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 27-MAR-2024, entry version 204. DE RecName: Full=Cubilin {ECO:0000303|PubMed:9572993}; 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 {ECO:0000303|PubMed:9572993}; DE Flags: Precursor; GN Name=CUBN; Synonyms=IFCR; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 36-41, FUNCTION, BINDING TO RP THE CBLIF-COBALAMIN COMPLEX, PROTEOLYTIC PROCESSING, TISSUE SPECIFICITY, RP AND 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., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., RA Durbin R.M., Hubbard T., 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., Verroust P.J., RA Moestrup S.K.; RT "The intrinsic factor-vitamin B12 receptor, cubilin, is a high-affinity RT apolipoprotein A-I receptor facilitating endocytosis of high-density RT lipoprotein."; RL Nat. Med. 5:656-661(1999). RN [5] RP INVOLVEMENT IN IGS1, VARIANT IGS1 LEU-1297, AND VARIANTS ILE-124; SER-253; RP THR-389; HIS-1032; TYR-1545; SER-1559; ILE-1769; PHE-2153; ARG-2575; RP ARG-2691; 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 receptor, RT cubilin, cause hereditary megaloblastic anaemia 1."; RL Nat. Genet. 21:309-313(1999). RN [6] 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., Moestrup S.K., RA 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 [7] 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 the RT apical uptake of transferrin in polarized epithelia."; RL Proc. Natl. Acad. Sci. U.S.A. 98:12491-12496(2001). RN [8] 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 [9] RP IDENTIFICATION IN A COMPLEX WITH LRP1 AND PID1, AND INTERACTION WITH LRP1 RP 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 a RT functional approach."; RL Mol. Cell. Proteomics 6:333-345(2007). RN [10] RP INTERACTION WITH AMN, SUBCELLULAR LOCATION, AND GLYCOSYLATION. 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). RN [11] RP INVOLVEMENT IN PROCHOB, VARIANTS PROCHOB MET-55; 1158-TRP--SER-3623 DEL; RP HIS-1303; 1487-ARG--SER-3623 DEL; 1810-ARG--SER-3623 DEL; TYR-1854; RP VAL-1928; TYR-1947; 2030-ARG--SER-3623 DEL; ARG-2261; TRP-2599; LEU-2822; RP 2831-CYS--SER-3623 DEL; 2833-TRP--SER-3623 DEL; 2903-GLN--SER-3623 DEL; RP SER-3018; ARG-3027; ARG-3308; 3317-GLN--SER-3623 DEL; CYS-3366; TYR-3492; RP ASP-3520; HIS-3609 AND 3618-ARG--SER-3623 DEL, AND VARIANTS VAL-1690; RP ASP-2157; VAL-2914 AND VAL-2984. RX PubMed=31613795; DOI=10.1172/jci129937; RA Bedin M., Boyer O., Servais A., Li Y., Villoing-Gaude L., Tete M.J., RA Cambier A., Hogan J., Baudouin V., Krid S., Bensman A., Lammens F., RA Louillet F., Ranchin B., Vigneau C., Bouteau I., Isnard-Bagnis C., RA Mache C.J., Schaefer T., Pape L., Goedel M., Huber T.B., Benz M., Klaus G., RA Hansen M., Latta K., Gribouval O., Moriniere V., Tournant C., Grohmann M., RA Kuhn E., Wagner T., Bole-Feysot C., Jabot-Hanin F., Nitschke P., RA Ahluwalia T.S., Koettgen A., Andersen C.B.F., Bergmann C., Antignac C., RA Simons M.; RT "Human C-terminal CUBN variants associate with chronic proteinuria and RT normal renal function."; RL J. Clin. Invest. 130:335-344(2020). RN [12] RP X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 932-1388 IN COMPLEX WITH CBLIF AND RP CALCIUM IONS, INTERACTION WITH CBLIF, IDENTIFICATION IN CUBAM COMPLEX, RP SUBUNIT, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-984; ASN-1092; ASN-1168; RP ASN-1217; ASN-1285; ASN-1307; ASN-1319 AND 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 [13] {ECO:0007744|PDB:6GJE} RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 26-135 IN COMPLEX WITH AMN, AND RP SUBCELLULAR LOCATION. 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). RN [14] RP CHARACTERIZATION OF VARIANT IGS1 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 anemia 1 RT causes impaired recognition of intrinsic factor-vitamin B(12) by cubilin."; RL Blood 96:405-409(2000). RN [15] RP VARIANTS [LARGE SCALE ANALYSIS] GLN-786; VAL-2252; VAL-2914 AND 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., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [16] RP VARIANT IGS1 LEU-337. RX PubMed=17668238; DOI=10.1007/s00431-007-0571-3; RA Hauck F.H., Tanner S.M., Henker J., Laass M.W.; RT "Imerslund-Graesbeck syndrome in a 15-year-old German girl caused by RT compound heterozygous mutations in CUBN."; RL Eur. J. Pediatr. 