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Protein

Angiopoietin-related protein 4

Gene

ANGPTL4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionDevelopmental protein
Biological processAngiogenesis, Differentiation

Enzyme and pathway databases

ReactomeiR-HSA-1989781 PPARA activates gene expression
R-HSA-381340 Transcriptional regulation of white adipocyte differentiation
R-HSA-8963889 Assembly of active LPL and LIPC lipase complexes

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

EuPathDBiHostDB:ENSG00000167772.11
HGNCiHGNC:16039 ANGPTL4
MIMi605910 gene
neXtProtiNX_Q9BY76

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

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...) asparagineSequence 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
ProteomicsDBi79597

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 Expressed in 178 organ(s), highest expression level in layer of synovial tissue
CleanExiHS_ANGPTL4
ExpressionAtlasiQ9BY76 baseline and differential
GenevisibleiQ9BY76 HS

Organism-specific databases

HPAiCAB033770
HPA007879

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi119316, 21 interactors
IntActiQ9BY76, 16 interactors
MINTiQ9BY76
STRINGi9606.ENSP00000301455

Structurei

Secondary structure

1406
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9BY76
SMRiQ9BY76
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

Keywords - Domaini

Coiled coil, Signal

Phylogenomic databases

eggNOGiKOG2579 Eukaryota
ENOG410ZYS4 LUCA
GeneTreeiENSGT00920000148942
HOGENOMiHOG000015386
HOVERGENiHBG001644
InParanoidiQ9BY76
KOiK08767
OMAiSTWDQDH
OrthoDBiEOG091G03M1
PhylomeDBiQ9BY76
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

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

This entry has 3 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
M0R2X8M0R2X8_HUMAN
Angiopoietin-related protein 4
ANGPTL4
129Annotation score:
M0R0N8M0R0N8_HUMAN
Angiopoietin-related protein 4
ANGPTL4
85Annotation score:
M0QZ51M0QZ51_HUMAN
Angiopoietin-related protein 4
ANGPTL4
96Annotation score:
M0R3A2M0R3A2_HUMAN
Angiopoietin-related protein 4
ANGPTL4
104Annotation score:
M0R369M0R369_HUMAN
Angiopoietin-related protein 4
ANGPTL4
128Annotation score:

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 → L1 PublicationCorresponds to variant dbSNP:rs761583091Ensembl.1
Natural variantiVAR_03264340E → K Associated with lower plasma levels of triglyceride and higher levels of HDL cholesterol. 1 PublicationCorresponds to variant dbSNP:rs116843064EnsemblClinVar.1
Natural variantiVAR_03264441M → I1 PublicationCorresponds to variant dbSNP:rs186754194Ensembl.1
Natural variantiVAR_03264567S → R1 PublicationCorresponds to variant dbSNP:rs538554190Ensembl.1
Natural variantiVAR_03264672R → L1 PublicationCorresponds to variant dbSNP:rs141831018Ensembl.1
Natural variantiVAR_03264777G → R1 PublicationCorresponds to variant dbSNP:rs568624939Ensembl.1
Natural variantiVAR_032648167E → K1 PublicationCorresponds to variant dbSNP:rs140640857Ensembl.1
Natural variantiVAR_032649174P → S1 PublicationCorresponds to variant dbSNP:rs1008363865Ensembl.1
Natural variantiVAR_032650190E → Q1 PublicationCorresponds to variant dbSNP:rs77938377Ensembl.1
Natural variantiVAR_032651196E → K1 Publication1
Natural variantiVAR_032652230R → C1 PublicationCorresponds to variant dbSNP:rs201026877Ensembl.1
Natural variantiVAR_032653233G → R1 Publication1
Natural variantiVAR_032654237F → V1 PublicationCorresponds to variant dbSNP:rs768374046Ensembl.1
Natural variantiVAR_032655251P → T1 PublicationCorresponds to variant dbSNP:rs376328756Ensembl.1
Natural variantiVAR_020428266T → M3 PublicationsCorresponds to variant dbSNP:rs1044250Ensembl.1
Natural variantiVAR_032656278R → Q1 PublicationCorresponds to variant dbSNP:rs35061979Ensembl.1
Natural variantiVAR_032657291V → M1 PublicationCorresponds to variant dbSNP:rs150000287Ensembl.1
Natural variantiVAR_032658293L → M1 PublicationCorresponds to variant dbSNP:rs775667046Ensembl.1
Natural variantiVAR_032659296E → V1 Publication1
Natural variantiVAR_032660307P → S1 PublicationCorresponds to variant dbSNP:rs751249880Ensembl.1
Natural variantiVAR_032661308V → M1 PublicationCorresponds to variant dbSNP:rs139998264Ensembl.1
Natural variantiVAR_032662336R → C1 PublicationCorresponds to variant dbSNP:rs140744493Ensembl.1
Natural variantiVAR_032663338D → E1 PublicationCorresponds to variant dbSNP:rs780121474Ensembl.1
Natural variantiVAR_032664349W → C1 PublicationCorresponds to variant dbSNP:rs1033145581Ensembl.1
Natural variantiVAR_032665361G → R1 PublicationCorresponds to variant dbSNP:rs755737249Ensembl.1
Natural variantiVAR_032666361G → S1 PublicationCorresponds to variant dbSNP:rs755737249Ensembl.1
Natural variantiVAR_032667371R → Q1 PublicationCorresponds to variant dbSNP:rs779488814Ensembl.1
Natural variantiVAR_032668384R → W1 PublicationCorresponds to variant dbSNP:rs146942305Ensembl.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

