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Protein

Angiopoietin-related protein 4

Gene

ANGPTL4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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. 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 similarity).By similarity2 Publications

GO - Molecular functioni

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

GO - Biological processi

  • angiogenesis Source: UniProtKB-KW
  • cell differentiation Source: UniProtKB-KW
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of endothelial cell apoptotic process Source: Ensembl
  • negative regulation of lipoprotein lipase activity Source: BHF-UCL
  • positive regulation of angiogenesis Source: UniProtKB
  • protein homooligomerization Source: Ensembl
  • response to hypoxia Source: UniProtKB
  • triglyceride homeostasis Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Angiogenesis, Differentiation

Enzyme and pathway databases

BioCyciZFISH:ENSG00000167772-MONOMER.
ReactomeiR-HSA-174800. Chylomicron-mediated lipid transport.
R-HSA-1989781. PPARA activates gene expression.
R-HSA-381340. Transcriptional regulation of white adipocyte differentiation.

Names & Taxonomyi

Protein namesi
Recommended name:
Angiopoietin-related protein 4
Alternative name(s):
Angiopoietin-like protein 4
Hepatic fibrinogen/angiopoietin-related protein
Short name:
HFARP
Gene namesi
Name:ANGPTL4
Synonyms:ARP4, HFARP, PGAR
ORF Names:PP1158, PSEC0166, UNQ171/PRO197
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:16039. ANGPTL4.

Subcellular locationi

  • Secreted 1 Publication
  • Secretedextracellular spaceextracellular matrix By similarity

  • Note: The unprocessed form interacts with the extracellular matrix. This may constitute a dynamic reservoir, a regulatory mechanism of the bioavailability of ANGPTL4 (By similarity).By similarity

GO - Cellular componenti

  • blood microparticle Source: UniProtKB
  • extracellular region Source: UniProtKB
  • extracellular space Source: MGI
  • proteinaceous extracellular matrix Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Extracellular matrix, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi51129.
MalaCardsiANGPTL4.
MIMi615881. phenotype.
OpenTargetsiENSG00000167772.
PharmGKBiPA24797.

Polymorphism and mutation databases

BioMutaiANGPTL4.
DMDMi25008123.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 25Sequence analysisAdd BLAST25
ChainiPRO_000000912426 – 406Angiopoietin-related protein 4Add BLAST381

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi177N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi188 ↔ 216PROSITE-ProRule annotation
Disulfide bondi341 ↔ 354PROSITE-ProRule annotation

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ9BY76.
MaxQBiQ9BY76.
PaxDbiQ9BY76.
PeptideAtlasiQ9BY76.
PRIDEiQ9BY76.

PTM databases

iPTMnetiQ9BY76.
PhosphoSitePlusiQ9BY76.

Expressioni

Tissue specificityi

Expressed at high levels in the placenta, heart, liver, muscle, pancreas and lung but expressed poorly in the brain and kidney.2 Publications

Gene expression databases

BgeeiENSG00000167772.
CleanExiHS_ANGPTL4.
ExpressionAtlasiQ9BY76. baseline and differential.
GenevisibleiQ9BY76. HS.

Organism-specific databases

HPAiCAB033770.

Interactioni

Subunit structurei

Homooligomer. The homooligomer undergoes proteolytic processing to release its carboxyl fibrinogen-like domain, which circulates as a monomer. The homooligomer unprocessed form is able to interact with the extracellular matrix (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-2968146,EBI-2968146
ITGB1P055562EBI-2968146,EBI-703066
ITGB5P180843EBI-2968146,EBI-1223434

GO - Molecular functioni

  • identical protein binding Source: IntAct

Protein-protein interaction databases

BioGridi119316. 21 interactors.
IntActiQ9BY76. 14 interactors.
STRINGi9606.ENSP00000301455.

Structurei

3D structure databases

ProteinModelPortaliQ9BY76.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini179 – 401Fibrinogen C-terminalPROSITE-ProRule annotationAdd BLAST223

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili100 – 143Sequence analysisAdd BLAST44

Sequence similaritiesi

Contains 1 fibrinogen C-terminal domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, Signal

Phylogenomic databases

eggNOGiKOG2579. Eukaryota.
ENOG410ZYS4. LUCA.
GeneTreeiENSGT00830000128240.
HOGENOMiHOG000015386.
HOVERGENiHBG001644.
InParanoidiQ9BY76.
KOiK08767.
OMAiVDFNRPW.
OrthoDBiEOG091G03M1.
PhylomeDBiQ9BY76.
TreeFamiTF329953.

