FBLN4_CRIGR
ID FBLN4_CRIGR Reviewed; 443 AA.
AC O55058;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 25-MAY-2022, entry version 111.
DE RecName: Full=EGF-containing fibulin-like extracellular matrix protein 2 {ECO:0000250|UniProtKB:O95967};
DE AltName: Full=Fibulin-4 {ECO:0000250|UniProtKB:O95967};
DE Short=FIBL-4;
DE AltName: Full=Protein H411;
DE Flags: Precursor;
GN Name=EFEMP2 {ECO:0000250|UniProtKB:O95967}; Synonyms=FBLN4;
OS Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Ovary;
RA Heine H., Delude R.L., Monks B., Golenbock D.T.;
RL Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Plays a crucial role in elastic fiber formation in tissue,
CC and in the formation of ultrastructural connections between elastic
CC laminae and smooth muscle cells in the aorta, therefore participates in
CC terminal differentiation and maturation of smooth muscle cell (SMC) and
CC in the mechanical properties and wall integrity maintenance of the
CC aorta. In addition, is involved in the control of collagen fibril
CC assembly in tissue throught proteolytic activation of LOX leading to
CC cross- linking of collagen and elastin. Also promotes ELN coacervation
CC and participates in the deposition of ELN coacervates on to
CC microfibrils but also regulates ELN cross- linking through LOX
CC interaction. Moreover adheres to the cells through heparin binding in a
CC calcium-dependent manner and regulates vascularlar smooth muscle cells
CC proliferation through angiotensin signaling.
CC {ECO:0000250|UniProtKB:Q9WVJ9}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. Multimer; allows heparin binding
CC (By similarity). Monomer (By similarity). Interacts with FBN1 (via N-
CC terminal domain); this interaction inhibits EFEMP2 binding to LOX and
CC ELN. Interacts with LOX (via propeptide); this interaction is strong
CC and facilitates formation of ternary complexes with ELN during elastic
CC fiber assembly; this interaction limits interaction of EFEMP2 with
CC FBLN5. Interacts with PITX2. Interacts with ELN with moderate affinity;
CC this interaction regulates ELN self-assembly maturation stage.
CC Interacts with FBLN5 with moderate affinity. Interacts with LOXL1 (via
CC propeptide), LTBP1 and TGFB1 stronger than with LOXL2 and LTBP3 (By
CC similarity). Interacts with PCOLCE. Interacts with collagen type IV
CC trimer (COL4A1-COL4A1-COL4A2), NID2 and moderately with COL15A1-derived
CC endostatin. Interacts with EMILIN1; this interaction promotes the
CC incorporation of EFEMP2 into the extracellular matrix (By similarity).
CC Interacts with LTBP4; the LTBP4 long form (LTBP4L) has a stronger
CC binding affinity than the LTBP4 short form and the LTBP4 long form
CC promotes fibrillar deposition of EFEMP2 (By similarity).
CC {ECO:0000250|UniProtKB:O95967, ECO:0000250|UniProtKB:Q9WVJ9}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000250|UniProtKB:Q9WVJ9}. Secreted, extracellular space,
CC extracellular matrix, basement membrane {ECO:0000250|UniProtKB:Q9WVJ9}.
CC Note=Localizes on the microfibrils surrounding ELN cores.
CC {ECO:0000250|UniProtKB:Q9WVJ9}.
CC -!- PTM: N-glycosylated; contains mostly complex-type glycans. Not O-
CC glycosylated. {ECO:0000250|UniProtKB:O95967}.
CC -!- PTM: Cleaved by ELANE; produces a 50-55 kDa fragment. Cleaved by MMP2
CC and MMP9; produces several fragments. {ECO:0000250|UniProtKB:O95967}.
CC -!- SIMILARITY: Belongs to the fibulin family. {ECO:0000305}.
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DR EMBL; AF046870; AAC03101.1; -; mRNA.
DR RefSeq; NP_001231778.1; NM_001244849.1.
DR AlphaFoldDB; O55058; -.
DR BMRB; O55058; -.
DR STRING; 10029.NP_001231778.1; -.
DR GeneID; 100736553; -.
DR KEGG; cge:100736553; -.
DR CTD; 30008; -.
DR eggNOG; KOG1217; Eukaryota.
DR OrthoDB; 1174178at2759; -.
DR GO; GO:0005604; C:basement membrane; ISS:UniProtKB.
