CUBN_HUMAN
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 03-AUG-2022, entry version 195.
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.
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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 GlyConnect; 2033; 1 N-Linked glycan (1 site).
DR GlyGen; O60494; 52 sites, 3 N-linked glycans (2 sites), 2 O-linked glycans (4 sites).
DR iPTMnet; O60494; -.
DR PhosphoSitePlus; O60494; -.
DR BioMuta; CUBN; -.
DR jPOST; O60494; -.
DR MassIVE; O60494; -.
DR PaxDb; O60494; -.
DR PeptideAtlas; O60494; -.
DR PRIDE; O60494; -.
DR ProteomicsDB; 49432; -.
DR Antibodypedia; 56802; 164 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 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; 4105at2759; -.
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; 10 hits in 1073 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 127 other tissues.
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; 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: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: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 Gene3D; 2.60.120.290; -; 27.
DR InterPro; IPR000859; CUB_dom.
DR InterPro; IPR028876; Cubilin.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR024731; EGF_dom.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR035914; Sperma_CUB_dom_sf.
DR PANTHER; PTHR45656:SF11; PTHR45656:SF11; 4.
DR Pfam; PF00431; CUB; 27.
DR Pfam; PF00008; EGF; 3.
DR Pfam; PF12947; EGF_3; 1.
DR Pfam; PF07645; EGF_CA; 3.
DR SMART; SM00042; CUB; 27.
DR SMART; SM00181; EGF; 8.
DR SMART; SM00179; EGF_CA; 7.
DR SUPFAM; SSF49854; SSF49854; 27.
DR 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 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; unknown pathological
FT significance; 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; unknown pathological significance;
FT results in 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; unknown pathological
FT significance; 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 (may be associated with albuminuria and
FT slightly increased glomerular filtration rate;
FT 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; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:31613795"
FT /id="VAR_084408"
FT VARIANT 1928
FT /note="G -> V (in PROCHOB; unknown pathological
FT significance; 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; unknown pathological
FT significance; 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 V-
FT 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 (may be associated with albuminuria and
FT slightly increased glomerular filtration rate;
FT 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; unknown pathological
FT significance; 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; unknown pathological
FT significance; 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; unknown pathological
FT significance; 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 may be associated with albuminuria and slightly increased
FT glomerular filtration rate; 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; associated with albuminuria in individuals of
FT European ancestry and African Americans, both with and
FT without diabetes; may be associated with increased risk of
FT developing persistent microalbuminuria in individuals with
FT type I diabetes; 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 F-
FT 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; unknown pathological
FT significance; dbSNP:rs370778353)"
FT /evidence="ECO:0000269|PubMed:31613795"
FT /id="VAR_084419"
FT VARIANT 3027
FT /note="G -> R (in PROCHOB; unknown pathological
FT significance; 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; unknown pathological
FT significance; 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; unknown pathological
FT significance; 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; unknown pathological
FT significance; dbSNP:rs764917718)"
FT /evidence="ECO:0000269|PubMed:31613795"
FT /id="VAR_084424"
FT VARIANT 3520
FT /note="G -> D (in PROCHOB; unknown pathological
FT 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; unknown pathological
FT significance; dbSNP:rs775742147)"
FT /evidence="ECO:0000269|PubMed:31613795"
FT /id="VAR_084426"
FT VARIANT 3618..3623
FT /note="Missing (in PROCHOB; unknown pathological
FT 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