Family and domain databases

CDDicd00087. FReD. 1 hit.
Gene3Di3.90.215.10. 2 hits.
4.10.530.10. 1 hit.
InterProiIPR028793. ANGPTL4.
IPR014716. Fibrinogen_a/b/g_C_1.
IPR014715. Fibrinogen_a/b/g_C_2.
IPR002181. Fibrinogen_a/b/g_C_dom.
IPR020837. Fibrinogen_CS.
[Graphical view]
PANTHERiPTHR19143:SF256. PTHR19143:SF256. 1 hit.
PfamiPF00147. Fibrinogen_C. 1 hit.
[Graphical view]
SMARTiSM00186. FBG. 1 hit.
[Graphical view]
SUPFAMiSSF56496. SSF56496. 1 hit.
PROSITEiPS00514. FIBRINOGEN_C_1. 1 hit.
PS51406. FIBRINOGEN_C_2. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9BY76-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSGAPTAGAA LMLCAATAVL LSAQGGPVQS KSPRFASWDE MNVLAHGLLQ
60 70 80 90 100
LGQGLREHAE RTRSQLSALE RRLSACGSAC QGTEGSTDLP LAPESRVDPE
110 120 130 140 150
VLHSLQTQLK AQNSRIQQLF HKVAQQQRHL EKQHLRIQHL QSQFGLLDHK
160 170 180 190 200
HLDHEVAKPA RRKRLPEMAQ PVDPAHNVSR LHRLPRDCQE LFQVGERQSG
210 220 230 240 250
LFEIQPQGSP PFLVNCKMTS DGGWTVIQRR HDGSVDFNRP WEAYKAGFGD
260 270 280 290 300
PHGEFWLGLE KVHSITGDRN SRLAVQLRDW DGNAELLQFS VHLGGEDTAY
310 320 330 340 350
SLQLTAPVAG QLGATTVPPS GLSVPFSTWD QDHDLRRDKN CAKSLSGGWW
360 370 380 390 400
FGTCSHSNLN GQYFRSIPQQ RQKLKKGIFW KTWRGRYYPL QATTMLIQPM

AAEAAS
Length:406
Mass (Da):45,214
Last modified:November 8, 2002 - v2
Checksum:i219E56FEB3F602AF
GO
Isoform 2 (identifier: Q9BY76-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     183-221: RLPRDCQELFQVGERQSGLFEIQPQGSPPFLVNCKMTSD → H

Note: Gene prediction based on EST data.
Show »
Length:368
Mass (Da):40,917
Checksum:i7D61B5306C3AF298
GO
Isoform 3 (identifier: Q9BY76-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-167: Missing.

Note: No experimental confirmation available.
Show »
Length:239
Mass (Da):26,853
Checksum:iFBB362F2DBDB6900
GO

Sequence cautioni

The sequence AAQ88642 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti55 – 71LREHA…SALER → CANTGAHPQSAERAGA in AAD41088 (Ref. 5) CuratedAdd BLAST17
Sequence conflicti60E → G in BAB40692 (PubMed:14583458).Curated1
Sequence conflicti175A → P in AAF62868 (PubMed:10698685).Curated1
Sequence conflicti237F → S in BAG64351 (PubMed:14702039).Curated1
Sequence conflicti251P → S in BAD96209 (Ref. 8) Curated1
Sequence conflicti270N → D (PubMed:14702039).Curated1
Sequence conflicti270N → D (Ref. 8) Curated1
Sequence conflicti277L → R in BAD96244 (Ref. 8) Curated1
Sequence conflicti304L → F in AAF62868 (PubMed:10698685).Curated1
Sequence conflicti363Y → H in BAD96209 (Ref. 8) Curated1
Sequence conflicti389P → S in AAF62868 (PubMed:10698685).Curated1

