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O60494 (CUBN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cubilin
Alternative name(s):
460 kDa receptor
Intestinal intrinsic factor receptor
Intrinsic factor-cobalamin receptor
Intrinsic factor-vitamin B12 receptor
Gene names
Name:CUBN
Synonyms:IFCR
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length3623 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Cotransporter which plays a role in lipoprotein, vitamin and iron metabolism, by facilitating their uptake. Binds to ALB, MB, Kappa and lambda-light chains, TF, hemoglobin, GC, SCGB1A1, APOA1, high density lipoprotein, and the GIF-cobalamin complex. The binding of all ligands requires calcium. Serves as important transporter in several absorptive epithelia, including intestine, renal proximal tubules and embryonic yolk sac. Interaction with LRP2 mediates its trafficking throughout vesicles and facilitates the uptake of specific ligands like GC, hemoglobin, ALB, TF and SCGB1A1. Interaction with AMN controls its trafficking to the plasma membrane and facilitates endocytosis of ligands. May play an important role in the development of the peri-implantation embryo through internalization of APOA1 and cholesterol. Binds to LGALS3 at the maternal-fetal interface. Ref.1 Ref.4 Ref.5 Ref.6 Ref.7

Subunit structure

Interacts with LRP2 in a dual-receptor complex in a calcium-dependent manner. Component of the cubam complex composed of CUBN and AMN. The cubam complex can oligomerize and form cubam trimers. Found in a complex with PID1/PCLI1, LRP1 and CUBNI. Interacts with LRP1 and PID1/PCLI1. Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9

Subcellular location

Endosome membrane; Peripheral membrane protein By similarity. Lysosome membrane; Peripheral membrane protein By similarity. Note: Colocalizes with AMN and LRP2 in the endocytotic apparatus of epithelial cells By similarity.

Tissue specificity

Expressed in kidney proximal tubule cells, placenta, visceral yolk-sac cells and in absorptive intestinal cells. Expressed in the epithelium of intestine and kidney.

Domain

The CUB domains 5 to 8 mediate binding to GIF and ALB. CUB domains 1 and 2 mediate interaction with LRP2.

Post-translational modification

The precursor is cleaved by a trans-Golgi proteinase furin. The result is a propeptide cleaved off. Ref.1

N-glycosylated. Ref.7 Ref.9

Involvement in disease

Recessive hereditary megaloblastic anemia 1 (RH-MGA1) [MIM:261100]: Due to selective malabsorption of vitamin B12. Defects in vitamin B12 absorption lead to impaired function of thymidine synthase. As a consequence DNA synthesis is interrupted. Rapidly dividing cells involved in erythropoiesis are particularly affected.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10 Ref.11

Sequence similarities

Contains 27 CUB domains.

Contains 7 EGF-like domains.

Ontologies

Keywords
   Biological processCholesterol metabolism
Endocytosis
Lipid metabolism
Protein transport
Steroid metabolism
Sterol metabolism
Transport
   Cellular componentEndosome
Lysosome
Membrane
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainEGF-like domain
Repeat
Signal
   LigandCalcium
Cobalamin
Cobalt
Metal-binding
   Molecular functionReceptor
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcholesterol metabolic process

Inferred from electronic annotation. Source: UniProtKB-KW

cobalamin metabolic process

Traceable author statement. Source: Reactome

cobalamin transport

Traceable author statement Ref.10. Source: ProtInc

lipoprotein metabolic process

Traceable author statement. Source: Reactome

lipoprotein transport

Inferred from electronic annotation. Source: Ensembl

receptor-mediated endocytosis

Non-traceable author statement PubMed 11994745. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

steroid metabolic process

Traceable author statement. Source: Reactome

tissue homeostasis

Non-traceable author statement PubMed 11994745. Source: UniProtKB

vitamin D metabolic process

Traceable author statement. Source: Reactome

vitamin metabolic process

Traceable author statement. Source: Reactome

water-soluble vitamin metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: Ensembl

