RELN_HUMAN
ID RELN_HUMAN Reviewed; 3460 AA.
AC P78509; A4D0P9; A4D0Q0; Q86UJ0; Q86UJ8; Q8NDV0; Q9UDQ2;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 3.
DT 03-AUG-2022, entry version 200.
DE RecName: Full=Reelin;
DE EC=3.4.21.-;
DE Flags: Precursor;
GN Name=RELN;
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] (ISOFORM 1).
RX PubMed=9049633; DOI=10.1101/gr.7.2.157;
RA DeSilva U., D'Arcangelo G., Braden V.V., Chen J., Miao G.G., Curran T.,
RA Green E.D.;
RT "The human reelin gene: isolation, sequencing, and mapping on chromosome
RT 7.";
RL Genome Res. 7:157-164(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [4]
RP ALTERNATIVE SPLICING.
RX PubMed=10328932; DOI=10.1006/exnr.1999.7019;
RA Lambert de Rouvroit C., Bernier B., Royaux I., de Bergeyck V.,
RA Goffinet A.M.;
RT "Evolutionarily conserved, alternative splicing of reelin during brain
RT development.";
RL Exp. Neurol. 156:229-238(1999).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=9861036; DOI=10.1073/pnas.95.26.15718;
RA Impagnatiello F., Guidotti A.R., Pesold C., Dwivedi Y., Caruncho H.,
RA Pisu M.G., Uzunov D.P., Smalheiser N.R., Davis J.M., Pandey G.N.,
RA Pappas G.D., Tueting P., Sharma R.P., Costa E.;
RT "A decrease of reelin expression as a putative vulnerability factor in
RT schizophrenia.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:15718-15723(1998).
RN [6]
RP INVOLVEMENT IN LIS2.
RX PubMed=10973257; DOI=10.1038/79246;
RA Hong S.E., Shugart Y.Y., Huang D.T., Shahwan S.A., Grant P.E.,
RA Hourihane J.O.B., Martin N.D.T., Walsh C.A.;
RT "Autosomal recessive lissencephaly with cerebellar hypoplasia is associated
RT with human RELN mutations.";
RL Nat. Genet. 26:93-96(2000).
RN [7]
RP ERRATUM OF PUBMED:10973257.
RA Hong S.E., Shugart Y.Y., Huang D.T., Shahwan S.A., Grant P.E.,
RA Hourihane J.O.B., Martin N.D.T., Walsh C.A.;
RL Nat. Genet. 27:225-225(2001).
RN [8]
RP POLYMORPHISM.
RX PubMed=11317216; DOI=10.1038/sj.mp.4000850;
RA Persico A.M., D'Agruma L., Maiorano N., Totaro A., Militerni R.,
RA Bravaccio C., Wassink T.H., Schneider C., Melmed R., Trillo S.,
RA Montecchi F., Palermo M., Pascucci T., Puglisi-Allegra S., Reichelt K.-L.,
RA Conciatori M., Marino R., Quattrocchi C.C., Baldi A., Zelante L.,
RA Gasparini P., Keller F.;
RT "Reelin gene alleles and haplotypes as a factor predisposing to autistic
RT disorder.";
RL Mol. Psychiatry 6:150-159(2001).
RN [9]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-305; ASN-1920 AND ASN-3015.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [10]
RP INVOLVEMENT IN ETL7, AND VARIANTS ETL7 LEU-672; CYS-723; GLY-763; ASN-798;
RP LEU-844; CYS-2783 AND LYS-3176.
RX PubMed=26046367; DOI=10.1016/j.ajhg.2015.04.020;
RA Dazzo E., Fanciulli M., Serioli E., Minervini G., Pulitano P., Binelli S.,
RA Di Bonaventura C., Luisi C., Pasini E., Striano S., Striano P., Coppola G.,
RA Chiavegato A., Radovic S., Spadotto A., Uzzau S., La Neve A.,
RA Giallonardo A.T., Mecarelli O., Tosatto S.C., Ottman R., Michelucci R.,
RA Nobile C.;
RT "Heterozygous reelin mutations cause autosomal-dominant lateral temporal
RT epilepsy.";
RL Am. J. Hum. Genet. 96:992-1000(2015).