Polymorphismi

Genetic variations in ANGPTL4 are associated with low plasma triglyceride levels and define the plasma triglyceride level quantitative trait locus (TGQTL) [MIMi:615881].1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0326425P → L.1 PublicationCorresponds to variant rs761583091dbSNPEnsembl.1
Natural variantiVAR_03264340E → K Associated with lower plasma levels of triglyceride and higher levels of HDL cholesterol. 1 PublicationCorresponds to variant rs116843064dbSNPEnsembl.1
Natural variantiVAR_03264441M → I.1 PublicationCorresponds to variant rs186754194dbSNPEnsembl.1
Natural variantiVAR_03264567S → R.1 PublicationCorresponds to variant rs538554190dbSNPEnsembl.1
Natural variantiVAR_03264672R → L.1 PublicationCorresponds to variant rs141831018dbSNPEnsembl.1
Natural variantiVAR_03264777G → R.1 PublicationCorresponds to variant rs568624939dbSNPEnsembl.1
Natural variantiVAR_032648167E → K.1 PublicationCorresponds to variant rs140640857dbSNPEnsembl.1
Natural variantiVAR_032649174P → S.1 Publication1
Natural variantiVAR_032650190E → Q.1 PublicationCorresponds to variant rs77938377dbSNPEnsembl.1
Natural variantiVAR_032651196E → K.1 Publication1
Natural variantiVAR_032652230R → C.1 PublicationCorresponds to variant rs201026877dbSNPEnsembl.1
Natural variantiVAR_032653233G → R.1 Publication1
Natural variantiVAR_032654237F → V.1 PublicationCorresponds to variant rs768374046dbSNPEnsembl.1
Natural variantiVAR_032655251P → T.1 PublicationCorresponds to variant rs376328756dbSNPEnsembl.1
Natural variantiVAR_020428266T → M.3 PublicationsCorresponds to variant rs1044250dbSNPEnsembl.1
Natural variantiVAR_032656278R → Q.1 PublicationCorresponds to variant rs35061979dbSNPEnsembl.1
Natural variantiVAR_032657291V → M.1 PublicationCorresponds to variant rs150000287dbSNPEnsembl.1
Natural variantiVAR_032658293L → M.1 PublicationCorresponds to variant rs775667046dbSNPEnsembl.1
Natural variantiVAR_032659296E → V.1 Publication1
Natural variantiVAR_032660307P → S.1 PublicationCorresponds to variant rs751249880dbSNPEnsembl.1
Natural variantiVAR_032661308V → M.1 PublicationCorresponds to variant rs139998264dbSNPEnsembl.1
Natural variantiVAR_032662336R → C.1 PublicationCorresponds to variant rs140744493dbSNPEnsembl.1
Natural variantiVAR_032663338D → E.1 PublicationCorresponds to variant rs780121474dbSNPEnsembl.1
Natural variantiVAR_032664349W → C.1 Publication1
Natural variantiVAR_032665361G → R.1 PublicationCorresponds to variant rs755737249dbSNPEnsembl.1
Natural variantiVAR_032666361G → S.1 PublicationCorresponds to variant rs755737249dbSNPEnsembl.1
Natural variantiVAR_032667371R → Q.1 PublicationCorresponds to variant rs779488814dbSNPEnsembl.1
Natural variantiVAR_032668384R → W.1 PublicationCorresponds to variant rs146942305dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0550921 – 167Missing in isoform 3. 1 PublicationAdd BLAST167
Alternative sequenceiVSP_047045183 – 221RLPRD…KMTSD → H in isoform 2. CuratedAdd BLAST39

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF169312 mRNA. Translation: AAF62868.1.
AF202636 mRNA. Translation: AAG22490.1.
AB056477 mRNA. Translation: BAB40692.1.
AF153606 mRNA. Translation: AAD41088.1.
AY358275 mRNA. Translation: AAQ88642.1. Different initiation.
AK303269 mRNA. Translation: BAG64351.1.
AK222489 mRNA. Translation: BAD96209.1.
AK222524 mRNA. Translation: BAD96244.1.
AC136469 Genomic DNA. No translation available.
CH471139 Genomic DNA. Translation: EAW68930.1.
CH471139 Genomic DNA. Translation: EAW68931.1.
BC023647 mRNA. Translation: AAH23647.1.
CCDSiCCDS12200.1. [Q9BY76-1]
CCDS42493.1. [Q9BY76-2]
RefSeqiNP_001034756.1. NM_001039667.2. [Q9BY76-2]
NP_647475.1. NM_139314.2. [Q9BY76-1]
UniGeneiHs.9613.

Genome annotation databases

EnsembliENST00000301455; ENSP00000301455; ENSG00000167772. [Q9BY76-1]
ENST00000393962; ENSP00000377534; ENSG00000167772. [Q9BY76-2]
ENST00000593998; ENSP00000472551; ENSG00000167772. [Q9BY76-1]
GeneIDi51129.
KEGGihsa:51129.
UCSCiuc002mjq.3. human. [Q9BY76-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF169312 mRNA. Translation: AAF62868.1.
AF202636 mRNA. Translation: AAG22490.1.
AB056477 mRNA. Translation: BAB40692.1.
AF153606 mRNA. Translation: AAD41088.1.
AY358275 mRNA. Translation: AAQ88642.1. Different initiation.
AK303269 mRNA. Translation: BAG64351.1.
AK222489 mRNA. Translation: BAD96209.1.
AK222524 mRNA. Translation: BAD96244.1.
AC136469 Genomic DNA. No translation available.
CH471139 Genomic DNA. Translation: EAW68930.1.
CH471139 Genomic DNA. Translation: EAW68931.1.
BC023647 mRNA. Translation: AAH23647.1.
CCDSiCCDS12200.1. [Q9BY76-1]
CCDS42493.1. [Q9BY76-2]
RefSeqiNP_001034756.1. NM_001039667.2. [Q9BY76-2]
NP_647475.1. NM_139314.2. [Q9BY76-1]
UniGeneiHs.9613.

3D structure databases

ProteinModelPortaliQ9BY76.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119316. 21 interactors.
IntActiQ9BY76. 14 interactors.
STRINGi9606.ENSP00000301455.

PTM databases

iPTMnetiQ9BY76.
PhosphoSitePlusiQ9BY76.

Polymorphism and mutation databases

BioMutaiANGPTL4.
DMDMi25008123.

Proteomic databases

EPDiQ9BY76.
MaxQBiQ9BY76.
PaxDbiQ9BY76.
PeptideAtlasiQ9BY76.
PRIDEiQ9BY76.

Protocols and materials databases

DNASUi51129.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000301455; ENSP00000301455; ENSG00000167772. [Q9BY76-1]
ENST00000393962; ENSP00000377534; ENSG00000167772. [Q9BY76-2]
ENST00000593998; ENSP00000472551; ENSG00000167772. [Q9BY76-1]
GeneIDi51129.
KEGGihsa:51129.
UCSCiuc002mjq.3. human. [Q9BY76-1]

Organism-specific databases

CTDi51129.
DisGeNETi51129.
GeneCardsiANGPTL4.
HGNCiHGNC:16039. ANGPTL4.
HPAiCAB033770.
MalaCardsiANGPTL4.
MIMi605910. gene.
615881. phenotype.
neXtProtiNX_Q9BY76.
OpenTargetsiENSG00000167772.
PharmGKBiPA24797.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2579. Eukaryota.
ENOG410ZYS4. LUCA.
GeneTreeiENSGT00830000128240.
HOGENOMiHOG000015386.
HOVERGENiHBG001644.
InParanoidiQ9BY76.
KOiK08767.
OMAiVDFNRPW.
OrthoDBiEOG091G03M1.
PhylomeDBiQ9BY76.
TreeFamiTF329953.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000167772-MONOMER.
ReactomeiR-HSA-174800. Chylomicron-mediated lipid transport.
R-HSA-1989781. PPARA activates gene expression.
R-HSA-381340. Transcriptional regulation of white adipocyte differentiation.

Miscellaneous databases

ChiTaRSiANGPTL4. human.
GeneWikiiANGPTL4.
GenomeRNAii51129.
PROiQ9BY76.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000167772.
CleanExiHS_ANGPTL4.
ExpressionAtlasiQ9BY76. baseline and differential.
GenevisibleiQ9BY76. HS.

Family and domain databases

CDDicd00087. FReD. 1 hit.
Gene3Di3.90.215.10. 2 hits.
4.10.530.10. 1 hit.
InterProiIPR028793. ANGPTL4.
IPR014716. Fibrinogen_a/b/g_C_1.
IPR014715. Fibrinogen_a/b/g_C_2.
IPR002181. Fibrinogen_a/b/g_C_dom.
IPR020837. Fibrinogen_CS.
[Graphical view]
PANTHERiPTHR19143:SF256. PTHR19143:SF256. 1 hit.
PfamiPF00147. Fibrinogen_C. 1 hit.
[Graphical view]
SMARTiSM00186. FBG. 1 hit.
[Graphical view]
SUPFAMiSSF56496. SSF56496. 1 hit.
PROSITEiPS00514. FIBRINOGEN_C_1. 1 hit.
PS51406. FIBRINOGEN_C_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiANGL4_HUMAN
AccessioniPrimary (citable) accession number: Q9BY76
Secondary accession number(s): A8MY84
, B4E089, D6W670, F5H0I2, Q53HQ6, Q53HU1, Q6UXN0, Q9HBV4, Q9NZU4, Q9Y5B3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 8, 2002
Last sequence update: November 8, 2002
Last modified: November 30, 2016
This is version 147 of the entry and version 2 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

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.