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UniProtKB/Swiss-Prot entry Q9Z1P8


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name ANGL4_MOUSE
Primary accession number Q9Z1P8
Secondary accession numbers Q78ZJ9 Q9JHX7 Q9JLX7
Integrated into Swiss-Prot on November 8, 2002
Sequence was last modified on May 1, 1999 (Sequence version 1)
Annotations were last modified on    November 25, 2008 (Entry version 65)
Name and origin of the protein
Protein name Angiopoietin-related protein 4 [Precursor]
Synonyms Angiopoietin-like 4
Hepatic fibrinogen/angiopoietin-related protein
HFARP
Fasting-induced adipose factor
Secreted protein Bk89
425O18-1
Gene name
Name: Angptl4
Synonyms: Farp, Fiaf, Ng27
From
Mus musculus (Mouse) [TaxID: 10090] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; Muroidea; Muridae; Murinae; Mus.
Protein existence 2: Evidence at transcript level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA].
DOI=10.1042/0264-6021:3460603; PubMed=10698685 [NCBI, ExPASy, EBI, Israel, Japan]
Kim I., Kim H.-G., Kim H., Kim H.-H., Park S.K., Uhm C.-S., Lee Z.H., Koh G.Y.;
"Hepatic expression, synthesis and secretion of a novel fibrinogen/angiopoietin-related protein that prevents endothelial-cell apoptosis.";
Biochem. J. 346:603-610(2000).
[2]
NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
TISSUE=White adipose tissue;
DOI=10.1074/jbc.M004029200; PubMed=10862772 [NCBI, ExPASy, EBI, Israel, Japan]
Kersten S., Mandard S., Tan N.S., Escher P., Metzger D., Chambon P., Gonzalez F.J., Desvergne B., Wahli W.;
"Characterization of the fasting-induced adipose factor FIAF, a novel peroxisome proliferator-activated receptor target gene.";
J. Biol. Chem. 275:28488-28493(2000).
[3]
NUCLEOTIDE SEQUENCE [MRNA], AND TRANSGENIC MICE.
PubMed=14583458 [NCBI, ExPASy, EBI, Israel, Japan]
Ito Y., Oike Y., Yasunaga K., Hamada K., Miyata K., Matsumoto S., Sugano S., Tanihara H., Masuho Y., Suda T.;
"Inhibition of angiogenesis and vascular leakiness by angiopoietin-related protein 4.";
Cancer Res. 63:6651-6657(2003).
[4]
NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE, INDUCTION, AND POSSIBLE FUNCTION.
TISSUE=Adipocyte;
DOI=10.1128/MCB.20.14.5343-5349.2000; PubMed=10866690 [NCBI, ExPASy, EBI, Israel, Japan]
Yoon J.C., Chickering T.W., Rosen E.D., Dussault B., Qin Y., Soukas A., Friedman J.M., Holmes W.E., Spiegelman B.M.;
"Peroxisome proliferator-activated receptor gamma target gene encoding a novel angiopoietin-related protein associated with adipose differentiation.";
Mol. Cell. Biol. 20:5343-5349(2000).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
STRAIN=C57BL/6J;
TISSUE=Skin, and Testis;
DOI=10.1126/science.1112014; PubMed=16141072 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"The transcriptional landscape of the mammalian genome.";
Science 309:1559-1563(2005).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
STRAIN=129/Sv;
DOI=10.1007/s00335-003-2329-1; PubMed=15112104 [NCBI, ExPASy, EBI, Israel, Japan]
Abe K., Yuzuriha M., Sugimoto M., Ko M.S., Brathwaite M.E., Waeltz P., Nagaraja R.;
"Gene content of the 750-kb critical region for mouse embryonic ectoderm lethal tcl-w5.";
Mamm. Genome 15:265-276(2004).
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
STRAIN=129;
DOI=10.1101/gr.1736803; PubMed=14656967 [NCBI, ExPASy, EBI, Israel, Japan]
Xie T., Rowen L., Aguado B., Ahearn M.E., Madan A., Qin S., Campbell R.D., Hood L.;
"Analysis of the gene-dense major histocompatibility complex class III region and its comparison to mouse.";
Genome Res. 13:2621-2636(2003).
[8]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Liver;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[9]
FUNCTION.
DOI=10.1073/pnas.0408452102; PubMed=15837923 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"Angiopoietin-like protein 4 decreases blood glucose and improves glucose tolerance but induces hyperlipidemia and hepatic steatosis in mice.";
Proc. Natl. Acad. Sci. U.S.A. 102:6086-6091(2005).
[10]
FUNCTION, AND SUBCELLULAR LOCATION.
DOI=10.1161/01.RES.0000250758.63358.91; PubMed=17068295 [NCBI, ExPASy, EBI, Israel, Japan]
Cazes A., Galaup A., Chomel C., Bignon M., Brechot N., Le Jan S., Weber H., Corvol P., Muller L., Germain S., Monnot C.;
"Extracellular matrix-bound angiopoietin-like 4 inhibits endothelial cell adhesion, migration, and sprouting and alters actin cytoskeleton.";
Circ. Res. 99:1207-1215(2006).
[11]
FUNCTION, AND XENOGRAFT MODELS.
DOI=10.1073/pnas.0609025103; PubMed=17130448 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"Angiopoietin-like 4 prevents metastasis through inhibition of vascular permeability and tumor cell motility and invasiveness.";
Proc. Natl. Acad. Sci. U.S.A. 103:18721-18726(2006).