CC -!- FUNCTION: Extracellular matrix serine protease that plays a role in
CC layering of neurons in the cerebral cortex and cerebellum. Regulates
CC microtubule function in neurons and neuronal migration. Affects
CC migration of sympathetic preganglionic neurons in the spinal cord,
CC where it seems to act as a barrier to neuronal migration. Enzymatic
CC activity is important for the modulation of cell adhesion. Binding to
CC the extracellular domains of lipoprotein receptors VLDLR and
CC LRP8/APOER2 induces tyrosine phosphorylation of DAB1 and modulation of
CC TAU phosphorylation (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Oligomer of disulfide-linked homodimers. Binds to the
CC ectodomains of VLDLR and LRP8/APOER2 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P78509-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P78509-2; Sequence=VSP_005575;
CC Name=3;
CC IsoId=P78509-3; Sequence=VSP_005576;
CC -!- TISSUE SPECIFICITY: Abundantly produced during brain ontogenesis by the
CC Cajal-Retzius cells and other pioneer neurons located in the
CC telencephalic marginal zone and by granule cells of the external
CC granular layer of the cerebellum. In adult brain, preferentially
CC expressed in GABAergic interneurons of prefrontal cortices, temporal
CC cortex, hippocampus and glutamatergic granule cells of cerebellum.
CC Expression is reduced to about 50% in patients with schizophrenia. Also
CC expressed in fetal and adult liver. {ECO:0000269|PubMed:9861036}.
CC -!- DEVELOPMENTAL STAGE: Expressed in fetal and postnatal brain and liver.
CC Expression in postnatal human brain is high in the cerebellum.
CC -!- DOMAIN: The basic C-terminal region is essential for secretion.
CC {ECO:0000250}.
CC -!- POLYMORPHISM: A polymorphic GGC triplet repeat located in the 5'-UTR
CC region of RELN gene, which harbors in the normal population 8 to 10
CC repeats, is significantly increased in autistic patients to carry 4 to
CC 23 additional repeats. {ECO:0000269|PubMed:11317216}.
CC -!- DISEASE: Lissencephaly 2 (LIS2) [MIM:257320]: A classic type
CC lissencephaly associated with ataxia, intellectual disability, seizures
CC and abnormalities of the cerebellum, hippocampus and brainstem.
CC {ECO:0000269|PubMed:10973257}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Epilepsy, familial temporal lobe, 7 (ETL7) [MIM:616436]: A
CC focal form of epilepsy characterized by recurrent seizures that arise
CC from foci within the temporal lobe. Seizures are usually accompanied by
CC sensory symptoms, most often auditory in nature.
CC {ECO:0000269|PubMed:26046367}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the reelin family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Reelin entry;
CC URL="https://en.wikipedia.org/wiki/Reelin";
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DR EMBL; U79716; AAC51105.1; -; mRNA.
DR EMBL; AC002067; AAM49151.1; -; Genomic_DNA.
DR EMBL; AC006981; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC073208; AAP22355.1; -; Genomic_DNA.
DR EMBL; AC005101; AAP22330.1; -; Genomic_DNA.
DR EMBL; AC000121; AAB46357.2; -; Genomic_DNA.
DR EMBL; AC006316; AAD29127.1; -; Genomic_DNA.
DR EMBL; AC005064; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH236947; EAL24410.1; -; Genomic_DNA.
DR EMBL; CH236947; EAL24411.1; -; Genomic_DNA.
DR CCDS; CCDS34722.1; -. [P78509-2]
DR CCDS; CCDS47680.1; -. [P78509-1]
DR RefSeq; NP_005036.2; NM_005045.3. [P78509-1]
DR RefSeq; NP_774959.1; NM_173054.2. [P78509-2]
DR SMR; P78509; -.
DR BioGRID; 111630; 15.
DR ComplexPortal; CPX-4424; Reelin complex.
DR IntAct; P78509; 1.
DR STRING; 9606.ENSP00000392423; -.
DR GlyConnect; 1972; 11 N-Linked glycans (6 sites).
DR GlyGen; P78509; 21 sites, 11 N-linked glycans (6 sites), 2 O-linked glycans (1 site).
DR iPTMnet; P78509; -.
DR PhosphoSitePlus; P78509; -.
DR BioMuta; RELN; -.
