPTL8 (By similarity). Interacts with ITGB3.By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000030280

Structurei

3D structure databases

ProteinModelPortaliQ9R182
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini237 – 455Fibrinogen C-terminalPROSITE-ProRule annotationAdd BLAST219

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni17 – 207Sufficient to inhibit LIPG/EL phospholipase activityBy similarityAdd BLAST191
Regioni17 – 165Sufficient to inhibit LPL lipase activityBy similarity1 PublicationAdd BLAST149
Regioni32 – 56Required for inhibition of LPL lipase activityBy similarityAdd BLAST25

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili85 – 206Sequence analysisAdd BLAST122

Domaini

The fibrinogen C-terminal domain is sufficient to mediate endothelial cell adhesion.By similarity

Keywords - Domaini

Coiled coil, Signal

Phylogenomic databases

eggNOGiKOG2579 Eukaryota
ENOG410ZYS4 LUCA
GeneTreeiENSGT00930000150813
HOGENOMiHOG000015386
HOVERGENiHBG001644
InParanoidiQ9R182
KOiK22288
OMAiFVHKTKG
OrthoDBiEOG091G03M1
PhylomeDBiQ9R182
TreeFamiTF329953

Family and domain databases

CDDicd00087 FReD, 1 hit
InterProiView protein in InterPro
IPR036056 Fibrinogen-like_C
IPR002181 Fibrinogen_a/b/g_C_dom
PfamiView protein in Pfam
PF00147 Fibrinogen_C, 1 hit
SMARTiView protein in SMART
SM00186 FBG, 1 hit
SUPFAMiSSF56496 SSF56496, 1 hit
PROSITEiView protein in PROSITE
PS51406 FIBRINOGEN_C_2, 1 hit

Sequencei

Sequence statusi: Complete.

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

Q9R182-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MHTIKLFLFV VPLVIASRVD PDLSSFDSAP SEPKSRFAML DDVKILANGL
60 70 80 90 100
LQLGHGLKDF VHKTKGQIND IFQKLNIFDQ SFYDLSLRTN EIKEEEKELR
110 120 130 140 150
RTTSTLQVKN EEVKNMSVEL NSKLESLLEE KTALQHKVRA LEEQLTNLIL
160 170 180 190 200
SPAGAQEHPE VTSLKSFVEQ QDNSIRELLQ SVEEQYKQLS QQHMQIKEIE
210 220 230 240 250
KQLRKTGIQE PSENSLSSKS RAPRTTPPLQ LNETENTEQD DLPADCSAVY
260 270 280 290 300
NRGEHTSGVY TIKPRNSQGF NVYCDTQSGS PWTLIQHRKD GSQDFNETWE
310 320 330 340 350
NYEKGFGRLD GEFWLGLEKI YAIVQQSNYI LRLELQDWKD SKHYVEYSFH
360 370 380 390 400
LGSHETNYTL HVAEIAGNIP GALPEHTDLM FSTWNHRAKG QLYCPESYSG
410 420 430 440 450
GWWWNDICGE NNLNGKYNKP RTKSRPERRR GIYWRPQSRK LYAIKSSKMM

LQPTT
Length:455
Mass (Da):52,543
Last modified:May 1, 2000 - v1
Checksum:i31609D3700D3F33D
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF162224 mRNA Translation: AAD45920.1
BC019491 mRNA Translation: AAH19491.1
CCDSiCCDS38817.1
RefSeqiNP_038941.1, NM_013913.4
UniGeneiMm.28341

Genome annotation databases

EnsembliENSMUST00000030280; ENSMUSP00000030280; ENSMUSG00000028553
GeneIDi30924
KEGGimmu:30924
UCSCiuc008tur.1 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF162224 mRNA Translation: AAD45920.1
BC019491 mRNA Translation: AAH19491.1
CCDSiCCDS38817.1
RefSeqiNP_038941.1, NM_013913.4
UniGeneiMm.28341

3D structure databases

ProteinModelPortaliQ9R182
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000030280

PTM databases

iPTMnetiQ9R182
PhosphoSitePlusiQ9R182

Proteomic databases

MaxQBiQ9R182
PaxDbiQ9R182
PRIDEiQ9R182

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000030280; ENSMUSP00000030280; ENSMUSG00000028553
GeneIDi30924
KEGGimmu:30924
UCSCiuc008tur.1 mouse

Organism-specific databases

CTDi27329
MGIiMGI:1353627 Angptl3

Phylogenomic databases

eggNOGiKOG2579 Eukaryota
ENOG410ZYS4 LUCA
GeneTreeiENSGT00930000150813
HOGENOMiHOG000015386
HOVERGENiHBG001644
InParanoidiQ9R182
KOiK22288
OMAiFVHKTKG
OrthoDBiEOG091G03M1
PhylomeDBiQ9R182
TreeFamiTF329953

Enzyme and pathway databases

ReactomeiR-MMU-8963889 Assembly of active LPL and LIPC lipase complexes

Miscellaneous databases

PROiPR:Q9R182
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000028553 Expressed in 68 organ(s), highest expression level in liver
CleanExiMM_ANGPTL3
ExpressionAtlasiQ9R182 baseline and differential
GenevisibleiQ9R182 MM

Family and domain databases

CDDicd00087 FReD, 1 hit
InterProiView protein in InterPro
IPR036056 Fibrinogen-like_C
IPR002181 Fibrinogen_a/b/g_C_dom
PfamiView protein in Pfam
PF00147 Fibrinogen_C, 1 hit
SMARTiView protein in SMART
SM00186 FBG, 1 hit
SUPFAMiSSF56496 SSF56496, 1 hit
PROSITEiView protein in PROSITE
PS51406 FIBRINOGEN_C_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiANGL3_MOUSE
AccessioniPrimary (citable) accession number: Q9R182
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 8, 2002
Last sequence update: May 1, 2000
Last modified: November 7, 2018
This is version 135 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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