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Protein

Angiopoietin-related protein 4

Gene

Angptl4

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

Functioni

Protein with hypoxia-induced expression in endothelial cells. May act as a regulator of angiogenesis and modulate tumorigenesis. Inhibits proliferation, migration, and tubule formation of endothelial cells and reduces vascular leakage. May exert a protective function on endothelial cells through an endocrine action. It is directly involved in regulating glucose homeostasis, lipid metabolism, and insulin sensitivity (By similarity). In response to hypoxia, the unprocessed form of the protein accumulates in the subendothelial extracellular matrix (ECM). The matrix-associated and immobilized unprocessed form limits the formation of actin stress fibers and focal contacts in the adhering endothelial cells and inhibits their adhesion. It also decreases motility of endothelial cells and inhibits the sprouting and tube formation.By similarity3 Publications

Miscellaneous

Transgenic mice that express ARP4 in the skin, driven by the keratinocyte promoter, show remarkable suppression of tumor growth within the dermal layer and decreased numbers of invading blood vessels.
In xenograft models, it inhibits both intra- and extravasation of tumor cells as well as vascular permeability leading to inhibition of metastases. Expression by tumor cells induces reorganization of the actin cytoskeleton through inhibition of actin stress fiber formation and vinculin localization at focal contacts. It might prevent the metastatic process by inhibiting vascular activity as well as tumor cell motility and invasiveness.

GO - Molecular functioni

  • enzyme inhibitor activity Source: UniProtKB
  • identical protein binding Source: MGI

GO - Biological processi

  • angiogenesis Source: InterPro
  • cellular response to starvation Source: UniProtKB
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of endothelial cell apoptotic process Source: MGI
  • negative regulation of lipoprotein lipase activity Source: UniProtKB
  • positive regulation of lipid metabolic process Source: UniProtKB
  • protein homooligomerization Source: Ensembl
  • response to hypoxia Source: Ensembl
  • triglyceride homeostasis Source: BHF-UCL

Enzyme and pathway databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
Angiopoietin-related protein 4
Alternative name(s):
425O18-1
Angiopoietin-like protein 4
Fasting-induced adipose factor
Hepatic fibrinogen/angiopoietin-related protein
Short name:
HFARP
Secreted protein Bk89
Gene namesi
Name:Angptl4
Synonyms:Farp, Fiaf, Ng27
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:1888999 Angptl4

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

Extracellular matrix, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Sequence analysisAdd BLAST23
ChainiPRO_000000912524 – 410Angiopoietin-related protein 4Add BLAST387

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi181N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi192 ↔ 220PROSITE-ProRule annotation
Glycosylationi236N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi242N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi345 ↔ 358PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ9Z1P8
PaxDbiQ9Z1P8
PRIDEiQ9Z1P8

PTM databases

PhosphoSitePlusiQ9Z1P8

Expressioni

Tissue specificityi

Predominantly expressed in adipose tissue and is strongly up-regulated by fasting in white adipose tissue and liver.1 Publication

Developmental stagei

Expressed at low levels in most organs and connective tissue at E13.5. Between E15.5 and E18.5, strongest expression in brown fat.1 Publication

Inductioni

Alterations in nutrition and leptin administration are found to modulate the expression in vivo.1 Publication

Gene expression databases

BgeeiENSMUSG00000002289
CleanExiMM_ANGPTL4
ExpressionAtlasiQ9Z1P8 baseline and differential
GenevisibleiQ9Z1P8 MM

Interactioni

Subunit structurei

Homooligomer. The homooligomer undergoes proteolytic processing to release its carboxyl fibrinogen-like domain, which circulates as a monomer (By similarity). The homooligomer unprocessed form is able to interact with the extracellular matrix, this interaction is found to be heparin/heparan sulfate proteoglycan dependent (in competition and direct binding assays).By similarity

GO - Molecular functioni

Protein-protein interaction databases

DIPiDIP-61311N
IntActiQ9Z1P8, 1 interactor
STRINGi10090.ENSMUSP00000002360

Structurei

3D structure databases

ProteinModelPortaliQ9Z1P8
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini183 – 405Fibrinogen C-terminalPROSITE-ProRule annotationAdd BLAST223