167:671-675(2008). RN [17] 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., Kutalik Z., RA Luan J., Zhao J.H., Hwang S.J., Akylbekova E., Kramer H., van der Harst P., RA Smith A.V., Lohman K., de Andrade M., Hayward C., Kollerits B., Tonjes A., RA Aspelund T., Ingelsson E., Eiriksdottir G., Launer L.J., Harris T.B., RA Shuldiner A.R., Mitchell B.D., Arking D.E., Franceschini N., Boerwinkle E., RA Egan J., Hernandez D., Reilly M., Townsend R.R., Lumley T., Siscovick D.S., RA Psaty B.M., Kestenbaum B., Haritunians T., Bergmann S., Vollenweider P., RA Waeber G., Mooser V., Waterworth D., Johnson A.D., Florez J.C., Meigs J.B., RA Lu X., 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., Devuyst O., RA Mychaleckyj J.C., Minelli C., Bakker S.J., Kedenko L., Paulweber B., RA Coassin S., Endlich K., Kroemer H.K., Biffar R., Stracke S., Volzke H., RA Stumvoll M., Magi R., Campbell H., Vitart V., Hastie N.D., Gudnason V., RA Kardia S.L., Liu Y., Polasek O., Curhan G., Kronenberg F., Prokopenko I., RA Rudan I., Arnlov J., Hallan S., Navis G., Parsa A., Ferrucci L., Coresh J., RA Shlipak M.G., Bull S.B., Paterson N.J., Wichmann H.E., Wareham N.J., RA Loos R.J., Rotter J.I., Pramstaller P.P., Cupples L.A., Beckmann J.S., RA Yang Q., Heid I.M., Rettig R., Dreisbach A.W., Bochud M., Fox C.S., RA Kao W.H.; RT "CUBN is a gene locus for albuminuria."; RL J. Am. Soc. Nephrol. 22:555-570(2011). RN [18] 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., Davies H., RA Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J., RA Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M., RA Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L., RA Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J., RA Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A., RA Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K., RA Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A.; RT "Exome sequencing identifies frequent mutation of the SWI/SNF complex gene RT PBRM1 in renal carcinoma."; RL Nature 469:539-542(2011). RN [19] 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). RN [20] RP VARIANTS IGS1 GLU-1112 AND LEU-1297, AND CHARACTERIZATION OF VARIANT IGS1 RP GLU-1112. RX PubMed=24156255; DOI=10.1186/1471-2350-14-111; RA Storm T., Zeitz C., Cases O., Amsellem S., Verroust P.J., Madsen M., RA Benoist J.F., Passemard S., Lebon S., Joensson I.M., Emma F., Koldsoe H., RA Hertz J.M., Nielsen R., Christensen E.I., Kozyraki R.; RT "Detailed investigations of proximal tubular function in Imerslund- RT Graesbeck syndrome."; RL BMC Med. Genet. 14:111-111(2013). CC -!- FUNCTION: Endocytic receptor which plays a role in lipoprotein, vitamin CC and iron metabolism by facilitating their uptake (PubMed:9572993, CC PubMed:10371504, PubMed:11717447, PubMed:11606717, PubMed:14576052). CC Acts together with LRP2 to mediate endocytosis of high-density CC lipoproteins, GC, hemoglobin, ALB, TF and SCGB1A1. Acts together with CC AMN to mediate endocytosis of the CBLIF-cobalamin complex CC (PubMed:9572993, PubMed:14576052). Binds to ALB, MB, Kappa and lambda- CC light chains, TF, hemoglobin, GC, SCGB1A1, APOA1, high density CC lipoprotein, and the CBLIF-cobalamin complex. Ligand binding requires CC calcium (PubMed:9572993). Serves as important transporter in several CC absorptive epithelia, including intestine, renal proximal tubules and CC embryonic yolk sac. May play an important role in the development of CC the peri-implantation embryo through internalization of APOA1 and CC cholesterol. Binds to 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 AMN (PubMed:14576052, PubMed:29402915, CC PubMed:20237569, PubMed:30523278). Component of the cubam complex CC composed of one CUBN trimer and one AMN chain (PubMed:30523278). The CC cubam complex can dimerize (By similarity). Interacts with LRP2 in a CC dual-receptor complex in a calcium-dependent manner. Found in a complex CC with PID1/PCLI1, LRP1 and CUBNI. Interacts with LRP1 and PID1/PCLI1. CC {ECO:0000250|UniProtKB:F1RWC3, 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, ECO:0000269|PubMed:29402915, CC ECO:0000269|PubMed:30523278}. CC -!- INTERACTION: CC O60494; Q9BXJ7: AMN; NbExp=3; IntAct=EBI-3953632, EBI-11510881; CC O60494; P27352: CBLIF; NbExp=2; IntAct=EBI-3953632, EBI-3953638; CC -!- SUBCELLULAR LOCATION: Apical cell membrane CC {ECO:0000250|UniProtKB:Q9JLB4}; Peripheral membrane protein CC {ECO:0000305}. Cell membrane {ECO:0000269|PubMed:14576052, CC ECO:0000269|PubMed:29402915, ECO:0000269|PubMed:30523278}; Peripheral CC membrane protein {ECO:0000305, ECO:0000305|PubMed:30523278}. Membrane, CC coated pit {ECO:0000269|PubMed:14576052}. Endosome CC {ECO:0000269|PubMed:14576052, ECO:0000269|PubMed:29402915}. Lysosome CC membrane {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 CC (PubMed:29402915, PubMed:30523278). Colocalizes with AMN and LRP2 in CC the endocytotic apparatus of epithelial cells (By similarity). CC {ECO:0000250|UniProtKB:O70244, ECO:0000269|PubMed:29402915, CC ECO:0000269|PubMed:30523278}. CC -!