apical plasma membrane

Inferred from direct assay Ref.7. Source: UniProt

brush border membrane

Non-traceable author statement PubMed 11994745. Source: UniProtKB

coated pit

Inferred from electronic annotation. Source: Ensembl

cytosol

Traceable author statement. Source: Reactome

endocytic vesicle

Inferred from direct assay Ref.7. Source: UniProt

endoplasmic reticulum

Inferred from electronic annotation. Source: Ensembl

endosome membrane

Traceable author statement. Source: Reactome

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 23376485. Source: UniProt

extrinsic component of external side of plasma membrane

Non-traceable author statement PubMed 11994745. Source: UniProtKB

lysosomal lumen

Traceable author statement. Source: Reactome

lysosomal membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

membrane

Traceable author statement PubMed 9478979. Source: ProtInc

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functioncalcium ion binding

Inferred from electronic annotation. Source: InterPro

cobalamin binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction Ref.7. Source: UniProt

protein homodimerization activity

Inferred from direct assay PubMed 10552972. Source: UniProtKB

receptor activity

Traceable author statement Ref.10. Source: ProtInc

transporter activity

Traceable author statement PubMed 9478979. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Potential
Propeptide24 – 3512Removed in mature form
PRO_0000046072
Chain36 – 36233588Cubilin
PRO_0000046073

Regions

Domain132 – 16837EGF-like 1
Domain170 – 21142EGF-like 2; calcium-binding Potential
Domain263 – 30442EGF-like 3; calcium-binding Potential
Domain305 – 34844EGF-like 4; calcium-binding Potential
Domain349 – 38537EGF-like 5
Domain395 – 43036EGF-like 6
Domain432 – 46837EGF-like 7; calcium-binding Potential
Domain474 – 586113CUB 1
Domain590 – 702113CUB 2
Domain708 – 816109CUB 3
Domain816 – 928113CUB 4
Domain932 – 1042111CUB 5
Domain1048 – 1161114CUB 6
Domain1165 – 1277113CUB 7
Domain1278 – 1389112CUB 8
Domain1391 – 1506116CUB 9
Domain1510 – 1619110CUB 10
Domain1620 – 1734115CUB 11
Domain1738 – 1850113CUB 12
Domain1852 – 1963112CUB 13
Domain1978 – 2091114CUB 14
Domain2092 – 2213122CUB 15
Domain2217 – 2334118CUB 16
Domain2336 – 2448113CUB 17
Domain2452 – 2565114CUB 18
Domain2570 – 2687118CUB 19
Domain2689 – 2801113CUB 20
Domain2805 – 2919115CUB 21
Domain2920 – 3035116CUB 22
Domain3037 – 3150114CUB 23
Domain3157 – 3274118CUB 24
Domain3278 – 3393116CUB 25
Domain3395 – 3507113CUB 26
Domain3511 – 3623113CUB 27

Sites

Metal binding9801Calcium 1
Metal binding9881Calcium 1
Metal binding10271Calcium 1
Metal binding10291Calcium 1
Metal binding10301Calcium 1; via carbonyl oxygen
Metal binding10961Calcium 2
Metal binding11051Calcium 2
Metal binding11461Calcium 2
Metal binding11481Calcium 2; via carbonyl oxygen
Metal binding11491Calcium 2; via carbonyl oxygen
Metal binding12131Calcium 3
Metal binding12211Calcium 3
Metal binding12621Calcium 3
Metal binding12641Calcium 3; via carbonyl oxygen
Metal binding12651Calcium 3; via carbonyl oxygen
Metal binding13281Calcium 4
Metal binding13361Calcium 4
Metal binding13731Calcium 4
Metal binding13751Calcium 4; via carbonyl oxygen
Site35 – 362Cleavage; by furin Potential