DR GO; GO:0071953; C:elastic fiber; ISS:UniProtKB.
DR GO; GO:0031012; C:extracellular matrix; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IEA:InterPro.
DR GO; GO:0001527; C:microfibril; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0008201; F:heparin binding; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0035904; P:aorta development; ISS:UniProtKB.
DR GO; GO:0060414; P:aorta smooth muscle tissue morphogenesis; ISS:UniProtKB.
DR GO; GO:0048251; P:elastic fiber assembly; ISS:UniProtKB.
DR GO; GO:1904706; P:negative regulation of vascular associated smooth muscle cell proliferation; ISS:UniProtKB.
DR GO; GO:1904831; P:positive regulation of aortic smooth muscle cell differentiation; ISS:UniProtKB.
DR GO; GO:1904028; P:positive regulation of collagen fibril organization; ISS:UniProtKB.
DR GO; GO:1905609; P:positive regulation of smooth muscle cell-matrix adhesion; ISS:UniProtKB.
DR GO; GO:1904026; P:regulation of collagen fibril organization; ISS:UniProtKB.
DR GO; GO:0097084; P:vascular associated smooth muscle cell development; ISS:UniProtKB.
DR InterPro; IPR026823; cEGF.
DR InterPro; IPR026824; Efemp2.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR PANTHER; PTHR24034:SF96; PTHR24034:SF96; 1.
DR Pfam; PF12662; cEGF; 2.
DR Pfam; PF07645; EGF_CA; 3.
DR SMART; SM00181; EGF; 5.
DR SMART; SM00179; EGF_CA; 6.
DR SUPFAM; SSF57184; SSF57184; 2.
DR PROSITE; PS00010; ASX_HYDROXYL; 4.
DR PROSITE; PS01186; EGF_2; 4.
DR PROSITE; PS50026; EGF_3; 4.
DR PROSITE; PS01187; EGF_CA; 6.
PE 2: Evidence at transcript level;
KW Basement membrane; Calcium; Disulfide bond; EGF-like domain;
KW Extracellular matrix; Glycoprotein; Repeat; Secreted; Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..443
FT /note="EGF-containing fibulin-like extracellular matrix
FT protein 2"
FT /id="PRO_0000007574"
FT DOMAIN 36..81
FT /note="EGF-like 1; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 123..163
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 164..202
FT /note="EGF-like 3; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 203..242
FT /note="EGF-like 4; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 243..282
FT /note="EGF-like 5; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 283..328
FT /note="EGF-like 6; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT SITE 87..88
FT /note="Cleavage; by ELANE"
FT /evidence="ECO:0000250|UniProtKB:O95967"
FT SITE 90..91
FT /note="Cleavage; by MMP2, MMP3, MMP7, MMP9, MMP12"
FT /evidence="ECO:0000250|UniProtKB:O95967"
FT SITE 92..93
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:O95967"
FT CARBOHYD 198
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 394
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 58..121
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 65..80
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 71..109
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 127..140
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 134..149
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 151..162
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 168..177
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 173..186
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 188..201
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 207..217
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 213..226
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 228..241
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 247..258
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 254..267
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 269..281
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 287..300
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 294..309
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 315..327
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
SQ SEQUENCE 443 AA; 49432 MW; 0BCFE5D7323D9E5F CRC64;
MLPFASCLPG SLLLWALLLL LLGAASPQDS EEPDSYTECT DGYEWDADSQ HCRDVNECLT
IPEACKGEMK CINHYGGYLC LPRSAAVIND LHGEGPPPPV PPAQHPNPCP PGYEPDEQES
CVDVDECAQA LHDCRPSQDC HNLPGSYQCT CPDGYRKVGP ECVDIDECRY RYCQHRCVNL
PGSFRCQCEP GFQLGPNNRS CVDVNECDMG APCEQRCFNS YGTFLCRCNQ GYELHRDGFS
CSDIDECSYS SYLCQYRCVN EPGRFSCHCP QGYQLLATRL CQDIDECETG AHQCSEAQTC
VNFHGGYRCV DTNRCVEPYV QVSDNRCFCP VSNPLCREQP SSIVHRYMSI TSERSVPADV
FQIQATSVYP GAYNAFQIRA GNTQGDFYIR QINNVSAMLV LARPVTGPRE YVLDLEMVTM
NSLMSYRASS VLRLTVFVGA YTF
