ANGL4_RAT
ID ANGL4_RAT Reviewed; 405 AA.
AC Q6TMA8;
DT 21-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Angiopoietin-related protein 4;
DE AltName: Full=Angiopoietin-like protein 4;
DE AltName: Full=Hepatic fibrinogen/angiopoietin-related protein;
DE Short=HFARP;
DE Contains:
DE RecName: Full=ANGPTL4 N-terminal chain;
DE Contains:
DE RecName: Full=ANGPTL4 C-terminal chain;
DE Flags: Precursor;
GN Name=Angptl4;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBUNIT, SUBCELLULAR LOCATION, AND
RP GLYCOSYLATION.
RC STRAIN=Wistar; TISSUE=Adipose tissue;
RX PubMed=14570927; DOI=10.1074/jbc.m307583200;
RA Ge H., Yang G., Huang L., Motola D.L., Pourbahrami T., Li C.;
RT "Oligomerization and regulated proteolytic processing of angiopoietin-like
RT protein 4.";
RL J. Biol. Chem. 279:2038-2045(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Mediates inactivation of the lipoprotein lipase LPL, and
CC thereby plays a role in the regulation of triglyceride clearance from
CC the blood serum and in lipid metabolism. May also play a role in
CC regulating glucose homeostasis and insulin sensitivity. Inhibits
CC proliferation, migration, and tubule formation of endothelial cells and
CC reduces vascular leakage (By similarity). Upon heterologous expression,
CC inhibits the adhesion of endothelial cell to the extracellular matrix
CC (ECM), and inhibits the reorganization of the actin cytoskeleton,
CC formation of actin stress fibers and focal adhesions in endothelial
CC cells that have adhered to ANGPTL4-containing ECM (in vitro) (By
CC similarity). Depending on context, may modulate tumor-related
CC angiogenesis (By similarity). {ECO:0000250|UniProtKB:Q9BY76,
CC ECO:0000250|UniProtKB:Q9Z1P8}.
CC -!- FUNCTION: [ANGPTL4 N-terminal chain]: Mediates inactivation of the
CC lipoprotein lipase LPL, and thereby plays an important role in the
CC regulation of triglyceride clearance from the blood serum and in lipid
CC metabolism. Has higher activity in LPL inactivation than the uncleaved
CC protein. {ECO:0000250|UniProtKB:Q9BY76}.
CC -!- SUBUNIT: Homooligomer; disulfide-linked via Cys residues in the N-
CC terminal part of the protein. The homooligomer undergoes proteolytic
CC processing to release its carboxyl fibrinogen-like domain, which
CC circulates as a monomer (PubMed:14570927). The homooligomer unprocessed
CC form is able to interact with the extracellular matrix (By similarity).
CC {ECO:0000250|UniProtKB:Q9BY76, ECO:0000269|PubMed:14570927}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:14570927}. Secreted,
CC extracellular space, extracellular matrix
CC {ECO:0000250|UniProtKB:Q9BY76}. Note=The unprocessed form interacts
CC with the extracellular matrix. This may constitute a dynamic reservoir,
CC a regulatory mechanism of the bioavailability of ANGPTL4.
CC {ECO:0000250|UniProtKB:Q9BY76}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:14570927}.
CC -!- PTM: [ANGPTL4 N-terminal chain]: Forms disulfide-linked dimers and
CC tetramers. {ECO:0000269|PubMed:14570927}.
CC -!- PTM: Cleaved into a smaller N-terminal chain and a larger chain that
CC contains the fibrinogen C-terminal domain; both cleaved and uncleaved
CC forms are detected in the extracellular space. The cleaved form is not
CC present within the cell. {ECO:0000305|PubMed:14570927}.
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DR EMBL; AY393999; AAQ93383.1; -; mRNA.
DR EMBL; BC078944; AAH78944.1; -; mRNA.
DR RefSeq; NP_954546.1; NM_199115.2.
DR AlphaFoldDB; Q6TMA8; -.
DR SMR; Q6TMA8; -.
DR STRING; 10116.ENSRNOP00000010031; -.
DR GlyGen; Q6TMA8; 3 sites.
DR PaxDb; Q6TMA8; -.
DR PRIDE; Q6TMA8; -.
DR Ensembl; ENSRNOT00000010031; ENSRNOP00000010031; ENSRNOG00000007545.
