FBLN4_MOUSE
ID FBLN4_MOUSE Reviewed; 443 AA.
AC Q9WVJ9;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=EGF-containing fibulin-like extracellular matrix protein 2 {ECO:0000305};
DE AltName: Full=Fibulin-4 {ECO:0000303|PubMed:16478991};
DE Short=FIBL-4;
DE AltName: Full=Mutant p53-binding protein 1;
DE Flags: Precursor;
GN Name=Efemp2 {ECO:0000312|MGI:MGI:1891209};
GN Synonyms=Fbln4, Mbp1 {ECO:0000303|PubMed:10380882};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH P53 MUTANTS.
RC STRAIN=C57BL/6J;
RX PubMed=10380882; DOI=10.1038/sj.onc.1202937;
RA Gallagher W.M., Argentini M., Sierra V., Bracco L., Debussche L.,
RA Conseiller E.;
RT "MBP1: a novel mutant p53-specific protein partner with oncogenic
RT properties.";
RL Oncogene 18:3608-3616(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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).
RN [3]
RP PROTEIN SEQUENCE OF 28-35, PYROGLUTAMATE FORMATION AT GLN-28, SUBUNIT,
RP INTERACTION WITH ELN; NID2; COLLAGEN TYPE IV TRIMER AND COL15A1-DERIVED
RP ENDOSTATIN, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=17324935; DOI=10.1074/jbc.m611029200;
RA Kobayashi N., Kostka G., Garbe J.H., Keene D.R., Baechinger H.P.,
RA Hanisch F.G., Markova D., Tsuda T., Timpl R., Chu M.L., Sasaki T.;
RT "A comparative analysis of the fibulin protein family. Biochemical
RT characterization, binding interactions, and tissue localization.";
RL J. Biol. Chem. 282:11805-11816(2007).
RN [4]
RP DISRUPTION PHENOTYPE, FUNCTION, AND INTERACTION WITH ELN.
RX PubMed=16478991; DOI=10.1128/mcb.26.5.1700-1709.2006;
RA McLaughlin P.J., Chen Q., Horiguchi M., Starcher B.C., Stanton J.B.,
RA Broekelmann T.J., Marmorstein A.D., McKay B., Mecham R., Nakamura T.,
RA Marmorstein L.Y.;
RT "Targeted disruption of fibulin-4 abolishes elastogenesis and causes
RT perinatal lethality in mice.";
RL Mol. Cell. Biol. 26:1700-1709(2006).
RN [5]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=19855011; DOI=10.1073/pnas.0908268106;
RA Horiguchi M., Inoue T., Ohbayashi T., Hirai M., Noda K., Marmorstein L.Y.,
RA Yabe D., Takagi K., Akama T.O., Kita T., Kimura T., Nakamura T.;
RT "Fibulin-4 conducts proper elastogenesis via interaction with cross-linking
RT enzyme lysyl oxidase.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:19029-19034(2009).
RN [6]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=20019329; DOI=10.1161/circresaha.109.207852;
RA Huang J., Davis E.C., Chapman S.L., Budatha M., Marmorstein L.Y.,
RA Word R.A., Yanagisawa H.;
RT "Fibulin-4 deficiency results in ascending aortic aneurysms: a potential
RT link between abnormal smooth muscle cell phenotype and aneurysm
RT progression.";
RL Circ. Res. 106:583-592(2010).
RN [7]
RP DISRUPTION PHENOTYPE, FUNCTION, AND MISCELLANEOUS.
RX PubMed=23636094; DOI=10.1126/scitranslmed.3005025;
RA Huang J., Yamashiro Y., Papke C.L., Ikeda Y., Lin Y., Patel M., Inagami T.,
RA Le V.P., Wagenseil J.E., Yanagisawa H.;
RT "Angiotensin-converting enzyme-induced activation of local angiotensin
RT signaling is required for ascending aortic aneurysms in fibulin-4-deficient
RT mice.";
RL Sci. Transl. Med. 5:183ra58-183ra58(2013).
RN [8]
RP INTERACTION WITH LTBP4.
RX PubMed=25713297; DOI=10.1242/dmm.018960;
RA Bultmann-Mellin I., Conradi A., Maul A.C., Dinger K., Wempe F., Wohl A.P.,
RA Imhof T., Wunderlich F.T., Bunck A.C., Nakamura T., Koli K., Bloch W.,
RA Ghanem A., Heinz A., von Melchner H., Sengle G., Sterner-Kock A.;
RT "Modeling autosomal recessive cutis laxa type 1C in mice reveals distinct
RT functions for Ltbp-4 isoforms.";
RL Dis. Model. Mech. 8:403-415(2015).
RN [9]
RP DISRUPTION PHENOTYPE, FUNCTION, AND INTERACTION WITH PCOLCE.
RX PubMed=26220971; DOI=10.1093/hmg/ddv308;
RA Papke C.L., Tsunezumi J., Ringuette L.J., Nagaoka H., Terajima M.,
RA Yamashiro Y., Urquhart G., Yamauchi M., Davis E.C., Yanagisawa H.;
RT "Loss of fibulin-4 disrupts collagen synthesis and maturation: implications
RT for pathology resulting from EFEMP2 mutations.";
RL Hum. Mol. Genet. 24:5867-5879(2015).
RN [10]
RP DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP AND MUTAGENESIS OF GLU-57.
RX PubMed=26178373; DOI=10.1074/jbc.m115.640425;
RA Igoucheva O., Alexeev V., Halabi C.M., Adams S.M., Stoilov I., Sasaki T.,
RA Arita M., Donahue A., Mecham R.P., Birk D.E., Chu M.L.;
RT "Fibulin-4 E57K Knock-in Mice Recapitulate Cutaneous, Vascular and Skeletal
RT Defects of Recessive Cutis Laxa 1B with both Elastic Fiber and Collagen
RT Fibril Abnormalities.";
RL J. Biol. Chem. 290:21443-21459(2015).
RN [11]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=26486174; DOI=10.1126/scisignal.aab3141;
RA Yamashiro Y., Papke C.L., Kim J., Ringuette L.J., Zhang Q.J., Liu Z.P.,
RA Mirzaei H., Wagenseil J.E., Davis E.C., Yanagisawa H.;
RT "Abnormal mechanosensing and cofilin activation promote the progression of
RT ascending aortic aneurysms in mice.";
RL Sci. Signal. 8:ra105-ra105(2015).
RN [12]
RP DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=26711913; DOI=10.1007/s00441-015-2346-x;
RA Markova D.Z., Pan T.C., Zhang R.Z., Zhang G., Sasaki T., Arita M.,
RA Birk D.E., Chu M.L.;
RT "Forelimb contractures and abnormal tendon collagen fibrillogenesis in
RT fibulin-4 null mice.";
RL Cell Tissue Res. 364:637-646(2016).
RN [13]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND
RP FUNCTION.
RX PubMed=26690653; DOI=10.1016/j.matbio.2015.12.002;
RA Sasaki T., Stoop R., Sakai T., Hess A., Deutzmann R.,
RA Schloetzer-Schrehardt U., Chu M.L., von der Mark K.;
RT "Loss of fibulin-4 results in abnormal collagen fibril assembly in bone,
RT caused by impaired lysyl oxidase processing and collagen cross-linking.";
RL Matrix Biol. 50:53-66(2016).
RN [14]
RP MUTAGENESIS OF GLU-57, AND FUNCTION.
RX PubMed=28508064; DOI=10.1126/sciadv.1602532;
RA Halabi C.M., Broekelmann T.J., Lin M., Lee V.S., Chu M.L., Mecham R.P.;
RT "Fibulin-4 is essential for maintaining arterial wall integrity in conduit
RT but not muscular arteries.";
RL Sci. Adv. 3:e1602532-e1602532(2017).
RN [15]
RP INTERACTION WITH EMILIN1.
RX PubMed=28717224; DOI=10.1038/s41598-017-05835-7;
RA Schiavinato A., Keene D.R., Imhof T., Doliana R., Sasaki T., Sengle G.;
RT "Fibulin-4 deposition requires EMILIN-1 in the extracellular matrix of
RT osteoblasts.";
RL Sci. Rep. 7:5526-5526(2017).