DR DMDM; 296452988; -.
DR MassIVE; P78509; -.
DR MaxQB; P78509; -.
DR PaxDb; P78509; -.
DR PeptideAtlas; P78509; -.
DR PRIDE; P78509; -.
DR ProteomicsDB; 57628; -. [P78509-1]
DR ProteomicsDB; 57629; -. [P78509-2]
DR ProteomicsDB; 57630; -. [P78509-3]
DR Antibodypedia; 3876; 229 antibodies from 28 providers.
DR DNASU; 5649; -.
DR Ensembl; ENST00000343529.9; ENSP00000345694.5; ENSG00000189056.15. [P78509-2]
DR Ensembl; ENST00000428762.6; ENSP00000392423.1; ENSG00000189056.15. [P78509-1]
DR GeneID; 5649; -.
DR KEGG; hsa:5649; -.
DR MANE-Select; ENST00000428762.6; ENSP00000392423.1; NM_005045.4; NP_005036.2.
DR UCSC; uc010liz.3; human. [P78509-1]
DR CTD; 5649; -.
DR DisGeNET; 5649; -.
DR GeneCards; RELN; -.
DR GeneReviews; RELN; -.
DR HGNC; HGNC:9957; RELN.
DR HPA; ENSG00000189056; Tissue enriched (brain).
DR MalaCards; RELN; -.
DR MIM; 257320; phenotype.
DR MIM; 600514; gene.
DR MIM; 616436; phenotype.
DR neXtProt; NX_P78509; -.
DR OpenTargets; ENSG00000189056; -.
DR Orphanet; 101046; Autosomal dominant epilepsy with auditory features.
DR Orphanet; 89844; Lissencephaly syndrome, Norman-Roberts type.
DR PharmGKB; PA34323; -.
DR VEuPathDB; HostDB:ENSG00000189056; -.
DR eggNOG; ENOG502QSIP; Eukaryota.
DR GeneTree; ENSGT00580000081623; -.
DR HOGENOM; CLU_000468_0_0_1; -.
DR InParanoid; P78509; -.
DR OMA; MGGGDCD; -.
DR OrthoDB; 9177at2759; -.
DR PhylomeDB; P78509; -.
DR TreeFam; TF106479; -.
DR PathwayCommons; P78509; -.
DR Reactome; R-HSA-8866376; Reelin signalling pathway.
DR SignaLink; P78509; -.
DR SIGNOR; P78509; -.
DR BioGRID-ORCS; 5649; 7 hits in 1078 CRISPR screens.
DR ChiTaRS; RELN; human.
DR GeneWiki; Reelin; -.
DR GenomeRNAi; 5649; -.
DR Pharos; P78509; Tbio.
DR PRO; PR:P78509; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; P78509; protein.
DR Bgee; ENSG00000189056; Expressed in olfactory bulb and 185 other tissues.
DR ExpressionAtlas; P78509; baseline and differential.
DR Genevisible; P78509; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0031012; C:extracellular matrix; IEA:Ensembl.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IEA:GOC.
DR GO; GO:0110157; C:reelin complex; IDA:ComplexPortal.
DR GO; GO:0070325; F:lipoprotein particle receptor binding; ISS:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008236; F:serine-type peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0070326; F:very-low-density lipoprotein particle receptor binding; ISS:BHF-UCL.
DR GO; GO:0008306; P:associative learning; IEA:Ensembl.
DR GO; GO:0007411; P:axon guidance; ISS:UniProtKB.
DR GO; GO:0007420; P:brain development; ISS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0000904; P:cell morphogenesis involved in differentiation; ISS:UniProtKB.
DR GO; GO:0007417; P:central nervous system development; ISS:UniProtKB.
DR GO; GO:0021800; P:cerebral cortex tangential migration; ISS:UniProtKB.
DR GO; GO:0016358; P:dendrite development; IEA:Ensembl.
DR GO; GO:0010001; P:glial cell differentiation; ISS:UniProtKB.
DR GO; GO:0021766; P:hippocampus development; ISS:BHF-UCL.
DR GO; GO:1904936; P:interneuron migration; IEA:Ensembl.
DR GO; GO:0097477; P:lateral motor column neuron migration; IEA:Ensembl.
