FBLN4_HUMAN
ID FBLN4_HUMAN Reviewed; 443 AA.
AC O95967; A8K7R4; B3KM31; B3KQT1; O75967;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 20-MAR-2007, sequence version 3.
DT 03-AUG-2022, entry version 213.
DE RecName: Full=EGF-containing fibulin-like extracellular matrix protein 2 {ECO:0000305};
DE AltName: Full=Fibulin-4 {ECO:0000303|PubMed:10601734};
DE Short=FIBL-4;
DE AltName: Full=Protein UPH1;
DE Flags: Precursor;
GN Name=EFEMP2 {ECO:0000312|HGNC:HGNC:3219}; Synonyms=FBLN4;
GN ORFNames=UNQ200/PRO226;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT VAL-259.
RC TISSUE=Melanoma;
RX PubMed=10601734; DOI=10.1016/s0945-053x(99)00038-4;
RA Giltay R., Timpl R., Kostka G.;
RT "Sequence, recombinant expression and tissue localization of two novel
RT extracellular matrix proteins, fibulin-3 and fibulin-4.";
RL Matrix Biol. 18:469-480(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT VAL-259.
RA Zemel R., Shaul Y.;
RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT VAL-259.
RX PubMed=10982184; DOI=10.1007/s004390051011;
RA Katsanis N., Venable S., Smith J.R., Lupski J.R.;
RT "Isolation of a paralog of the Doyne honeycomb retinal dystrophy gene from
RT the multiple retinopathy critical region on 11q13.";
RL Hum. Genet. 106:66-72(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-259.
RC TISSUE=Embryo, and Synovium;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-259.
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-259.
RC TISSUE=Placenta;
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-259.
RC TISSUE=Brain;
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 [9]
RP PROTEIN SEQUENCE OF 24-31 AND 93-100, GLYCOSYLATION, CLEAVAGE BY MMP3;
RP MMP7; MMP9 AND MMP12, FUNCTION, AND SUBUNIT.
RX PubMed=23782690; DOI=10.1074/jbc.m112.439158;
RA Djokic J., Fagotto-Kaufmann C., Bartels R., Nelea V., Reinhardt D.P.;
RT "Fibulin-3, -4, and -5 are highly susceptible to proteolysis, interact with
RT cells and heparin, and form multimers.";
RL J. Biol. Chem. 288:22821-22835(2013).
RN [10]
RP PROTEIN SEQUENCE OF 88-94 AND 91-98, CHARACTERIZATION OF VARIANTS ARCL1B
RP LYS-57; LYS-126; TYR-267; CYS-279 AND THR-397, GLYCOSYLATION, SUBCELLULAR
RP LOCATION, FUNCTION, INTERACTION WITH LOX; LOXL1; LOXL2; LTBP1; LTBP3; LTBP4
RP AND TGFB1, AND CLEAVAGE BY ELANE; MMP2 AND MMP9.
RX PubMed=27339457; DOI=10.1016/j.matbio.2016.06.003;
RA Sasaki T., Hanisch F.G., Deutzmann R., Sakai L.Y., Sakuma T., Miyamoto T.,
RA Yamamoto T., Hannappel E., Chu M.L., Lanig H., von der Mark K.;
RT "Functional consequence of fibulin-4 missense mutations associated with
RT vascular and skeletal abnormalities and cutis laxa.";
RL Matrix Biol. 56:132-149(2016).
RN [11]
RP INTERACTION WITH FBN1.
RX PubMed=17255108; DOI=10.1074/jbc.m608204200;
RA El-Hallous E., Sasaki T., Hubmacher D., Getie M., Tiedemann K.,
RA Brinckmann J., Baetge B., Davis E.C., Reinhardt D.P.;
RT "Fibrillin-1 interactions with fibulins depend on the first hybrid domain
RT and provide an adaptor function to tropoelastin.";
RL J. Biol. Chem. 282:8935-8946(2007).
RN [12]
RP FUNCTION.
RX PubMed=18973305; DOI=10.1021/bi8005384;
RA Cirulis J.T., Bellingham C.M., Davis E.C., Hubmacher D., Reinhardt D.P.,
RA Mecham R.P., Keeley F.W.;
RT "Fibrillins, fibulins, and matrix-associated glycoprotein modulate the
RT kinetics and morphology of in vitro self-assembly of a recombinant elastin-
RT like polypeptide.";
RL Biochemistry 47:12601-12613(2008).
RN [13]
RP INTERACTION WITH FBN1.
