CUBN_MOUSE
ID CUBN_MOUSE Reviewed; 3623 AA.
AC Q9JLB4; B1AX10;
DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Cubilin;
DE AltName: Full=Intrinsic factor-cobalamin receptor;
DE Flags: Precursor;
GN Name=Cubn; Synonyms=Ifcr;
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP PROTEIN SEQUENCE OF 811-823; 1849-1862; 2101-2107; 2146-2157; 2530-2538;
RP 2545-2553 AND 3399-3407, INTERACTION WITH LGALS3, GLYCOSYLATION, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, AND FUNCTION.
RX PubMed=11856751; DOI=10.1074/jbc.m200331200;
RA Crider-Pirkle S., Billingsley P., Faust C., Hardy D.M., Lee V.,
RA Weitlauf H.;
RT "Cubilin, a binding partner for galectin-3 in the murine utero-placental
RT complex.";
RL J. Biol. Chem. 277:15904-15912(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2792-3623, TISSUE SPECIFICITY, INTERACTION
RP WITH HIGH DENSITY LIPOPROTEIN, AND FUNCTION.
RC TISSUE=Ectoplacental cone;
RX PubMed=10766831; DOI=10.1074/jbc.275.16.12003;
RA Hammad S.M., Barth J.L., Knaak C., Argraves W.S.;
RT "Megalin acts in concert with cubilin to mediate endocytosis of high
RT density lipoproteins.";
RL J. Biol. Chem. 275:12003-12008(2000).
RN [4]
RP INTERACTION WITH SCGB1A1, AND FUNCTION.
RX PubMed=11278724; DOI=10.1074/jbc.m010679200;
RA Burmeister R., Boee I.-M., Nykjaer A., Jacobsen C., Moestrup S.K.,
RA Verroust P., Christensen E.I., Lund J., Willnow T.E.;
RT "A two-receptor pathway for catabolism of Clara cell secretory protein in
RT the kidney.";
RL J. Biol. Chem. 276:13295-13301(2001).
RN [5]
RP DEVELOPMENTAL STAGE.
RX PubMed=14983511; DOI=10.1002/ar.a.10123;
RA Drake C.J., Fleming P.A., Larue A.C., Barth J.L., Chintalapudi M.R.,
RA Argraves W.S.;
RT "Differential distribution of cubilin and megalin expression in the mouse
RT embryo.";
RL Anat. Rec. 277:163-170(2004).
RN [6]
RP INTERACTION WITH AMN, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15342463; DOI=10.1242/dev.01341;
RA Strope S., Rivi R., Metzger T., Manova K., Lacy E.;
RT "Mouse amnionless, which is required for primitive streak assembly,
RT mediates cell-surface localization and endocytic function of cubilin on
RT visceral endoderm and kidney proximal tubules.";
RL Development 131:4787-4795(2004).
RN [7]
RP DEVELOPMENTAL STAGE.
RX PubMed=15616221; DOI=10.1095/biolreprod.104.036913;
RA Assemat E., Vinot S., Gofflot F., Linsel-Nitschke P., Illien F.,
RA Chatelet F., Verroust P.J., Louvet-Vallee S., Rinninger F., Kozyraki R.;
RT "Expression and role of cubilin in the internalization of nutrients during
RT the peri-implantation development of the rodent embryo.";
RL Biol. Reprod. 72:1079-1086(2005).
RN [8]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-2085; ASN-2925 AND ASN-3125.
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, and Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Endocytic receptor which plays a role in lipoprotein, vitamin
CC and iron metabolism by facilitating their uptake. Acts together with
CC LRP2 to mediate endocytosis of high-density lipoproteins, GC,
CC hemoglobin, ALB, TF and SCGB1A1. Acts together with AMN to mediate
CC endocytosis of the CBLIF-cobalamin complex. Binds to ALB, MB, Kappa and
CC lambda-light chains, TF, hemoglobin, GC, SCGB1A1, APOA1, high density
CC lipoprotein, and the CBLIF-cobalamin complex. Ligand binding requires
CC calcium. Serves as important transporter in several absorptive
CC epithelia, including intestine, renal proximal tubules and embryonic
CC yolk sac. May play an important role in the development of the peri-
CC implantation embryo through internalization of APOA1 and cholesterol.