DR GO; GO:0021819; P:layer formation in cerebral cortex; IEA:Ensembl.
DR GO; GO:0007626; P:locomotory behavior; IEA:Ensembl.
DR GO; GO:0007616; P:long-term memory; IEA:Ensembl.
DR GO; GO:0060291; P:long-term synaptic potentiation; IEA:Ensembl.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; ISS:BHF-UCL.
DR GO; GO:0001764; P:neuron migration; ISS:UniProtKB.
DR GO; GO:0097114; P:NMDA glutamate receptor clustering; IEA:Ensembl.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR GO; GO:2000969; P:positive regulation of AMPA receptor activity; ISS:BHF-UCL.
DR GO; GO:0032793; P:positive regulation of CREB transcription factor activity; ISS:BHF-UCL.
DR GO; GO:0061003; P:positive regulation of dendritic spine morphogenesis; ISS:BHF-UCL.
DR GO; GO:2000463; P:positive regulation of excitatory postsynaptic potential; ISS:BHF-UCL.
DR GO; GO:1902078; P:positive regulation of lateral motor column neuron migration; IEA:Ensembl.
DR GO; GO:1900273; P:positive regulation of long-term synaptic potentiation; ISS:BHF-UCL.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISS:BHF-UCL.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISS:BHF-UCL.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IEA:Ensembl.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; ISS:UniProtKB.
DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; ISS:BHF-UCL.
DR GO; GO:0051057; P:positive regulation of small GTPase mediated signal transduction; ISS:UniProtKB.
DR GO; GO:0090129; P:positive regulation of synapse maturation; ISS:BHF-UCL.
DR GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; ISS:BHF-UCL.
DR GO; GO:0032008; P:positive regulation of TOR signaling; IEA:Ensembl.
DR GO; GO:0097119; P:postsynaptic density protein 95 clustering; IEA:Ensembl.
DR GO; GO:0035418; P:protein localization to synapse; IEA:Ensembl.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0097120; P:receptor localization to synapse; IEA:Ensembl.
DR GO; GO:0038026; P:reelin-mediated signaling pathway; ISS:BHF-UCL.
DR GO; GO:0050795; P:regulation of behavior; ISS:BHF-UCL.
DR GO; GO:0045664; P:regulation of neuron differentiation; IC:ComplexPortal.
DR GO; GO:2001222; P:regulation of neuron migration; IC:ComplexPortal.
DR GO; GO:2000310; P:regulation of NMDA receptor activity; ISS:BHF-UCL.
DR GO; GO:0060025; P:regulation of synaptic activity; IC:ComplexPortal.
DR GO; GO:0048265; P:response to pain; ISS:UniProtKB.
DR GO; GO:0021511; P:spinal cord patterning; ISS:UniProtKB.
DR GO; GO:0021517; P:ventral spinal cord development; IEA:Ensembl.
DR CDD; cd08544; Reeler; 1.
DR Gene3D; 2.60.40.4060; -; 1.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR041161; EGF_Tenascin.
DR InterPro; IPR002861; Reeler_dom.
DR InterPro; IPR042307; Reeler_sf.
DR InterPro; IPR034968; Reelin.
DR InterPro; IPR036278; Sialidase_sf.
DR PANTHER; PTHR11841; PTHR11841; 12.
DR Pfam; PF18720; EGF_Tenascin; 1.
DR Pfam; PF02014; Reeler; 1.
DR SMART; SM00181; EGF; 8.
DR SUPFAM; SSF50939; SSF50939; 4.
DR PROSITE; PS00022; EGF_1; 7.
DR PROSITE; PS01186; EGF_2; 6.
DR PROSITE; PS50026; EGF_3; 5.