RX PubMed=19349279; DOI=10.1074/jbc.m809348200;
RA Ono R.N., Sengle G., Charbonneau N.L., Carlberg V., Baechinger H.P.,
RA Sasaki T., Lee-Arteaga S., Zilberberg L., Rifkin D.B., Ramirez F.,
RA Chu M.L., Sakai L.Y.;
RT "Latent transforming growth factor beta-binding proteins and fibulins
RT compete for fibrillin-1 and exhibit exquisite specificities in binding
RT sites.";
RL J. Biol. Chem. 284:16872-16881(2009).
RN [14]
RP SUBUNIT, INTERACTION WITH ELN; LOX; FBLN5 AND FBN1, AND FUNCTION.
RX PubMed=19570982; DOI=10.1074/jbc.m109.019364;
RA Choudhury R., McGovern A., Ridley C., Cain S.A., Baldwin A., Wang M.C.,
RA Guo C., Mironov A. Jr., Drymoussi Z., Trump D., Shuttleworth A.,
RA Baldock C., Kielty C.M.;
RT "Differential regulation of elastic fiber formation by fibulin-4 and -5.";
RL J. Biol. Chem. 284:24553-24567(2009).
RN [15]
RP INTERACTION WITH LOX.
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 [16]
RP INTERACTION WITH PITX2.
RX PubMed=22919265;
RA Acharya M., Sharp M.W., Mirzayans F., Footz T., Huang L., Birdi C.,
RA Walter M.A.;
RT "Yeast two-hybrid analysis of a human trabecular meshwork cDNA library
RT identified EFEMP2 as a novel PITX2 interacting protein.";
RL Mol. Vis. 18:2182-2189(2012).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [18]
RP STRUCTURE BY NMR OF 54-123, AND DISULFIDE BONDS.
RG Northeast structural genomics consortium (NESG);
RT "Solution NMR structure of the EGF-like 1 domain of human fibulin-4.";
RL Submitted (JUL-2009) to the PDB data bank.
RN [19]
RP VARIANT ARCL1B LYS-57.
RX PubMed=16685658; DOI=10.1086/504304;
RA Hucthagowder V., Sausgruber N., Kim K.H., Angle B., Marmorstein L.Y.,
RA Urban Z.;
RT "Fibulin-4: a novel gene for an autosomal recessive cutis laxa syndrome.";
RL Am. J. Hum. Genet. 78:1075-1080(2006).
RN [20]
RP VARIANT ARCL1B CYS-279.
RX PubMed=17937443; DOI=10.1002/ajmg.a.31980;
RA Dasouki M., Markova D., Garola R., Sasaki T., Charbonneau N.L., Sakai L.Y.,
RA Chu M.L.;
RT "Compound heterozygous mutations in fibulin-4 causing neonatal lethal
RT pulmonary artery occlusion, aortic aneurysm, arachnodactyly, and mild cutis
RT laxa.";
RL Am. J. Med. Genet. A 143:2635-2641(2007).
RN [21]
RP VARIANT ARCL1B TYR-267.
RX PubMed=19664000; DOI=10.1111/j.1399-0004.2009.01204.x;
RA Hoyer J., Kraus C., Hammersen G., Geppert J.P., Rauch A.;
RT "Lethal cutis laxa with contractural arachnodactyly, overgrowth and soft
RT tissue bleeding due to a novel homozygous fibulin-4 gene mutation.";
RL Clin. Genet. 76:276-281(2009).
RN [22]
RP VARIANTS ARCL1B LYS-126; VAL-126 AND THR-397, CHARACTERIZATION OF VARIANTS
RP ARCL1B LYS-126 AND TYR-267, AND SUBCELLULAR LOCATION.
RX PubMed=20389311; DOI=10.1038/ejhg.2010.45;
RA Renard M., Holm T., Veith R., Callewaert B.L., Ades L.C., Baspinar O.,
RA Pickart A., Dasouki M., Hoyer J., Rauch A., Trapane P., Earing M.G.,
RA Coucke P.J., Sakai L.Y., Dietz H.C., De Paepe A.M., Loeys B.L.;
RT "Altered TGFbeta signaling and cardiovascular manifestations in patients
RT with autosomal recessive cutis laxa type I caused by fibulin-4
RT deficiency.";
RL Eur. J. Hum. Genet. 18:895-901(2010).
RN [23]
RP VARIANTS ARCL1B ALA-203 AND CYS-227.
RX PubMed=22943132; DOI=10.1186/1750-1172-7-61;
RA Kappanayil M., Nampoothiri S., Kannan R., Renard M., Coucke P., Malfait F.,
RA Menon S., Ravindran H.K., Kurup R., Faiyaz-Ul-Haque M., Kumar K.,
RA De Paepe A.;
RT "Characterization of a distinct lethal arteriopathy syndrome in twenty-two
RT infants associated with an identical, novel mutation in FBLN4 gene,
RT confirms fibulin-4 as a critical determinant of human vascular
RT elastogenesis.";
RL Orphanet J. Rare Dis. 7:61-61(2012).
