CUBN_PIG
ID CUBN_PIG Reviewed; 3625 AA.
AC F1RWC3;
DT 31-JUL-2019, integrated into UniProtKB/Swiss-Prot.
DT 22-NOV-2017, sequence version 3.
DT 03-AUG-2022, entry version 78.
DE RecName: Full=Cubilin;
DE AltName: Full=Intrinsic factor-cobalamin receptor;
DE Flags: Precursor;
GN Name=CUBN; Synonyms=IFCR;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823 {ECO:0000312|Proteomes:UP000008227};
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Duroc;
RG Porcine genome sequencing project;
RL Submitted (NOV-2009) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP STRUCTURE BY ELECTRON MICROSCOPY IN COMPLEX WITH AMN, SUBUNIT, DOMAIN, AND
RP TISSUE SPECIFICITY.
RX PubMed=30523278; DOI=10.1038/s41467-018-07468-4;
RA Larsen C., Etzerodt A., Madsen M., Skjodt K., Moestrup S.K.,
RA Andersen C.B.F.;
RT "Structural assembly of the megadalton-sized receptor for intestinal
RT vitamin B12 uptake and kidney protein reabsorption.";
RL Nat. Commun. 9:5204-5204(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:0000250|UniProtKB:O60494}.
CC -!- SUBUNIT: Interacts with AMN. Component of the cubam complex composed of
CC one CUBN trimer and one AMN chain (PubMed:30523278). The cubam complex
CC can dimerize (PubMed:30523278). 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:O60494,
CC ECO:0000269|PubMed:30523278}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000250|UniProtKB:Q9JLB4}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:O60494}. Cell membrane
CC {ECO:0000250|UniProtKB:O60494}; Peripheral membrane protein
CC {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: Detected in kidney cortex (at protein level).
CC {ECO:0000269|PubMed:30523278}.
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:0000269|PubMed:30523278}.
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:0000250|UniProtKB:O60494}.
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DR EMBL; AEMK02000074; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR SMR; F1RWC3; -.
DR STRING; 9823.ENSSSCP00000011764; -.
DR PaxDb; F1RWC3; -.
DR PeptideAtlas; F1RWC3; -.
DR PRIDE; F1RWC3; -.
DR eggNOG; KOG4292; Eukaryota.
DR HOGENOM; CLU_006258_0_0_1; -.
DR InParanoid; F1RWC3; -.
DR OMA; RGFTVRW; -.
DR TreeFam; TF316506; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-KW.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0038024; F:cargo receptor activity; IEA:InterPro.
DR GO; GO:0031419; F:cobalamin binding; IEA:UniProtKB-KW.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
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; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR035914; Sperma_CUB_dom_sf.
DR PANTHER; PTHR45656:SF11; PTHR45656:SF11; 3.
DR Pfam; PF00431; CUB; 27.
DR Pfam; PF00008; EGF; 2.
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 SUPFAM; SSF57184; SSF57184; 1.
DR PROSITE; PS00010; ASX_HYDROXYL; 3.
DR PROSITE; PS01180; CUB; 27.
DR PROSITE; PS00022; EGF_1; 4.
DR PROSITE; PS01186; EGF_2; 1.
DR PROSITE; PS50026; EGF_3; 7.
DR PROSITE; PS01187; EGF_CA; 3.