Amino acid modifications

Modified residue30081Phosphothreonine By similarity
Glycosylation31N-linked (GlcNAc...) Potential
Glycosylation1051N-linked (GlcNAc...) Potential
Glycosylation4281N-linked (GlcNAc...) Potential
Glycosylation4821N-linked (GlcNAc...) Potential
Glycosylation7111N-linked (GlcNAc...) Potential
Glycosylation7491N-linked (GlcNAc...) Potential
Glycosylation7811N-linked (GlcNAc...) Potential
Glycosylation8571N-linked (GlcNAc...) Potential
Glycosylation9571N-linked (GlcNAc...) Potential
Glycosylation9841N-linked (GlcNAc...) Ref.9
Glycosylation10921N-linked (GlcNAc...) Ref.9
Glycosylation11681N-linked (GlcNAc...) Ref.9
Glycosylation12171N-linked (GlcNAc...) Ref.9
Glycosylation12851N-linked (GlcNAc...) Ref.9
Glycosylation13071N-linked (GlcNAc...) Ref.9
Glycosylation13191N-linked (GlcNAc...) Ref.9
Glycosylation13321N-linked (GlcNAc...) Ref.9
Glycosylation15001N-linked (GlcNAc...) Potential
Glycosylation15511N-linked (GlcNAc...) Potential
Glycosylation16461N-linked (GlcNAc...) Potential
Glycosylation18021N-linked (GlcNAc...) Potential
Glycosylation18191N-linked (GlcNAc...) Potential
Glycosylation18851N-linked (GlcNAc...) Potential
Glycosylation20851N-linked (GlcNAc...) Potential
Glycosylation21171N-linked (GlcNAc...) Potential
Glycosylation22741N-linked (GlcNAc...) Potential
Glycosylation23861N-linked (GlcNAc...) Potential
Glycosylation24001N-linked (GlcNAc...) Potential
Glycosylation25311N-linked (GlcNAc...) Potential
Glycosylation25811N-linked (GlcNAc...) Potential
Glycosylation25921N-linked (GlcNAc...) Potential
Glycosylation26101N-linked (GlcNAc...) Potential
Glycosylation28131N-linked (GlcNAc...) Potential
Glycosylation29231N-linked (GlcNAc...) Potential
Glycosylation29451N-linked (GlcNAc...) Potential
Glycosylation30421N-linked (GlcNAc...) Potential
Glycosylation31031N-linked (GlcNAc...) Potential
Glycosylation31251N-linked (GlcNAc...) Potential
Glycosylation31651N-linked (GlcNAc...) Potential
Glycosylation32681N-linked (GlcNAc...) Potential
Glycosylation32831N-linked (GlcNAc...) Potential
Glycosylation32901N-linked (GlcNAc...) Potential
Glycosylation32951N-linked (GlcNAc...) Potential
Glycosylation33571N-linked (GlcNAc...) Potential
Glycosylation34301N-linked (GlcNAc...) Potential
Glycosylation34571N-linked (GlcNAc...) Potential
Glycosylation35331N-linked (GlcNAc...) Potential
Glycosylation35761N-linked (GlcNAc...) Potential
Disulfide bond136 ↔ 147 By similarity
Disulfide bond141 ↔ 156 By similarity