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:27339457). In addition, is involved in the control of
CC collagen fibril assembly in tissue throught proteolytic activation of
CC LOX leading to cross- linking of collagen and elastin (By similarity).
CC Also promotes ELN coacervation and participates in the deposition of
CC ELN coacervates on to microfibrils but also regulates ELN
CC cross- linking through LOX interaction (PubMed:18973305,
CC PubMed:19570982). Moreover adheres to the cells through heparin binding
CC in a calcium-dependent manner and regulates vascularlar smooth muscle
CC cells proliferation through angiotensin signaling (PubMed:23782690).
CC {ECO:0000250|UniProtKB:Q9WVJ9, ECO:0000269|PubMed:18973305,
CC ECO:0000269|PubMed:19570982, ECO:0000269|PubMed:23782690,
CC ECO:0000269|PubMed:27339457}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (PubMed:19570982,
CC PubMed:23782690). Multimer; allows heparin binding (PubMed:23782690).
CC Monomer (By similarity). Interacts with FBN1 (via N-terminal domain);
CC this interaction inhibits EFEMP2 binding to LOX and ELN
CC (PubMed:17255108, PubMed:19349279, PubMed:19570982). Interacts with LOX
CC (via propeptide); this interaction is strong and facilitates formation
CC of ternary complexes with ELN during elastic fiber assembly; this
CC interaction limits interaction of EFEMP2 with FBLN5 (PubMed:19855011,
CC PubMed:19570982, PubMed:27339457). Interacts with PITX2
CC (PubMed:22919265). Interacts with ELN with moderate affinity; this
CC interaction regulates ELN self-assembly maturation stage
CC (PubMed:19570982). Interacts with FBLN5 with moderate affinity
CC (PubMed:19570982). Interacts with LOXL1 (via propeptide), LTBP1 and
CC TGFB1 stronger than with LOXL2 and LTBP3 (PubMed:27339457). Interacts
CC with PCOLCE (By similarity). Interacts with collagen type IV trimer
CC (COL4A1-COL4A1-COL4A2), NID2 and moderately with COL15A1-derived
CC endostatin (By similarity). Interacts with EMILIN1; this interaction
CC promotes the incorporation of EFEMP2 into the extracellular matrix (By
CC similarity). Interacts with LTBP4; the LTBP4 long form (LTBP4L) has a
CC stronger binding affinity than the LTBP4 short form and the LTBP4 long
CC form promotes fibrillar deposition of EFEMP2 (PubMed:27339457).
CC {ECO:0000250|UniProtKB:Q9WVJ9, ECO:0000269|PubMed:17255108,
CC ECO:0000269|PubMed:19349279, ECO:0000269|PubMed:19570982,
CC ECO:0000269|PubMed:19855011, ECO:0000269|PubMed:22919265,
CC ECO:0000269|PubMed:23782690, ECO:0000269|PubMed:27339457}.
CC -!- INTERACTION:
CC O95967; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-743414, EBI-10173507;
CC O95967; Q9Y4X0: AMMECR1; NbExp=3; IntAct=EBI-743414, EBI-8583355;
CC O95967; Q9Y4X0-3: AMMECR1; NbExp=3; IntAct=EBI-743414, EBI-12823597;
CC O95967; Q9NYG5-2: ANAPC11; NbExp=3; IntAct=EBI-743414, EBI-12224467;
CC O95967; Q9BXS5: AP1M1; NbExp=3; IntAct=EBI-743414, EBI-541426;
CC O95967; Q96B67: ARRDC3; NbExp=3; IntAct=EBI-743414, EBI-2875665;
CC O95967; P54259: ATN1; NbExp=3; IntAct=EBI-743414, EBI-945980;
CC O95967; P54253: ATXN1; NbExp=8; IntAct=EBI-743414, EBI-930964;
CC O95967; P46379-2: BAG6; NbExp=3; IntAct=EBI-743414, EBI-10988864;
CC O95967; P01024: C3; NbExp=3; IntAct=EBI-743414, EBI-905851;
CC O95967; Q7Z6I8: C5orf24; NbExp=3; IntAct=EBI-743414, EBI-9995695;
