Angiopoietin-related protein 4 precursor

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Reviewed, UniProtKB/Swiss-Prot Q9BY76 (ANGL4_HUMAN)

Last modified January 19, 2010. Version 82. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    Angiopoietin-related protein 4
Alternative name(s):
    Angiopoietin-like protein 4
    Hepatic fibrinogen/angiopoietin-related protein
      Short name=HFARP

Gene names

Name:	ANGPTL4
Synonyms:	ARP4, HFARP, PGAR
ORF Names:	PP1158, PSEC0166, UNQ171/PRO197

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	406 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Protein with hypoxia-induced expression in endothelial cells. May act as a regulator of angiogenesis and modulate tumorgenesis. 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. Ref.2 Ref.4 Ref.9
Subunit structure	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.
Subcellular location	Secreted. Secreted › extracellular space › extracellular 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. Ref.1
Tissue specificity	Expressed at high levels in the placenta, heart, liver, muscle, pancreas and lung but expressed poorly in the brain and kidney. Ref.9 Ref.1
Post-translational modification	N-glycosylated. Ref.1
Sequence similarities	Contains 1 fibrinogen C-terminal domain.

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Ontologies

Keywords
Biological process	Angiogenesis Differentiation
Cellular component	Extracellular matrix Secreted
Coding sequence diversity	Polymorphism
Domain	Coiled coil Signal
Molecular function	Developmental protein
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	angiogenesis Inferred from electronic annotation. Source: UniProtKB-KW cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of apoptosis Ref.1 Inferred from direct assay. Source: UniProtKB negative regulation of lipoprotein lipase activity Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of angiogenesis Ref.3 Traceable author statement. Source: UniProtKB response to hypoxia Non-traceable author statement. Source: UniProtKB signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	extracellular space Ref.1 Inferred from direct assay. Source: MGI intracellular membrane-bounded organelle Inferred from direct assay. Source: HPA proteinaceous extracellular matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	enzyme inhibitor activity Inferred from sequence or structural similarity. Source: UniProtKB receptor binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 25

Potential

Chain

26 – 406

381

Angiopoietin-related protein 4

PRO_0000009124

Regions

Domain

179 – 401

223

Fibrinogen C-terminal

Coiled coil

100 – 143

Potential

Amino acid modifications

Glycosylation

177

N-linked (GlcNAc...) Potential

Disulfide bond

188 ↔ 216

By similarity

Disulfide bond

341 ↔ 354

By similarity

Natural variations

Natural variant

P → L

VAR_032642

Natural variant

E → K Associated with lower plasma levels of triglyceride and higher levels of HDL cholesterol. Ref.10