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.
  • SUBUNIT: 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.
  • TISSUE SPECIFICITY: Predominantly expressed in adipose tissue and is strongly up-regulated by fasting in white adipose tissue and liver.
  • 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.
  • INDUCTION: Alterations in nutrition and leptin administration are found to modulate the expression in vivo.
  • 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.
  • MISCELLANEOUS: 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.
  • SIMILARITY: Contains 1 fibrinogen C-terminal domain.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
AF169313; AAF62869.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF278699; AAF86342.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AB054540; BAB83079.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF123261; AAF42969.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AK014564; BAB29431.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AK132761; BAE21342.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF528162; AAO17378.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF110520; AAC97965.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC006611; AAH06611.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC021343; AAH21343.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC025797; AAH25797.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
RefSeq NP_065606.1; -.
UniGene Mm.196189
3D structure databases
HSSP P02679; 3FIB. [HSSP ENTRY / PDB]
ModBase Q9Z1P8.
Organism-specific databases
MGI MGI:1888999; Angptl4.
Gene expression databases
ArrayExpress Q9Z1P8; -.
CleanEx MM_ANGPTL4; -.
GermOnline ENSMUSG00000002289; Mus musculus.
Ontologies
GO
GO:0005615; Cellular component: extracellular space (inferred from direct assay from MGI).
GO:0005578; Cellular component: proteinaceous extracellular matrix (inferred from electronic annotation from UniProtKB-KW).
GO:0004857; Molecular function: enzyme inhibitor activity (inferred from direct assay from UniProtKB).
GO:0005102; Molecular function: receptor binding (inferred from electronic annotation from InterPro).
GO:0009267; Biological process: cellular response to starvation (non-traceable author statement from UniProtKB).
GO:0043066; Biological process: negative regulation of apoptosis (inferred from direct assay from UniProtKB).
GO:0051005; Biological process: negative regulation of lipoprotein lipase activity (inferred from direct assay from UniProtKB).
GO:0045834; Biological process: positive regulation of lipid metabolic process (non-traceable author statement from UniProtKB).
GO:0007165; Biological process: signal transduction (inferred from electronic annotation from InterPro).
QuickGo view.
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.
Graphical view of domain structure.
Gene3D G3DSA:3.90.215.10; Fibrinogen_a/b/g_C_1; 1.
G3DSA:4.10.530.10; Fibrinogen_a/b/g_C_2; 1.
Pfam PF00147; Fibrinogen_C; 1.
Pfam graphical view of domain structure.
SMART SM00186; FBG; 1.
SMART graphical view of domain structure.
PROSITE PS00514; FIBRINOGEN_C_1; 1.
PS51406; FIBRINOGEN_C_2; 1.
PROSITE graphical view of domain structure (profiles).
ProtoNet Q9Z1P8.
Genome annotation databases
Ensembl ENSMUSG00000002289; Mus musculus. [Contig view]
GeneID 57875; -.
KEGG mmu:57875; -.
Phylogenomic databases
HOGENOM Q9Z1P8; -.
HOVERGEN Q9Z1P8; -.
Other
NextBio 314033; -.
SOURCE Angptl4; Mus musculus.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
Coiled coil; Extracellular matrix; Glycoprotein; Secreted; Signal.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
SIGNAL   1    23  23     Potential. 
CHAIN   24   410  387     Angiopoietin-related protein 4. PRO_0000009125
DOMAIN   183   405  223     Fibrinogen C-terminal. 
COILED   104   152  49     Potential. 
CARBOHYD   181   181        N-linked (GlcNAc...) (Potential). 
CARBOHYD   236   236        N-linked (GlcNAc...) (Potential). 
CARBOHYD   242   242        N-linked (GlcNAc...) (Potential). 
DISULFID   192   220        By similarity. 
DISULFID   345   358        By similarity. 
CONFLICT   168   170        RLP -> KLS (in Ref. 4; AAF42969). 
CONFLICT   180   180        P -> S (in Ref. 4; AAF42969). 
CONFLICT   189   189        P -> A (in Ref. 4; AAF42969). 
CONFLICT   272   272        N -> D (in Ref. 2 and 4). 
Sequence information
Length: 410 AA [This is the length of the unprocessed precursor] Molecular weight: 45538 Da [This is the MW of the unprocessed precursor] CRC64: BCEE2259921D6D81 [This is a checksum on the sequence]
        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 

Q9Z1P8 in FASTA format

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