CC O95967; Q6NVV7: CDPF1; NbExp=3; IntAct=EBI-743414, EBI-2802782;
CC O95967; Q16740: CLPP; NbExp=3; IntAct=EBI-743414, EBI-1056029;
CC O95967; Q8NE01: CNNM3; NbExp=3; IntAct=EBI-743414, EBI-741032;
CC O95967; Q02930-3: CREB5; NbExp=8; IntAct=EBI-743414, EBI-10192698;
CC O95967; P42830: CXCL5; NbExp=3; IntAct=EBI-743414, EBI-12175919;
CC O95967; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-743414, EBI-3867333;
CC O95967; Q18PE1: DOK7; NbExp=3; IntAct=EBI-743414, EBI-3046647;
CC O95967; P15502: ELN; NbExp=5; IntAct=EBI-743414, EBI-1222108;
CC O95967; Q9BQ89: FAM110A; NbExp=3; IntAct=EBI-743414, EBI-1752811;
CC O95967; Q5TZK3: FAM74A6; NbExp=3; IntAct=EBI-743414, EBI-10247271;
CC O95967; Q86YD7: FAM90A1; NbExp=3; IntAct=EBI-743414, EBI-6658203;
CC O95967; Q9UBX5: FBLN5; NbExp=3; IntAct=EBI-743414, EBI-947897;
CC O95967; P35555: FBN1; NbExp=3; IntAct=EBI-743414, EBI-2505934;
CC O95967; Q969U6: FBXW5; NbExp=3; IntAct=EBI-743414, EBI-741068;
CC O95967; Q9C0B1-2: FTO; NbExp=3; IntAct=EBI-743414, EBI-18138793;
CC O95967; P56524: HDAC4; NbExp=3; IntAct=EBI-743414, EBI-308629;
CC O95967; Q96JK4-2: HHIPL1; NbExp=3; IntAct=EBI-743414, EBI-12083878;
CC O95967; P37235: HPCAL1; NbExp=3; IntAct=EBI-743414, EBI-749311;
CC O95967; Q9H2F3: HSD3B7; NbExp=3; IntAct=EBI-743414, EBI-3918847;
CC O95967; Q96MM6: HSPA12B; NbExp=3; IntAct=EBI-743414, EBI-10291310;
CC O95967; P24592: IGFBP6; NbExp=3; IntAct=EBI-743414, EBI-947015;
CC O95967; Q14005-2: IL16; NbExp=3; IntAct=EBI-743414, EBI-17178971;
CC O95967; Q0VD86: INCA1; NbExp=3; IntAct=EBI-743414, EBI-6509505;
CC O95967; P18084: ITGB5; NbExp=3; IntAct=EBI-743414, EBI-1223434;
CC O95967; Q13351: KLF1; NbExp=3; IntAct=EBI-743414, EBI-8284732;
CC O95967; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-743414, EBI-10171774;
CC O95967; Q8IUC1: KRTAP11-1; NbExp=3; IntAct=EBI-743414, EBI-1052037;
CC O95967; P59991: KRTAP12-2; NbExp=3; IntAct=EBI-743414, EBI-10176379;
CC O95967; Q3SY46: KRTAP13-3; NbExp=5; IntAct=EBI-743414, EBI-10241252;
CC O95967; Q3LI72: KRTAP19-5; NbExp=3; IntAct=EBI-743414, EBI-1048945;
CC O95967; Q6PEX3: KRTAP26-1; NbExp=3; IntAct=EBI-743414, EBI-3957672;
CC O95967; Q9BYR7: KRTAP3-2; NbExp=3; IntAct=EBI-743414, EBI-751260;
CC O95967; P52954: LBX1; NbExp=3; IntAct=EBI-743414, EBI-20141748;
CC O95967; Q5T7P2: LCE1A; NbExp=3; IntAct=EBI-743414, EBI-11962058;
CC O95967; Q5T751: LCE1C; NbExp=3; IntAct=EBI-743414, EBI-12224199;
CC O95967; Q5T753: LCE1E; NbExp=3; IntAct=EBI-743414, EBI-11955335;
CC O95967; Q5TA81: LCE2C; NbExp=3; IntAct=EBI-743414, EBI-11973993;
CC O95967; Q5TA82: LCE2D; NbExp=3; IntAct=EBI-743414, EBI-10246750;
CC O95967; Q5TA76: LCE3A; NbExp=3; IntAct=EBI-743414, EBI-9394625;
CC O95967; Q5T5A8: LCE3C; NbExp=3; IntAct=EBI-743414, EBI-10245291;
CC O95967; Q9BYE3: LCE3D; NbExp=3; IntAct=EBI-743414, EBI-6658837;
CC O95967; Q5T5B0: LCE3E; NbExp=3; IntAct=EBI-743414, EBI-10245456;
CC O95967; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-743414, EBI-739832;
CC O95967; P28300: LOX; NbExp=7; IntAct=EBI-743414, EBI-3893481;
CC O95967; Q99750: MDFI; NbExp=3; IntAct=EBI-743414, EBI-724076;
CC O95967; P50222: MEOX2; NbExp=3; IntAct=EBI-743414, EBI-748397;
CC O95967; P52815: MRPL12; NbExp=3; IntAct=EBI-743414, EBI-358272;