- TISSUE SPECIFICITY: Detected in kidney cortex (at protein level) CC (PubMed:9572993). Expressed in kidney proximal tubule cells, placenta, CC visceral yolk-sac cells and in absorptive intestinal cells. Expressed CC in the epithelium of intestine and kidney. CC {ECO:0000269|PubMed:9572993}. CC -!- DOMAIN: The CUB domains 5 to 8 mediate binding to CBLIF and ALB. CUB CC domains 1 and 2 mediate interaction with LRP2. CC {ECO:0000250|UniProtKB:O70244}. CC -!- DOMAIN: The cubam complex is composed of a 400 Angstrom long stem and a CC globular crown region. The stem region is probably formed by AMN and CC the CUBN N-terminal region, including the EGF-like domains. The crown CC is probably formed by the CUBN CUB domains. CC {ECO:0000250|UniProtKB:F1RWC3}. CC -!- PTM: The precursor is cleaved by a trans-Golgi proteinase furin, CC removing a propeptide. {ECO:0000269|PubMed:9572993}. CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:14576052, CC ECO:0000269|PubMed:20237569, ECO:0000269|PubMed:29402915}. CC -!- DISEASE: Imerslund-Grasbeck syndrome 1 (IGS1) [MIM:261100]: A form of CC Imerslund-Grasbeck syndrome, a rare autosomal recessive disorder CC characterized by vitamin B12 deficiency commonly resulting in CC megaloblastic anemia, which is responsive to parenteral vitamin B12 CC therapy and appears in infancy or early childhood. Clinical CC manifestations include failure to thrive, infections and neurological CC damage. Mild proteinuria, with no signs of kidney disease, is present CC in about half of the patients. {ECO:0000269|PubMed:10080186, CC ECO:0000269|PubMed:10887099, ECO:0000269|PubMed:17668238, CC ECO:0000269|PubMed:24156255}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Proteinuria, chronic benign (PROCHOB) [MIM:618884]: An CC autosomal recessive condition characterized by isolated, non- CC progressive proteinuria in absence of renal disease and hypertension. CC Onset of proteinuria is in the first decade of life. CC {ECO:0000269|PubMed:31613795}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; 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 PDB; 3KQ4; X-ray; 3.30 A; B/D/F=932-1388. DR PDB; 6GJE; X-ray; 2.30 A; B/C/D=26-135. DR PDBsum; 3KQ4; -. DR PDBsum; 6GJE; -. DR SMR; O60494; -. DR BioGRID; 113724; 10. DR ComplexPortal; CPX-5774; Cubam cobalamin uptake receptor complex. DR CORUM; O60494; -. DR DIP; DIP-58583N; -. DR IntAct; O60494; 4. DR MINT; O60494; -. DR STRING; 9606.ENSP00000367064; -. DR DrugBank; DB00115; Cyanocobalamin. DR DrugBank; DB00200; Hydroxocobalamin. DR TCDB; 9.B.87.1.34; the selenoprotein p receptor (selp-receptor) family. DR GlyConnect; 2033; 1 N-Linked glycan (1 site). DR GlyCosmos; O60494; 51 sites, 5 glycans. DR GlyGen; O60494; 54 sites, 3 N-linked glycans (2 sites), 3 O-linked glycans (6 sites). DR iPTMnet; O60494; -. DR PhosphoSitePlus; O60494; -. DR BioMuta; CUBN; -. DR jPOST; O60494; -. DR MassIVE; O60494; -. DR PaxDb; 9606-ENSP00000367064; -. DR PeptideAtlas; O60494; -. DR ProteomicsDB; 49432; -. DR Antibodypedia; 56802; 180 antibodies from 20 providers. DR DNASU; 8029; -. DR Ensembl; ENST00000377833.10; ENSP00000367064.4; ENSG00000107611.16. DR GeneID; 8029; -. DR KEGG; hsa:8029; -. DR MANE-Select; ENST00000377833.10; ENSP00000367064.4; NM_001081.4; NP_001072.2. DR UCSC; uc001ioo.4; human. DR AGR; HGNC:2548; -. DR CTD; 8029; -. DR DisGeNET; 8029; -. DR GeneCards; CUBN; -. DR HGNC; HGNC:2548; CUBN. DR HPA; ENSG00000107611; Tissue enriched (kidney). DR MalaCards; CUBN; -. DR MIM; 261100; phenotype. DR MIM; 602997; gene. DR MIM; 618884; phenotype. DR neXtProt; NX_O60494; -. DR OpenTargets; ENSG00000107611; -. DR Orphanet; 35858; Imerslund-Graesbeck syndrome. DR PharmGKB; PA27044; -. DR VEuPathDB; HostDB:ENSG00000107611; -. DR eggNOG; KOG4292; Eukaryota. DR GeneTree; ENSGT00940000155299; -. DR HOGENOM; CLU_000172_1_0_1; -. DR InParanoid; O60494; -. DR OMA; RGFTVRW; -. DR OrthoDB; 2917265at2759; -. DR PhylomeDB; O60494; -. DR TreeFam; TF316224; -. DR PathwayCommons; O60494; -. DR Reactome; R-HSA-196791; Vitamin D (calciferol) metabolism. DR Reactome; R-HSA-3359462; Defective AMN causes MGA1. DR Reactome; R-HSA-3359463; Defective CUBN causes MGA1. DR Reactome; R-HSA-8964011; HDL clearance. DR Reactome; R-HSA-9758881; Uptake of dietary cobalamins into enterocytes. DR SignaLink; O60494; -. DR BioGRID-ORCS; 8029; 12 hits in 1153 CRISPR screens. DR ChiTaRS; CUBN; human. DR EvolutionaryTrace; O60494; -. DR GeneWiki; Cubilin; -. DR GenomeRNAi; 8029; -. DR Pharos; O60494; Tbio. DR PRO; PR:O60494; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; O60494; Protein. DR Bgee; ENSG00000107611; Expressed in adult organism and 129 other cell types or tissues. DR ExpressionAtlas; O60494; baseline and differential. 