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Database: UniProt
Entry: O60494
LinkDB: O60494
Original site: O60494 
ID   CUBN_HUMAN              Reviewed;        3623 AA.
AC   O60494; B0YIZ4; Q5VTA6; Q96RU9;
DT   07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT   02-NOV-2010, sequence version 5.
DT   10-APR-2019, entry version 175.
DE   RecName: Full=Cubilin;
DE   AltName: Full=460 kDa receptor;
DE   AltName: Full=Intestinal intrinsic factor receptor;
DE   AltName: Full=Intrinsic factor-cobalamin receptor;
DE   AltName: Full=Intrinsic factor-vitamin B12 receptor;
DE   Flags: Precursor;
GN   Name=CUBN; Synonyms=IFCR;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 36-41, FUNCTION,
RP   BINDING TO THE CBLIF-COBALAMIN COMPLEX, PROTEOLYTIC PROCESSING, AND
RP   VARIANTS SER-253; TYR-1545; ILE-1769; TYR-2162 AND TRP-2717.
RX   PubMed=9572993;
RA   Kozyraki R., Kristiansen M., Silahtaroglu A., Hansen C., Jacobsen C.,
RA   Tommerup N., Verroust P.J., Moestrup S.K.;
RT   "The human intrinsic factor-vitamin B12 receptor, cubilin: molecular
RT   characterization and chromosomal mapping of the gene to 10p within the
RT   autosomal recessive megaloblastic anemia (MGA1) region.";
RL   Blood 91:3593-3600(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG   NHLBI resequencing and genotyping service (RS&G);
RL   Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15164054; DOI=10.1038/nature02462;
RA   Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA   Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA   Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA   Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA   Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA   Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA   Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA   Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA   Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA   Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA   Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA   Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA   Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA   Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA   Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA   Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA   Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA   Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA   Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA   Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA   Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA   Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA   Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA   Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA   Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 10.";
RL   Nature 429:375-381(2004).
RN   [4]
RP   INTERACTION WITH APOA1, AND FUNCTION.
RX   PubMed=10371504; DOI=10.1038/9504;
RA   Kozyraki R., Fyfe J., Kristiansen M., Gerdes C., Jacobsen C., Cui S.,
RA   Christensen E.I., Aminoff M., de la Chapelle A., Krahe R.,
RA   Verroust P.J., Moestrup S.K.;
RT   "The intrinsic factor-vitamin B12 receptor, cubilin, is a high-
RT   affinity apolipoprotein A-I receptor facilitating endocytosis of high-
RT   density lipoprotein.";
RL   Nat. Med. 5:656-661(1999).
RN   [5]
RP   INTERACTION WITH GC, AND FUNCTION.
RX   PubMed=11717447; DOI=10.1073/pnas.241516998;
RA   Nykjaer A., Fyfe J.C., Kozyraki R., Leheste J.-R., Jacobsen C.,
RA   Nielsen M.S., Verroust P.J., Aminoff M., de la Chapelle A.,
RA   Moestrup S.K., Ray R., Gliemann J., Willnow T.E., Christensen E.I.;
RT   "Cubilin dysfunction causes abnormal metabolism of the steroid hormone
RT   25(OH) vitamin D(3).";
RL   Proc. Natl. Acad. Sci. U.S.A. 98:13895-13900(2001).
RN   [6]
RP   INTERACTION WITH TF, AND FUNCTION.
RX   PubMed=11606717; DOI=10.1073/pnas.211291398;
RA   Kozyraki R., Fyfe J., Verroust P.J., Jacobsen C., Dautry-Varsat A.,
RA   Gburek J., Willnow T.E., Christensen E.I., Moestrup S.K.;
RT   "Megalin-dependent cubilin-mediated endocytosis is a major pathway for
RT   the apical uptake of transferrin in polarized epithelia.";
RL   Proc. Natl. Acad. Sci. U.S.A. 98:12491-12496(2001).
RN   [7]
RP   INTERACTION WITH AMN, GLYCOSYLATION, AND FUNCTION.
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   [8]
RP   IDENTIFICATION IN A COMPLEX WITH LRP1 AND PID1, AND INTERACTION WITH
RP   LRP1 AND PID1.
RX   PubMed=17124247; DOI=10.1074/mcp.M600289-MCP200;
RA   Caratu G., Allegra D., Bimonte M., Schiattarella G.G., D'Ambrosio C.,
RA   Scaloni A., Napolitano M., Russo T., Zambrano N.;
RT   "Identification of the ligands of protein interaction domains through
RT   a functional approach.";
RL   Mol. Cell. Proteomics 6:333-345(2007).
RN   [9]
RP   X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 932-1388 IN COMPLEX WITH
RP   CBLIF AND CALCIUM IONS, INTERACTION WITH CBLIF, IDENTIFICATION IN
RP   CUBAM COMPLEX, SUBUNIT, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-984;
RP   ASN-1092; ASN-1168; ASN-1217; ASN-1285; ASN-1307; ASN-1319 AND
RP   ASN-1332.
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   [10]
RP   VARIANT RH-MGA1 LEU-1297, AND VARIANTS ILE-124; SER-253; THR-389;
RP   HIS-1032; TYR-1545; SER-1559; ILE-1769; PHE-2153; ARG-2575; ARG-2691;
RP   ILE-2879; VAL-2984; GLY-3002; ILE-3422 AND LYS-3552.
RX   PubMed=10080186; DOI=10.1038/6831;
RA   Aminoff M., Carter J.E., Chadwick R.B., Johnson C., Graesbeck R.,
RA   Abdelaal M.A., Broch H., Jenner L.B., Verroust P.J., Moestrup S.K.,
RA   de la Chapelle A., Krahe R.;
RT   "Mutations in CUBN, encoding the intrinsic factor-vitamin B12
RT   receptor, cubilin, cause hereditary megaloblastic anaemia 1.";
RL   Nat. Genet. 21:309-313(1999).
RN   [11]
RP   CHARACTERIZATION OF VARIANT RH-MGA1 LEU-1297.
RX   PubMed=10887099;
RA   Kristiansen M., Aminoff M., Jacobsen C., de La Chapelle A., Krahe R.,
RA   Verroust P.J., Moestrup S.K.;
RT   "Cubilin P1297L mutation associated with hereditary megaloblastic
RT   anemia 1 causes impaired recognition of intrinsic factor-vitamin B(12)
RT   by cubilin.";
RL   Blood 96:405-409(2000).
RN   [12]
RP   VARIANTS [LARGE SCALE ANALYSIS] GLN-786; VAL-2252; VAL-2914 AND
RP   VAL-3189.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA   Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA   Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA   Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA   Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal
RT   cancers.";
RL   Science 314:268-274(2006).