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili104 – 152Sequence analysisAdd BLAST49

Keywords - Domaini

Coiled coil, Signal

Phylogenomic databases

eggNOGiKOG2579 Eukaryota
ENOG410ZYS4 LUCA
GeneTreeiENSGT00890000139379
HOGENOMiHOG000015386
HOVERGENiHBG001644
InParanoidiQ9Z1P8
KOiK08767
OMAiSTWDQDH
OrthoDBiEOG091G03M1
PhylomeDBiQ9Z1P8
TreeFamiTF329953

Family and domain databases

CDDicd00087 FReD, 1 hit
InterProiView protein in InterPro
IPR028793 ANGPTL4
IPR036056 Fibrinogen-like_C
IPR002181 Fibrinogen_a/b/g_C_dom
IPR020837 Fibrinogen_CS
PANTHERiPTHR19143:SF256 PTHR19143:SF256, 1 hit
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
PS00514 FIBRINOGEN_C_1, 1 hit
PS51406 FIBRINOGEN_C_2, 1 hit

Sequencei

Sequence statusi: Complete.

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

Q9Z1P8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRCAPTAGAA LVLCAATAGL LSAQGRPAQP EPPRFASWDE MNLLAHGLLQ
60 70 80 90 100
LGHGLREHVE RTRGQLGALE RRMAACGNAC QGPKGKDAPF KDSEDRVPEG
110 120 130 140 150
QTPETLQSLQ TQLKAQNSKI QQLFQKVAQQ QRYLSKQNLR IQNLQSQIDL
160 170 180 190 200
LAPTHLDNGV DKTSRGKRLP KMTQLIGLTP NATHLHRPPR DCQELFQEGE
210 220 230 240 250
RHSGLFQIQP LGSPPFLVNC EMTSDGGWTV IQRRLNGSVD FNQSWEAYKD
260 270 280 290 300
GFGDPQGEFW LGLEKMHSIT GNRGSQLAVQ LQDWDGNAKL LQFPIHLGGE
310 320 330 340 350
DTAYSLQLTE PTANELGATN VSPNGLSLPF STWDQDHDLR GDLNCAKSLS
360 370 380 390 400
GGWWFGTCSH SNLNGQYFHS IPRQRQERKK GIFWKTWKGR YYPLQATTLL
410
IQPMEATAAS
Length:410
Mass (Da):45,538
Last modified:May 1, 1999 - v1
Checksum:iBCEE2259921D6D81
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti168 – 170RLP → KLS in AAF42969 (PubMed:10866690).Curated3
Sequence conflicti180P → S in AAF42969 (PubMed:10866690).Curated1
Sequence conflicti189P → A in AAF42969 (PubMed:10866690).Curated1
Sequence conflicti272N → D in AAF86342 (PubMed:10862772).Curated1
Sequence conflicti272N → D in AAF42969 (PubMed:10866690).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF169313 mRNA Translation: AAF62869.1
AF278699 mRNA Translation: AAF86342.1
AB054540 mRNA Translation: BAB83079.1
AF123261 mRNA Translation: AAF42969.1
AK014564 mRNA Translation: BAB29431.1
AK132761 mRNA Translation: BAE21342.1
AF528162 Genomic DNA Translation: AAO17378.1
AF110520 Genomic DNA Translation: AAC97965.1
BC006611 mRNA Translation: AAH06611.1
BC021343 mRNA Translation: AAH21343.1
BC025797 mRNA Translation: AAH25797.1
CCDSiCCDS28629.1
RefSeqiNP_065606.2, NM_020581.2
UniGeneiMm.196189

Genome annotation databases

EnsembliENSMUST00000002360; ENSMUSP00000002360; ENSMUSG00000002289
GeneIDi57875
KEGGimmu:57875
UCSCiuc008bzp.2 mouse

Similar proteinsi

Entry informationi

Entry nameiANGL4_MOUSE
AccessioniPrimary (citable) accession number: Q9Z1P8
Secondary accession number(s): Q78ZJ9, Q9JHX7, Q9JLX7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 8, 2002
Last sequence update: May 1, 1999
Last modified: March 28, 2018
This is version 143 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health