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; IEA:UniProtKB-KW. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0030139; C:endocytic vesicle; IDA:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; IEA:Ensembl. DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell. 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:0043202; C:lysosomal lumen; TAS:Reactome. DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; IDA:ComplexPortal. DR GO; GO:0031528; C:microvillus membrane; IDA:MGI. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0043235; C:receptor complex; IPI:ComplexPortal. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0038024; F:cargo receptor activity; IDA:MGI. DR GO; GO:0031419; F:cobalamin binding; IEA:UniProtKB-KW. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0038023; F:signaling receptor activity; TAS:ProtInc. DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW. DR GO; GO:0009235; P:cobalamin metabolic process; IDA:MGI. DR GO; GO:0015889; P:cobalamin transport; IDA:ComplexPortal. DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl. DR GO; GO:0042953; P:lipoprotein transport; IEA:Ensembl. DR GO; GO:0006898; P:receptor-mediated endocytosis; NAS:UniProtKB. DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl. DR GO; GO:0001894; P:tissue homeostasis; NAS:UniProtKB. DR CDD; cd00041; CUB; 27. DR CDD; cd22201; cubilin_NTD; 1. DR CDD; cd00054; EGF_CA; 6. DR Gene3D; 2.10.25.10; Laminin; 7. DR Gene3D; 2.60.120.290; Spermadhesin, CUB domain; 27. DR InterPro; IPR000859; CUB_dom. 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; PTHR24251:SF37; CUB DOMAIN-CONTAINING PROTEIN; 1. DR PANTHER; PTHR24251; OVOCHYMASE-RELATED; 1. 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; SSF57196; EGF/Laminin; 6. DR SUPFAM; SSF57184; Growth factor receptor domain; 1. DR SUPFAM; SSF49854; Spermadhesin, CUB domain; 27. 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. DR Genevisible; O60494; HS. 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 Direct protein sequencing; Disease variant; Disulfide bond; KW EGF-like domain; Endocytosis; Endosome; Glycoprotein; Lipid metabolism; KW Lysosome; Membrane; Metal-binding; Phosphoprotein; Protein transport; KW Receptor; Reference proteome; Repeat; Signal; Steroid metabolism; KW Sterol metabolism; Transport. FT SIGNAL 1..23 FT /evidence="ECO:0000255" FT PROPEP 24..35 FT /note="Removed in mature form" FT /evidence="ECO:0000269|PubMed:9572993" FT /id="PRO_0000046072" FT CHAIN 36..3623 FT /note="Cubilin" FT /id="PRO_0000046073" FT DOMAIN 132..168 FT /note="EGF-like 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 170..211 FT /note="EGF-like 2; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 263..304 FT /note="EGF-like 3; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 305..348 FT /note="EGF-like 4; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 349..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 816..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 42..49 FT /note="Interaction with AMN" FT /evidence="ECO:0000269|PubMed:30523278" FT BINDING 980 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000305|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT BINDING 988 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000305|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT BINDING 1027 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000305|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT BINDING 1029 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000305|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT BINDING 1030 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000305|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT BINDING 1096 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000305|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT BINDING 1105 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000305|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT BINDING 1146 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000305|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT BINDING 1148 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000305|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT BINDING 1149 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000305|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT BINDING 1213 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000305|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT BINDING 1221 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000305|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT BINDING 1262 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000305|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT BINDING 1264 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000305|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT BINDING 1265 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000305|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT BINDING 1328 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000305|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT BINDING 1336 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000305|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT BINDING 1373 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000305|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT BINDING 1375 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000305|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT SITE 35..36 FT /note="Cleavage; by furin" FT /evidence="ECO:0000255" FT MOD_RES 3008 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:O70244" FT CARBOHYD 105 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 482 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 711 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 749 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 781 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 857 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 957 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 984 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT CARBOHYD 1092 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT CARBOHYD 1168 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT CARBOHYD 1217 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT CARBOHYD 1285 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT CARBOHYD 1307 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT CARBOHYD 1319 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT CARBOHYD 1332 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT CARBOHYD 1500 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1551 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1646 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1802 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1819 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1885 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 2386 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 2592 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 2923 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 3042 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 3103 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 3295 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 3430 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 3457 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 3533 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 3576 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 136..147 FT /evidence="ECO:0000250" FT DISULFID 141..156 FT /evidence="ECO:0000250" FT DISULFID 158..167 FT /evidence="ECO:0000250" FT DISULFID 174..190 FT /evidence="ECO:0000250" FT DISULFID 184..199 FT /evidence="ECO:0000250" FT DISULFID 201..210 FT /evidence="ECO:0000250" FT DISULFID 267..280 FT /evidence="ECO:0000250" FT DISULFID 274..289 FT /evidence="ECO:0000250" FT DISULFID 292..303 FT /evidence="ECO:0000250" FT DISULFID 353..366 FT /evidence="ECO:0000250" FT DISULFID 360..