RN   [13]
RP   VARIANT VAL-2984.
RX   PubMed=21355061; DOI=10.1681/ASN.2010060598;
RG   CKDGen Consortium;
RA   Boger C.A., Chen M.H., Tin A., Olden M., Kottgen A., de Boer I.H.,
RA   Fuchsberger C., O'Seaghdha C.M., Pattaro C., Teumer A., Liu C.T.,
RA   Glazer N.L., Li M., O'Connell J.R., Tanaka T., Peralta C.A.,
RA   Kutalik Z., Luan J., Zhao J.H., Hwang S.J., Akylbekova E., Kramer H.,
RA   van der Harst P., Smith A.V., Lohman K., de Andrade M., Hayward C.,
RA   Kollerits B., Tonjes A., Aspelund T., Ingelsson E., Eiriksdottir G.,
RA   Launer L.J., Harris T.B., Shuldiner A.R., Mitchell B.D., Arking D.E.,
RA   Franceschini N., Boerwinkle E., Egan J., Hernandez D., Reilly M.,
RA   Townsend R.R., Lumley T., Siscovick D.S., Psaty B.M., Kestenbaum B.,
RA   Haritunians T., Bergmann S., Vollenweider P., Waeber G., Mooser V.,
RA   Waterworth D., Johnson A.D., Florez J.C., Meigs J.B., Lu X.,
RA   Turner S.T., Atkinson E.J., Leak T.S., Aasarod K., Skorpen F.,
RA   Syvanen A.C., Illig T., Baumert J., Koenig W., Kramer B.K.,
RA   Devuyst O., Mychaleckyj J.C., Minelli C., Bakker S.J., Kedenko L.,
RA   Paulweber B., Coassin S., Endlich K., Kroemer H.K., Biffar R.,
RA   Stracke S., Volzke H., Stumvoll M., Magi R., Campbell H., Vitart V.,
RA   Hastie N.D., Gudnason V., Kardia S.L., Liu Y., Polasek O., Curhan G.,
RA   Kronenberg F., Prokopenko I., Rudan I., Arnlov J., Hallan S.,
RA   Navis G., Parsa A., Ferrucci L., Coresh J., Shlipak M.G., Bull S.B.,
RA   Paterson N.J., Wichmann H.E., Wareham N.J., Loos R.J., Rotter J.I.,
RA   Pramstaller P.P., Cupples L.A., Beckmann J.S., Yang Q., Heid I.M.,
RA   Rettig R., Dreisbach A.W., Bochud M., Fox C.S., Kao W.H.;
RT   "CUBN is a gene locus for albuminuria.";
RL   J. Am. Soc. Nephrol. 22:555-570(2011).
RN   [14]
RP   VARIANT GLY-3258.
RX   PubMed=21248752; DOI=10.1038/nature09639;
RA   Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P.,
RA   Davies H., Jones D., Lin M.L., Teague J., Bignell G., Butler A.,
RA   Cho J., Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C.,
RA   Jia M., Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A.,
RA   Mudie L., Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S.,
RA   Kahnoski R.J., Anema J., Tuveson D.A., Perez-Mancera P.A.,
RA   Mustonen V., Fischer A., Adams D.J., Rust A., Chan-On W., Subimerb C.,
RA   Dykema K., Furge K., Campbell P.J., Teh B.T., Stratton M.R.,
RA   Futreal P.A.;
RT   "Exome sequencing identifies frequent mutation of the SWI/SNF complex
RT   gene PBRM1 in renal carcinoma.";
RL   Nature 469:539-542(2011).
RN   [15]
RP   VARIANTS PHE-2153; VAL-2984 AND GLY-3002.
RX   PubMed=23114252; DOI=10.1186/1471-2369-13-142;
RA   Tzur S., Wasser W.G., Rosset S., Skorecki K.;
RT   "Linkage disequilibrium analysis reveals an albuminuria risk haplotype
RT   containing three missense mutations in the cubilin gene with striking
RT   differences among European and African ancestry populations.";
RL   BMC Nephrol. 13:142-142(2012).
CC   -!- FUNCTION: Cotransporter which plays a role in lipoprotein, vitamin
CC       and iron metabolism, by facilitating their uptake. Binds to ALB,
CC       MB, Kappa and lambda-light chains, TF, hemoglobin, GC, SCGB1A1,
CC       APOA1, high density lipoprotein, and the CBLIF-cobalamin complex.
CC       The binding of all ligands requires calcium. Serves as important
CC       transporter in several absorptive epithelia, including intestine,
CC       renal proximal tubules and embryonic yolk sac. Interaction with
CC       LRP2 mediates its trafficking throughout vesicles and facilitates
CC       the uptake of specific ligands like GC, hemoglobin, ALB, TF and
CC       SCGB1A1. Interaction with AMN controls its trafficking to the
CC       plasma membrane and facilitates endocytosis of ligands. May play
CC       an important role in the development of the peri-implantation
CC       embryo through internalization of APOA1 and cholesterol. Binds to
CC       LGALS3 at the maternal-fetal interface.
CC       {ECO:0000269|PubMed:10371504, ECO:0000269|PubMed:11606717,
CC       ECO:0000269|PubMed:11717447, ECO:0000269|PubMed:14576052,
CC       ECO:0000269|PubMed:9572993}.
CC   -!- SUBUNIT: Interacts with LRP2 in a dual-receptor complex in a
CC       calcium-dependent manner. Component of the cubam complex composed
CC       of CUBN and AMN. The cubam complex can oligomerize and form cubam
CC       trimers. Found in a complex with PID1/PCLI1, LRP1 and CUBNI.
CC       Interacts with LRP1 and PID1/PCLI1. {ECO:0000269|PubMed:10371504,
CC       ECO:0000269|PubMed:11606717, ECO:0000269|PubMed:11717447,
CC       ECO:0000269|PubMed:14576052, ECO:0000269|PubMed:17124247,
CC       ECO:0000269|PubMed:20237569}.
CC   -!- SUBCELLULAR LOCATION: Apical cell membrane
CC       {ECO:0000250|UniProtKB:Q9JLB4}; Peripheral membrane protein
CC       {ECO:0000305}. Cell membrane {ECO:0000269|PubMed:14576052};
CC       Peripheral membrane protein {ECO:0000305}. Membrane, coated pit
CC       {ECO:0000269|PubMed:14576052}. Endosome
CC       {ECO:0000269|PubMed:14576052}. Lysosome membrane {ECO:0000250};
CC       Peripheral membrane protein {ECO:0000250}. Note=Colocalizes with
CC       AMN and LRP2 in the endocytotic apparatus of epithelial cells.