PE 1: Evidence at protein level;
KW Calcium; Cell membrane; Cholesterol metabolism;
KW Cleavage on pair of basic residues; Coated pit; Cobalamin; Cobalt;
KW Disulfide bond; EGF-like domain; Endosome; Glycoprotein; Lipid metabolism;
KW Lysosome; Membrane; Metal-binding; Phosphoprotein; Protein transport;
KW Reference proteome; Repeat; Signal; Steroid metabolism; Sterol metabolism;
KW Transport.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..36
FT /note="Removed in mature form"
FT /evidence="ECO:0000250|UniProtKB:O60494"
FT /id="PRO_0000447669"
FT CHAIN 37..3625
FT /note="Cubilin"
FT /evidence="ECO:0000255"
FT /id="PRO_5012768130"
FT DOMAIN 133..169
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 171..212
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 264..305
FT /note="EGF-like 3; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 306..349
FT /note="EGF-like 4; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 350..394
FT /note="EGF-like 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 396..431
FT /note="EGF-like 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 433..469
FT /note="EGF-like 7; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 475..587
FT /note="CUB 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 591..703
FT /note="CUB 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 709..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 1045..1163
FT /note="CUB 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 1167..1279
FT /note="CUB 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 1280..1391
FT /note="CUB 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 1393..1508
FT /note="CUB 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 1512..1621
FT /note="CUB 10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 1622..1736
FT /note="CUB 11"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 1740..1852
FT /note="CUB 12"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 1854..1965
FT /note="CUB 13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 1980..2093
FT /note="CUB 14"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 2094..2215
FT /note="CUB 15"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 2219..2336
FT /note="CUB 16"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 2338..2450
FT /note="CUB 17"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 2454..2567
FT /note="CUB 18"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 2572..2689
FT /note="CUB 19"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 2691..2803
FT /note="CUB 20"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 2807..2921
FT /note="CUB 21"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 2922..3037
FT /note="CUB 22"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 3039..3152
FT /note="CUB 23"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 3159..3276
FT /note="CUB 24"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 3280..3397
FT /note="CUB 25"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 3397..3509
FT /note="CUB 26"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 3513..3625
FT /note="CUB 27"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT REGION 43..50
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 1029
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 1097
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O60494"
FT BINDING 1107
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O60494"
FT BINDING 1148
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O60494"
FT BINDING 1215
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:O60494"
FT BINDING 1223
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 1266
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:O60494"
FT BINDING 1267
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:O60494"
FT BINDING 1330
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:O60494"
FT BINDING 1338
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 BINDING 1377
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:O60494"
FT SITE 36..37
FT /note="Cleavage; by furin"
FT /evidence="ECO:0000255"
FT MOD_RES 3010
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O70244"
FT CARBOHYD 106
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 429
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 712
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 984
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1048
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1170
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1219
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1287
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1309
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1321
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1334
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1502
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1553
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1648
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1804
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1821
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1887
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2087
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2119
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2276
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2388
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2402
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2533
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2583
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2594
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2612
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2887
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2925
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2928
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2947
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3044
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3105
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3127
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3270
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3285
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3359
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3432
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3459
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3535
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 137..148
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 142..157
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 159..168
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 175..191
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 185..200
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 202..211
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 268..281
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 275..290
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 293..304
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 310..325
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 317..334
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 337..348
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 354..367
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 361..377
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 379..393
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 400..410
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 405..419
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 421..430
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 437..448
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 442..457
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 459..468
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 475..501
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 528..550
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 591..617
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 644..666
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 709..734
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 761..779
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 817..842
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 869..891
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 932..958
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 985..1005
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 1104..1126
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 1167..1193
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 1220..1242
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 1280..1308
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 1335..1353
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 1393..1419
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 1446..1468
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 1512..1538
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 1565..1583
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 1622..1649
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 1677..1699
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 1740..1766
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 1793..1814
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 1907..1929
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 1980..2008
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 2034..2056
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 2094..2120
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 2219..2249
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 2277..2299
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 2338..2365
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 2392..2413
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 2454..2480
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 2507..2529
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 2572..2601
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 2630..2651
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 2691..2717
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 2744..2766
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 2807..2833
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 2862..2885
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 2922..2948
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 2979..3001
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 3039..3066
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 3093..3115
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 3159..3187
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 3217..3239
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 3280..3308
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 3334..3356
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 3397..3423
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 3450..3472
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 3513..3539
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 3566..3588
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
SQ SEQUENCE 3625 AA; 397366 MW; FB7BC4184199CC28 CRC64;
MVNNMSLLFL WSLVIFLTFA ESYGEAGGPE LQRHKRNTEL QQPRMAAERG NLVFFTGLAQ
NIEFRTGSQG KIKLNDEDVG ECLRQIQKNK FDIMNLKRGI IGLPQNVSSQ IHQLESKLVD
LERRFQSLQL TVDGKVCSSN PCQNGATCLN LHDSFFCICP SQWKGPLCSD DVNECEIYSG
TPLGCQNGAT CINTPGSYSC LCSPETHGPQ CASKYDDCEG GSEMRCVHGI CEDLTRVQAG
EPRFRCICHA GWTSPSNSTA CTLDRDECSS WPAPCSALVP CFNTLGSFYC GACPTGWQGN
GYICEDINEC EINNGGCSVA PPVECVNTPG SYYCPSCPPG YQGDGRMCTL IDLCSVNNGG
CHPHAACSLI LGSLPLCTCL PGYTGNGYGL HGCVPLSNVC LTRPCLHGQC METASGYVCN
CDSGWAGMNC TENINECLSN PCLNGGTCVD GINAFSCECT RFWTGSLCHL PQQVCGGTMS
DVSGSFSYMS PDVGYVHDVD CFWVLRTEEG KVLRITFTFF QLESVDNCPH EFLQIHDGDS
PAAFPLGRFC GSSPPHELLS SDNALYFHFF SEHLRNERGF TIRWETRQPE CGGVLTGTYG
SLKSPGYPGK YPPGRDCVWK VIASPDLLIT FTFGTLSLEH HDDCRKDYLE IRDGPLHQDP
VLGKFCTSLS VPPLQTTGPF ARIHFHSDNQ INDQGFHITY LTTPSDLHCG GNFTDPEGLL
SPDLSGPFTH SRQCIYVITQ PLGEQIQVNF THVELEGQSG CSQSYIEVRD DQTLLGKVCG
NETPSHIKSI TNSIWIRLKI DASVVRASFG AAYQVACGGE LTGEGVIRSP FYPNVYPGER
ICRWTIHQPQ SQVVLLNFTA FEMGSSAHCD TDYIEIGSSP VLGSPENKKY CGTDIPSFIT
SVYNSLHVVF VKSSSTENHG FMAKFSTEAL ACGEILTESS GIIQSPGHPN IYPHGVNCTW
HILVQPGHLI HLEIRQFHLE FHYNCTRDYL EIYDTVSDTS LGRYCGKSIP PSLTSNTNSL
KLIFVADADL AYEGFVINYE ATDASAGNTT ALLYRRIWIF TSPNFPSNYP NNMECIYRIT
VETSQQIALH FTDFSLEEPI GGACAADYVE ITNGGYASSP PLGKYCGSNP PPRIISHSNK
LWLKFKSDFF GSGPGFSAYW DGSLTGCGGN LTTPTGTFTS PNYPMPYYHS SECFWWLKSS
HGSPFELEFN DFHLEYHPNC TLDYLDVYDG LSTSSHLLTR LCGNEKPPLI RSTGDSMSLK
LRTDEGQQGG GFLVKYQQTC DNVVIVNRTY GILESIHYPK PYSVNQRCNW TIQATAGNTV
NYTFLAFELE SHANCSTDYL ELYDGPQRMG RFCGAVIPPS GSTTGSRLQV LFHTDGVGQG
ERGFQMQWLV HGCGGELSGD TGTFSSPGYP VGYPANKECI WYIHSSPGSS IQLTIHDFDV
EYHATCNFDV LEIYGGPDFH SPRIAQLCVQ RSAENPMQVS STGNELALRF KTDSSVNGRG
FNVSWRAVPG GCGGIFQAPS GEIHSPNYPS PYRSNTECTW LIQVEKNHRV LLNFTDFDLE
PQDSCIMAFD GLSSATARLV GVCGRQQLSN PIISTGSSLF VRFQSGPSRQ SRGFRAQFRQ
ACGGHILTDS FDTISSPRFP ASYPNNQNCS WIIQAQPPFN HITLSFSHFG LESSSTCTRD
FVEILDGSHS DAPLRGRYCG SSMPHPITSF GNALMLRFVS DSSVNFDGFH ATYVASTSAC
GGIFHMAEGI FNSPGYPEVY PSNVECVWNI ASSPGNQLQL SFITFQLEDS RDCSRDFVEI
REGNATGRLV GRYCGNVLPL NYSSIIGHDL WIKFVSDGSG SGVGFQAAFN NIFGNDHIVG
THGKVASPLW PRNYPHNSNY QWIVNVNESQ VIHGRILEMD VEGTFNCYYD KLRIYDGADI
HSRLIGTYCG AQTESFSSTG SSLTFQFSSD SSISGRGFLL EWFAMDASDG PLPTIATGAC
GGFLRTGDAP VFLYSPGWPG SYSNGADCMW LIQAPDSTVE LNILSLDIES HRTCDYDKLV
IRDGDNNMAQ ELAVLCGREI PGPIRSTGEY MTIRFTSDFS VTRAGFNASF HKSCGGYLHA
DRGIITSPGY PEAYTSNLNC SWHVQVQQGL SIAVHFEQPF QVSNRDAFCN QGDYLVLKNG
PDIYSPPLGP HGGNGRFCGS RPSSTLFTSD NELFVQFISD NSNEGQGFKI TYEAKSLACG
GNIYIHDADS SGYVASPNHP DNYPQHADCI WVIAAPSGRP IRLEFEDQFS IEITPNCTSS
YLELRDGADS NAPVLAKFCG TSLPPSQLSS GEVMYLRFRS DNSPTHAGFK AKYSIAQCGG
TVTGQSGVIE SSGYPALPYA NNLFCEWRLQ GLSGHYLTIH FEDFNLQNSS GCERDFVEIW
ENHTSGNLLG RYCGNTVPDS IDTSGNVALV RFVTDGFLTA SGFRLRFDSS MEGCGGDLQG
PTGTFTAPNY LNPNPHGWMC EWRITVQEGR RVTLTLNDLR LEAHPFCNSE HVAVFNGIRS
NSPQLEKRCS SVNGSNEIRS SGNTMKVVYF TDGSRPYGGF TASYTSSEDA VCGGSLTNSP
EGNFTSPGYD GTRNYSRNLN CEWTLSNSNQ GNSSIYIDFE DFYLESHQDC QFDVLEFRVD
NADGLLIWRL CGSSKPTMPL VIPYPQVWIH FVTNERVEHI GFRARYSFTD CGGIQIGDHG
VISSPNYPAS YDSLTHCSWL LEAPQGHTIT LTFSDFDIEA HASCAWDSVT VRNGGSPGSP
IIGHYCGSSN PRTIQSGSNQ LVVIFNTDSS VQNGGFYATW NTETSGCGGI LHSDTGTIRS
PHWPQNFPEN SRCSWTVITH PSKHLEISFD NNFLIPSGDS QCLNSFVKVW AGTQEADKDL
LATSCGNVSP GRIITPRNAF TAVFQSQETP AQGFSASFLS RCGRNFTNPS GYIVSPNYPK
QYDNNMNCTY IIEASPLSVI LLKVVSFHLE ARSTVSGSCD SDGVHIIRGH SLSSTPLVTL
CGDEALSPVT ISGPVLLNFY SNAHTTDFGF KFSYRITPCG GTFNLSFGII KSPSYSYSNY
PNDMHCLYTV TVRDDRVIQL KFNDFDLVPS TFCSQDYLEI YDGSNISDPL LGKFCGSTLP
PNVKSSNNTM FLVFKTDSVH TARGWKISFR ETLGPQQGCG GYLTGSTHTF GSPDSDSNGR
YDKNLNCIWF ITAPVNKLIK LTFSTFALEA ATSLQRCIYD YVKLYDGDSE NANLAGTFCG
STVPAPFISS GNFLTVQFVS DSSLEREGFN ATYTLLDMPC GGTYNATWTS QSIWSPSSSD
PDVPLTTCTW VIEAPLHQQV EITVWTFQLH SQDCDQNYLE FRDPPERNGN PGIRFCGRNA
SAVPTFYSSL STAIIIFKSE VFNTDSRVGF TYRIAGCSRE YQKAFGRLRS PGWPAGYASD
ADCAVVLRAP QNHTISLFFH AFGLEDSGGC TRDFLEVRNG SESTSPLLGK YCGTLLPNPI
FSQSRDLYLR FKSDSATSGR GYEIIWTSSP SGCGGTLYGD SGLVTSPGYP GTYPNHTHCE
WVIIAPGGRP VTVSFSFISI DDPGECVQNY LMLYDGPDAN SPSSGPYCGA DTDVAPFAAS
SHRVFIRFHA EAAARPSALR LTWAS