CC Binds to LGALS3 at the maternal-fetal interface.
CC {ECO:0000269|PubMed:10766831, ECO:0000269|PubMed:11278724,
CC ECO:0000269|PubMed:11856751, ECO:0000269|PubMed:15342463}.
CC -!- SUBUNIT: Interacts with AMN. Component of the cubam complex composed of
CC one CUBN trimer and one AMN chain (By similarity). The cubam complex
CC can dimerize (By similarity). Interacts with LRP2 in a dual-receptor
CC complex in a calcium-dependent manner. Found in a complex with
CC PID1/PCLI1, LRP1 and CUBNI. Interacts with LRP1 and PID1/PCLI1 (By
CC similarity). {ECO:0000250|UniProtKB:F1RWC3,
CC ECO:0000250|UniProtKB:O60494}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:15342463}; Peripheral membrane protein
CC {ECO:0000305}. Cell membrane {ECO:0000250|UniProtKB:O60494}; Peripheral
CC membrane protein {ECO:0000250|UniProtKB:O60494}. Membrane, coated pit
CC {ECO:0000250|UniProtKB:O60494}. Endosome
CC {ECO:0000250|UniProtKB:O60494}. Lysosome membrane
CC {ECO:0000250|UniProtKB:O70244}; Peripheral membrane protein
CC {ECO:0000305}. Note=Lacks a transmembrane domain and depends on
CC interaction with AMN for location at the plasma membrane (By
CC similarity). Colocalizes with AMN and LRP2 in the endocytotic apparatus
CC of epithelial cells (By similarity). {ECO:0000250|UniProtKB:O60494,
CC ECO:0000250|UniProtKB:O70244}.
CC -!- TISSUE SPECIFICITY: Expressed in kidney, thymus, ileum, placenta, small
CC intestine and yolk sac. In kidney expressed on the apical brush border
CC surface of proximal tubular cells, in particular in endosomes and
CC recycling membranes vesicles, so-called dense apical tubules, which
CC carry internalized receptors back to the cell surface. Expressed in
CC fetal membranes of yolk sac, placenta of pregnant females.
CC {ECO:0000269|PubMed:10766831, ECO:0000269|PubMed:11856751}.
CC -!- DEVELOPMENTAL STAGE: Detected in yolk sac endoderm as early as day 6
CC and is present at the apical surface of those cells throughout the
CC remainder of pregnancy. Apical expression is pronounced in the
CC extraembryonic visceral endoderm (VE) of 6-9.5 dpc. Expressed by a
CC subpopulation of cells dispersed within the 7.5 dpc embryonic endoderm
CC and having a migratory morphology. First detected at the eight-cell
CC stage. At the 32-cell stage expressed in all outer cells which are at
CC the origin of the trophectoderm (TE). During the blastocyst stage,
CC expression is predominant at the apical membrane of the TE cells.
CC {ECO:0000269|PubMed:11856751, ECO:0000269|PubMed:14983511,
CC ECO:0000269|PubMed:15616221}.
CC -!- DOMAIN: The CUB domains 5 to 8 mediate binding to CBLIF and ALB. CUB
CC domains 1 and 2 mediate interaction with LRP2.
CC {ECO:0000250|UniProtKB:O70244}.
CC -!- DOMAIN: The cubam complex is composed of a 400 Angstrom long stem and a
CC globular crown region. The stem region is probably formed by AMN and
CC the CUBN N-terminal region, including the EGF-like domains. The crown
CC is probably formed by the CUBN CUB domains.
CC {ECO:0000250|UniProtKB:F1RWC3}.
