Reviewed, UniProtKB/Swiss-Prot Q9Z1P8 (ANGL4_MOUSE)

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
Fasting-induced adipose factor
Secreted protein Bk89
425O18-1

Gene names

Name:	Angptl4
Synonyms:	Farp, Fiaf, Ng27

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	410 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level.

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 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. Ref.4 Ref.9 Ref.10 Ref.11
Subunit structure	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).
Subcellular location	Secreted. Secreted › extracellular space › extracellular matrix. Note: The unprocessed form interacts with the extracellular matrix. This may constitute a dynamic reservoir, a regulatory mechanism of the bioavailability of ANGPTL4. Ref.10
Tissue specificity	Predominantly expressed in adipose tissue and is strongly up-regulated by fasting in white adipose tissue and liver. Ref.2
Developmental stage	Expressed at low levels in most organs and connective tissue at E13.5. Between E15.5 and E18.5, strongest expression in brown fat. Ref.4
Induction	Alterations in nutrition and leptin administration are found to modulate the expression in vivo. Ref.4
Involvement in disease	Elevated levels of expression in models of obesity and diabetes.
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 permeabilty 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.
Sequence similarities	Contains 1 fibrinogen C-terminal domain.

Ontologies

Keywords
Cellular component	Extracellular matrix Secreted
Domain	Coiled coil Signal
PTM	Disulfide bond Glycoprotein
Gene Ontology (GO)
Biological process	cellular response to starvation Ref.2 Non-traceable author statement. Source: UniProtKB negative regulation of apoptosis Ref.1 Inferred from direct assay. Source: UniProtKB negative regulation of lipoprotein lipase activity Inferred from direct assay. Source: UniProtKB positive regulation of lipid metabolic process Non-traceable author statement. Source: UniProtKB signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	extracellular space Ref.4 Inferred from direct assay. Source: MGI proteinaceous extracellular matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	enzyme inhibitor activity Inferred from direct assay. Source: UniProtKB receptor binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 23	23	Potential
	Chain	24 – 410	387	Angiopoietin-related protein 4		PRO_0000009125
Regions
	Domain	183 – 405	223	Fibrinogen C-terminal
	Coiled coil	104 – 152	49	Potential
Amino acid modifications
	Glycosylation	181	1	N-linked (GlcNAc...) Potential
	Glycosylation	236	1	N-linked (GlcNAc...) Potential
	Glycosylation	242	1	N-linked (GlcNAc...) Potential
	Disulfide bond	192 ↔ 220		By similarity
	Disulfide bond	345 ↔ 358		By similarity
Experimental info
	Sequence conflict	168 – 170	3	RLP → KLS in AAF42969. Ref.4
	Sequence conflict	180	1	P → S in AAF42969. Ref.4
	Sequence conflict	189	1	P → A in AAF42969. Ref.4
	Sequence conflict	272	1	N → D Ref.2
	Sequence conflict	272	1	N → D Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q9Z1P8-1 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: BCEE2259921D6D81	FASTA	410	45,538
	10 20 30 40 50 60 MRCAPTAGAA LVLCAATAGL LSAQGRPAQP EPPRFASWDE MNLLAHGLLQ LGHGLREHVE 70 80 90 100 110 120 RTRGQLGALE RRMAACGNAC QGPKGKDAPF KDSEDRVPEG QTPETLQSLQ TQLKAQNSKI 130 140 150 160 170 180 QQLFQKVAQQ QRYLSKQNLR IQNLQSQIDL LAPTHLDNGV DKTSRGKRLP KMTQLIGLTP 190 200 210 220 230 240 NATHLHRPPR DCQELFQEGE RHSGLFQIQP LGSPPFLVNC EMTSDGGWTV IQRRLNGSVD 250 260 270 280 290 300 FNQSWEAYKD GFGDPQGEFW LGLEKMHSIT GNRGSQLAVQ LQDWDGNAKL LQFPIHLGGE 310 320 330 340 350 360 DTAYSLQLTE PTANELGATN VSPNGLSLPF STWDQDHDLR GDLNCAKSLS GGWWFGTCSH 370 380 390 400 410 SNLNGQYFHS IPRQRQERKK GIFWKTWKGR YYPLQATTLL IQPMEATAAS

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].
[2]	"Characterization of the fasting-induced adipose factor FIAF, a novel peroxisome proliferator-activated receptor target gene." Kersten S., Mandard S., Tan N.S., Escher P., Metzger D., Chambon P., Gonzalez F.J., Desvergne B., Wahli W. J. Biol. Chem. 275:28488-28493(2000) [PubMed: 10862772] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: White adipose tissue.
[3]	"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], TRANSGENIC MICE.
[4]	"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], DEVELOPMENTAL STAGE, INDUCTION, POSSIBLE FUNCTION. Tissue: Adipocyte.
[5]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Skin and Testis.
[6]	"Gene content of the 750-kb critical region for mouse embryonic ectoderm lethal tcl-w5." Abe K., Yuzuriha M., Sugimoto M., Ko M.S., Brathwaite M.E., Waeltz P., Nagaraja R. Mamm. Genome 15:265-276(2004) [PubMed: 15112104] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: 129/Sv.
[7]	"Analysis of the gene-dense major histocompatibility complex class III region and its comparison to mouse." Xie T., Rowen L., Aguado B., Ahearn M.E., Madan A., Qin S., Campbell R.D., Hood L. Genome Res. 13:2621-2636(2003) [PubMed: 14656967] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: 129.
[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: Liver.
[9]	"Angiopoietin-like protein 4 decreases blood glucose and improves glucose tolerance but induces hyperlipidemia and hepatic steatosis in mice." Xu A., Lam M.C., Chan K.W., Wang Y., Zhang J., Hoo R.L., Xu J.Y., Chen B., Chow W.S., Tso A.W., Lam K.S. Proc. Natl. Acad. Sci. U.S.A. 102:6086-6091(2005) [PubMed: 15837923] [Abstract] Cited for: FUNCTION.
[10]	"Extracellular matrix-bound angiopoietin-like 4 inhibits endothelial cell adhesion, migration, and sprouting and alters actin cytoskeleton." Cazes A., Galaup A., Chomel C., Bignon M., Brechot N., Le Jan S., Weber H., Corvol P., Muller L., Germain S., Monnot C. Circ. Res. 99:1207-1215(2006) [PubMed: 17068295] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[11]	"Angiopoietin-like 4 prevents metastasis through inhibition of vascular permeability and tumor cell motility and invasiveness." Galaup A., Cazes A., Le Jan S., Philippe J., Connault E., Le Coz E., Mekid H., Mir L.M., Opolon P., Corvol P., Monnot C., Germain S. Proc. Natl. Acad. Sci. U.S.A. 103:18721-18726(2006) [PubMed: 17130448] [Abstract] Cited for: FUNCTION, XENOGRAFT MODELS.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00130325.
RefSeq	NP_065606.2.
UniGene	Mm.196189
3D structure databases
SMR	Q9Z1P8. Positions 106-408.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9Z1P8.
Proteomic databases
PRIDE	Q9Z1P8.
Genome annotation databases
Ensembl	ENSMUST00000002360; ENSMUSP00000002360; ENSMUSG00000002289; Mus musculus. [Genome view]
GeneID	57875.
KEGG	mmu:57875.
UCSC	uc008bzp.1. mouse.
Organism-specific databases
CTD	57875.
MGI	MGI:1888999. Angptl4.
Phylogenomic databases
HOGENOM	HBG713975.
HOVERGEN	HBG001644.
InParanoid	Q9Z1P8.
OMA	MRCAPTA.
OrthoDB	EOG9QJV6X.
PhylomeDB	Q9Z1P8.
Gene expression databases
ArrayExpress	Q9Z1P8.
Bgee	Q9Z1P8.
CleanEx	MM_ANGPTL4.
Genevestigator	Q9Z1P8.
GermOnline	ENSMUSG00000002289. Mus musculus.
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]
SUPFAM	SSF56496. Fibrinogen_a/b/g_C. 1 hit.
PROSITE	PS00514. FIBRINOGEN_C_1. 1 hit. PS51406. FIBRINOGEN_C_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	314033.
SOURCE	Search...

Entry information

Entry name

ANGL4_MOUSE

Accession

Primary (citable) accession number: Q9Z1P8
Secondary accession number(s): Q78ZJ9, Q9JHX7, Q9JLX7

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 8, 2002
Last sequence update:	May 1, 1999
Last modified:	March 2, 2010
This is version 78 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)