Disulfide bond158 ↔ 167 By similarity
Disulfide bond174 ↔ 190 By similarity
Disulfide bond184 ↔ 199 By similarity
Disulfide bond201 ↔ 210 By similarity
Disulfide bond267 ↔ 280 By similarity
Disulfide bond274 ↔ 289 By similarity
Disulfide bond292 ↔ 303 By similarity
Disulfide bond353 ↔ 366 By similarity
Disulfide bond360 ↔ 376 By similarity
Disulfide bond399 ↔ 409 By similarity
Disulfide bond404 ↔ 418 By similarity
Disulfide bond420 ↔ 429 By similarity
Disulfide bond436 ↔ 447 By similarity
Disulfide bond441 ↔ 456 By similarity
Disulfide bond458 ↔ 467 By similarity
Disulfide bond474 ↔ 500 By similarity
Disulfide bond527 ↔ 549 By similarity
Disulfide bond590 ↔ 616 By similarity
Disulfide bond643 ↔ 665 By similarity
Disulfide bond708 ↔ 734 By similarity
Disulfide bond869 ↔ 891 By similarity
Disulfide bond932 ↔ 958 Ref.9
Disulfide bond985 ↔ 1005 Ref.9
Disulfide bond1048 ↔ 1074 Ref.9
Disulfide bond1165 ↔ 1191 Ref.9
Disulfide bond1218 ↔ 1240 Ref.9
Disulfide bond1278 ↔ 1306 Ref.9
Disulfide bond1333 ↔ 1351 Ref.9
Disulfide bond1391 ↔ 1417 By similarity
Disulfide bond1444 ↔ 1466 By similarity
Disulfide bond1510 ↔ 1536 By similarity
Disulfide bond1563 ↔ 1581 By similarity
Disulfide bond1620 ↔ 1647 By similarity
Disulfide bond1675 ↔ 1697 By similarity
Disulfide bond1738 ↔ 1764 By similarity
Disulfide bond1791 ↔ 1812 By similarity
Disulfide bond1905 ↔ 1927 By similarity
Disulfide bond1978 ↔ 2006 By similarity
Disulfide bond2032 ↔ 2054 By similarity
Disulfide bond2092 ↔ 2118 By similarity
Disulfide bond2217 ↔ 2247 By similarity
Disulfide bond2275 ↔ 2297 By similarity
Disulfide bond2336 ↔ 2363 By similarity
Disulfide bond2390 ↔ 2411 By similarity
Disulfide bond2452 ↔ 2478 By similarity
Disulfide bond2505 ↔ 2527 By similarity
Disulfide bond2570 ↔ 2599 By similarity
Disulfide bond2628 ↔ 2649 By similarity
Disulfide bond2689 ↔ 2715 By similarity
Disulfide bond2742 ↔ 2764 By similarity
Disulfide bond2805 ↔ 2831 By similarity
Disulfide bond2860 ↔ 2883 By similarity
Disulfide bond2920 ↔ 2946 By similarity
Disulfide bond2977 ↔ 2999 By similarity
Disulfide bond3037 ↔ 3064 By similarity
Disulfide bond3091 ↔ 3113 By similarity
Disulfide bond3157 ↔ 3185 By similarity
Disulfide bond3215 ↔ 3237 By similarity
Disulfide bond3278 ↔ 3306 By similarity
Disulfide bond3332 ↔ 3354 By similarity
Disulfide bond3395 ↔ 3421 By similarity
Disulfide bond3448 ↔ 3470 By similarity
Disulfide bond3511 ↔ 3537 By similarity
Disulfide bond3564 ↔ 3586 By similarity