DR PROSITE; PS51019; REELIN; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Cell adhesion; Developmental protein;
KW Disease variant; Disulfide bond; EGF-like domain; Epilepsy;
KW Extracellular matrix; Glycoprotein; Hydrolase; Lissencephaly;
KW Metal-binding; Protease; Reference proteome; Repeat; Secreted;
KW Serine protease; Signal; Zinc.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..3460
FT /note="Reelin"
FT /id="PRO_0000030304"
FT DOMAIN 26..190
FT /note="Reelin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00363"
FT REPEAT 592..603
FT /note="BNR 1"
FT DOMAIN 670..701
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 798..809
FT /note="BNR 2"
FT REPEAT 951..962
FT /note="BNR 3"
FT DOMAIN 1029..1060
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 1156..1167
FT /note="BNR 4"
FT REPEAT 1322..1333
FT /note="BNR 5"
FT DOMAIN 1408..1441
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 1534..1545
FT /note="BNR 6"
FT REPEAT 1685..1696
FT /note="BNR 7"
FT DOMAIN 1764..1795
FT /note="EGF-like 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 1883..1894
FT /note="BNR 8"
FT REPEAT 2042..2053
FT /note="BNR 9"
FT DOMAIN 2128..2160
FT /note="EGF-like 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 2249..2260
FT /note="BNR 10"
FT REPEAT 2398..2409
FT /note="BNR 11"
FT DOMAIN 2477..2508
FT /note="EGF-like 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 2597..2608
FT /note="BNR 12"
FT REPEAT 2777..2788
FT /note="BNR 13"
FT DOMAIN 2852..2883
FT /note="EGF-like 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 2978..2989
FT /note="BNR 14"
FT REPEAT 3142..3154
FT /note="BNR 15"
FT DOMAIN 3227..3259
FT /note="EGF-like 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 3362..3373
FT /note="BNR 16"
FT BINDING 2060
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 2073
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 2178
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 2263
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 2396
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 2398
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 2459
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT CARBOHYD 140
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 257
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 289
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 305
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 628
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1266
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1599
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1749
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1920
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 2144
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2268
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2316
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2568
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2961
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3015
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 3072
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3184
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3411
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3438
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 40..126
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 154..178
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 539..580
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 608..613
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 674..684