CC O95967; P50539-3: MXI1; NbExp=3; IntAct=EBI-743414, EBI-10211940;
CC O95967; Q6NSM0: NR1D2; NbExp=3; IntAct=EBI-743414, EBI-10250949;
CC O95967; Q9P121-3: NTM; NbExp=3; IntAct=EBI-743414, EBI-12027160;
CC O95967; Q7Z417: NUFIP2; NbExp=6; IntAct=EBI-743414, EBI-1210753;
CC O95967; P32242: OTX1; NbExp=3; IntAct=EBI-743414, EBI-740446;
CC O95967; Q99572: P2RX7; NbExp=3; IntAct=EBI-743414, EBI-1753251;
CC O95967; P78337: PITX1; NbExp=3; IntAct=EBI-743414, EBI-748265;
CC O95967; O75360: PROP1; NbExp=3; IntAct=EBI-743414, EBI-9027467;
CC O95967; Q8WWY3: PRPF31; NbExp=6; IntAct=EBI-743414, EBI-1567797;
CC O95967; B1ATL7: PRR32; NbExp=3; IntAct=EBI-743414, EBI-18587059;
CC O95967; P43115-12: PTGER3; NbExp=3; IntAct=EBI-743414, EBI-10234038;
CC O95967; Q12829: RAB40B; NbExp=3; IntAct=EBI-743414, EBI-3915431;
CC O95967; Q9NYW8: RBAK; NbExp=3; IntAct=EBI-743414, EBI-1210429;
CC O95967; P10745: RBP3; NbExp=3; IntAct=EBI-743414, EBI-12806054;
CC O95967; Q93062: RBPMS; NbExp=3; IntAct=EBI-743414, EBI-740322;
CC O95967; Q9BQY4: RHOXF2; NbExp=2; IntAct=EBI-743414, EBI-372094;
CC O95967; Q8WVD3: RNF138; NbExp=3; IntAct=EBI-743414, EBI-749039;
CC O95967; O43765: SGTA; NbExp=7; IntAct=EBI-743414, EBI-347996;
CC O95967; Q96EQ0: SGTB; NbExp=8; IntAct=EBI-743414, EBI-744081;
CC O95967; O15375: SLC16A5; NbExp=3; IntAct=EBI-743414, EBI-12874738;
CC O95967; Q9UHI7-3: SLC23A1; NbExp=3; IntAct=EBI-743414, EBI-11998660;
CC O95967; Q6ZT89-3: SLC25A48; NbExp=3; IntAct=EBI-743414, EBI-12065614;
CC O95967; Q96E40: SPACA9; NbExp=3; IntAct=EBI-743414, EBI-722584;
CC O95967; Q86W54-2: SPATA24; NbExp=3; IntAct=EBI-743414, EBI-12041693;
CC O95967; A0A024R4B0: SPATA3; NbExp=5; IntAct=EBI-743414, EBI-14123856;
CC O95967; Q6RVD6: SPATA8; NbExp=3; IntAct=EBI-743414, EBI-8635958;
CC O95967; Q9C004: SPRY4; NbExp=3; IntAct=EBI-743414, EBI-354861;
CC O95967; O75716: STK16; NbExp=6; IntAct=EBI-743414, EBI-749295;
CC O95967; Q9BT49: THAP7; NbExp=3; IntAct=EBI-743414, EBI-741350;
CC O95967; Q08117-2: TLE5; NbExp=6; IntAct=EBI-743414, EBI-11741437;
CC O95967; O43711: TLX3; NbExp=3; IntAct=EBI-743414, EBI-3939165;
CC O95967; Q96RU7: TRIB3; NbExp=3; IntAct=EBI-743414, EBI-492476;
CC O95967; Q8IWZ5: TRIM42; NbExp=5; IntAct=EBI-743414, EBI-5235829;
CC O95967; Q9UMX0: UBQLN1; NbExp=5; IntAct=EBI-743414, EBI-741480;
CC O95967; Q9UMX0-2: UBQLN1; NbExp=3; IntAct=EBI-743414, EBI-10173939;
CC O95967; Q9UK80: USP21; NbExp=3; IntAct=EBI-743414, EBI-373242;
CC O95967; Q14585: ZNF345; NbExp=3; IntAct=EBI-743414, EBI-2818408;
CC O95967; Q96NG5: ZNF558; NbExp=3; IntAct=EBI-743414, EBI-373363;
CC O95967; Q68EA5: ZNF57; NbExp=3; IntAct=EBI-743414, EBI-8490788;
CC O95967; Q9P0T4: ZNF581; NbExp=3; IntAct=EBI-743414, EBI-745520;
CC O95967; Q96SQ5: ZNF587; NbExp=3; IntAct=EBI-743414, EBI-6427977;
CC O95967; Q9BS34: ZNF670; NbExp=3; IntAct=EBI-743414, EBI-745276;
CC O95967; Q32M78: ZNF699; NbExp=3; IntAct=EBI-743414, EBI-10217363;
CC O95967; Q9H5H4: ZNF768; NbExp=3; IntAct=EBI-743414, EBI-1210580;
CC O95967; Q6NX45: ZNF774; NbExp=3; IntAct=EBI-743414, EBI-10251462;
CC O95967; Q96EG3: ZNF837; NbExp=3; IntAct=EBI-743414, EBI-11962574;
CC O95967; P09022: Hoxa1; Xeno; NbExp=3; IntAct=EBI-743414, EBI-3957603;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000269|PubMed:20389311, ECO:0000269|PubMed:27339457}.
CC Secreted, extracellular space, extracellular matrix, basement membrane
CC {ECO:0000250|UniProtKB:Q9WVJ9}. Note=Localizes on the microfibrils
CC surrounding ELN cores. {ECO:0000250|UniProtKB:Q9WVJ9}.
CC -!- PTM: N-glycosylated; contains mostly complex-type glycans
CC (PubMed:27339457, PubMed:23782690). Not O-glycosylated
CC (PubMed:27339457). {ECO:0000269|PubMed:23782690,
CC ECO:0000269|PubMed:27339457}.
CC -!- PTM: Cleaved by ELANE; produces a 50-55 kDa fragment (PubMed:27339457).
CC Cleaved by MMP2 and MMP9; produces several fragments (PubMed:27339457).
CC {ECO:0000269|PubMed:27339457}.
CC -!- DISEASE: Cutis laxa, autosomal recessive, 1B (ARCL1B) [MIM:614437]: A
CC connective tissue disorder characterized by loose, hyperextensible skin
CC with decreased resilience and elasticity leading to a premature aged
CC appearance. Face, hands, feet, joints, and torso may be differentially
CC affected. The clinical spectrum of autosomal recessive cutis laxa is
CC highly heterogeneous with respect to organ involvement and severity.
CC ARCL1B features include emphysema, lethal pulmonary artery occlusion,
CC aortic aneurysm, cardiopulmonary insufficiency, birth fractures,
CC arachnodactyly, and fragility of blood vessels.
CC {ECO:0000269|PubMed:16685658, ECO:0000269|PubMed:17937443,
CC ECO:0000269|PubMed:19664000, ECO:0000269|PubMed:20389311,
CC ECO:0000269|PubMed:22943132, ECO:0000269|PubMed:27339457}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the fibulin family. {ECO:0000305}.
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DR EMBL; AJ132819; CAA10791.2; -; mRNA.
DR EMBL; AF093119; AAC62108.1; -; mRNA.
DR EMBL; AF109121; AAF65188.1; -; mRNA.
DR EMBL; AK000980; BAG50843.1; -; mRNA.
DR EMBL; AK292079; BAF84768.1; -; mRNA.
DR EMBL; AY358899; AAQ89258.1; -; mRNA.
DR EMBL; AK075453; BAG52143.1; -; mRNA.
DR EMBL; AP001201; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC010456; AAH10456.1; -; mRNA.
DR CCDS; CCDS8116.1; -.
DR RefSeq; NP_058634.4; NM_016938.4.
DR PDB; 2KL7; NMR; -; A=54-123.
DR PDBsum; 2KL7; -.
DR AlphaFoldDB; O95967; -.
DR BMRB; O95967; -.
DR SMR; O95967; -.
DR BioGRID; 119026; 135.
DR DIP; DIP-34518N; -.
DR IntAct; O95967; 159.
DR MINT; O95967; -.
DR STRING; 9606.ENSP00000309953; -.
DR GlyConnect; 1199; 7 N-Linked glycans (1 site).
DR GlyGen; O95967; 2 sites, 6 N-linked glycans (1 site).
DR iPTMnet; O95967; -.
DR PhosphoSitePlus; O95967; -.
DR BioMuta; EFEMP2; -.
DR jPOST; O95967; -.
DR MassIVE; O95967; -.
DR PaxDb; O95967; -.
DR PeptideAtlas; O95967; -.
DR PRIDE; O95967; -.
DR ProteomicsDB; 51148; -.
DR Antibodypedia; 16033; 391 antibodies from 33 providers.
DR DNASU; 30008; -.
DR Ensembl; ENST00000307998.11; ENSP00000309953.6; ENSG00000172638.13.
DR Ensembl; ENST00000531972.5; ENSP00000435295.1; ENSG00000172638.13.
DR GeneID; 30008; -.
DR KEGG; hsa:30008; -.
DR MANE-Select; ENST00000307998.11; ENSP00000309953.6; NM_016938.5; NP_058634.4.