DR GeneID; 362850; -.
DR KEGG; rno:362850; -.
DR UCSC; RGD:735058; rat.
DR CTD; 51129; -.
DR RGD; 735058; Angptl4.
DR eggNOG; KOG2579; Eukaryota.
DR GeneTree; ENSGT00940000159478; -.
DR HOGENOM; CLU_038628_2_1_1; -.
DR InParanoid; Q6TMA8; -.
DR OMA; INCAKHL; -.
DR OrthoDB; 357340at2759; -.
DR PhylomeDB; Q6TMA8; -.
DR TreeFam; TF329953; -.
DR Reactome; R-RNO-8963889; Assembly of active LPL and LIPC lipase complexes.
DR PRO; PR:Q6TMA8; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Bgee; ENSRNOG00000007545; Expressed in liver and 18 other tissues.
DR Genevisible; Q6TMA8; RN.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; ISO:RGD.
DR GO; GO:0004857; F:enzyme inhibitor activity; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0072577; P:endothelial cell apoptotic process; IEA:Ensembl.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:0043086; P:negative regulation of catalytic activity; TAS:RGD.
DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; ISO:RGD.
DR GO; GO:0051005; P:negative regulation of lipoprotein lipase activity; ISO:RGD.
DR GO; GO:0043335; P:protein unfolding; ISO:RGD.
DR GO; GO:0019216; P:regulation of lipid metabolic process; TAS:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0070328; P:triglyceride homeostasis; ISO:RGD.
DR CDD; cd00087; FReD; 1.
DR Gene3D; 3.90.215.10; -; 1.
DR InterPro; IPR028793; ANGPTL4.
DR InterPro; IPR036056; Fibrinogen-like_C.
DR InterPro; IPR014716; Fibrinogen_a/b/g_C_1.
DR InterPro; IPR002181; Fibrinogen_a/b/g_C_dom.
DR InterPro; IPR020837; Fibrinogen_CS.
DR PANTHER; PTHR19143:SF256; PTHR19143:SF256; 2.
DR Pfam; PF00147; Fibrinogen_C; 1.
DR SMART; SM00186; FBG; 1.
DR SUPFAM; SSF56496; SSF56496; 1.
DR PROSITE; PS00514; FIBRINOGEN_C_1; 1.
DR PROSITE; PS51406; FIBRINOGEN_C_2; 1.
PE 1: Evidence at protein level;
KW Angiogenesis; Coiled coil; Disulfide bond; Extracellular matrix;
KW Glycoprotein; Lipid metabolism; Reference proteome; Secreted; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..405
FT /note="Angiopoietin-related protein 4"
FT /id="PRO_0000009126"
FT CHAIN 24..163
FT /note="ANGPTL4 N-terminal chain"
FT /id="PRO_0000446865"
FT CHAIN 164..405
FT /note="ANGPTL4 C-terminal chain"
FT /id="PRO_0000446866"
FT DOMAIN 178..400
FT /note="Fibrinogen C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT COILED 54..146
FT /evidence="ECO:0000255"
FT SITE 163..164
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:Q9BY76"
FT CARBOHYD 176
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 231
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 237
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 187..215
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT DISULFID 340..353
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
SQ SEQUENCE 405 AA; 44951 MW; 3C54185DE5989E46 CRC64;
MRCAPTAGAA LVLCAATAGL LSAQGRPAQP EPPRFASWDE MNLLAHGLLQ LGHGLREHVE
RTRGQLGALE RRMAACGNAC QGPKGTDPKD RVPEGQAPET LQSLQTQLKA QNSKIQQLFQ
KVAQQQRYLS KQNLRIQNLQ SQIDLLTPTH LDNGVDKTSR GKRLPKMAQL IGLTPNATRL
HRPPRDCQEL FQEGERHSGL FQIQPLGSPP FLVNCEMTSD GGWTVIQRRL NGSVDFNQSW
EAYKDGFGDP QGEFWLGLEK MHSITGDRGS QLAVQLQDWD GNAKLLQFPI HLGGEDTAYS
LQLTEPTANE LGATNVSPNG LSLPFSTWDQ DHDLRGDLNC AKSLSGGWWF GTCSHSNLNG
QYFHSIPRQR QQRKKGIFWK TWKGRYYPLQ ATTLLIQPME ATAAS