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 869..891 FT /evidence="ECO:0000250" FT DISULFID 932..958 FT /evidence="ECO:0000269|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT DISULFID 985..1005 FT /evidence="ECO:0000269|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT DISULFID 1048..1074 FT /evidence="ECO:0000269|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT DISULFID 1165..1191 FT /evidence="ECO:0000269|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT DISULFID 1218..1240 FT /evidence="ECO:0000269|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT DISULFID 1278..1306 FT /evidence="ECO:0000269|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT DISULFID 1333..1351 FT /evidence="ECO:0000269|PubMed:20237569, FT ECO:0007744|PDB:3KQ4" FT DISULFID 1391..1417 FT /evidence="ECO:0000250" FT DISULFID 1444..1466 FT /evidence="ECO:0000250" FT DISULFID 1510..1536 FT /evidence="ECO:0000250" FT DISULFID 1563..1581 FT /evidence="ECO:0000250" FT DISULFID 1620..1647 FT /evidence="ECO:0000250" FT DISULFID 1675..1697 FT /evidence="ECO:0000250" FT DISULFID 1738..1764 FT /evidence="ECO:0000250" FT DISULFID 1791..1812 FT /evidence="ECO:0000250" FT DISULFID 1905..1927 FT /evidence="ECO:0000250" FT DISULFID 1978..2006 FT /evidence="ECO:0000250" FT DISULFID 2032..2054 FT /evidence="ECO:0000250" FT DISULFID 2092..2118 FT /evidence="ECO:0000250" FT DISULFID 2217..2247 FT /evidence="ECO:0000250" FT DISULFID 2275..2297 FT /evidence="ECO:0000250" FT DISULFID 2336..2363 FT /evidence="ECO:0000250" FT DISULFID 2390..2411 FT /evidence="ECO:0000250" FT DISULFID 2452..2478 FT /evidence="ECO:0000250" FT DISULFID 2505..2527 FT /evidence="ECO:0000250" FT DISULFID 2570..2599 FT /evidence="ECO:0000250" FT DISULFID 2628..2649 FT /evidence="ECO:0000250" FT DISULFID 2689..2715 FT /evidence="ECO:0000250" FT DISULFID 2742..2764 FT /evidence="ECO:0000250" FT DISULFID 2805..2831 FT /evidence="ECO:0000250" FT DISULFID 2860..2883 FT /evidence="ECO:0000250" FT DISULFID 2920..2946 FT /evidence="ECO:0000250" FT DISULFID 2977..2999 FT /evidence="ECO:0000250" FT DISULFID 3037..3064 FT /evidence="ECO:0000250" FT DISULFID 3091..3113 FT /evidence="ECO:0000250" FT DISULFID 3157..3185 FT /evidence="ECO:0000250" FT DISULFID 3215..3237 FT /evidence="ECO:0000250" FT DISULFID 3278..3306 FT /evidence="ECO:0000250" FT DISULFID 3332..3354 FT /evidence="ECO:0000250" FT DISULFID 3395..3421 FT /evidence="ECO:0000250" FT DISULFID 3448..3470 FT /evidence="ECO:0000250" FT DISULFID 3511..3537 FT /evidence="ECO:0000250" FT DISULFID 3564..3586 FT /evidence="ECO:0000250" FT VARIANT 55 FT /note="T -> M (in PROCHOB; uncertain significance; FT dbSNP:rs774556167)" FT /evidence="ECO:0000269|PubMed:31613795" FT /id="VAR_084400" FT VARIANT 66 FT /note="G -> R (in dbSNP:rs12259370)" FT /id="VAR_047443" FT VARIANT 124 FT /note="F -> I (in dbSNP:rs1801220)" FT /evidence="ECO:0000269|PubMed:10080186" FT /id="VAR_025284" FT VARIANT 253 FT /note="F -> S (in dbSNP:rs1801222)" FT /evidence="ECO:0000269|PubMed:10080186, FT ECO:0000269|PubMed:9572993" FT /id="VAR_025285" FT VARIANT 335 FT /note="A -> T (in dbSNP:rs57335729)" FT /id="VAR_061154" FT VARIANT 337 FT /note="P -> L (in IGS1; dbSNP:rs202153130)" FT /evidence="ECO:0000269|PubMed:17668238" FT /id="VAR_084401" FT VARIANT 389 FT /note="P -> T (in dbSNP:rs1801224)" FT /evidence="ECO:0000269|PubMed:10080186" FT /id="VAR_025286" FT VARIANT 504 FT /note="I -> M (in dbSNP:rs2228053)" FT /id="VAR_047444" FT VARIANT 730 FT /note="H -> Y (in dbSNP:rs7905349)" FT /id="VAR_047445" FT VARIANT 786 FT /note="H -> Q (in a breast cancer sample; somatic mutation; FT dbSNP:rs1228797857)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_035829" FT VARIANT 969 FT /note="L -> V (in dbSNP:rs11254354)" FT /id="VAR_047446" FT VARIANT 1032 FT /note="Y -> H (in dbSNP:rs1801227)" FT /evidence="ECO:0000269|PubMed:10080186" FT /id="VAR_025287" FT VARIANT 1112 FT /note="G -> E (in IGS1; uncertain significance; results in FT intracellular retention of the mutant protein)" FT /evidence="ECO:0000269|PubMed:24156255" FT /id="VAR_084402" FT VARIANT 1158..3623 FT /note="Missing (in PROCHOB)" FT /evidence="ECO:0000269|PubMed:31613795" FT /id="VAR_084403" FT VARIANT 1297 FT /note="P -> L (in IGS1; decreases strongly the CBLIF FT binding affinity; dbSNP:rs121434430)" FT /evidence="ECO:0000269|PubMed:10080186, FT ECO:0000269|PubMed:10887099, ECO:0000269|PubMed:24156255" FT /id="VAR_025288" FT VARIANT 1303 FT /note="N -> H (in PROCHOB; uncertain significance; FT dbSNP:rs200203056)" FT /evidence="ECO:0000269|PubMed:31613795" FT /id="VAR_084404" FT VARIANT 1487..3623 FT /note="Missing (in PROCHOB)" FT /evidence="ECO:0000269|PubMed:31613795" FT /id="VAR_084405" FT VARIANT 1545 FT /note="N -> Y" FT /evidence="ECO:0000269|PubMed:10080186, FT ECO:0000269|PubMed:9572993" FT /id="VAR_025289" FT VARIANT 1559 FT /note="P -> S (in dbSNP:rs1801231)" FT /evidence="ECO:0000269|PubMed:10080186" FT /id="VAR_025290" FT VARIANT 1690 FT /note="A -> V (found in individuals with albuminuria; FT uncertain significance; dbSNP:rs141640975)" FT /evidence="ECO:0000269|PubMed:31613795" FT /id="VAR_084406" FT VARIANT 1769 FT /note="V -> I (in dbSNP:rs74116778)" FT /evidence="ECO:0000269|PubMed:10080186, FT ECO:0000269|PubMed:9572993" FT /id="VAR_025291" FT VARIANT 1775 FT /note="R -> W (in dbSNP:rs1276708)" FT /id="VAR_047447" FT VARIANT 1810..3623 FT /note="Missing (in PROCHOB)" FT /evidence="ECO:0000269|PubMed:31613795" FT /id="VAR_084407" FT VARIANT 1840 FT /note="G -> S (in dbSNP:rs2271462)" FT /id="VAR_047448" FT VARIANT 1854 FT /note="D -> Y (in PROCHOB; uncertain significance)" FT /evidence="ECO:0000269|PubMed:31613795" FT /id="VAR_084408" FT VARIANT 1928 FT /note="G -> V (in PROCHOB; uncertain significance; FT dbSNP:rs201513648)" FT /evidence="ECO:0000269|PubMed:31613795" FT /id="VAR_084409" FT VARIANT 1935 FT /note="S -> G (in dbSNP:rs41289305)" FT /id="VAR_047449" FT VARIANT 1947 FT /note="S -> Y (in PROCHOB; uncertain significance; FT dbSNP:rs147617753)" FT /evidence="ECO:0000269|PubMed:31613795" FT /id="VAR_084410" FT VARIANT 1971 FT /note="P -> T (in dbSNP:rs2356590)" FT /id="VAR_047450" FT VARIANT 2030..3623 FT /note="Missing (in PROCHOB)" FT /evidence="ECO:0000269|PubMed:31613795" FT /id="VAR_084411" FT VARIANT 2153 FT /note="L -> F (higher frequency in West Africans than in FT individuals of European ancestry; occurs with variants FT V-2984 and G-3002 only in individuals of European ancestry; FT dbSNP:rs62619939)" FT /evidence="ECO:0000269|PubMed:10080186, FT ECO:0000269|PubMed:23114252" FT /id="VAR_025292" FT VARIANT 2157 FT /note="N -> D (in dbSNP:rs144360241)" FT /evidence="ECO:0000269|PubMed:31613795" FT /id="VAR_084412" FT VARIANT 2162 FT /note="C -> Y (in dbSNP:rs1276712)" FT /evidence="ECO:0000269|PubMed:9572993" FT /id="VAR_025293" FT VARIANT 2252 FT /note="A -> V (in a colorectal cancer sample; somatic FT mutation; dbSNP:rs529856485)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_035830" FT VARIANT 2261 FT /note="L -> R (in PROCHOB; uncertain significance; FT dbSNP:rs779959064)" FT /evidence="ECO:0000269|PubMed:31613795" FT /id="VAR_084413" FT VARIANT 2263 FT /note="F -> C (in dbSNP:rs2271460)" FT /id="VAR_047451" FT VARIANT 2444 FT /note="R -> Q (in dbSNP:rs11254274)" FT /id="VAR_047452" FT VARIANT 2575 FT /note="P -> R (in dbSNP:rs3740168)" FT /evidence="ECO:0000269|PubMed:10080186" FT /id="VAR_025294" FT VARIANT 2599 FT /note="C -> W (in PROCHOB; uncertain significance; FT dbSNP:rs138758085)" FT /evidence="ECO:0000269|PubMed:31613795" FT /id="VAR_084414" FT VARIANT 2691 FT /note="G -> R (in dbSNP:rs1801237)" FT /evidence="ECO:0000269|PubMed:10080186" FT /id="VAR_025295" FT VARIANT 2717 FT /note="S -> W (in dbSNP:rs2796835)" FT /evidence="ECO:0000269|PubMed:9572993" FT /id="VAR_025296" FT VARIANT 2822 FT /note="P -> L (in PROCHOB; uncertain significance; FT dbSNP:rs776663892)" FT /evidence="ECO:0000269|PubMed:31613795" FT /id="VAR_084415" FT VARIANT 2831..3623 FT /note="Missing (in PROCHOB)" FT /evidence="ECO:0000269|PubMed:31613795" FT /id="VAR_084416" FT VARIANT 2833..3623 FT /note="Missing (in PROCHOB)" FT /evidence="ECO:0000269|PubMed:31613795" FT /id="VAR_084417" FT VARIANT 2879 FT /note="L -> I (in dbSNP:rs1801238)" FT /evidence="ECO:0000269|PubMed:10080186" FT /id="VAR_025297" FT VARIANT 2903..3623 FT /note="Missing (in PROCHOB)" FT /evidence="ECO:0000269|PubMed:31613795" FT /id="VAR_084418" FT VARIANT 2914 FT /note="A -> V (in a breast cancer sample; somatic mutation; FT dbSNP:rs45551835)" FT /evidence="ECO:0000269|PubMed:16959974, FT ECO:0000269|PubMed:31613795" FT /id="VAR_035831" FT VARIANT 2968 FT /note="E -> Q (in dbSNP:rs45569534)" FT /id="VAR_047453" FT VARIANT 2984 FT /note="I -> V (not found in West Africans; occurs with FT variants F-2153 and G-3002 only in individuals of European FT ancestry; dbSNP:rs1801239)" FT /evidence="ECO:0000269|PubMed:10080186, FT ECO:0000269|PubMed:21355061, ECO:0000269|PubMed:23114252, FT ECO:0000269|PubMed:31613795" FT /id="VAR_025298" FT VARIANT 3002 FT /note="E -> G (higher frequency in West Africans than in FT individuals of European ancestry; occurs with variants FT F-2153 and V-2984 only in individuals of European ancestry; FT dbSNP:rs1801240)" FT /evidence="ECO:0000269|PubMed:10080186, FT ECO:0000269|PubMed:23114252" FT /id="VAR_025299" FT VARIANT 3018 FT /note="Y -> S (in PROCHOB; uncertain