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 691..700
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 894..936
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 967..974
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1033..1043
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1050..1059
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1270..1309
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1338..1347
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1632..1672
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1701..1708
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 2100
FT /note="Interchain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 2132..2142
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 2136..2148
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 2150..2159
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 2194..2234
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 2347..2386
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 2392..2558
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 2543..2583
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 2793..2800
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 2856..2866
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 2860..2871
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 2873..2882
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 2918..2965
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 3159..3169
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 3231..3241
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 3235..3247
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 3249..3258
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 3295..3345
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT VAR_SEQ 3428..3460
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_005576"
FT VAR_SEQ 3428..3429
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_005575"
FT VARIANT 672
FT /note="P -> L (in ETL7; dbSNP:rs201044262)"
FT /evidence="ECO:0000269|PubMed:26046367"
FT /id="VAR_073862"
FT VARIANT 723
FT /note="Y -> C (in ETL7; dbSNP:rs768119894)"
FT /evidence="ECO:0000269|PubMed:26046367"
FT /id="VAR_073863"
FT VARIANT 763
FT /note="D -> G (in ETL7; dbSNP:rs794727998)"
FT /evidence="ECO:0000269|PubMed:26046367"
FT /id="VAR_073864"
FT VARIANT 798
FT /note="H -> N (in ETL7; dbSNP:rs794727996)"
FT /evidence="ECO:0000269|PubMed:26046367"
FT /id="VAR_073865"
FT VARIANT 844
FT /note="P -> L (in ETL7; dbSNP:rs797045000)"
FT /evidence="ECO:0000269|PubMed:26046367"
FT /id="VAR_073866"
FT VARIANT 978
FT /note="T -> A (in dbSNP:rs3025962)"
FT /id="VAR_047977"
FT VARIANT 997
FT /note="L -> V (in dbSNP:rs362691)"
FT /id="VAR_047978"
FT VARIANT 1703
FT /note="P -> R (in dbSNP:rs2229860)"
FT /id="VAR_057712"
FT VARIANT 2783
FT /note="G -> C (in ETL7; dbSNP:rs794727997)"
FT /evidence="ECO:0000269|PubMed:26046367"
FT /id="VAR_073867"
FT VARIANT 3176
FT /note="E -> K (in ETL7; dbSNP:rs794727999)"
FT /evidence="ECO:0000269|PubMed:26046367"
FT /id="VAR_073868"
FT CONFLICT 752
FT /note="D -> E (in Ref. 1; AAC51105)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 3460 AA; 388388 MW; 9A398EC17FA4EE1B CRC64;
MERSGWARQT FLLALLLGAT LRARAAAGYY PRFSPFFFLC THHGELEGDG EQGEVLISLH
IAGNPTYYVP GQEYHVTIST STFFDGLLVT GLYTSTSVQA SQSIGGSSAF GFGIMSDHQF
GNQFMCSVVA SHVSHLPTTN LSFIWIAPPA GTGCVNFMAT ATHRGQVIFK DALAQQLCEQ
GAPTDVTVHP HLAEIHSDSI ILRDDFDSYH QLQLNPNIWV ECNNCETGEQ CGAIMHGNAV
