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 27-MAR-2024, entry version 185. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 GlyCosmos; Q9WVJ9; 2 sites, No reported glycans. DR GlyGen; Q9WVJ9; 2 sites. DR PhosphoSitePlus; Q9WVJ9; -. DR MaxQB; Q9WVJ9; -. DR PaxDb; 10090-ENSMUSP00000064719; -. DR ProteomicsDB; 271875; -. DR Pumba; Q9WVJ9; -. DR Antibodypedia; 16033; 415 antibodies from 33 providers. DR DNASU; 58859; -. DR Ensembl; ENSMUST00000165485.8; ENSMUSP00000133016.2; ENSMUSG00000024909.16. DR Ensembl; ENSMUST00000166303.9; ENSMUSP00000128827.3; ENSMUSG00000024909.16. DR GeneID; 58859; -. DR KEGG; mmu:58859; -. DR UCSC; uc008gdl.2; mouse. DR AGR; MGI:1891209; -. 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 OrthoDB; 19806at2759; -. DR PhylomeDB; Q9WVJ9; -. DR Reactome; R-MMU-2129379; Molecules associated with elastic fibres. DR BioGRID-ORCS; 58859; 7 hits in 76 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 211 other cell types or tissues. DR ExpressionAtlas; Q9WVJ9; baseline and differential. 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 CDD; cd00054; EGF_CA; 3. DR Gene3D; 2.10.25.10; Laminin; 6. DR InterPro; IPR026823; cEGF. DR InterPro; IPR001881; EGF-like_Ca-bd_dom. DR InterPro; IPR013032; EGF-like_CS. 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; EGF-CONTAINING FIBULIN-LIKE EXTRACELLULAR MATRIX PROTEIN 2; 1. DR PANTHER; PTHR24034; EGF-LIKE DOMAIN-CONTAINING PROTEIN; 1. DR Pfam; PF12662; cEGF; 2. DR Pfam; PF07645; EGF_CA; 3. DR Pfam; PF12661; hEGF; 1. DR PRINTS; PR00907; THRMBOMODULN. DR SMART; SM00181; EGF; 5. DR SMART; SM00179; EGF_CA; 6. DR SUPFAM; SSF57184; Growth factor receptor domain; 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. DR Genevisible; Q9WVJ9; MM. 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 //