CC       {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Expressed in kidney proximal tubule cells,
CC       placenta, visceral yolk-sac cells and in absorptive intestinal
CC       cells. Expressed in the epithelium of intestine and kidney.
CC   -!- DOMAIN: The CUB domains 5 to 8 mediate binding to CBLIF and ALB.
CC       CUB domains 1 and 2 mediate interaction with LRP2.
CC   -!- PTM: The precursor is cleaved by a trans-Golgi proteinase furin.
CC       The result is a propeptide cleaved off.
CC       {ECO:0000269|PubMed:9572993}.
CC   -!- PTM: N-glycosylated. {ECO:0000269|PubMed:14576052,
CC       ECO:0000269|PubMed:20237569}.
CC   -!- DISEASE: Recessive hereditary megaloblastic anemia 1 (RH-MGA1)
CC       [MIM:261100]: Due to selective malabsorption of vitamin B12.
CC       Defects in vitamin B12 absorption lead to impaired function of
CC       thymidine synthase. As a consequence DNA synthesis is interrupted.
CC       Rapidly dividing cells involved in erythropoiesis are particularly
CC       affected. {ECO:0000269|PubMed:10080186,
CC       ECO:0000269|PubMed:10887099}. Note=The disease is caused by
CC       mutations affecting the gene represented in this entry.
DR   EMBL; AF034611; AAC82612.1; -; mRNA.
DR   EMBL; EF444970; ACA05973.1; -; Genomic_DNA.
DR   EMBL; EF444970; ACA05974.1; -; Genomic_DNA.
DR   EMBL; AC067747; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL365215; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL596445; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL731551; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS7113.1; -.
DR   PIR; T09456; T09456.
DR   RefSeq; NP_001072.2; NM_001081.3.
DR   UniGene; Hs.166206; -.
DR   PDB; 3KQ4; X-ray; 3.30 A; B/D/F=932-1388.
DR   PDB; 6GJE; X-ray; 2.30 A; B/C/D=1-3623.
DR   PDBsum; 3KQ4; -.
DR   PDBsum; 6GJE; -.
DR   ProteinModelPortal; O60494; -.
DR   SMR; O60494; -.
DR   BioGrid; 113724; 10.
DR   CORUM; O60494; -.
DR   DIP; DIP-58583N; -.
DR   IntAct; O60494; 3.
DR   MINT; O60494; -.
DR   STRING; 9606.ENSP00000367064; -.
DR   DrugBank; DB00115; Cyanocobalamin.
DR   DrugBank; DB00200; Hydroxocobalamin.
DR   iPTMnet; O60494; -.
DR   PhosphoSitePlus; O60494; -.
DR   BioMuta; CUBN; -.
DR   EPD; O60494; -.
DR   PaxDb; O60494; -.
DR   PeptideAtlas; O60494; -.
DR   PRIDE; O60494; -.
DR   ProteomicsDB; 49432; -.
DR   Ensembl; ENST00000377833; ENSP00000367064; ENSG00000107611.
DR   GeneID; 8029; -.
DR   KEGG; hsa:8029; -.
DR   UCSC; uc001ioo.4; human.
DR   CTD; 8029; -.
DR   DisGeNET; 8029; -.
DR   EuPathDB; HostDB:ENSG00000107611.14; -.
DR   GeneCards; CUBN; -.
DR   H-InvDB; HIX0035313; -.
DR   H-InvDB; HIX0035577; -.
DR   HGNC; HGNC:2548; CUBN.
DR   HPA; HPA004133; -.
DR   HPA; HPA043854; -.
DR   MalaCards; CUBN; -.
DR   MIM; 261100; phenotype.
DR   MIM; 602997; gene.
DR   neXtProt; NX_O60494; -.
DR   OpenTargets; ENSG00000107611; -.
DR   Orphanet; 35858; Imerslund-Graesbeck syndrome.
DR   PharmGKB; PA27044; -.
DR   eggNOG; KOG3714; Eukaryota.
DR   eggNOG; ENOG410ZPX7; LUCA.
DR   GeneTree; ENSGT00940000155299; -.
DR   HOGENOM; HOG000049236; -.
DR   HOVERGEN; HBG080357; -.
DR   InParanoid; O60494; -.
DR   KO; K14616; -.
DR   OMA; YSFTDCG; -.
DR   OrthoDB; 4105at2759; -.
DR   PhylomeDB; O60494; -.
DR   TreeFam; TF316224; -.
DR   Reactome; R-HSA-196741; Cobalamin (Cbl, vitamin B12) transport and metabolism.
DR   Reactome; R-HSA-196791; Vitamin D (calciferol) metabolism.
DR   Reactome; R-HSA-3359462; Defective AMN causes hereditary megaloblastic anemia 1.
DR   Reactome; R-HSA-3359463; Defective CUBN causes hereditary megaloblastic anemia 1.
DR   Reactome; R-HSA-8964011; HDL clearance.
DR   ChiTaRS; CUBN; human.
DR   EvolutionaryTrace; O60494; -.
DR   GeneWiki; Cubilin; -.
DR   GenomeRNAi; 8029; -.
DR   PRO; PR:O60494; -.
DR   Proteomes; UP000005640; Chromosome 10.
DR   Bgee; ENSG00000107611; Expressed in 121 organ(s), highest expression level in cortex of kidney.
DR   ExpressionAtlas; O60494; baseline and differential.
DR   Genevisible; O60494; HS.
DR   GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR   GO; GO:0031526; C:brush border membrane; ISS:UniProtKB.
DR   GO; GO:0005905; C:clathrin-coated pit; IBA:GO_Central.
DR   GO; GO:0030135; C:coated vesicle; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0030139; C:endocytic vesicle; IDA:UniProtKB.
DR   GO; GO:0030666; C:endocytic vesicle membrane; IBA:GO_Central.
DR   GO; GO:0005783; C:endoplasmic reticulum; IEA:Ensembl.
DR   GO; GO:0010008; C:endosome membrane; TAS:Reactome.
DR   GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB.
DR   GO; GO:0031232; C:extrinsic component of external side of plasma membrane; NAS:UniProtKB.
DR   GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
DR   GO; GO:0005798; C:Golgi-associated vesicle; IBA:GO_Central.
DR   GO; GO:0008328; C:ionotropic glutamate receptor complex; IBA:GO_Central.
DR   GO; GO:0043202; C:lysosomal lumen; IBA:GO_Central.
DR   GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; TAS:ProtInc.
DR   GO; GO:0032589; C:neuron projection membrane; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0045202; C:synapse; IBA:GO_Central.
DR   GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR   GO; GO:0038024; F:cargo receptor activity; IBA:GO_Central.
DR   GO; GO:0016247; F:channel regulator activity; IBA:GO_Central.
DR   GO; GO:0031419; F:cobalamin binding; IEA:UniProtKB-KW.
DR   GO; GO:0008144; F:drug binding; ISS:UniProtKB.
DR   GO; GO:0030492; F:hemoglobin binding; IBA:GO_Central.
DR   GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR   GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR   GO; GO:0005215; F:transporter activity; TAS:ProtInc.
DR   GO; GO:0008344; P:adult locomotory behavior; IBA:GO_Central.
DR   GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR   GO; GO:0042366; P:cobalamin catabolic process; IBA:GO_Central.
DR   GO; GO:0009235; P:cobalamin metabolic process; TAS:Reactome.
DR   GO; GO:0015889; P:cobalamin transport; IBA:GO_Central.
DR   GO; GO:0020028; P:endocytic hemoglobin import; IBA:GO_Central.
DR   GO; GO:0034384; P:high-density lipoprotein particle clearance; TAS:Reactome.
DR   GO; GO:0006972; P:hyperosmotic response; IBA:GO_Central.
DR   GO; GO:0001701; P:in utero embryonic development; IBA:GO_Central.
DR   GO; GO:0042953; P:lipoprotein transport; IEA:Ensembl.
DR   GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; IBA:GO_Central.
DR   GO; GO:0070207; P:protein homotrimerization; IBA:GO_Central.
DR   GO; GO:0006898; P:receptor-mediated endocytosis; NAS:UniProtKB.
DR   GO; GO:0040012; P:regulation of locomotion; IBA:GO_Central.
DR   GO; GO:0009617; P:response to bacterium; IEA:Ensembl.
DR   GO; GO:0007584; P:response to nutrient; IBA:GO_Central.
DR   GO; GO:0001966; P:thigmotaxis; IBA:GO_Central.
DR   GO; GO:0001894; P:tissue homeostasis; NAS:UniProtKB.
DR   GO; GO:0042359; P:vitamin D metabolic process; TAS:Reactome.
DR   CDD; cd00041; CUB; 27.
DR   Gene3D; 2.60.120.290; -; 27.
DR   InterPro; IPR000859; CUB_dom.
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; IPR009030; Growth_fac_rcpt_cys_sf.
DR   InterPro; IPR035914; Sperma_CUB_dom_sf.
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   SUPFAM; SSF57184; SSF57184; 1.
DR   PROSITE; PS00010; ASX_HYDROXYL; 4.
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; 3.
PE   1: Evidence at protein level;
KW   3D-structure; Calcium; Cell membrane; Cholesterol metabolism;
KW   Cleavage on pair of basic residues; Coated pit; Cobalamin; Cobalt;
KW   Complete proteome; Direct protein sequencing; Disease mutation;
KW   Disulfide bond; EGF-like domain; Endocytosis; Endosome; Glycoprotein;
KW   Lipid metabolism; Lysosome; Membrane; Metal-binding; Phosphoprotein;
KW   Polymorphism; Protein transport; Receptor; Reference proteome; Repeat;
KW   Signal; Steroid metabolism; Sterol metabolism; Transport.
FT   SIGNAL        1     23       {ECO:0000255}.
FT   PROPEP       24     35       Removed in mature form.
FT                                {ECO:0000269|PubMed:9572993}.
FT                                /FTId=PRO_0000046072.
FT   CHAIN        36   3623       Cubilin.
FT                                /FTId=PRO_0000046073.
FT   DOMAIN      132    168       EGF-like 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      170    211       EGF-like 2; calcium-binding.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DOMAIN      263    304       EGF-like 3; calcium-binding.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DOMAIN      305    348       EGF-like 4; calcium-binding.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DOMAIN      349    385       EGF-like 5. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      395    430       EGF-like 6. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      432    468       EGF-like 7; calcium-binding.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DOMAIN      474    586       CUB 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00059}.
FT   DOMAIN      590    702       CUB 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00059}.
FT   DOMAIN      708    816       CUB 3. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00059}.
FT   DOMAIN      816    928       CUB 4. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00059}.
FT   DOMAIN      932   1042       CUB 5. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00059}.
FT   DOMAIN     1048   1161       CUB 6. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00059}.
FT   DOMAIN     1165   1277       CUB 7. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00059}.
FT   DOMAIN     1278   1389       CUB 8. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00059}.
FT   DOMAIN     1391   1506       CUB 9. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00059}.
FT   DOMAIN     1510   1619       CUB 10. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00059}.
FT   DOMAIN     1620   1734       CUB 11. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00059}.
FT   DOMAIN     1738   1850       CUB 12. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00059}.
FT   DOMAIN     1852   1963       CUB 13. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00059}.
FT   DOMAIN     1978   2091       CUB 14. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00059}.
FT   DOMAIN     2092   2213       CUB 15. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00059}.
FT   DOMAIN     2217   2334       CUB 16. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00059}.
FT   DOMAIN     2336   2448       CUB 17. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00059}.
FT   DOMAIN     2452   2565       CUB 18. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00059}.
FT   DOMAIN     2570   2687       CUB 19. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00059}.
FT   DOMAIN     2689   2801       CUB 20. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00059}.
FT   DOMAIN     2805   2919       CUB 21. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00059}.
FT   DOMAIN     2920   3035       CUB 22. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00059}.
FT   DOMAIN     3037   3150       CUB 23. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00059}.
FT   DOMAIN     3157   3274       CUB 24. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00059}.
FT   DOMAIN     3278   3393       CUB 25. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00059}.
FT   DOMAIN     3395   3507       CUB 26. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00059}.
FT   DOMAIN     3511   3623       CUB 27. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00059}.
FT   METAL       980    980       Calcium 1.
FT   METAL       988    988       Calcium 1.
FT   METAL      1027   1027       Calcium 1.
FT   METAL      1029   1029       Calcium 1.
FT   METAL      1030   1030       Calcium 1; via carbonyl oxygen.
FT   METAL      1096   1096       Calcium 2.
FT   METAL      1105   1105       Calcium 2.
FT   METAL      1146   1146       Calcium 2.
FT   METAL      1148   1148       Calcium 2; via carbonyl oxygen.
FT   METAL      1149   1149       Calcium 2; via carbonyl oxygen.
FT   METAL      1213   1213       Calcium 3.
FT   METAL      1221   1221       Calcium 3.
FT   METAL      1262   1262       Calcium 3.
FT   METAL      1264   1264       Calcium 3; via carbonyl oxygen.
FT   METAL      1265   1265       Calcium 3; via carbonyl oxygen.
FT   METAL      1328   1328       Calcium 4.
FT   METAL      1336   1336       Calcium 4.
FT   METAL      1373   1373       Calcium 4.
FT   METAL      1375   1375       Calcium 4; via carbonyl oxygen.
FT   SITE         35     36       Cleavage; by furin. {ECO:0000255}.
FT   MOD_RES    3008   3008       Phosphothreonine.
FT                                {ECO:0000250|UniProtKB:O70244}.
FT   CARBOHYD    105    105       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    428    428       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    482    482       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    711    711       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    749    749       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    781    781       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    857    857       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    957    957       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    984    984       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000269|PubMed:20237569}.
FT   CARBOHYD   1092   1092       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000269|PubMed:20237569}.
FT   CARBOHYD   1168   1168       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000269|PubMed:20237569}.
FT   CARBOHYD   1217   1217       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000269|PubMed:20237569}.
FT   CARBOHYD   1285   1285       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000269|PubMed:20237569}.
FT   CARBOHYD   1307   1307       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000269|PubMed:20237569}.
FT   CARBOHYD   1319   1319       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000269|PubMed:20237569}.
FT   CARBOHYD   1332   1332       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000269|PubMed:20237569}.
FT   CARBOHYD   1500   1500       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   1551   1551       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   1646   1646       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   1802   1802       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   1819   1819       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   1885   1885       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   2085   2085       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   2117   2117       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   2274   2274       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   2386   2386       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   2400   2400       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   2531   2531       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   2581   2581       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   2592   2592       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   2610   2610       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   2813   2813       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   2923   2923       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   2945   2945       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   3042   3042       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   3103   3103       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   3125   3125       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   3165   3165       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   3268   3268       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   3283   3283       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   3290   3290       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   3295   3295       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   3357   3357       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   3430   3430       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   3457   3457       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   3533   3533       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   3576   3576       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID    136    147       {ECO:0000250}.
FT   DISULFID    141    156       {ECO:0000250}.
FT   DISULFID    158    167       {ECO:0000250}.
FT   DISULFID    174    190       {ECO:0000250}.
FT   DISULFID    184    199       {ECO:0000250}.
FT   DISULFID    201    210       {ECO:0000250}.
FT   DISULFID    267    280       {ECO:0000250}.
FT   DISULFID    274    289       {ECO:0000250}.
FT   DISULFID    292    303       {ECO:0000250}.
FT   DISULFID    353    366       {ECO:0000250}.
FT   DISULFID    360    376       {ECO:0000250}.
FT   DISULFID    399    409       {ECO:0000250}.
FT   DISULFID    404    418       {ECO:0000250}.
FT   DISULFID    420    429       {ECO:0000250}.
FT   DISULFID    436    447       {ECO:0000250}.
FT   DISULFID    441    456       {ECO:0000250}.
FT   DISULFID    458    467       {ECO:0000250}.
FT   DISULFID    474    500       {ECO:0000250}.
FT   DISULFID    527    549       {ECO:0000250}.
FT   DISULFID    590    616       {ECO:0000250}.
FT   DISULFID    643    665       {ECO:0000250}.
FT   DISULFID    708    734       {ECO:0000250}.
FT   DISULFID    869    891       {ECO:0000250}.
FT   DISULFID    932    958       {ECO:0000269|PubMed:20237569}.
FT   DISULFID    985   1005       {ECO:0000269|PubMed:20237569}.
FT   DISULFID   1048   1074       {ECO:0000269|PubMed:20237569}.
FT   DISULFID   1165   1191       {ECO:0000269|PubMed:20237569}.
FT   DISULFID   1218   1240       {ECO:0000269|PubMed:20237569}.
FT   DISULFID   1278   1306       {ECO:0000269|PubMed:20237569}.
FT   DISULFID   1333   1351       {ECO:0000269|PubMed:20237569}.
FT   DISULFID   1391   1417       {ECO:0000250}.
FT   DISULFID   1444   1466       {ECO:0000250}.
FT   DISULFID   1510   1536       {ECO:0000250}.
FT   DISULFID   1563   1581       {ECO:0000250}.
FT   DISULFID   1620   1647       {ECO:0000250}.
FT   DISULFID   1675   1697       {ECO:0000250}.
FT   DISULFID   1738   1764       {ECO:0000250}.
FT   DISULFID   1791   1812       {ECO:0000250}.
FT   DISULFID   1905   1927       {ECO:0000250}.
FT   DISULFID   1978   2006       {ECO:0000250}.
FT   DISULFID   2032   2054       {ECO:0000250}.
FT   DISULFID   2092   2118       {ECO:0000250}.
FT   DISULFID   2217   2247       {ECO:0000250}.
FT   DISULFID   2275   2297       {ECO:0000250}.
FT   DISULFID   2336   2363       {ECO:0000250}.
FT   DISULFID   2390   2411       {ECO:0000250}.
FT   DISULFID   2452   2478       {ECO:0000250}.
FT   DISULFID   2505   2527       {ECO:0000250}.
FT   DISULFID   2570   2599       {ECO:0000250}.
FT   DISULFID   2628   2649       {ECO:0000250}.
FT   DISULFID   2689   2715       {ECO:0000250}.
FT   DISULFID   2742   2764       {ECO:0000250}.
FT   DISULFID   2805   2831       {ECO:0000250}.
FT   DISULFID   2860   2883       {ECO:0000250}.
FT   DISULFID   2920   2946       {ECO:0000250}.
FT   DISULFID   2977   2999       {ECO:0000250}.
FT   DISULFID   3037   3064       {ECO:0000250}.
FT   DISULFID   3091   3113       {ECO:0000250}.
FT   DISULFID   3157   3185       {ECO:0000250}.
FT   DISULFID   3215   3237       {ECO:0000250}.
FT   DISULFID   3278   3306       {ECO:0000250}.
FT   DISULFID   3332   3354       {ECO:0000250}.
FT   DISULFID   3395   3421       {ECO:0000250}.
FT   DISULFID   3448   3470       {ECO:0000250}.
FT   DISULFID   3511   3537       {ECO:0000250}.
FT   DISULFID   3564   3586       {ECO:0000250}.
FT   VARIANT      66     66       G -> R (in dbSNP:rs12259370).
FT                                /FTId=VAR_047443.
FT   VARIANT     124    124       F -> I (in dbSNP:rs1801220).
FT                                {ECO:0000269|PubMed:10080186}.
FT                                /FTId=VAR_025284.
FT   VARIANT     253    253       F -> S (in dbSNP:rs1801222).
FT                                {ECO:0000269|PubMed:10080186,
FT                                ECO:0000269|PubMed:9572993}.
FT                                /FTId=VAR_025285.
FT   VARIANT     335    335       A -> T (in dbSNP:rs57335729).
FT                                /FTId=VAR_061154.
FT   VARIANT     389    389       P -> T (in dbSNP:rs1801224).
FT                                {ECO:0000269|PubMed:10080186}.
FT                                /FTId=VAR_025286.
FT   VARIANT     504    504       I -> M (in dbSNP:rs2228053).
FT                                /FTId=VAR_047444.
FT   VARIANT     730    730       H -> Y (in dbSNP:rs7905349).
FT                                /FTId=VAR_047445.
FT   VARIANT     786    786       H -> Q (in a breast cancer sample;
FT                                somatic mutation; dbSNP:rs1228797857).
FT                                {ECO:0000269|PubMed:16959974}.
FT                                /FTId=VAR_035829.
FT   VARIANT     969    969       L -> V (in dbSNP:rs11254354).
FT                                /FTId=VAR_047446.
FT   VARIANT    1032   1032       Y -> H (in dbSNP:rs1801227).
FT                                {ECO:0000269|PubMed:10080186}.
FT                                /FTId=VAR_025287.
FT   VARIANT    1297   1297       P -> L (in RH-MGA1; decreases strongly
FT                                the CBLIF binding affinity;
FT                                dbSNP:rs121434430).
FT                                {ECO:0000269|PubMed:10080186,
FT                                ECO:0000269|PubMed:10887099}.
FT                                /FTId=VAR_025288.
FT   VARIANT    1545   1545       N -> Y. {ECO:0000269|PubMed:10080186,
FT                                ECO:0000269|PubMed:9572993}.
FT                                /FTId=VAR_025289.
FT   VARIANT    1559   1559       P -> S (in dbSNP:rs1801231).
FT                                {ECO:0000269|PubMed:10080186}.
FT                                /FTId=VAR_025290.
FT   VARIANT    1769   1769       V -> I (in dbSNP:rs74116778).
FT                                {ECO:0000269|PubMed:10080186,
FT                                ECO:0000269|PubMed:9572993}.
FT                                /FTId=VAR_025291.
FT   VARIANT    1775   1775       R -> W (in dbSNP:rs1276708).
FT                                /FTId=VAR_047447.
FT   VARIANT    1840   1840       G -> S (in dbSNP:rs2271462).
FT                                /FTId=VAR_047448.
FT   VARIANT    1935   1935       S -> G (in dbSNP:rs41289305).
FT                                /FTId=VAR_047449.
FT   VARIANT    1971   1971       P -> T (in dbSNP:rs2356590).
FT                                /FTId=VAR_047450.
FT   VARIANT    2153   2153       L -> F (higher frequency in West Africans
FT                                than in individuals of European ancestry;
FT                                occurs with variants V-2984 and G-3002
FT                                only in individuals of European ancestry;
FT                                dbSNP:rs62619939).
FT                                {ECO:0000269|PubMed:10080186,
FT                                ECO:0000269|PubMed:23114252}.
FT                                /FTId=VAR_025292.
FT   VARIANT    2162   2162       C -> Y (in dbSNP:rs1276712).
FT                                {ECO:0000269|PubMed:9572993}.
FT                                /FTId=VAR_025293.
FT   VARIANT    2252   2252       A -> V (in a colorectal cancer sample;
FT                                somatic mutation; dbSNP:rs529856485).
FT                                {ECO:0000269|PubMed:16959974}.
FT                                /FTId=VAR_035830.
FT   VARIANT    2263   2263       F -> C (in dbSNP:rs2271460).
FT                                /FTId=VAR_047451.
FT   VARIANT    2444   2444       R -> Q (in dbSNP:rs11254274).
FT                                /FTId=VAR_047452.
FT   VARIANT    2575   2575       P -> R (in dbSNP:rs3740168).
FT                                {ECO:0000269|PubMed:10080186}.
FT                                /FTId=VAR_025294.
FT   VARIANT    2691   2691       G -> R (in dbSNP:rs1801237).
FT                                {ECO:0000269|PubMed:10080186}.
FT                                /FTId=VAR_025295.
FT   VARIANT    2717   2717       S -> W (in dbSNP:rs2796835).
FT                                {ECO:0000269|PubMed:9572993}.
FT                                /FTId=VAR_025296.
FT   VARIANT    2879   2879       L -> I (in dbSNP:rs1801238).
FT                                {ECO:0000269|PubMed:10080186}.
FT                                /FTId=VAR_025297.
FT   VARIANT    2914   2914       A -> V (in a breast cancer sample;
FT                                somatic mutation; dbSNP:rs45551835).
FT                                {ECO:0000269|PubMed:16959974}.
FT                                /FTId=VAR_035831.
FT   VARIANT    2968   2968       E -> Q (in dbSNP:rs45569534).
FT                                /FTId=VAR_047453.
FT   VARIANT    2984   2984       I -> V (not found in West Africans;
FT                                occurs with variants F-2153 and G-3002
FT                                only in individuals of European ancestry;
FT                                associated with albuminuria in
FT                                individuals of European ancestry and
FT                                African Americans, both with and without
FT                                diabetes; associated with 42% increased
FT                                risk of developing persistent
FT                                microalbuminuria in individuals with type
FT                                I diabetes; dbSNP:rs1801239).
FT                                {ECO:0000269|PubMed:10080186,
FT                                ECO:0000269|PubMed:21355061,
FT                                ECO:0000269|PubMed:23114252}.
FT                                /FTId=VAR_025298.
FT   VARIANT    3002   3002       E -> G (higher frequency in West Africans
FT                                than in individuals of European ancestry;
FT                                occurs with variants F-2153 and V-2984
FT                                only in individuals of European ancestry;
FT                                dbSNP:rs1801240).
FT                                {ECO:0000269|PubMed:10080186,
FT                                ECO:0000269|PubMed:23114252}.
FT                                /FTId=VAR_025299.
FT   VARIANT    3189   3189       I -> V (in a breast cancer sample;
FT                                somatic mutation; dbSNP:rs111265129).
FT                                {ECO:0000269|PubMed:16959974}.
FT                                /FTId=VAR_035832.
FT   VARIANT    3258   3258       S -> G (found in a renal cell carcinoma
FT                                case; somatic mutation).
FT                                {ECO:0000269|PubMed:21248752}.
FT                                /FTId=VAR_064704.
FT   VARIANT    3422   3422       T -> I (in dbSNP:rs1801230).
FT                                {ECO:0000269|PubMed:10080186}.
FT                                /FTId=VAR_025300.
FT   VARIANT    3432   3432       T -> S (in dbSNP:rs7898873).
FT                                /FTId=VAR_055714.
FT   VARIANT    3552   3552       N -> K (in dbSNP:rs1801232).
FT                                {ECO:0000269|PubMed:10080186}.
FT                                /FTId=VAR_025301.
FT   CONFLICT     25     25       A -> R (in Ref. 1; AAC82612).
FT                                {ECO:0000305}.
FT   CONFLICT    146    146       T -> N (in Ref. 1; AAC82612).
FT                                {ECO:0000305}.
FT   STRAND       43     47       {ECO:0000244|PDB:6GJE}.
FT   STRAND       50     54       {ECO:0000244|PDB:6GJE}.
FT   STRAND       61     64       {ECO:0000244|PDB:6GJE}.
FT   STRAND       70     73       {ECO:0000244|PDB:6GJE}.
FT   HELIX        78     99       {ECO:0000244|PDB:6GJE}.
FT   HELIX       106    110       {ECO:0000244|PDB:6GJE}.
FT   HELIX       113    120       {ECO:0000244|PDB:6GJE}.
FT   STRAND      938    942       {ECO:0000244|PDB:3KQ4}.
FT   STRAND      959    963       {ECO:0000244|PDB:3KQ4}.
FT   STRAND      966    972       {ECO:0000244|PDB:3KQ4}.
FT   STRAND      987    993       {ECO:0000244|PDB:3KQ4}.
FT   STRAND      997   1004       {ECO:0000244|PDB:3KQ4}.
FT   STRAND     1016   1025       {ECO:0000244|PDB:3KQ4}.
FT   STRAND     1038   1046       {ECO:0000244|PDB:3KQ4}.
FT   STRAND     1048   1052       {ECO:0000244|PDB:3KQ4}.
FT   TURN       1062   1065       {ECO:0000244|PDB:3KQ4}.
FT   STRAND     1073   1078       {ECO:0000244|PDB:3KQ4}.
FT   STRAND     1087   1094       {ECO:0000244|PDB:3KQ4}.
FT   STRAND     1104   1114       {ECO:0000244|PDB:3KQ4}.
FT   STRAND     1119   1123       {ECO:0000244|PDB:3KQ4}.
FT   STRAND     1125   1127       {ECO:0000244|PDB:3KQ4}.
FT   STRAND     1135   1137       {ECO:0000244|PDB:3KQ4}.
FT   STRAND     1139   1144       {ECO:0000244|PDB:3KQ4}.
FT   STRAND     1153   1159       {ECO:0000244|PDB:3KQ4}.
FT   STRAND     1171   1177       {ECO:0000244|PDB:3KQ4}.
FT   TURN       1179   1182       {ECO:0000244|PDB:3KQ4}.
FT   STRAND     1190   1195       {ECO:0000244|PDB:3KQ4}.
FT   STRAND     1203   1209       {ECO:0000244|PDB:3KQ4}.
FT   STRAND     1220   1230       {ECO:0000244|PDB:3KQ4}.
FT   STRAND     1233   1239       {ECO:0000244|PDB:3KQ4}.
FT   STRAND     1251   1253       {ECO:0000244|PDB:3KQ4}.
FT   STRAND     1255   1260       {ECO:0000244|PDB:3KQ4}.
FT   STRAND     1271   1276       {ECO:0000244|PDB:3KQ4}.
FT   STRAND     1279   1283       {ECO:0000244|PDB:3KQ4}.
FT   STRAND     1287   1292       {ECO:0000244|PDB:3KQ4}.
FT   TURN       1294   1297       {ECO:0000244|PDB:3KQ4}.
FT   STRAND     1305   1311       {ECO:0000244|PDB:3KQ4}.
FT   STRAND     1319   1326       {ECO:0000244|PDB:3KQ4}.
FT   TURN       1331   1334       {ECO:0000244|PDB:3KQ4}.
FT   STRAND     1335   1342       {ECO:0000244|PDB:3KQ4}.
FT   STRAND     1345   1350       {ECO:0000244|PDB:3KQ4}.
FT   STRAND     1362   1371       {ECO:0000244|PDB:3KQ4}.
FT   STRAND     1381   1386       {ECO:0000244|PDB:3KQ4}.
SQ   SEQUENCE   3623 AA;  398736 MW;  8D602663C6D4751F CRC64;
     MMNMSLPFLW SLLTLLIFAE VNGEAGELEL QRQKRSINLQ QPRMATERGN LVFLTGSAQN
     IEFRTGSLGK IKLNDEDLSE CLHQIQKNKE DIIELKGSAI GLPQNISSQI YQLNSKLVDL
     ERKFQGLQQT VDKKVCSSNP CQNGGTCLNL HDSFFCICPP QWKGPLCSAD VNECEIYSGT
     PLSCQNGGTC VNTMGSYSCH CPPETYGPQC ASKYDDCEGG SVARCVHGIC EDLMREQAGE
     PKYSCVCDAG WMFSPNSPAC TLDRDECSFQ PGPCSTLVQC FNTQGSFYCG ACPTGWQGNG
     YICEDINECE INNGGCSVAP PVECVNTPGS SHCQACPPGY QGDGRVCTLT DICSVSNGGC
     HPDASCSSTL GSLPLCTCLP GYTGNGYGPN GCVQLSNICL SHPCLNGQCI DTVSGYFCKC
     DSGWTGVNCT ENINECLSNP CLNGGTCVDG VDSFSCECTR LWTGALCQVP QQVCGESLSG
     INGSFSYRSP DVGYVHDVNC FWVIKTEMGK VLRITFTFFR LESMDNCPHE FLQVYDGDSS
     SAFQLGRFCG SSLPHELLSS DNALYFHLYS EHLRNGRGFT VRWETQQPEC GGILTGPYGS
     IKSPGYPGNY PPGRDCVWIV VTSPDLLVTF TFGTLSLEHH DDCNKDYLEI RDGPLYQDPL
     LGKFCTTFSV PPLQTTGPFA RIHFHSDSQI SDQGFHITYL TSPSDLRCGG NYTDPEGELF
     LPELSGPFTH TRQCVYMMKQ PQGEQIQINF THVELQCQSD SSQNYIEVRD GETLLGKVCG
     NGTISHIKSI TNSVWIRFKI DASVEKASFR AVYQVACGDE LTGEGVIRSP FFPNVYPGER
     TCRWTIHQPQ SQVILLNFTV FEIGSSAHCE TDYVEIGSSS ILGSPENKKY CGTDIPSFIT
     SVYNFLYVTF VKSSSTENHG FMAKFSAEDL ACGEILTEST GTIQSPGHPN VYPHGINCTW
     HILVQPNHLI HLMFETFHLE FHYNCTNDYL EVYDTDSETS LGRYCGKSIP PSLTSSGNSL
     MLVFVTDSDL AYEGFLINYE AISAATACLQ DYTDDLGTFT SPNFPNNYPN NWECIYRITV
     RTGQLIAVHF TNFSLEEAIG NYYTDFLEIR DGGYEKSPLL GIFYGSNLPP TIISHSNKLW
     LKFKSDQIDT RSGFSAYWDG SSTGCGGNLT TSSGTFISPN YPMPYYHSSE CYWWLKSSHG
     SAFELEFKDF HLEHHPNCTL DYLAVYDGPS SNSHLLTQLC GDEKPPLIRS SGDSMFIKLR
     TDEGQQGRGF KAEYRQTCEN VVIVNQTYGI LESIGYPNPY SENQHCNWTI RATTGNTVNY
     TFLAFDLEHH INCSTDYLEL YDGPRQMGRY CGVDLPPPGS TTSSKLQVLL LTDGVGRREK
     GFQMQWFVYG CGGELSGATG SFSSPGFPNR YPPNKECIWY IRTDPGSSIQ LTIHDFDVEY
     HSRCNFDVLE IYGGPDFHSP RIAQLCTQRS PENPMQVSST GNELAIRFKT DLSINGRGFN
     ASWQAVTGGC GGIFQAPSGE IHSPNYPSPY RSNTDCSWVI RVDRNHRVLL NFTDFDLEPQ
     DSCIMAYDGL SSTMSRLART CGREQLANPI VSSGNSLFLR FQSGPSRQNR GFRAQFRQAC
     GGHILTSSFD TVSSPRFPAN YPNNQNCSWI IQAQPPLNHI TLSFTHFELE RSTTCARDFV
     EILDGGHEDA PLRGRYCGTD MPHPITSFSS ALTLRFVSDS SISAGGFHTT VTASVSACGG
     TFYMAEGIFN SPGYPDIYPP NVECVWNIVS SPGNRLQLSF ISFQLEDSQD CSRDFVEIRE
     GNATGHLVGR YCGNSFPLNY SSIVGHTLWV RFISDGSGSG TGFQATFMKI FGNDNIVGTH
     GKVASPFWPE NYPHNSNYQW TVNVNASHVV HGRILEMDIE EIQNCYYDKL RIYDGPSIHA
     RLIGAYCGTQ TESFSSTGNS LTFHFYSDSS ISGKGFLLEW FAVDAPDGVL PTIAPGACGG
     FLRTGDAPVF LFSPGWPDSY SNRVDCTWLI QAPDSTVELN ILSLDIESHR TCAYDSLVIR
     DGDNNLAQQL AVLCGREIPG PIRSTGEYMF IRFTSDSSVT RAGFNASFHK SCGGYLHADR
     GIITSPKYPE TYPSNLNCSW HVLVQSGLTI AVHFEQPFQI PNGDSSCNQG DYLVLRNGPD
     ICSPPLGPPG GNGHFCGSHA SSTLFTSDNQ MFVQFISDHS NEGQGFKIKY EAKSLACGGN
     VYIHDADSAG YVTSPNHPHN YPPHADCIWI LAAPPETRIQ LQFEDRFDIE VTPNCTSNYL
     ELRDGVDSDA PILSKFCGTS LPSSQWSSGE VMYLRFRSDN SPTHVGFKAK YSIAQCGGRV
     PGQSGVVESI GHPTLPYRDN LFCEWHLQGL SGHYLTISFE DFNLQNSSGC EKDFVEIWDN
     HTSGNILGRY CGNTIPDSID TSSNTAVVRF VTDGSVTASG FRLRFESSME ECGGDLQGSI
     GTFTSPNYPN PNPHGRICEW RITAPEGRRI TLMFNNLRLA THPSCNNEHV IVFNGIRSNS
     PQLEKLCSSV NVSNEIKSSG NTMKVIFFTD GSRPYGGFTA SYTSSEDAVC GGSLPNTPEG
     NFTSPGYDGV RNYSRNLNCE WTLSNPNQGN SSISIHFEDF YLESHQDCQF DVLEFRVGDA
     DGPLMWRLCG PSKPTLPLVI PYSQVWIHFV TNERVEHIGF HAKYSFTDCG GIQIGDSGVI
     TSPNYPNAYD SLTHCSSLLE APQGHTITLT FSDFDIEPHT TCAWDSVTVR NGGSPESPII
     GQYCGNSNPR TIQSGSNQLV VTFNSDHSLQ GGGFYATWNT QTLGCGGIFH SDNGTIRSPH
     WPQNFPENSR CSWTAITHKS KHLEISFDNN FLIPSGDGQC QNSFVKVWAG TEEVDKALLA
     TGCGNVAPGP VITPSNTFTA VFQSQEAPAQ GFSASFVSRC GSNFTGPSGY IISPNYPKQY
     DNNMNCTYVI EANPLSVVLL TFVSFHLEAR SAVTGSCVND GVHIIRGYSV MSTPFATVCG
     DEMPAPLTIA GPVLLNFYSN EQITDFGFKF SYRIISCGGV FNFSSGIITS PAYSYADYPN
     DMHCLYTITV SDDKVIELKF SDFDVVPSTS CSHDYLAIYD GANTSDPLLG KFCGSKRPPN
     VKSSNNSMLL VFKTDSFQTA KGWKMSFRQT LGPQQGCGGY LTGSNNTFAS PDSDSNGMYD
     KNLNCVWIII APVNKVIHLT FNTFALEAAS TRQRCLYDYV KLYDGDSENA NLAGTFCGST
     VPAPFISSGN FLTVQFISDL TLEREGFNAT YTIMDMPCGG TYNATWTPQN ISSPNSSDPD
     VPFSICTWVI DSPPHQQVKI TVWALQLTSQ DCTQNYLQLQ DSPQGHGNSR FQFCGRNASA
     VPVFYSSMST AMVIFKSGVV NRNSRMSFTY QIADCNRDYH KAFGNLRSPG WPDNYDNDKD
     CTVTLTAPQN HTISLFFHSL GIENSVECRN DFLEVRNGSN SNSPLLGKYC GTLLPNPVFS
     QNNELYLRFK SDSVTSDRGY EIIWTSSPSG CGGTLYGDRG SFTSPGYPGT YPNNTYCEWV
     LVAPAGRLVT INFYFISIDD PGDCVQNYLT LYDGPNASSP SSGPYCGGDT SIAPFVASSN
     QVFIKFHADY ARRPSAFRLT WDS
//
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