Natural variations

Natural variant661G → R.
Corresponds to variant rs12259370 [ dbSNP | Ensembl ].
VAR_047443
Natural variant1241F → I. Ref.10
Corresponds to variant rs1801220 [ dbSNP | Ensembl ].
VAR_025284
Natural variant2531F → S. Ref.1 Ref.10
Corresponds to variant rs1801222 [ dbSNP | Ensembl ].
VAR_025285
Natural variant3351A → T.
Corresponds to variant rs57335729 [ dbSNP | Ensembl ].
VAR_061154
Natural variant3891P → T. Ref.10
Corresponds to variant rs1801224 [ dbSNP | Ensembl ].
VAR_025286
Natural variant5041I → M.
Corresponds to variant rs2228053 [ dbSNP | Ensembl ].
VAR_047444
Natural variant7301H → Y.
Corresponds to variant rs7905349 [ dbSNP | Ensembl ].
VAR_047445
Natural variant7861H → Q in a breast cancer sample; somatic mutation. Ref.12
VAR_035829
Natural variant9691L → V.
Corresponds to variant rs11254354 [ dbSNP | Ensembl ].
VAR_047446
Natural variant10321Y → H. Ref.10
Corresponds to variant rs1801227 [ dbSNP | Ensembl ].
VAR_025287
Natural variant12971P → L in RH-MGA1; decreases strongly the GIF binding affinity. Ref.10 Ref.11
Corresponds to variant rs28939699 [ dbSNP | Ensembl ].
VAR_025288
Natural variant15451N → Y. Ref.1 Ref.10
VAR_025289
Natural variant15591P → S. Ref.10
Corresponds to variant rs1801231 [ dbSNP | Ensembl ].
VAR_025290
Natural variant17691V → I. Ref.1 Ref.10
Corresponds to variant rs74116778 [ dbSNP | Ensembl ].
VAR_025291
Natural variant17751R → W.
Corresponds to variant rs1276708 [ dbSNP | Ensembl ].
VAR_047447
Natural variant18401G → S.
Corresponds to variant rs2271462 [ dbSNP | Ensembl ].
VAR_047448
Natural variant19351S → G.
Corresponds to variant rs41289305 [ dbSNP | Ensembl ].
VAR_047449
Natural variant19711P → T.
Corresponds to variant rs2356590 [ dbSNP | Ensembl ].
VAR_047450
Natural variant21531L → F. Ref.10
Corresponds to variant rs62619939 [ dbSNP | Ensembl ].
VAR_025292
Natural variant21621C → Y. Ref.1
Corresponds to variant rs1276712 [ dbSNP | Ensembl ].
VAR_025293
Natural variant22521A → V in a colorectal cancer sample; somatic mutation. Ref.12
VAR_035830
Natural variant22631F → C.
Corresponds to variant rs2271460 [ dbSNP | Ensembl ].
VAR_047451
Natural variant24441R → Q.
Corresponds to variant rs11254274 [ dbSNP | Ensembl ].
VAR_047452
Natural variant25751P → R. Ref.10
Corresponds to variant rs3740168 [ dbSNP | Ensembl ].
VAR_025294
Natural variant26911G → R. Ref.10
Corresponds to variant rs1801237 [ dbSNP | Ensembl ].
VAR_025295
Natural variant27171S → W. Ref.1
Corresponds to variant rs2796835 [ dbSNP | Ensembl ].
VAR_025296
Natural variant28791L → I. Ref.10
Corresponds to variant rs45474496 [ dbSNP | Ensembl ].
VAR_025297
Natural variant29141A → V in a breast cancer sample; somatic mutation. Ref.12
Corresponds to variant rs45551835 [ dbSNP | Ensembl ].
VAR_035831
Natural variant29681E → Q.
Corresponds to variant rs45569534 [ dbSNP | Ensembl ].
VAR_047453
Natural variant29841I → V. Ref.10
Corresponds to variant rs1801239 [ dbSNP | Ensembl ].
VAR_025298
Natural variant30021E → G. Ref.10
Corresponds to variant rs1801240 [ dbSNP | Ensembl ].
VAR_025299
Natural variant31891I → V in a breast cancer sample; somatic mutation. Ref.12
VAR_035832
Natural variant32581S → G Found in a renal cell carcinoma case; somatic mutation. Ref.13
VAR_064704
Natural variant34221T → I. Ref.10
Corresponds to variant rs1801230 [ dbSNP | Ensembl ].
VAR_025300
Natural variant34321T → S.
Corresponds to variant rs7898873 [ dbSNP | Ensembl ].
VAR_055714
Natural variant35521N → K. Ref.10
Corresponds to variant rs1801232 [ dbSNP | Ensembl ].
VAR_025301

Experimental info

Sequence conflict251A → R in AAC82612. Ref.1
Sequence conflict1461T → N in AAC82612. Ref.1

Secondary structure

........................................................................ 3623
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O60494 [UniParc].

Last modified November 2, 2010. Version 5.
Checksum: 8D602663C6D4751F

FASTA3,623398,736
        10         20         30         40         50         60 
MMNMSLPFLW SLLTLLIFAE VNGEAGELEL QRQKRSINLQ QPRMATERGN LVFLTGSAQN 

        70         80         90        100        110        120 
IEFRTGSLGK IKLNDEDLSE CLHQIQKNKE DIIELKGSAI GLPQNISSQI YQLNSKLVDL 

       130        140        150        160        170        180 
ERKFQGLQQT VDKKVCSSNP CQNGGTCLNL HDSFFCICPP QWKGPLCSAD VNECEIYSGT 

       190        200        210        220        230        240 
PLSCQNGGTC VNTMGSYSCH CPPETYGPQC ASKYDDCEGG SVARCVHGIC EDLMREQAGE 