significance; FT dbSNP:rs370778353)" FT /evidence="ECO:0000269|PubMed:31613795" FT /id="VAR_084419" FT VARIANT 3027 FT /note="G -> R (in PROCHOB; uncertain significance; FT dbSNP:rs150202444)" FT /evidence="ECO:0000269|PubMed:31613795" FT /id="VAR_084420" FT VARIANT 3189 FT /note="I -> V (in a breast cancer sample; somatic mutation; FT dbSNP:rs111265129)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_035832" FT VARIANT 3258 FT /note="S -> G (found in a renal cell carcinoma case; FT somatic mutation)" FT /evidence="ECO:0000269|PubMed:21248752" FT /id="VAR_064704" FT VARIANT 3308 FT /note="W -> R (in PROCHOB; uncertain significance; FT dbSNP:rs752843169)" FT /evidence="ECO:0000269|PubMed:31613795" FT /id="VAR_084421" FT VARIANT 3317..3623 FT /note="Missing (in PROCHOB)" FT /evidence="ECO:0000269|PubMed:31613795" FT /id="VAR_084422" FT VARIANT 3366 FT /note="S -> C (in PROCHOB; uncertain significance; FT dbSNP:rs201157846)" FT /evidence="ECO:0000269|PubMed:31613795" FT /id="VAR_084423" FT VARIANT 3422 FT /note="T -> I (in dbSNP:rs1801230)" FT /evidence="ECO:0000269|PubMed:10080186" FT /id="VAR_025300" FT VARIANT 3432 FT /note="T -> S (in dbSNP:rs7898873)" FT /id="VAR_055714" FT VARIANT 3492 FT /note="D -> Y (in PROCHOB; uncertain significance; FT dbSNP:rs764917718)" FT /evidence="ECO:0000269|PubMed:31613795" FT /id="VAR_084424" FT VARIANT 3520 FT /note="G -> D (in PROCHOB; uncertain significance)" FT /evidence="ECO:0000269|PubMed:31613795" FT /id="VAR_084425" FT VARIANT 3552 FT /note="N -> K (in dbSNP:rs1801232)" FT /evidence="ECO:0000269|PubMed:10080186" FT /id="VAR_025301" FT VARIANT 3609 FT /note="D -> H (in PROCHOB; uncertain significance; FT dbSNP:rs775742147)" FT /evidence="ECO:0000269|PubMed:31613795" FT /id="VAR_084426" FT VARIANT 3618..3623 FT /note="Missing (in PROCHOB; uncertain significance)" FT /evidence="ECO:0000269|PubMed:31613795" FT /id="VAR_084427" FT CONFLICT 25 FT /note="A -> R (in Ref. 1; AAC82612)" FT /evidence="ECO:0000305" FT CONFLICT 146 FT /note="T -> N (in Ref. 1; AAC82612)" FT /evidence="ECO:0000305" FT STRAND 43..47 FT /evidence="ECO:0007829|PDB:6GJE" FT STRAND 50..54 FT /evidence="ECO:0007829|PDB:6GJE" FT STRAND 61..64 FT /evidence="ECO:0007829|PDB:6GJE" FT STRAND 70..73 FT /evidence="ECO:0007829|PDB:6GJE" FT HELIX 78..99 FT /evidence="ECO:0007829|PDB:6GJE" FT HELIX 106..110 FT /evidence="ECO:0007829|PDB:6GJE" FT HELIX 113..120 FT /evidence="ECO:0007829|PDB:6GJE" FT STRAND 938..942 FT /evidence="ECO:0007829|PDB:3KQ4" FT STRAND 959..963 FT /evidence="ECO:0007829|PDB:3KQ4" FT STRAND 966..972 FT /evidence="ECO:0007829|PDB:3KQ4" FT STRAND 987..993 FT /evidence="ECO:0007829|PDB:3KQ4" FT STRAND 997..1004 FT /evidence="ECO:0007829|PDB:3KQ4" FT STRAND 1016..1025 FT /evidence="ECO:0007829|PDB:3KQ4" FT STRAND 1038..1046 FT /evidence="ECO:0007829|PDB:3KQ4" FT STRAND 1048..1052 FT /evidence="ECO:0007829|PDB:3KQ4" FT TURN 1062..1065 FT /evidence="ECO:0007829|PDB:3KQ4" FT STRAND 1073..1078 FT /evidence="ECO:0007829|PDB:3KQ4" FT STRAND 1087..1094 FT /evidence="ECO:0007829|PDB:3KQ4" FT STRAND 1104..1114 FT /evidence="ECO:0007829|PDB:3KQ4" FT STRAND 1119..1123 FT /evidence="ECO:0007829|PDB:3KQ4" FT STRAND 1125..1127 FT /evidence="ECO:0007829|PDB:3KQ4" FT STRAND 1135..1137 FT /evidence="ECO:0007829|PDB:3KQ4" FT STRAND 1139..1144 FT /evidence="ECO:0007829|PDB:3KQ4" FT STRAND 1153..1159 FT /evidence="ECO:0007829|PDB:3KQ4" FT STRAND 1171..1177 FT /evidence="ECO:0007829|PDB:3KQ4" FT TURN 1179..1182 FT /evidence="ECO:0007829|PDB:3KQ4" FT STRAND 1190..1195 FT /evidence="ECO:0007829|PDB:3KQ4" FT STRAND 1203..1209 FT /evidence="ECO:0007829|PDB:3KQ4" FT STRAND 1220..1230 FT /evidence="ECO:0007829|PDB:3KQ4" FT STRAND 1233..1239 FT /evidence="ECO:0007829|PDB:3KQ4" FT STRAND 1251..1253 FT /evidence="ECO:0007829|PDB:3KQ4" FT STRAND 1255..1260 FT /evidence="ECO:0007829|PDB:3KQ4" FT STRAND 1271..1276 FT /evidence="ECO:0007829|PDB:3KQ4" FT STRAND 1279..1283 FT /evidence="ECO:0007829|PDB:3KQ4" FT STRAND 1287..1292 FT /evidence="ECO:0007829|PDB:3KQ4" FT TURN 1294..1297 FT /evidence="ECO:0007829|PDB:3KQ4" FT STRAND 1305..1311 FT /evidence="ECO:0007829|PDB:3KQ4" FT STRAND 1319..1326 FT /evidence="ECO:0007829|PDB:3KQ4" FT TURN 1331..1334 FT /evidence="ECO:0007829|PDB:3KQ4" FT STRAND 1335..1342 FT /evidence="ECO:0007829|PDB:3KQ4" FT STRAND 1345..1350 FT /evidence="ECO:0007829|PDB:3KQ4" FT STRAND 1362..1371 FT /evidence="ECO:0007829|PDB:3KQ4" FT STRAND 1381..1386 FT /evidence="ECO:0007829|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 //