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 (PubMed:16478991, PubMed:19855011, PubMed:20019329,
CC PubMed:26486174, PubMed:26711913, PubMed:28508064). In addition, is
CC involved in the control of collagen fibril assembly in tissue throught
CC proteolytic activation of LOX leading to cross- linking of collagen and
CC elastin (PubMed:26690653, PubMed:26711913, PubMed:26220971,
CC PubMed:26178373). Also promotes ELN coacervation and participates in
CC the deposition of ELN coacervates on to microfibrils but also regulates
CC ELN cross- linking through LOX interaction (PubMed:17324935). Moreover
CC adheres to the cells through heparin binding in a calcium-dependent
CC manner and regulates vascularlar smooth muscle cells proliferation
CC through angiotensin signaling (PubMed:23636094).
CC {ECO:0000269|PubMed:16478991, ECO:0000269|PubMed:17324935,
CC ECO:0000269|PubMed:19855011, ECO:0000269|PubMed:20019329,
CC ECO:0000269|PubMed:23636094, ECO:0000269|PubMed:26178373,
CC ECO:0000269|PubMed:26220971, ECO:0000269|PubMed:26486174,
CC ECO:0000269|PubMed:26690653, ECO:0000269|PubMed:26711913,
CC ECO:0000269|PubMed:28508064}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Multimer; allows
CC heparin binding (By similarity). Monomer (PubMed:17324935). Binds
CC preferentially to p53 mutants (PubMed:10380882). Interacts with FBN1
CC (via N-terminal domain); this interaction inhibits EFEMP2 binding to
CC LOX and ELN (By similarity). Interacts with ELN with moderate affinity;
CC this interaction regulates ELN self-assembly maturation stage
CC (PubMed:16478991, PubMed:17324935). Interacts with PCOLCE
CC (PubMed:26220971). Interacts with collagen type IV trimer (COL4A1-
CC COL4A1-COL4A2), NID2 and moderately with COL15A1-derived endostatin
CC (PubMed:17324935). Interacts with EMILIN1; this interaction promotes
CC the incorporation of EFEMP2 into the extracellular matrix
CC (PubMed:28717224). Interacts with LTBP4; the LTBP4 long form (LTBP4L)
CC has a stronger binding affinity than the LTBP4 short form and the LTBP4
CC long form promotes fibrillar deposition of EFEMP2 (PubMed:25713297).
CC Interacts with LOX (via propeptide); this interaction is strong and
CC facilitates formation of ternary complexes with ELN during elastic
CC fiber assembly; this interaction limits interaction of EFEMP2 with
CC FBLN5 (By similarity). Interacts with PITX2 (By similarity). Interacts
CC with FBLN5 with moderate affinity (By similarity). Interacts with LOXL1
CC (via propeptide), LTBP1 and TGFB1 stronger than with LOXL2 and LTBP3
CC (By similarity). {ECO:0000250|UniProtKB:O95967,
CC ECO:0000269|PubMed:10380882, ECO:0000269|PubMed:16478991,
CC ECO:0000269|PubMed:17324935, ECO:0000269|PubMed:25713297,
CC ECO:0000269|PubMed:26220971, ECO:0000269|PubMed:28717224}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000269|PubMed:17324935, ECO:0000269|PubMed:26178373,
CC ECO:0000269|PubMed:26690653}. Secreted, extracellular space,
CC extracellular matrix, basement membrane {ECO:0000269|PubMed:17324935}.
CC Note=Localizes on the microfibrils surrounding ELN cores.
CC {ECO:0000269|PubMed:17324935}.
CC -!- TISSUE SPECIFICITY: Expressed in elastic fibers of the skin, near the
CC dermal-epidermal junction, surrounding the hair follicles and
CC throughout the dermis (PubMed:26178373). Expressed in tendon around
CC tenocytes (PubMed:26711913). Prominently expressed in cartilage, bone,
CC perichondrium and ligaments. Also detected in bone marrow stroma
CC (PubMed:26690653). Expressed in aorta, lung, and esophagus
CC (PubMed:17324935). {ECO:0000269|PubMed:17324935,
CC ECO:0000269|PubMed:26178373, ECO:0000269|PubMed:26690653,
CC ECO:0000269|PubMed:26711913}.
CC -!- DEVELOPMENTAL STAGE: At E(15), found in the perichondrium of the
CC developing bone. At E(14) detected in the lung parenchyma.
CC {ECO:0000269|PubMed:17324935}.
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 -!- DISRUPTION PHENOTYPE: Homozygous mice for the EFEMP2 gene appear to be
CC outwardly normal (PubMed:16478991, PubMed:28508064). Homozygous mice
CC exhibit severe lung and vascular defects including emphysema, artery
CC tortuosity, irregularity, aneurysm, rupture, and resulting hemorrhages
CC (PubMed:16478991, PubMed:19855011, PubMed:26178373, PubMed:28508064).
CC Mice died perinatally (PubMed:16478991, PubMed:19855011). Mice with
CC conditional knockout of EFEMP2, in vascular smooth muscle, grow
CC normally, are fertile and exhibit an arterial stiffness
CC (PubMed:19855011). Mice with conditional knockout of EFEMP2, in
CC endothelial cell (EC) are healthy with an normal aorta
CC (PubMed:20019329). Mice with conditional knockout of EFEMP2, in smooth
CC muscle cells, die spontaneously at approximately 2 months of age
CC despite absence of embryonic or neonatal lethality. Aortae exhibit
CC large aneurysms exclusively in the ascending aorta. Aneurysms are
CC observed with complete penetrance (PubMed:20019329, PubMed:26486174,
CC PubMed:23636094, PubMed:26220971). Homozygous mice for the EFEMP2 gene
CC die within 1-2 days after birth. Embryos at 19 dpc show bilateral
CC forelimb contractures (PubMed:26711913, PubMed:26690653). Newborn
CC homozygous mice demonstrate normal morphology of the skeleton
CC (PubMed:26690653). {ECO:0000269|PubMed:16478991,
CC ECO:0000269|PubMed:19855011, ECO:0000269|PubMed:20019329,
CC ECO:0000269|PubMed:23636094, ECO:0000269|PubMed:26178373,
CC ECO:0000269|PubMed:26220971, ECO:0000269|PubMed:26486174,
CC ECO:0000269|PubMed:26690653, ECO:0000269|PubMed:26711913,
CC ECO:0000269|PubMed:28508064}.
CC -!- MISCELLANEOUS: Aneurysm may be prevent with postnatal administration of
CC ACE inhibitor and/or angiotensin II receptor blocker (ARB).
CC {ECO:0000269|PubMed:23636094}.
CC -!- SIMILARITY: Belongs to the fibulin family. {ECO:0000305}.
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DR EMBL; AF104223; AAD45219.1; -; mRNA.
DR EMBL; BC012269; AAH12269.1; -; mRNA.
DR CCDS; CCDS29466.1; -.
DR RefSeq; NP_067449.3; NM_021474.3.
DR RefSeq; XP_006531871.1; XM_006531808.1.
DR AlphaFoldDB; Q9WVJ9; -.
DR BioGRID; 208447; 3.
DR IntAct; Q9WVJ9; 1.
DR STRING; 10090.ENSMUSP00000064719; -.
DR GlyGen; Q9WVJ9; 2 sites.
DR PhosphoSitePlus; Q9WVJ9; -.
DR MaxQB; Q9WVJ9; -.
DR PaxDb; Q9WVJ9; -.
DR PRIDE; Q9WVJ9; -.
DR ProteomicsDB; 271875; -.
DR Antibodypedia; 16033; 391 antibodies from 33 providers.
DR DNASU; 58859; -.
DR Ensembl; ENSMUST00000165485; ENSMUSP00000133016; ENSMUSG00000024909.
DR Ensembl; ENSMUST00000166303; ENSMUSP00000128827; ENSMUSG00000024909.
DR GeneID; 58859; -.
DR KEGG; mmu:58859; -.
DR UCSC; uc008gdl.2; mouse.
DR CTD; 30008; -.
DR MGI; MGI:1891209; Efemp2.
DR VEuPathDB; HostDB:ENSMUSG00000024909; -.
DR eggNOG; KOG1217; Eukaryota.
DR GeneTree; ENSGT00940000159437; -.
DR HOGENOM; CLU_004826_0_1_1; -.
DR InParanoid; Q9WVJ9; -.
DR OMA; DPLTEHC; -.
DR PhylomeDB; Q9WVJ9; -.
DR Reactome; R-MMU-2129379; Molecules associated with elastic fibres.
DR BioGRID-ORCS; 58859; 7 hits in 71 CRISPR screens.
DR ChiTaRS; Efemp2; mouse.
DR PRO; PR:Q9WVJ9; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q9WVJ9; protein.
DR Bgee; ENSMUSG00000024909; Expressed in humerus cartilage element and 208 other tissues.
DR ExpressionAtlas; Q9WVJ9; baseline and differential.
DR Genevisible; Q9WVJ9; MM.
DR GO; GO:0005604; C:basement membrane; IDA:UniProtKB.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0071953; C:elastic fiber; IMP:UniProtKB.
DR GO; GO:0031012; C:extracellular matrix; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
DR GO; GO:0001527; C:microfibril; IDA: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; IMP:UniProtKB.
DR GO; GO:0060414; P:aorta smooth muscle tissue morphogenesis; IMP:UniProtKB.
DR GO; GO:0060840; P:artery development; IMP:MGI.
DR GO; GO:0048251; P:elastic fiber assembly; IMP:UniProtKB.
DR GO; GO:1904706; P:negative regulation of vascular associated smooth muscle cell proliferation; IMP:UniProtKB.
DR GO; GO:1904831; P:positive regulation of aortic smooth muscle cell differentiation; IMP:UniProtKB.
DR GO; GO:1904028; P:positive regulation of collagen fibril organization; IMP: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; IMP:UniProtKB.
DR GO; GO:0097084; P:vascular associated smooth muscle cell development; IMP: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; 3.
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 1: Evidence at protein level;
KW Basement membrane; Calcium; Direct protein sequencing; Disulfide bond;
KW EGF-like domain; Extracellular matrix; Glycoprotein;
KW Pyrrolidone carboxylic acid; Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..27
FT /evidence="ECO:0000269|PubMed:17324935"
FT CHAIN 28..443
FT /note="EGF-containing fibulin-like extracellular matrix
FT protein 2"
FT /id="PRO_0000007576"
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 REGION 91..117
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 MOD_RES 28
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:17324935"
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"
FT MUTAGEN 57
FT /note="E->K: Knockin mutant mice are viable and survive
FT into adulthood. Mice display abnormalities in multiple
FT organ systems, including loose skin, bent forelimb, aortic
FT aneurysm, tortuous artery, and pulmonary emphysema. In
FT addition to elastic fiber abnormalities in the skin and
FT large arteries, collagen fibrils are irregularly shaped,
FT with many large fibrils in the dermis. Mice have large
FT artery stiffness and systolic hypertension. Reduces protein
FT secretion."
FT /evidence="ECO:0000269|PubMed:26178373,
FT ECO:0000269|PubMed:28508064"
FT CONFLICT 30
FT /note="P -> T (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 443 AA; 49425 MW; 4969C0328A23DD88 CRC64;
MLPFASCLPG SLLLWAFLLL LLGAASPQDP EEPDSYTECT DGYEWDADSQ HCRDVNECLT
IPEACKGEMK CINHYGGYLC LPRSAAVISD LHGEGPPPPA AHAQQPNPCP QGYEPDEQES
CVDVDECTQA LHDCRPSQDC HNLPGSYQCT CPDGYRKIGP ECVDIDECRY RYCQHRCVNL
PGSFRCQCEP GFQLGPNNRS CVDVNECDMG APCEQRCFNS YGTFLCRCNQ GYELHRDGFS
CSDIDECGYS SYLCQYRCVN EPGRFSCHCP QGYQLLATRL CQDIDECETG AHQCSEAQTC
VNFHGGYRCV DTNRCVEPYV QVSDNRCLCP ASNPLCREQP SSIVHRYMSI TSERSVPADV
FQIQATSVYP GAYNAFQIRS GNTQGDFYIR QINNVSAMLV LARPVTGPRE YVLDLEMVTM
NSLMSYRASS VLRLTVFVGA YTF