       250        260        270        280        290        300 
PKYSCVCDAG WMFSPNSPAC TLDRDECSFQ PGPCSTLVQC FNTQGSFYCG ACPTGWQGNG 

       310        320        330        340        350        360 
YICEDINECE INNGGCSVAP PVECVNTPGS SHCQACPPGY QGDGRVCTLT DICSVSNGGC 

       370        380        390        400        410        420 
HPDASCSSTL GSLPLCTCLP GYTGNGYGPN GCVQLSNICL SHPCLNGQCI DTVSGYFCKC 

       430        440        450        460        470        480 
DSGWTGVNCT ENINECLSNP CLNGGTCVDG VDSFSCECTR LWTGALCQVP QQVCGESLSG 

       490        500        510        520        530        540 
INGSFSYRSP DVGYVHDVNC FWVIKTEMGK VLRITFTFFR LESMDNCPHE FLQVYDGDSS 

       550        560        570        580        590        600 
SAFQLGRFCG SSLPHELLSS DNALYFHLYS EHLRNGRGFT VRWETQQPEC GGILTGPYGS 

       610        620        630        640        650        660 
IKSPGYPGNY PPGRDCVWIV VTSPDLLVTF TFGTLSLEHH DDCNKDYLEI RDGPLYQDPL 

       670        680        690        700        710        720 
LGKFCTTFSV PPLQTTGPFA RIHFHSDSQI SDQGFHITYL TSPSDLRCGG NYTDPEGELF 

       730        740        750        760        770        780 
LPELSGPFTH TRQCVYMMKQ PQGEQIQINF THVELQCQSD SSQNYIEVRD GETLLGKVCG 

       790        800        810        820        830        840 
NGTISHIKSI TNSVWIRFKI DASVEKASFR AVYQVACGDE LTGEGVIRSP FFPNVYPGER 

       850        860        870        880        890        900 
TCRWTIHQPQ SQVILLNFTV FEIGSSAHCE TDYVEIGSSS ILGSPENKKY CGTDIPSFIT 

       910        920        930        940        950        960 
SVYNFLYVTF VKSSSTENHG FMAKFSAEDL ACGEILTEST GTIQSPGHPN VYPHGINCTW 

       970        980        990       1000       1010       1020 
HILVQPNHLI HLMFETFHLE FHYNCTNDYL EVYDTDSETS LGRYCGKSIP PSLTSSGNSL 

      1030       1040       1050       1060       1070       1080 
MLVFVTDSDL AYEGFLINYE AISAATACLQ DYTDDLGTFT SPNFPNNYPN NWECIYRITV 

      1090       1100       1110       1120       1130       1140 
RTGQLIAVHF TNFSLEEAIG NYYTDFLEIR DGGYEKSPLL GIFYGSNLPP TIISHSNKLW 

      1150       1160       1170       1180       1190       1200 
LKFKSDQIDT RSGFSAYWDG SSTGCGGNLT TSSGTFISPN YPMPYYHSSE CYWWLKSSHG 

      1210       1220       1230       1240       1250       1260 
SAFELEFKDF HLEHHPNCTL DYLAVYDGPS SNSHLLTQLC GDEKPPLIRS SGDSMFIKLR 

      1270       1280       1290       1300       1310       1320 
TDEGQQGRGF KAEYRQTCEN VVIVNQTYGI LESIGYPNPY SENQHCNWTI RATTGNTVNY 

      1330       1340       1350       1360       1370       1380 
TFLAFDLEHH INCSTDYLEL YDGPRQMGRY CGVDLPPPGS TTSSKLQVLL LTDGVGRREK 

      1390       1400       1410       1420       1430       1440 
GFQMQWFVYG CGGELSGATG SFSSPGFPNR YPPNKECIWY IRTDPGSSIQ LTIHDFDVEY 

      1450       1460       1470       1480       1490       1500 
HSRCNFDVLE IYGGPDFHSP RIAQLCTQRS PENPMQVSST GNELAIRFKT DLSINGRGFN 