VAR_032643

Natural variant

M → I

VAR_032644

Natural variant

S → R

VAR_032645

Natural variant

R → L

VAR_032646

Natural variant

G → R

VAR_032647

Natural variant

167

E → K

VAR_032648

Natural variant

174

P → S

VAR_032649

Natural variant

190

E → Q

VAR_032650

Natural variant

196

E → K

VAR_032651

Natural variant

230

R → C

VAR_032652

Natural variant

233

G → R

VAR_032653

Natural variant

237

F → V

VAR_032654

Natural variant

251

P → T

VAR_032655

Natural variant

266

T → M: dbSNP rs1044250. Ref.1 Ref.10 Ref.7

VAR_020428

Natural variant

278

R → Q: dbSNP rs35061979. Ref.10

VAR_032656

Natural variant

291

V → M

VAR_032657

Natural variant

293

L → M

VAR_032658

Natural variant

296

E → V

VAR_032659

Natural variant

307

P → S

VAR_032660

Natural variant

308

V → M

VAR_032661

Natural variant

336

R → C

VAR_032662

Natural variant

338

D → E

VAR_032663

Natural variant

349

W → C

VAR_032664

Natural variant

361

G → R

VAR_032665

Natural variant

361

G → S

VAR_032666

Natural variant

371

R → Q

VAR_032667

Natural variant

384

R → W

VAR_032668

Experimental info

Sequence conflict

55 – 71

LREHA…SALER → CANTGAHPQSAERAGA in AAD41088. Ref.5

Sequence conflict

E → G in BAB40692. Ref.4

Sequence conflict

175

A → P in AAF62868. Ref.1

Sequence conflict

251

P → S in BAD96209. Ref.7

Sequence conflict

270

N → D in BAD96209. Ref.7

Sequence conflict

277

L → R in BAD96244. Ref.7

Sequence conflict

304

L → F in AAF62868. Ref.1

Sequence conflict

363

Y → H in BAD96209. Ref.7

Sequence conflict

389

P → S in AAF62868. Ref.1

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Sequences

Sequence

Length

Mass (Da)

Tools

Q9BY76-1 [UniParc].

Last modified November 8, 2002. Version 2.
Checksum: 219E56FEB3F602AF
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FASTA

406

45,214

        10         20         30         40         50         60 
MSGAPTAGAA LMLCAATAVL LSAQGGPVQS KSPRFASWDE MNVLAHGLLQ LGQGLREHAE 

        70         80         90        100        110        120 
RTRSQLSALE RRLSACGSAC QGTEGSTDLP LAPESRVDPE VLHSLQTQLK AQNSRIQQLF 

       130        140        150        160        170        180 
HKVAQQQRHL EKQHLRIQHL QSQFGLLDHK HLDHEVAKPA RRKRLPEMAQ PVDPAHNVSR 

       190        200        210        220        230        240 
LHRLPRDCQE LFQVGERQSG LFEIQPQGSP PFLVNCKMTS DGGWTVIQRR HDGSVDFNRP 

       250        260        270        280        290        300 
WEAYKAGFGD PHGEFWLGLE KVHSITGDRN SRLAVQLRDW DGNAELLQFS VHLGGEDTAY 

       310        320        330        340        350        360 
SLQLTAPVAG QLGATTVPPS GLSVPFSTWD QDHDLRRDKN CAKSLSGGWW FGTCSHSNLN 

       370        380        390        400 
GQYFRSIPQQ RQKLKKGIFW KTWRGRYYPL QATTMLIQPM AAEAAS

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Hepatic expression, synthesis and secretion of a novel fibrinogen/angiopoietin-related protein that prevents endothelial-cell apoptosis." Kim I., Kim H.-G., Kim H., Kim H.-H., Park S.K., Uhm C.-S., Lee Z.H., Koh G.Y. Biochem. J. 346:603-610(2000) [PubMed: 10698685] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, SUBCELLULAR LOCATION, GLYCOSYLATION, VARIANT MET-266.
[2]	"Peroxisome proliferator-activated receptor gamma target gene encoding a novel angiopoietin-related protein associated with adipose differentiation." Yoon J.C., Chickering T.W., Rosen E.D., Dussault B., Qin Y., Soukas A., Friedman J.M., Holmes W.E., Spiegelman B.M. Mol. Cell. Biol. 20:5343-5349(2000) [PubMed: 10866690] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], POSSIBLE FUNCTION. Tissue: Aortic endothelium.
[3]	"Cloning of a novel gene, ANGPTL4 and the functional study in angiogenesis." Zhu H., Li J., Qin W., Yang Y., He X., Wan D., Gu J. Zhonghua Yi Xue Za Zhi 82:94-99(2002) [PubMed: 11953136] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[4]	"Inhibition of angiogenesis and vascular leakiness by angiopoietin-related protein 4." Ito Y., Oike Y., Yasunaga K., Hamada K., Miyata K., Matsumoto S., Sugano S., Tanihara H., Masuho Y., Suda T. Cancer Res. 63:6651-6657(2003) [PubMed: 14583458] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION. Tissue: Placenta.
[5]	"A catalogue of genes in the human dermal papilla cells as identified by expressed sequence tags." Kim M.K., Kim Y.H., Seo J.M., Lee H.M., Chung H.J., Sohn M.Y., Hwang S.Y., Im S.U., Jung E.J., Lee J.H., Kim J.C. Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Hair follicle dermal papilla.
[6]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT MET-266. Tissue: Adipose tissue.
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pancreas.
[9]	"Expression and function of hepatocellular carcinoma-related gene pp1158." Zhu H., Li J., Wan D., Yang Y., Qin W., Ge C., Yao M., Gu J. Zhonghua Zhong Liu Za Zhi 24:123-125(2002) [PubMed: 12015030] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[10]	"Population-based resequencing of ANGPTL4 uncovers variations that reduce triglycerides and increase HDL." Romeo S., Pennacchio L.A., Fu Y., Boerwinkle E., Tybjaerg-Hansen A., Hobbs H.H., Cohen J.C. Nat. Genet. 39:513-516(2007) [PubMed: 17322881] [Abstract] Cited for: VARIANTS LEU-5; LYS-40; ILE-41; ARG-67; LEU-72; ARG-77; LYS-167; SER-174; GLN-190; LYS-196; CYS-230; ARG-233; VAL-237; THR-251; MET-266; GLN-278; MET-291; MET-293; VAL-296; SER-307; MET-308; CYS-336; GLU-338; CYS-349; SER-361; ARG-361; GLN-371 AND TRP-384.
+	Additional computationally mapped references.