CC -!- PTM: The precursor is cleaved by a trans-Golgi proteinase furin,
CC removing a propeptide. {ECO:0000250|UniProtKB:O60494}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:11856751,
CC ECO:0000269|PubMed:19349973}.
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; AL773538; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL928807; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF197159; AAF61487.1; -; mRNA.
DR CCDS; CCDS38048.1; -.
DR RefSeq; NP_001074553.1; NM_001081084.2.
DR SMR; Q9JLB4; -.
DR BioGRID; 211163; 8.
DR ComplexPortal; CPX-5847; Cubam cobalamin uptake receptor complex.
DR CORUM; Q9JLB4; -.
DR IntAct; Q9JLB4; 2.
DR MINT; Q9JLB4; -.
DR STRING; 10090.ENSMUSP00000089009; -.
DR GlyGen; Q9JLB4; 39 sites.
DR iPTMnet; Q9JLB4; -.
DR PhosphoSitePlus; Q9JLB4; -.
DR jPOST; Q9JLB4; -.
DR MaxQB; Q9JLB4; -.
DR PaxDb; Q9JLB4; -.
DR PeptideAtlas; Q9JLB4; -.
DR PRIDE; Q9JLB4; -.
DR ProteomicsDB; 284061; -.
DR Antibodypedia; 56802; 164 antibodies from 20 providers.
DR Ensembl; ENSMUST00000091436; ENSMUSP00000089009; ENSMUSG00000026726.
DR GeneID; 65969; -.
DR KEGG; mmu:65969; -.
DR UCSC; uc008ijz.1; mouse.
DR CTD; 8029; -.
DR MGI; MGI:1931256; Cubn.
DR VEuPathDB; HostDB:ENSMUSG00000026726; -.
DR eggNOG; KOG4292; Eukaryota.
DR GeneTree; ENSGT00940000155299; -.
DR HOGENOM; CLU_000172_1_0_1; -.
DR InParanoid; Q9JLB4; -.
DR OMA; RGFTVRW; -.
DR OrthoDB; 4105at2759; -.
DR PhylomeDB; Q9JLB4; -.
DR TreeFam; TF316224; -.
DR BioGRID-ORCS; 65969; 5 hits in 74 CRISPR screens.
DR ChiTaRS; Cubn; mouse.
DR PRO; PR:Q9JLB4; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q9JLB4; protein.
DR Bgee; ENSMUSG00000026726; Expressed in primitive streak and 82 other tissues.
DR Genevisible; Q9JLB4; MM.
DR GO; GO:0045177; C:apical part of cell; IDA:MGI.
DR GO; GO:0016324; C:apical plasma membrane; IDA:MGI.
DR GO; GO:0005903; C:brush border; IDA:MGI.
DR GO; GO:0031526; C:brush border membrane; ISS:UniProtKB.
DR GO; GO:0005905; C:clathrin-coated pit; IDA:MGI.
DR GO; GO:0030135; C:coated vesicle; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0030139; C:endocytic vesicle; IDA:MGI.
DR GO; GO:0030666; C:endocytic vesicle membrane; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0005768; C:endosome; IDA:MGI.
DR GO; GO:0070062; C:extracellular exosome; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR GO; GO:0005798; C:Golgi-associated vesicle; ISO:MGI.
DR GO; GO:0043202; C:lysosomal lumen; ISO:MGI.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0031528; C:microvillus membrane; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0043235; C:receptor complex; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0038024; F:cargo receptor activity; ISO:MGI.
DR GO; GO:0031419; F:cobalamin binding; IEA:UniProtKB-KW.
DR GO; GO:0030492; F:hemoglobin binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0038023; F:signaling receptor activity; ISO:MGI.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0042366; P:cobalamin catabolic process; ISO:MGI.
DR GO; GO:0009235; P:cobalamin metabolic process; ISO:MGI.
DR GO; GO:0015889; P:cobalamin transport; ISO:MGI.
DR GO; GO:0020028; P:endocytic hemoglobin import into cell; ISO:MGI.
DR GO; GO:0051649; P:establishment of localization in cell; IDA:MGI.
DR GO; GO:0001701; P:in utero embryonic development; ISO:MGI.
DR GO; GO:0042953; P:lipoprotein transport; IDA:MGI.
DR GO; GO:0006898; P:receptor-mediated endocytosis; IMP:MGI.
DR GO; GO:0009617; P:response to bacterium; IEP:MGI.
DR GO; GO:0007584; P:response to nutrient; ISO:MGI.
DR CDD; cd00041; CUB; 27.
DR Gene3D; 2.60.120.290; -; 27.
DR InterPro; IPR000859; CUB_dom.
DR InterPro; IPR028876; Cubilin.
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; IPR024731; EGF_dom.
DR InterPro; IPR035914; Sperma_CUB_dom_sf.
DR PANTHER; PTHR45656:SF11; PTHR45656:SF11; 4.
DR Pfam; PF00431; CUB; 27.
DR Pfam; PF00008; EGF; 2.
DR Pfam; PF12947; EGF_3; 1.
DR Pfam; PF07645; EGF_CA; 3.
DR Pfam; PF12661; hEGF; 1.
DR SMART; SM00042; CUB; 27.
DR SMART; SM00181; EGF; 8.
DR SMART; SM00179; EGF_CA; 7.
DR SUPFAM; SSF49854; SSF49854; 27.
DR PROSITE; PS00010; ASX_HYDROXYL; 3.
DR PROSITE; PS01180; CUB; 27.
DR PROSITE; PS00022; EGF_1; 4.
DR PROSITE; PS01186; EGF_2; 2.
DR PROSITE; PS50026; EGF_3; 6.
DR PROSITE; PS01187; EGF_CA; 4.
PE 1: Evidence at protein level;
KW Calcium; Cell membrane; Cholesterol metabolism;
KW Cleavage on pair of basic residues; Coated pit; Cobalamin; Cobalt;
KW Direct protein sequencing; Disulfide bond; EGF-like domain; Endosome;
KW Glycoprotein; Lipid metabolism; Lysosome; Membrane; Metal-binding;
KW Phosphoprotein; Protein transport; Reference proteome; Repeat; Signal;
KW Steroid metabolism; Sterol metabolism; Transport.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..32
FT /note="Removed in mature form"
FT /evidence="ECO:0000250|UniProtKB:O60494"
FT /id="PRO_0000046074"
FT CHAIN 33..3623
FT /note="Cubilin"
FT /id="PRO_0000046075"
FT DOMAIN 129..165
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 167..208
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 260..301
FT /note="EGF-like 3; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 302..345
FT /note="EGF-like 4; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 346..385
FT /note="EGF-like 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 395..430
FT /note="EGF-like 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 432..468
FT /note="EGF-like 7; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 474..586
FT /note="CUB 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 590..702
FT /note="CUB 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 708..816
FT /note="CUB 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 817..928
FT /note="CUB 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 932..1042
FT /note="CUB 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 1048..1161
FT /note="CUB 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 1165..1277
FT /note="CUB 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 1278..1389
FT /note="CUB 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 1391..1506
FT /note="CUB 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 1510..1619
FT /note="CUB 10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 1620..1734
FT /note="CUB 11"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 1738..1850
FT /note="CUB 12"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 1852..1963
FT /note="CUB 13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 1978..2091
FT /note="CUB 14"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 2092..2213
FT /note="CUB 15"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 2217..2334
FT /note="CUB 16"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 2336..2448
FT /note="CUB 17"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 2452..2565
FT /note="CUB 18"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 2570..2687
FT /note="CUB 19"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 2689..2801
FT /note="CUB 20"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 2805..2919
FT /note="CUB 21"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 2920..3035
FT /note="CUB 22"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 3037..3150
FT /note="CUB 23"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 3157..3274
FT /note="CUB 24"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 3278..3393
FT /note="CUB 25"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 3395..3507
FT /note="CUB 26"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 3511..3623
FT /note="CUB 27"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT REGION 39..46
FT /note="Interaction with AMN"
FT /evidence="ECO:0000250|UniProtKB:O60494"
FT BINDING 980
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O60494"
FT BINDING 988
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O60494"
FT BINDING 1027
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O60494"
FT BINDING 1030
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O60494"
FT BINDING 1096
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O60494"
FT BINDING 1105
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O60494"
FT BINDING 1146
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O60494"
FT BINDING 1213
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:O60494"
FT BINDING 1221
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:O60494"
FT BINDING 1262
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:O60494"
FT BINDING 1264
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:O60494"
FT BINDING 1265
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:O60494"
FT BINDING 1328
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:O60494"
FT BINDING 1336
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:O60494"
FT BINDING 1373
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:O60494"
FT BINDING 1375
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:O60494"
FT SITE 32..33
FT /note="Cleavage; by furin"
FT /evidence="ECO:0000255"
FT MOD_RES 3008
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O70244"
FT CARBOHYD 95
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 428
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 491
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 711
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 749
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 781
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 857
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 957
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1043
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1168
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1217
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1285
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1307
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1319
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1332
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1500
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1551
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1646
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1802
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1819
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1967
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2085
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 2117
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2274
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2400
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2531
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2581
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2610
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2813
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2925
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 2989
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3106
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3125
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 3268
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3283
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3290
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3357
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3457
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3533
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 133..144
FT /evidence="ECO:0000250"
FT DISULFID 138..153
FT /evidence="ECO:0000250"
FT DISULFID 155..164
FT /evidence="ECO:0000250"
FT DISULFID 171..187
FT /evidence="ECO:0000250"
FT DISULFID 181..196
FT /evidence="ECO:0000250"
FT DISULFID 198..207
FT /evidence="ECO:0000250"
FT DISULFID 264..277
FT /evidence="ECO:0000250"
FT DISULFID 271..286
FT /evidence="ECO:0000250"
FT DISULFID 289..300
FT /evidence="ECO:0000250"
FT DISULFID 350..363
FT /evidence="ECO:0000250"
FT DISULFID 357..376
FT /evidence="ECO:0000250"
FT DISULFID 399..409
FT /evidence="ECO:0000250"
FT DISULFID 404..418
FT /evidence="ECO:0000250"
FT DISULFID 420..429
FT /evidence="ECO:0000250"
FT DISULFID 436..447
FT /evidence="ECO:0000250"
FT DISULFID 441..456
FT /evidence="ECO:0000250"
FT DISULFID 458..467
FT /evidence="ECO:0000250"
FT DISULFID 474..500
FT /evidence="ECO:0000250"
FT DISULFID 527..549
FT /evidence="ECO:0000250"
FT DISULFID 590..616
FT /evidence="ECO:0000250"
FT DISULFID 643..665
FT /evidence="ECO:0000250"
FT DISULFID 708..734
FT /evidence="ECO:0000250"
FT DISULFID 761..779
FT /evidence="ECO:0000250"
FT DISULFID 817..842
FT /evidence="ECO:0000250"
FT DISULFID 869..891
FT /evidence="ECO:0000250"
FT DISULFID 932..958
FT /evidence="ECO:0000250"
FT DISULFID 985..1005
FT /evidence="ECO:0000250"
FT DISULFID 1048..1074
FT /evidence="ECO:0000250"
FT DISULFID 1165..1191
FT /evidence="ECO:0000250"
FT DISULFID 1218..1240
FT /evidence="ECO:0000250"
FT DISULFID 1278..1306
FT /evidence="ECO:0000250"
FT DISULFID 1333..1351
FT /evidence="ECO:0000250"
FT DISULFID 1391..1417
FT /evidence="ECO:0000250"
FT DISULFID 1444..1466
FT /evidence="ECO:0000250"
FT DISULFID 1510..1536
FT /evidence="ECO:0000250"
FT DISULFID 1563..1581
FT /evidence="ECO:0000250"
FT DISULFID 1620..1647
FT /evidence="ECO:0000250"
FT DISULFID 1675..1697
FT /evidence="ECO:0000250"
FT DISULFID 1738..1764
FT /evidence="ECO:0000250"
FT DISULFID 1791..1812
FT /evidence="ECO:0000250"
FT DISULFID 1905..1927
FT /evidence="ECO:0000250"
FT DISULFID 1978..2006
FT /evidence="ECO:0000250"
FT DISULFID 2032..2054
FT /evidence="ECO:0000250"
FT DISULFID 2092..2118
FT /evidence="ECO:0000250"
FT DISULFID 2217..2247
FT /evidence="ECO:0000250"
FT DISULFID 2275..2297
FT /evidence="ECO:0000250"
FT DISULFID 2336..2363
FT /evidence="ECO:0000250"
FT DISULFID 2390..2411
FT /evidence="ECO:0000250"
FT DISULFID 2452..2478
FT /evidence="ECO:0000250"
FT DISULFID 2505..2527
FT /evidence="ECO:0000250"
FT DISULFID 2570..2599
FT /evidence="ECO:0000250"
FT DISULFID 2628..2649
FT /evidence="ECO:0000250"
FT DISULFID 2689..2715
FT /evidence="ECO:0000250"
FT DISULFID 2742..2764
FT /evidence="ECO:0000250"
FT DISULFID 2805..2831
FT /evidence="ECO:0000250"
FT DISULFID 2860..2883
FT /evidence="ECO:0000250"
FT DISULFID 2920..2946
FT /evidence="ECO:0000250"
FT DISULFID 2977..2999
FT /evidence="ECO:0000250"
FT DISULFID 3037..3064
FT /evidence="ECO:0000250"
FT DISULFID 3091..3113
FT /evidence="ECO:0000250"
FT DISULFID 3157..3185
FT /evidence="ECO:0000250"
FT DISULFID 3215..3237
FT /evidence="ECO:0000250"
FT DISULFID 3278..3306
FT /evidence="ECO:0000250"
FT DISULFID 3332..3354
FT /evidence="ECO:0000250"
FT DISULFID 3395..3421
FT /evidence="ECO:0000250"
FT DISULFID 3448..3470
FT /evidence="ECO:0000250"
FT DISULFID 3511..3537
FT /evidence="ECO:0000250"
FT DISULFID 3564..3586
FT /evidence="ECO:0000250"
FT CONFLICT 811..813
FT /note="ADY -> NDL (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 819
FT /note="G -> S (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 822..823
FT /note="RG -> QD (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 1859
FT /note="T -> Q (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 2105
FT /note="S -> P (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 2146..2148
FT /note="SCS -> YGA (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 2152
FT /note="Y -> L (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 2156
FT /note="R -> S (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 2531
FT /note="N -> S (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 2536..2538
FT /note="FKS -> WTK (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 3623 AA; 399097 MW; C105089FE0E0F1ED CRC64;
MASHFLWGFV TLLMVPGLDG ETGTPEQKLQ KRIADLHQPR MTTEEGNLVF LTSSAQNIEF
RTGSLGKIKL NDDDLGECLH QIQRNKDDII DLKRNTTGLP QNILSQVHQL NSKLVDLERD
FQSLQQNVER KVCSSNPCHN GGTCVNLHDS FICICPSQWK GLFCSEDVNE CVLYAGTPFG
CQSGSTCVNT MGSFRCDCTP DTYGPQCASK YNDCEQGSQQ LCKHGICEDL QRVYHGQLRF
NCICDAGWTT LPNGISCTED KDECSLQPSP CSEHAQCFNT QGSFYCGACP KGWQGNGYQC
QDINECEINN GGCSQAPLVP CLNTPGSFTC GNCPAGFSGD GRVCTPLDIC SIHNGGCHPD
ATCSSSSVLG SLLPVCTCPP GYTGNGYGSN GCVRLSNMCS RHPCVNGQCI ETVSSYFCKC
DSGWFGQNCT ENINECVSNP CLNGGTCIDG VNGFTCDCTS SWTGYYCQTP QAACGGILSG
TQGTFAYQSP NDTYVHNVNC FWVVRTDEEK VLHITFTFFD LESASNCPRE YLQIHDGDSS
ADFPLGRYCG STPPQGVHSS ANSLYFHLYS EYIKRGRGFT ARWEAKLPEC GGILTGNYGS
ITSPGYPGNY PPGRDCVWNL LVSPGSLITF TFGTLSLESH NDCSKDYLEI RDGPFHHDPI
LGKFCTSLST PPLQTTGPAA RIHFHSDSET SDKGFHITYL TTPSDLYCGG NYTDTEGELL
LPPLTGPFSH SRQCVYLISQ PQGEQIVINF THVELESQRG CSHTFIEVGD HESLLRKICG
NETLFPIRSI SNNVWIRLRI DALVQKASFR ADYQVACGGE LRGEGVIRSP FYPNAYAGRR
TCRWTISQPP REVVLLNFTD FQIGSSSSCD TDYIEIGPSS VLGSPGNEKF CGTNIPSFIT
SVYNVLYVTF VKSSSMENRG FMAMFSSEKL ECGKVLTEST GIIESPGHPN VYPSGVNCTW
HIVVQRGQLI RLVFSSFYLE FHYNCANDYL EVYDTIAQTS LGRYCGKSIP PSLTSSSHSI
KLIFVSDSAL AHEGFSINYE AINASSVCLY DYTDNFGRLS SPNFPNNYPH NWNCVYRITV
GLNQQIALHF TDFALEDYFG PKCVDFVEIR DGGFETSPLI GIYCGSVFPP RIISHSNKLW
LRFKSDTALT ARGFSAYWDA SSTGCGGNLT TPTGVLTSPN YPMPYYHSSE CYWRLEASRG
SPFLLEFQDF HLEHHPNCSL DYLAVFDGPS TNSRLINKLC GDTPPAPIRS SKDIVLLKLR
TDAGQQGRGF EINYRQTCDN VVIVNKTSGI LESINYPNPY DKDQRCNWTI QATTGNTVNY
TFLEFDVENY VNCSTDYLEL YDGPQRIGRY CGENIPPPGA TTGSKLIVVF HTDGVDSGEK
GFKMHWFIHG CGGEMSGTMG SFSSPGYPNS YPHNKECIWN IRVAPGNSIQ LTIHDFDVEY
HASCKYDTLE IYTGLDFHSP RIAQLCSRSP SANPMQISST DNELAIRFKT DSSLNGRGFN
ASWRAVPGGC GGIFQVSRGE IHSPNYPNNY RANTECSWII QVEKYHRVLL NITDFDLEAT
DSCLMTYDGS SSANTRVATV CGRQQPPNSI TSSGNSLFVR FQSGSSSQSR GFRAQFRQEC
GAHIITDSSD SISSPLYPAN YPNNQNCTWI IEAQPPFNHI ALSFTHFHLQ SSTDCTRDFV
EILDGRDSDA PVQGRYCGTS LPHPIISFGN ALTVRFVSDS VYGFDGFHAI YSASTSACGG
TFYTGDGIFN SPGYPEDYHS NTECVWNIAS SPGNHLQLSF LSFQLENSLN CNKDFVEIRE
GNATGHLMGR YCGNSLPGNY SSIEGHNLWV RFVSDGSGTG MGFQARFKNI FGNDNIVGTH
GKIATPFWPG NYPLNSNYRW TVNVDSSHII HGRILEMDIE LTTNCFYDSL KIYDGFDIHS
RLIGTYCGTQ RESFSSSRNS LTFQFSSDSS KSGRGFLLEW FAVDVSNVTL PTIAPGACGG
YMVTGDTPVF FFSPGWPGPY GNGADCIWII YAPDSTVELN ILSMDIEAQL SCSYDKLIIK
DGDSRLSQQL AVLCGRSVPG PIRSTGEYMY IRFTSDGSVT GAGFNASFQK SCGGYLHADR
GIITSPKYPD NYLPNLNCSW HVLVQSGLTI AVHFEQPFQI QNRDSSCSQG DYLVLRNGPD
NHSPPLGPSG GNGRFCGIYT PSTLFTSDNE MFIQFISDNS NGGQGFKIRY EAKSLACGGT
IYIHDANSDG YVTSPNYPAN YPQHAECIWI LEAPSGRSIQ LQFEDQFNIE ETPNCSASYL
ELRDGANSNA PVLSKLCGHT LPRNWVSSRG LMYLKFHTEG GSGYMGFKAK YSIVSCGGTV
SGDSGVIESV GYPTRLYANN VFCQWHIQGL PGHYLTIRFE DFNLQSSPGC AKDFVEIWEN
HTSGILLGRY CGNSIPSSVD TSSNVASIRF VTDGSVTDSG FRLQFKSSRE VCGGDLHGPT
GTFTSPNYPN PNPHPRICEW TINVHEGRQI ILTFTNLRLS TQQSCNTEHL IVFNGIRNNS
PRLQKLCSRV NVTNEFKSSG NTMKVIFFTD GSRPYGGFTA SYTSSEDAVC GGTLPSVSGG
NFSSPGYNGI RDYARNLDCE WTLSNPNREN SSISIHFLGL SLESHQDCTF DVLEFRVGNA
DGPLIEKFCS LSAPRVPLVI PYPQVWIHFV SNERVEYTGF YVEYSFTNCG GIQTGENGVI
SSPNYPNLYS RWTQCSWLLE APEGHTITLT FSDFSVENHP TCTSDSVTVR NGDSPGSPII
GRYCGQSVPG PIQSGSNQLV VTFNTNNQGQ SRGFYATWNT NTLGCGGTLH SDNGTIKSPH
WPQTFPENSR CSWTAVTHES KHWEISFDSN FRIPSSDSQC RNSFVKVWEG MLETNDALLA
TSCGNVAPSP IVTLGNIFTA VFQSEEMPAQ GFSASFISRC GRTFNSSTGD IVSPNFPKHY
DNNMNCNYYI DVAPQSLVIL TFVSFHLEDR SAVSGTCDYD GLHIIKGHNL SSTPLVTICG
SETLRPLTID GPVMLNFYSD AYITDFGFKI SYRVANCGGI YSGTYGVLNS PSFSYTNYPN
NVYCVYSLQV RNDRLILLRF NDFEIVPSNL CSHDYLEVFD GPSIGNRSIG KFCGSTLPQV
IKSTNNSLTL LFKTDSSQTA RGWKVSFRET IGPQQGCGGY LTEDSKSFVS PDHDSDGLYD
KGLNCIWYII APENKLVKLT FNAFTLEEPS SPGKCTFDYV QIADGASINS YLGGRFCGSS
RPAPFISSGN FLTVQFVSDI SIQMRGFNAT YTFVDMPCGG TYNATSMPQN TSSPQLSNIR
RPFSTCTWVI EAPPHQQVQI TVWKLQLPSQ DCSRSSLELQ DSEQTNGNQV TQFCGANYTT
LPVFYSSGST AVVVFKSDFL NRNSRVHFTY EIADCNREYN QAFGNLKSPG WPQGYANNLD
CSIILRAPQN HRISLFFYWF QLEDSRQCMN DFLEVRNGSS SSSPLLGKYC SNLLPNPIFS
QSNELYLHFH SDDSDTHHGY EIIWASSPTG CGGTLLGNEG ILANPGFPDS YPNNTHCEWT
IVAPSGRPLS VGFPFLSIDS PGGCDQNYLI LFNGPDANSP PFGPFCGIDT VVAPFHASSN
RVFIRFHAEY ATVSSGFEIM WSS