Similar proteinsi

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

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
6EUBX-ray2.30A184-406[»]
ProteinModelPortaliQ9BY76
SMRiQ9BY76
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119316, 21 interactors
IntActiQ9BY76, 16 interactors
MINTiQ9BY76
STRINGi9606.ENSP00000301455

PTM databases

iPTMnetiQ9BY76
PhosphoSitePlusiQ9BY76

Polymorphism and mutation databases

BioMutaiANGPTL4
DMDMi25008123

Proteomic databases

EPDiQ9BY76
MaxQBiQ9BY76
PaxDbiQ9BY76
PeptideAtlasiQ9BY76
PRIDEiQ9BY76
ProteomicsDBi79597

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
EuPathDBiHostDB:ENSG00000167772.11
GeneCardsiANGPTL4
HGNCiHGNC:16039 ANGPTL4
HPAiCAB033770
HPA007879
MalaCardsiANGPTL4
MIMi605910 gene
615881 phenotype
neXtProtiNX_Q9BY76
OpenTargetsiENSG00000167772
PharmGKBiPA24797
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2579 Eukaryota
ENOG410ZYS4 LUCA
GeneTreeiENSGT00920000148942
HOGENOMiHOG000015386
HOVERGENiHBG001644
InParanoidiQ9BY76
KOiK08767
OMAiSTWDQDH
OrthoDBiEOG091G03M1
PhylomeDBiQ9BY76
TreeFamiTF329953

Enzyme and pathway databases

ReactomeiR-HSA-1989781 PPARA activates gene expression
R-HSA-381340 Transcriptional regulation of white adipocyte differentiation
R-HSA-8963889 Assembly of active LPL and LIPC lipase complexes

Miscellaneous databases

ChiTaRSiANGPTL4 human
GeneWikiiANGPTL4
GenomeRNAii51129
PROiPR:Q9BY76
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000167772 Expressed in 178 organ(s), highest expression level in layer of synovial tissue
CleanExiHS_ANGPTL4
ExpressionAtlasiQ9BY76 baseline and differential
GenevisibleiQ9BY76 HS

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
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 historyiIntegrated into UniProtKB/Swiss-Prot: November 8, 2002
Last sequence update: November 8, 2002
Last modified: September 12, 2018
This is version 161 of the entry and version 2 of the sequence. See 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

3D-structure, Complete proteome, Reference proteome

Documents

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