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Cross-references

Sequence databases
EMBL GenBank DDBJ	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. AK222489 mRNA. Translation: BAD96209.1. AK222524 mRNA. Translation: BAD96244.1. BC023647 mRNA. Translation: AAH23647.1.
IPI	IPI00153060.
RefSeq	NP_001034756.1. NP_647475.1.
UniGene	Hs.9613
3D structure databases
SMR	Q9BY76. Positions 186-400.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9BY76.
Proteomic databases
PRIDE	Q9BY76.
Genome annotation databases
Ensembl	ENST00000301455; ENSP00000301455; ENSG00000167772; Homo sapiens. [Genome view]
GeneID	51129.
KEGG	hsa:51129.
UCSC	uc002mjq.1. human.
Organism-specific databases
CTD	51129.
GeneCards	GC19P008335.
H-InvDB	HIX0027444.
HGNC	HGNC:16039. ANGPTL4.
HPA	HPA007879.
MIM	605910. gene.
PharmGKB	PA24797.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG09521.
HOVERGEN	Q9BY76.
InParanoid	Q9BY76.
OMA	MRCAPTA.
OrthoDB	EOG9QJV6X.
PhylomeDB	Q9BY76.
Enzyme and pathway databases
Reactome	REACT_602. Metabolism of lipids and lipoproteins.
Gene expression databases
ArrayExpress	Q9BY76.
Bgee	Q9BY76.
CleanEx	HS_ANGPTL4.
Genevestigator	Q9BY76.
GermOnline	ENSG00000167772. Homo sapiens.
Family and domain databases
InterPro	IPR002181. Fibrinogen_a/b/g_C. IPR014716. Fibrinogen_a/b/g_C_1. IPR014715. Fibrinogen_a/b/g_C_2. IPR020837. Fibrinogen_CS. [Graphical view]
Gene3D	G3DSA:3.90.215.10. Fibrinogen_a/b/g_C_1. 1 hit. G3DSA:4.10.530.10. Fibrinogen_a/b/g_C_2. 1 hit.
Pfam	PF00147. Fibrinogen_C. 1 hit. [Graphical view]
SMART	SM00186. FBG. 1 hit. [Graphical view]
PROSITE	PS00514. FIBRINOGEN_C_1. 1 hit. PS51406. FIBRINOGEN_C_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	53949.
SOURCE	Search...

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Entry information

Entry name

ANGL4_HUMAN

Accession

Primary (citable) accession number: Q9BY76
Secondary accession number(s): Q53HQ6

Q9Y5B3

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 8, 2002
Last sequence update:	November 8, 2002
Last modified:	January 19, 2010
This is version 82 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.

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SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents