CUBN_RAT
ID CUBN_RAT Reviewed; 3623 AA.
AC O70244;
DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1999, sequence version 2.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Cubilin;
DE AltName: Full=460 kDa receptor;
DE AltName: Full=Glycoprotein 280;
DE Short=gp280;
DE AltName: Full=Intrinsic factor-cobalamin receptor;
DE AltName: Full=Intrinsic factor-vitamin B12 receptor;
DE Flags: Precursor;
GN Name=Cubn; Synonyms=Ifcr;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 41-53; 85-93; 120-130;
RP 530-547; 578-581; 1843-1856 AND 2070-2076, FUNCTION, INTERACTION WITH LRP2,
RP SUBCELLULAR LOCATION, AND GLYCOSYLATION.
RC TISSUE=Kidney cortex;
RX PubMed=9478979; DOI=10.1074/jbc.273.9.5235;
RA Moestrup S.K., Kozyraki R., Kristiansen M., Kaysen J.H., Rasmussen H.H.,
RA Brault D., Pontillon F., Goda F.O., Christensen E.I., Hammond T.G.,
RA Verroust P.J.;
RT "The intrinsic factor-vitamin B12 receptor and target of teratogenic
RT antibodies is a megalin-binding peripheral membrane protein with homology
RT to developmental proteins.";
RL J. Biol. Chem. 273:5235-5242(1998).
RN [2]
RP BINDING TO CBLIF-COBALAMIN COMPLEX, TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=9153271; DOI=10.1172/jci119411;
RA Seetharam B., Christensen E.I., Moestrup S.K., Hammond T.G., Verroust P.J.;
RT "Identification of rat yolk sac target protein of teratogenic antibodies,
RT gp280, as intrinsic factor-cobalamin receptor.";
RL J. Clin. Invest. 99:2317-2322(1997).
RN [3]
RP INTERACTION WITH KAPPA-LIGHT AND LAMBDA-LIGHT CHAINS.
RX PubMed=9691015; DOI=10.1152/ajprenal.1998.275.2.f246;
RA Batuman V., Verroust P.J., Navar G.L., Kaysen J.H., Goda F.O.,
RA Campbell W.C., Simon E., Pontillon F., Lyles M., Bruno J., Hammond T.G.;
RT "Myeloma light chains are ligands for cubilin (gp280).";
RL Am. J. Physiol. 275:F246-F254(1998).
RN [4]
RP DOMAIN.
RX PubMed=10400683; DOI=10.1074/jbc.274.29.20540;
RA Kristiansen M., Kozyraki R., Jacobsen C., Nexoe E., Verroust P.J.,
RA Moestrup S.K.;
RT "Molecular dissection of the intrinsic factor-vitamin B12 receptor,
RT cubilin, discloses regions important for membrane association and ligand
RT binding.";
RL J. Biol. Chem. 274:20540-20544(1999).
RN [5]
RP INTERACTION WITH ALB, AND FUNCTION.
RX PubMed=10811843; DOI=10.1172/jci8862;
RA Birn H., Fyfe J.C., Jacobsen C., Mounier F., Verroust P.J., Oerskov H.,
RA Willnow T.E., Moestrup S.K., Christensen E.I.;
RT "Cubilin is an albumin binding protein important for renal tubular albumin
RT reabsorption.";
RL J. Clin. Invest. 105:1353-1361(2000).
RN [6]
RP INTERACTION WITH HEMOGLOBIN, AND FUNCTION.
RX PubMed=11805171; DOI=10.1681/asn.v132423;
RA Gburek J., Verroust P.J., Willnow T.E., Fyfe J.C., Nowacki W., Jacobsen C.,
RA Moestrup S.K., Christensen E.I.;
RT "Megalin and cubilin are endocytic receptors involved in renal clearance of
RT hemoglobin.";
RL J. Am. Soc. Nephrol. 13:423-430(2002).
RN [7]
RP INTERACTION WITH MB, AND FUNCTION.
RX PubMed=12724130; DOI=10.1152/ajprenal.00062.2003;
RA Gburek J., Birn H., Verroust P.J., Goj B., Jacobsen C., Moestrup S.K.,
RA Willnow T.E., Christensen E.I.;
RT "Renal uptake of myoglobin is mediated by the endocytic receptors megalin
RT and cubilin.";
RL Am. J. Physiol. 285:F451-F458(2003).
RN [8]
RP INTERACTION WITH AMN.
RX PubMed=14576052; DOI=10.1182/blood-2003-08-2852;
RA Fyfe J.C., Madsen M., Hoejrup P., Christensen E.I., Tanner S.M.,
RA de la Chapelle A., He Q., Moestrup S.K.;
RT "The functional cobalamin (vitamin B12)-intrinsic factor receptor is a
RT novel complex of cubilin and amnionless.";
RL Blood 103:1573-1579(2004).
RN [9]
RP DEVELOPMENTAL STAGE, AND FUNCTION.
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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-3008, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT regulation of aquaporin-2 phosphorylation at two sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
RN [11]
RP SUBUNIT.
RX PubMed=20237569; DOI=10.1038/nature08874;
RA Andersen C.B., Madsen M., Storm T., Moestrup S.K., Andersen G.R.;
RT "Structural basis for receptor recognition of vitamin-B(12)-intrinsic
RT factor complexes.";
RL Nature 464:445-448(2010).
RN [12]
RP SUBCELLULAR LOCATION, INTERACTION WITH AMN, GLYCOSYLATION AT ASN-711;
RP ASN-749; ASN-781 AND ASN-857, AND MUTAGENESIS OF GLY-142; CYS-222; PRO-334;
RP ARG-651; GLY-653; ASN-711; ASN-749; ASN-781; SER-829; ASN-857 AND SER-865.
RX PubMed=29402915; DOI=10.1038/s41598-018-20731-4;
RA Udagawa T., Harita Y., Miura K., Mitsui J., Ode K.L., Morishita S.,
RA Urae S., Kanda S., Kajiho Y., Tsurumi H., Ueda H.R., Tsuji S., Saito A.,
RA Oka A.;
RT "Amnionless-mediated glycosylation is crucial for cell surface targeting of
RT cubilin in renal and intestinal cells.";
RL Sci. Rep. 8:2351-2351(2018).
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:10811843, ECO:0000269|PubMed:11805171,
CC ECO:0000269|PubMed:12724130, ECO:0000269|PubMed:15616221,
CC ECO:0000269|PubMed:9153271, ECO:0000269|PubMed:9478979}.
CC -!- SUBUNIT: Interacts with AMN (PubMed:14576052, PubMed:29402915).
CC Component of the cubam complex composed of one CUBN trimer and one AMN
CC chain (By similarity). The cubam complex can dimerize (By similarity).
CC Interacts with LRP2 in a dual-receptor complex in a calcium-dependent
CC manner (PubMed:9478979). Found in a complex with PID1/PCLI1, LRP1 and
CC CUBNI. Interacts with LRP1 and PID1/PCLI1 (PubMed:20237569) (By
CC similarity). {ECO:0000250|UniProtKB:F1RWC3,
CC ECO:0000250|UniProtKB:O60494, ECO:0000269|PubMed:14576052,
CC ECO:0000269|PubMed:20237569, ECO:0000269|PubMed:29402915,
CC ECO:0000269|PubMed:9478979}.
CC -!- INTERACTION:
CC O70244; O70244: Cubn; NbExp=2; IntAct=EBI-3954161, EBI-3954161;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:29402915};
CC Peripheral membrane protein {ECO:0000305|PubMed:29402915}. Endosome
CC membrane {ECO:0000269|PubMed:9478979}; Peripheral membrane protein
CC {ECO:0000269|PubMed:9478979}. Lysosome membrane
CC {ECO:0000269|PubMed:9478979}; Peripheral membrane protein
CC {ECO:0000269|PubMed:9478979}. Note=Lacks a transmembrane domain and
CC depends on 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 (PubMed:9478979). {ECO:0000250|UniProtKB:O60494,
CC ECO:0000269|PubMed:9478979}.
CC -!- TISSUE SPECIFICITY: Expressed to intestinal, renal and yalk sac apical
CC membranes. In kidney, expressed in the proximal tubule.
CC {ECO:0000269|PubMed:9153271}.
CC -!- DEVELOPMENTAL STAGE: Expressed at 6 dpc in primitive endoderm cells, in
CC apical membrane invaginations, in endocytic vesicles, endoplasmic
CC reticulum and Golgi apparatus. At the egg cylinder stage (7-8 dpc),
CC expressed in visceral and parietal endoderm. From the early headfold
CC stage (8.9 dpc), expressed in ectodermal cells lining the proamniotic
CC cavity. At 10 dpc, detected in the newly forming neuroepithelium.
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:0000269|PubMed:10400683}.
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:29402915,
CC ECO:0000269|PubMed:9478979}.
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DR EMBL; AF022247; AAC71661.1; -; mRNA.
DR PIR; T08618; T08618.
DR RefSeq; NP_445784.1; NM_053332.2.
DR SMR; O70244; -.
DR BioGRID; 249486; 1.
DR CORUM; O70244; -.
DR STRING; 10116.ENSRNOP00000048477; -.
DR GlyGen; O70244; 42 sites.
DR iPTMnet; O70244; -.
DR PhosphoSitePlus; O70244; -.
DR PaxDb; O70244; -.
DR PRIDE; O70244; -.
DR GeneID; 80848; -.
DR KEGG; rno:80848; -.
DR UCSC; RGD:68355; rat.
DR CTD; 8029; -.
DR RGD; 68355; Cubn.
DR eggNOG; KOG4292; Eukaryota.
DR InParanoid; O70244; -.
DR OrthoDB; 4105at2759; -.
DR PhylomeDB; O70244; -.
DR Reactome; R-RNO-196791; Vitamin D (calciferol) metabolism.
DR Reactome; R-RNO-8964011; HDL clearance.
DR Reactome; R-RNO-9758881; Uptake of dietary cobalamins into enterocytes.
DR PRO; PR:O70244; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0045177; C:apical part of cell; ISO:RGD.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0005903; C:brush border; ISO:RGD.
DR GO; GO:0031526; C:brush border membrane; IDA:UniProtKB.
DR GO; GO:0005905; C:clathrin-coated pit; IDA:UniProtKB.
DR GO; GO:0030135; C:coated vesicle; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0030139; C:endocytic vesicle; ISO:RGD.
DR GO; GO:0030666; C:endocytic vesicle membrane; IDA:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR GO; GO:0005768; C:endosome; ISO:RGD.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; ISO:RGD.
DR GO; GO:0005794; C:Golgi apparatus; ISO:RGD.
DR GO; GO:0005798; C:Golgi-associated vesicle; IDA:RGD.
DR GO; GO:0043202; C:lysosomal lumen; IDA:RGD.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IDA:RGD.
DR GO; GO:0031528; C:microvillus membrane; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0043235; C:receptor complex; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0038024; F:cargo receptor activity; IMP:UniProtKB.
DR GO; GO:0031419; F:cobalamin binding; IEA:UniProtKB-KW.
DR GO; GO:0030492; F:hemoglobin binding; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0038023; F:signaling receptor activity; IDA:RGD.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0042366; P:cobalamin catabolic process; IMP:RGD.
DR GO; GO:0009235; P:cobalamin metabolic process; ISO:RGD.
DR GO; GO:0015889; P:cobalamin transport; IMP:UniProtKB.
DR GO; GO:0020028; P:endocytic hemoglobin import into cell; IMP:RGD.
DR GO; GO:0001701; P:in utero embryonic development; IDA:RGD.
DR GO; GO:0042953; P:lipoprotein transport; ISO:RGD.
DR GO; GO:0006898; P:receptor-mediated endocytosis; IDA:RGD.
DR GO; GO:0009617; P:response to bacterium; ISO:RGD.
DR GO; GO:0007584; P:response to nutrient; IMP:RGD.
DR GO; GO:0006766; P:vitamin metabolic process; TAS:RGD.
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; 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; 3.
DR Pfam; PF12947; EGF_3; 1.
DR Pfam; PF07645; EGF_CA; 3.
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; 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_0000046076"
FT CHAIN 33..3623
FT /note="Cubilin"
FT /id="PRO_0000046077"
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:0007744|PubMed:16641100"
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:0000305|PubMed:29402915"
FT CARBOHYD 749
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305|PubMed:29402915"
FT CARBOHYD 781
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305|PubMed:29402915"
FT CARBOHYD 857
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305|PubMed:29402915"
FT CARBOHYD 957
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 984
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 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 1671
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 2085
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
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 2875
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2945
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2989
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3042
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:0000255"
FT CARBOHYD 3165
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
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 3400
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3430
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 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 MUTAGEN 142
FT /note="G->E: No effect on trafficking to the cell surface."
FT /evidence="ECO:0000269|PubMed:29402915"
FT MUTAGEN 222
FT /note="C->S: Decreased AMN-dependent trafficking to the
FT cell surface."
FT /evidence="ECO:0000269|PubMed:29402915"
FT MUTAGEN 334
FT /note="P->L: No effect on trafficking to the cell surface."
FT /evidence="ECO:0000269|PubMed:29402915"
FT MUTAGEN 651
FT /note="R->G: No effect on trafficking to the cell surface."
FT /evidence="ECO:0000269|PubMed:29402915"
FT MUTAGEN 653
FT /note="G->A,S: No effect on trafficking to the cell
FT surface."
FT /evidence="ECO:0000269|PubMed:29402915"
FT MUTAGEN 653
FT /note="G->R: Decreased AMN-dependent trafficking to the
FT cell surface."
FT /evidence="ECO:0000269|PubMed:29402915"
FT MUTAGEN 711
FT /note="N->D: Impaired glycosylation and loss of export to
FT the cell surface; when associated with D-749; D-781 and D-
FT 857."
FT /evidence="ECO:0000269|PubMed:29402915"
FT MUTAGEN 749
FT /note="N->D: Impaired glycosylation and loss of export to
FT the cell surface; when associated with D-711; D-781 and D-
FT 857."
FT /evidence="ECO:0000269|PubMed:29402915"
FT MUTAGEN 781
FT /note="N->D: Impaired glycosylation and loss of export to
FT the cell surface; when associated with D-711; D-749 and D-
FT 857."
FT /evidence="ECO:0000269|PubMed:29402915"
FT MUTAGEN 829
FT /note="S->L: Decreased AMN-dependent trafficking to the
FT cell surface."
FT /evidence="ECO:0000269|PubMed:29402915"
FT MUTAGEN 857
FT /note="N->D: Impaired glycosylation and loss of export to
FT the cell surface; when associated with D-711; D-749 and D-
FT 781."
FT /evidence="ECO:0000269|PubMed:29402915"
FT MUTAGEN 865
FT /note="S->N: No effect on trafficking to the cell surface."
FT /evidence="ECO:0000269|PubMed:29402915"
SQ SEQUENCE 3623 AA; 398987 MW; 39FB792AC6545240 CRC64;
MSSQFLWGFV TLLMIAELDG KTGKPEQRGQ KRIADLHQPR MTTEEGNLVF LTSSTQNIEF
RTGSLGKIKL NDEDLGECLH QIQRNKDDII DLRKNTTGLP QNILSQVHQL NSKLVDLERD
FQNLQQNVER KVCSSNPCLN GGTCVNLHDS FVCICPSQWK GLFCSEDVNE CVVYSGTPFG
CQSGSTCVNT VGSFRCDCTP DTYGPQCASK YNDCEQGSKQ LCKHGICEDL QRVHHGQPNF
HCICDAGWTT PPNGISCTED KDECSLQPSP CSEHAQCFNT QGSFYCGACP KGWQGNGYEC
QDINECEINN GGCSQAPLVP CLNTPGSFSC GNCPAGFSGD GRVCTPVDIC SIHNGGCHPE
ATCSSSPVLG SFLPVCTCPP GYTGNGYGSN GCVRLSNICS RHPCVNGQCI ETVSSYFCKC
DSGWSGQNCT ENINDCSSNP CLNGGTCIDG INGFTCDCTS SWTGYYCQTP QAACGGILSG
TQGTFAYHSP NDTYIHNVNC FWIVRTDEEK VLHVTFTFFD LESASNCPRE YLQIHDGDSS
ADFPLGRYCG SRPPQGIHSS ANALYFHLYS EYIRSGRGFT ARWEAKLPEC GGILTDNYGS
ITSPGYPGNY PPGRDCVWQV LVNPNSLITF TFGTLSLESH NDCSKDYLEI RDGPFHQDPV
LGKFCTSLST PPLKTTGPAA RIHFHSDSET SDKGFHITYL TTQSDLDCGG NYTDTDGELL
LPPLSGPFSH SRQCVYLITQ AQGEQIVINF THVELESQMG CSHTYIEVGD HDSLLRKICG
NETLFPIRSV SNKVWIRLRI DALVQKASFR ADYQVACGGM LRGEGFFRSP FYPNAYPGRR
TCRWTISQPQ RQVVLLNFTD FQIGSSASCD TDYIEIGPSS VLGSPGNEKF CSSNIPSFIT
SVYNILYVTF VKSSSMENRG FTAKFSSDKL ECGEVLTAST GIIESPGHPN VYPRGVNCTW
HVVVQRGQLI RLEFSSFYLE FHYNCTNDYL EIYDTAAQTF LGRYCGKSIP PSLTSNSNSI
KLIFVSDSAL AHEGFSINYE AIDASSVCLY DYTDNFGMLS SPNFPNNYPS NWECIYRITV
GLNQQIALHF TDFTLEDYFG SQCVDFVEIR DGGYETSPLV GIYCGSVLPP TIISHSNKLW
LKFKSDAALT AKGFSAYWDG SSTGCGGNLT TPTGVLTSPN YPMPYYHSSE CYWRLEASHG
SPFELEFQDF HLEHHPSCSL DYLAVFDGPT TNSRLIDKLC GDTTPAPIRS NKDVVLLKLR
TDAGQQGRGF EINFRQRCDN VVIVNKTSGI LESINYPNPY DKNQRCNWTI QATTGNTVNY
TFLGFDVESY MNCSTDYVEL YDGPQWMGRY CGNNMPPPGA TTGSQLHVLF HTDGINSGEK
GFKMQWFTHG CGGEMSGTAG SFSSPGYPNS YPHNKECIWN IRVAPGSSIQ LTIHDFDVEY
HTSCNYDSLE IYAGLDFNSP RIAQLCSQSP SANPMQVSST GNELAIRFKT DSTLNGRGFN
ASWRAVPGGC GGIIQLSRGE IHSPNYPNNY RANTECSWII QVERHHRVLL NITDFDLEAP
DSCLRLMDGS SSTNARVASV CGRQQPPNSI IASGNSLFVR FRSGSSSQNR GFRAEFREEC
GGRIMTDSSD TIFSPLYPHN YLHNQNCSWI IEAQPPFNHI TLSFTHFQLQ NSTDCTRDFV
EILDGNDYDA PVQGRYCGFS LPHPIISFGN ALTVRFVTDS TRSFEGFRAI YSASTSSCGG
SFYTLDGIFN SPDYPADYHP NAECVWNIAS SPGNRLQLSF LSFNLENSLN CNKDFVEIRE
GNATGHLIGR YCGNSLPGNY SSAEGHSLWV RFVSDGSGTG MGFQARFKNI FGNNNIVGTH
GKIASPFWPG KYPYNSNYKW VVNVDAYHII HGRILEMDIE PTTNCFYDSL KIYDGFDTHS
RLIGTYCGTQ TESFSSSRNS LTFQFSSDSS VSGRGFLLEW FAVDVSDSTP PTIAPGACGG
FMVTGDTPVH IFSPGWPREY ANGADCIWII YAPDSTVELN ILSLDIEPQQ SCNYDKLIVK
DGDSDLSPEL AVLCGVSPPG PIRSTGEYMY IRFTSDTSVA GTGFNASFHK SCGGYLHADR
GVITSPKYPD TYLPNLNCSW HVLVQTGLTI AVHFEQPFQI QNRDSFCSQG DYLVLRNGPD
NHSPPLGPSG RNGRFCGMYA PSTLFTSGNE MFVQFISDSS NGGQGFKIRY EAKSLACGGT
VYIHDADSDG YLTSPNYPAN YPQHAECIWI LEAPPGRSIQ LQFEDQFNIE DTPNCSVSYL
ELRDGANSNA RLVSKLCGHT LPHSWVSSRE RIYLKFHTDG GSSYMGFKAK YSIASCGGTV
SGDSGVIESI GYPTLPYANN VFCQWFIRGL PGHYLTLSFE DFNLQSSPGC TKDFVEIWEN
HTSGRVLGRY CGNSTPSSVD TSSNVASVKF VTDGSVTASG FRLQFKSSRQ VCGGDLHGPT
GTFTSPNYPN PNPHARICEW TITVQEGRRI VLTFTNLRLS TQPSCNSEHL IVFNGIRSNS
PLLQKLCSRV NVTNEFKSSG NTMKVVFFTD GSRPYGGFTA SYTSTEDAVC GGFLPSVSGG
NFSSPGYNGI RDYARNLDCE WTLSNPNREN SSISIYFLEL SIESHQDCTF DVLEFRVGDA
DGPLIEKFCS LSAPTAPLVI PYPQVWIHFV SNERVEYTGF YIEYSFTDCG GIRTGDNGVI
SSPNYPNLYS AWTHCSWLLK APEGHTITLT FSDFLLEAHP TCTSDSVTVR NGDSPGSPVI
GRYCGQSVPR PIQSGSNQLI VTFNTNNQGQ TRGFYATWTT NALGCGGTFH SANGTIKSPH
WPQTFPENSR CSWTVITHES KHWEISFDSN FRIPSSDSQC QNSFVKVWEG RLMINKTLLA
TSCGDVAPSP IVTSGNIFTA VFQSEEMAAQ GFSASFISRC GRTFNTSPGD IISPNFPKQY
DNNMNCTYLI DADPQSLVIL TFVSFHLEDR SAITGTCDHD GLHIIKGRNL SSTPLVTICG
SETLRPLTVD GPVLLNFYSD AYTTDFGFKI SYRAITCGGI YNESSGILRS PSYSYSNYPN
NLYCVYSLHV RSSRVIIIRF NDFDVAPSNL CAHDFLEVFD GPSIGNRSLG KFCGSTRPQT
VKSTNSSLTL LFKTDSSQTA RGWKIFFRET IGPQQGCGGY LTEDNQSFVS PDSDSNGRYD
KGLSCIWYIV APENKLVKLT FNVFTLEGPS SAGSCVYDYV QIADGASINS YLGGKFCGSR
MPAPFISSGN FLTFQFVSDV TVEMRGFNAT YTFVDMPCGG TYNATSTPQN ASSPHLSNIG
RPYSTCTWVI AAPPQQQVQI TVWDLQLPSQ DCSQSYLELQ DSVQTGGNRV TQFCGANYTT
LPVFYSSMST AVVVFKSGVL NRNSQVQFSY QIADCNREYN QTFGNLKSPG WPQNYDNNLD
CTIILRAPQN HSISLFFYWF QLEDSRQCMN DFLEVRNGGS STSPLLDKYC SNLLPNPVFS
QSNELYLHFH SDHSVTNNGY EIIWTSSAAG CGGTLLGDEG IFTNPGFPDS YPNNTHCEWT
IVAPSGRPVS VGFPFLSIDS SGGCDQNYLI VFNGPDANSP PFGPLCGINT GIAPFYASSN
RVFIRFHAEY TTRLSGFEIM WSS