DR UCSC; uc001ofy.5; human.
DR CTD; 30008; -.
DR DisGeNET; 30008; -.
DR GeneCards; EFEMP2; -.
DR GeneReviews; EFEMP2; -.
DR HGNC; HGNC:3219; EFEMP2.
DR HPA; ENSG00000172638; Low tissue specificity.
DR MalaCards; EFEMP2; -.
DR MIM; 604633; gene.
DR MIM; 614437; phenotype.
DR neXtProt; NX_O95967; -.
DR OpenTargets; ENSG00000172638; -.
DR Orphanet; 90349; Autosomal recessive cutis laxa type 1.
DR Orphanet; 314718; Lethal arteriopathy syndrome due to fibulin-4 deficiency.
DR PharmGKB; PA27653; -.
DR VEuPathDB; HostDB:ENSG00000172638; -.
DR eggNOG; KOG1217; Eukaryota.
DR GeneTree; ENSGT00940000159437; -.
DR HOGENOM; CLU_004826_0_1_1; -.
DR InParanoid; O95967; -.
DR OMA; DPLTEHC; -.
DR OrthoDB; 1174178at2759; -.
DR PhylomeDB; O95967; -.
DR TreeFam; TF317514; -.
DR PathwayCommons; O95967; -.
DR Reactome; R-HSA-2129379; Molecules associated with elastic fibres.
DR SignaLink; O95967; -.
DR SIGNOR; O95967; -.
DR BioGRID-ORCS; 30008; 7 hits in 1071 CRISPR screens.
DR ChiTaRS; EFEMP2; human.
DR EvolutionaryTrace; O95967; -.
DR GeneWiki; EFEMP2; -.
DR GenomeRNAi; 30008; -.
DR Pharos; O95967; Tbio.
DR PRO; PR:O95967; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; O95967; protein.
DR Bgee; ENSG00000172638; Expressed in stromal cell of endometrium and 197 other tissues.
DR ExpressionAtlas; O95967; baseline and differential.
DR Genevisible; O95967; HS.
DR GO; GO:0005604; C:basement membrane; ISS:UniProtKB.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0071953; C:elastic fiber; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0031012; C:extracellular matrix; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:1903561; C:extracellular vesicle; HDA:UniProtKB.
DR GO; GO:0001527; C:microfibril; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005201; F:extracellular matrix structural constituent; TAS:ProtInc.
DR GO; GO:0008201; F:heparin binding; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA: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; IMP: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; IMP: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 1: Evidence at protein level;
KW 3D-structure; Basement membrane; Calcium; Direct protein sequencing;
KW Disease variant; Disulfide bond; EGF-like domain; Extracellular matrix;
KW Glycoprotein; Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000269|PubMed:23782690"
FT CHAIN 24..443
FT /note="EGF-containing fibulin-like extracellular matrix
FT protein 2"
FT /id="PRO_0000007575"
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:0000269|PubMed:27339457"
FT SITE 90..91
FT /note="Cleavage; by MMP2, MMP3, MMP7, MMP9, MMP12"
FT /evidence="ECO:0000269|PubMed:23782690,
FT ECO:0000269|PubMed:27339457"
FT SITE 92..93
FT /note="Cleavage"
FT /evidence="ECO:0000269|PubMed:23782690"
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 ECO:0000269|Ref.18"
FT DISULFID 65..80
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|Ref.18"
FT DISULFID 71..109
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|Ref.18"
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 VARIANT 57
FT /note="E -> K (in ARCL1B; does not affect secretion;
FT decreased elastic fiber assembly; loss of interaction with
FT collagen type IV trimer, FBN1, highly glycosylated form of
FT LOX and LTBP1; Does not affect interaction with LOX when
FT LOX is non-glycosylated; proteolyzed by PLG;
FT dbSNP:rs119489101)"
FT /evidence="ECO:0000269|PubMed:16685658,
FT ECO:0000269|PubMed:27339457"
FT /id="VAR_027019"
FT VARIANT 126
FT /note="E -> K (in ARCL1B; slightly decreased protein
FT abundance in patient dermal fibroblasts; increased
FT transforming growth factor beta receptor signaling pathway
FT in patient fibroblasts; strongly decreased secretion;
FT decreased elastic fiber assembly; loss of interaction with
FT collagen type IV trimer, FBN1 and LTBP1; decreased
FT interaction with LOXL2; new fragments proteolyzed by ELANE;
FT new one fragment proteolyzed by MMP2)"
FT /evidence="ECO:0000269|PubMed:20389311,
FT ECO:0000269|PubMed:27339457"
FT /id="VAR_084029"
FT VARIANT 126
FT /note="E -> V (in ARCL1B)"
FT /evidence="ECO:0000269|PubMed:20389311"
FT /id="VAR_084030"
FT VARIANT 203
FT /note="D -> A (in ARCL1B)"
FT /evidence="ECO:0000269|PubMed:22943132"
FT /id="VAR_084031"
FT VARIANT 227
FT /note="R -> C (in ARCL1B)"
FT /evidence="ECO:0000269|PubMed:22943132"
FT /id="VAR_084032"
FT VARIANT 259
FT /note="I -> V (in dbSNP:rs601314)"
FT /evidence="ECO:0000269|PubMed:10601734,
FT ECO:0000269|PubMed:10982184, ECO:0000269|PubMed:12975309,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:16303743, ECO:0000269|Ref.2"
FT /id="VAR_027020"
FT VARIANT 267
FT /note="C -> Y (in ARCL1B; loss of protein expression in
FT patient dermal fibroblasts; increased transforming growth
FT factor beta receptor signaling pathway in patient
FT fibroblasts; loss of protein expression; strongly decreased
FT secretion; dbSNP:rs193302866)"
FT /evidence="ECO:0000269|PubMed:19664000,
FT ECO:0000269|PubMed:20389311, ECO:0000269|PubMed:27339457"
FT /id="VAR_067069"
FT VARIANT 279
FT /note="R -> C (in ARCL1B; loss of secretion;
FT dbSNP:rs119489102)"
FT /evidence="ECO:0000269|PubMed:17937443,
FT ECO:0000269|PubMed:20389311, ECO:0000269|PubMed:27339457"
FT /id="VAR_067070"
FT VARIANT 397
FT /note="A -> T (in ARCL1B; increased N-glycosylation;
FT introduced an extra O-glycosylation site; does not affect
FT secretion; decreased elastic fiber assembly; decreased
FT interaction with collagen type IV trimer, FBN1, ELN, LTBP1,
FT LOXL1 and LOXL2; new fragments proteolyzed by ELANE)"
FT /evidence="ECO:0000269|PubMed:20389311,
FT ECO:0000269|PubMed:27339457"
FT /id="VAR_084033"
FT CONFLICT 5
FT /note="A -> T (in Ref. 1; CAA10791)"
FT /evidence="ECO:0000305"
FT CONFLICT 24..27
FT /note="SASP -> APLA (in Ref. 9; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 44..51
FT /note="EWDPDSQH -> TQTAN (in Ref. 2; AAC62108)"
FT /evidence="ECO:0000305"
FT CONFLICT 46
FT /note="D -> G (in Ref. 4; BAF84768)"
FT /evidence="ECO:0000305"
FT CONFLICT 96
FT /note="P -> L (in Ref. 4; BAG50843)"
FT /evidence="ECO:0000305"
FT CONFLICT 103..111
FT /note="AQHPNPCPP -> VNTQPLPT (in Ref. 2; AAC62108)"
FT /evidence="ECO:0000305"
FT CONFLICT 294
FT /note="C -> W (in Ref. 2; AAC62108)"
FT /evidence="ECO:0000305"
FT CONFLICT 354..356
FT /note="RSV -> AER (in Ref. 2; AAC62108)"
FT /evidence="ECO:0000305"
FT CONFLICT 355
FT /note="S -> R (in Ref. 3; AAF65188)"
FT /evidence="ECO:0000305"
FT STRAND 68..73
FT /evidence="ECO:0007829|PDB:2KL7"
FT STRAND 78..82
FT /evidence="ECO:0007829|PDB:2KL7"
FT STRAND 113..116
FT /evidence="ECO:0007829|PDB:2KL7"
SQ SEQUENCE 443 AA; 49405 MW; 9315CFBBAA0FD3A7 CRC64;
MLPCASCLPG SLLLWALLLL LLGSASPQDS EEPDSYTECT DGYEWDPDSQ HCRDVNECLT
IPEACKGEMK CINHYGGYLC LPRSAAVIND LHGEGPPPPV PPAQHPNPCP PGYEPDDQDS
CVDVDECAQA LHDCRPSQDC HNLPGSYQCT CPDGYRKIGP ECVDIDECRY RYCQHRCVNL
PGSFRCQCEP GFQLGPNNRS CVDVNECDMG APCEQRCFNS YGTFLCRCHQ GYELHRDGFS
CSDIDECSYS SYLCQYRCIN EPGRFSCHCP QGYQLLATRL CQDIDECESG AHQCSEAQTC
VNFHGGYRCV DTNRCVEPYI QVSENRCLCP ASNPLCREQP SSIVHRYMTI TSERSVPADV
FQIQATSVYP GAYNAFQIRA GNSQGDFYIR QINNVSAMLV LARPVTGPRE YVLDLEMVTM
NSLMSYRASS VLRLTVFVGA YTF