TFCEPYGPRE LITTGLNTTT ASVLQFSIGS GSCRFSYSDP SIIVLYAKNN SADWIQLEKI
RAPSNVSTII HILYLPEDAK GENVQFQWKQ ENLRVGEVYE ACWALDNILI INSAHRQVVL
EDSLDPVDTG NWLFFPGATV KHSCQSDGNS IYFHGNEGSE FNFATTRDVD LSTEDIQEQW
SEEFESQPTG WDVLGAVIGT ECGTIESGLS MVFLKDGERK LCTPSMDTTG YGNLRFYFVM
GGICDPGNSH ENDIILYAKI EGRKEHITLD TLSYSSYKVP SLVSVVINPE LQTPATKFCL
RQKNHQGHNR NVWAVDFFHV LPVLPSTMSH MIQFSINLGC GTHQPGNSVS LEFSTNHGRS
WSLLHTECLP EICAGPHLPH STVYSSENYS GWNRITIPLP NAALTRNTRI RWRQTGPILG
NMWAIDNVYI GPSCLKFCSG RGQCTRHGCK CDPGFSGPAC EMASQTFPMF ISESFGSSRL
SSYHNFYSIR GAEVSFGCGV LASGKALVFN KDGRRQLITS FLDSSQSRFL QFTLRLGSKS
VLSTCRAPDQ PGEGVLLHYS YDNGITWKLL EHYSYLSYHE PRIISVELPG DAKQFGIQFR
WWQPYHSSQR EDVWAIDEII MTSVLFNSIS LDFTNLVEVT QSLGFYLGNV QPYCGHDWTL
CFTGDSKLAS SMRYVETQSM QIGASYMIQF SLVMGCGQKY TPHMDNQVKL EYSTNHGLTW
HLVQEECLPS MPSCQEFTSA SIYHASEFTQ WRRVIVLLPQ KTWSSATRFR WSQSYYTAQD
EWALDSIYIG QQCPNMCSGH GSCDHGICRC DQGYQGTECH PEAALPSTIM SDFENQNGWE
SDWQEVIGGE IVKPEQGCGV ISSGSSLYFS KAGKRQLVSW DLDTSWVDFV QFYIQIGGES
ASCNKPDSRE EGVLLQYSNN GGIQWHLLAE MYFSDFSKPR FVYLELPAAA KTPCTRFRWW
QPVFSGEDYD QWAVDDIIIL SEKQKQIIPV INPTLPQNFY EKPAFDYPMN QMSVWLMLAN
EGMVKNETFC AATPSAMIFG KSDGDRFAVT RDLTLKPGYV LQFKLNIGCA NQFSSTAPVL
LQYSHDAGMS WFLVKEGCYP ASAGKGCEGN SRELSEPTMY HTGDFEEWTR ITIVIPRSLA
SSKTRFRWIQ ESSSQKNVPP FGLDGVYISE PCPSYCSGHG DCISGVCFCD LGYTAAQGTC
VSNVPNHNEM FDRFEGKLSP LWYKITGAQV GTGCGTLNDG KSLYFNGPGK REARTVPLDT
RNIRLVQFYI QIGSKTSGIT CIKPRTRNEG LIVQYSNDNG ILWHLLRELD FMSFLEPQII
SIDLPQDAKT PATAFRWWQP QHGKHSAQWA LDDVLIGMND SSQTGFQDKF DGSIDLQANW
YRIQGGQVDI DCLSMDTALI FTENIGKPRY AETWDFHVSA STFLQFEMSM GCSKPFSNSH
SVQLQYSLNN GKDWHLVTEE CVPPTIGCLH YTESSIYTSE RFQNWKRITV YLPLSTISPR
TRFRWIQANY TVGADSWAID NVVLASGCPW MCSGRGICDA GRCVCDRGFG GPYCVPVVPL
PSILKDDFNG NLHPDLWPEV YGAERGNLNG ETIKSGTSLI FKGEGLRMLI SRDLDCTNTM
YVQFSLRFIA KSTPERSHSI LLQFSISGGI TWHLMDEFYF PQTTNILFIN VPLPYTAQTN
ATRFRLWQPY NNGKKEEIWI VDDFIIDGNN VNNPVMLLDT FDFGPREDNW FFYPGGNIGL
YCPYSSKGAP EEDSAMVFVS NEVGEHSITT RDLNVNENTI IQFEINVGCS TDSSSADPVR
LEFSRDFGAT WHLLLPLCYH SSSHVSSLCS TEHHPSSTYY AGTMQGWRRE VVHFGKLHLC
GSVRFRWYQG FYPAGSQPVT WAIDNVYIGP QCEEMCNGQG SCINGTKCIC DPGYSGPTCK
ISTKNPDFLK DDFEGQLESD RFLLMSGGKP SRKCGILSSG NNLFFNEDGL RMLMTRDLDL
SHARFVQFFM RLGCGKGVPD PRSQPVLLQY SLNGGLSWSL LQEFLFSNSS NVGRYIALEI
PLKARSGSTR LRWWQPSENG HFYSPWVIDQ ILIGGNISGN TVLEDDFTTL DSRKWLLHPG
GTKMPVCGST GDALVFIEKA STRYVVSTDV AVNEDSFLQI DFAASCSVTD SCYAIELEYS
VDLGLSWHPL VRDCLPTNVE CSRYHLQRIL VSDTFNKWTR ITLPLPPYTR SQATRFRWHQ
PAPFDKQQTW AIDNVYIGDG CIDMCSGHGR CIQGNCVCDE QWGGLYCDDP ETSLPTQLKD
NFNRAPSSQN WLTVNGGKLS TVCGAVASGM ALHFSGGCSR LLVTVDLNLT NAEFIQFYFM
YGCLITPNNR NQGVLLEYSV NGGITWNLLM EIFYDQYSKP GFVNILLPPD AKEIATRFRW
WQPRHDGLDQ NDWAIDNVLI SGSADQRTVM LDTFSSAPVP QHERSPADAG PVGRIAFDMF
MEDKTSVNEH WLFHDDCTVE RFCDSPDGVM LCGSHDGREV YAVTHDLTPT EGWIMQFKIS
VGCKVSEKIA QNQIHVQYST DFGVSWNYLV PQCLPADPKC SGSVSQPSVF FPTKGWKRIT
YPLPESLVGN PVRFRFYQKY SDMQWAIDNF YLGPGCLDNC RGHGDCLREQ CICDPGYSGP
NCYLTHTLKT FLKERFDSEE IKPDLWMSLE GGSTCTECGI LAEDTALYFG GSTVRQAVTQ
DLDLRGAKFL QYWGRIGSEN NMTSCHRPIC RKEGVLLDYS TDGGITWTLL HEMDYQKYIS
VRHDYILLPE DALTNTTRLR WWQPFVISNG IVVSGVERAQ WALDNILIGG AEINPSQLVD
TFDDEGTSHE ENWSFYPNAV RTAGFCGNPS FHLYWPNKKK DKTHNALSSR ELIIQPGYMM
QFKIVVGCEA TSCGDLHSVM LEYTKDARSD SWQLVQTQCL PSSSNSIGCS PFQFHEATIY
NSVNSSSWKR ITIQLPDHVS SSATQFRWIQ KGEETEKQSW AIDHVYIGEA CPKLCSGHGY
CTTGAICICD ESFQGDDCSV FSHDLPSYIK DNFESARVTE ANWETIQGGV IGSGCGQLAP
YAHGDSLYFN GCQIRQAATK PLDLTRASKI MFVLQIGSMS QTDSCNSDLS GPHAVDKAVL
LQYSVNNGIT WHVIAQHQPK DFTQAQRVSY NVPLEARMKG VLLRWWQPRH NGTGHDQWAL
DHVEVVLVST RKQNYMMNFS RQHGLRHFYN RRRRSLRRYP