      1510       1520       1530       1540       1550       1560 
ASWQAVTGGC GGIFQAPSGE IHSPNYPSPY RSNTDCSWVI RVDRNHRVLL NFTDFDLEPQ 

      1570       1580       1590       1600       1610       1620 
DSCIMAYDGL SSTMSRLART CGREQLANPI VSSGNSLFLR FQSGPSRQNR GFRAQFRQAC 

      1630       1640       1650       1660       1670       1680 
GGHILTSSFD TVSSPRFPAN YPNNQNCSWI IQAQPPLNHI TLSFTHFELE RSTTCARDFV 

      1690       1700       1710       1720       1730       1740 
EILDGGHEDA PLRGRYCGTD MPHPITSFSS ALTLRFVSDS SISAGGFHTT VTASVSACGG 

      1750       1760       1770       1780       1790       1800 
TFYMAEGIFN SPGYPDIYPP NVECVWNIVS SPGNRLQLSF ISFQLEDSQD CSRDFVEIRE 

      1810       1820       1830       1840       1850       1860 
GNATGHLVGR YCGNSFPLNY SSIVGHTLWV RFISDGSGSG TGFQATFMKI FGNDNIVGTH 

      1870       1880       1890       1900       1910       1920 
GKVASPFWPE NYPHNSNYQW TVNVNASHVV HGRILEMDIE EIQNCYYDKL RIYDGPSIHA 

      1930       1940       1950       1960       1970       1980 
RLIGAYCGTQ TESFSSTGNS LTFHFYSDSS ISGKGFLLEW FAVDAPDGVL PTIAPGACGG 

      1990       2000       2010       2020       2030       2040 
FLRTGDAPVF LFSPGWPDSY SNRVDCTWLI QAPDSTVELN ILSLDIESHR TCAYDSLVIR 

      2050       2060       2070       2080       2090       2100 
DGDNNLAQQL AVLCGREIPG PIRSTGEYMF IRFTSDSSVT RAGFNASFHK SCGGYLHADR 

      2110       2120       2130       2140       2150       2160 
GIITSPKYPE TYPSNLNCSW HVLVQSGLTI AVHFEQPFQI PNGDSSCNQG DYLVLRNGPD 

      2170       2180       2190       2200       2210       2220 
ICSPPLGPPG GNGHFCGSHA SSTLFTSDNQ MFVQFISDHS NEGQGFKIKY EAKSLACGGN 

      2230       2240       2250       2260       2270       2280 
VYIHDADSAG YVTSPNHPHN YPPHADCIWI LAAPPETRIQ LQFEDRFDIE VTPNCTSNYL 

      2290       2300       2310       2320       2330       2340 
ELRDGVDSDA PILSKFCGTS LPSSQWSSGE VMYLRFRSDN SPTHVGFKAK YSIAQCGGRV 

      2350       2360       2370       2380       2390       2400 
PGQSGVVESI GHPTLPYRDN LFCEWHLQGL SGHYLTISFE DFNLQNSSGC EKDFVEIWDN 

      2410       2420       2430       2440       2450       2460 
HTSGNILGRY CGNTIPDSID TSSNTAVVRF VTDGSVTASG FRLRFESSME ECGGDLQGSI 

      2470       2480       2490       2500       2510       2520 
GTFTSPNYPN PNPHGRICEW RITAPEGRRI TLMFNNLRLA THPSCNNEHV IVFNGIRSNS 

      2530       2540       2550       2560       2570       2580 
PQLEKLCSSV NVSNEIKSSG NTMKVIFFTD GSRPYGGFTA SYTSSEDAVC GGSLPNTPEG 

      2590       2600       2610       2620       2630       2640 
NFTSPGYDGV RNYSRNLNCE WTLSNPNQGN SSISIHFEDF YLESHQDCQF DVLEFRVGDA 

      2650       2660       2670       2680       2690       2700 
DGPLMWRLCG PSKPTLPLVI PYSQVWIHFV TNERVEHIGF HAKYSFTDCG GIQIGDSGVI 

      2710       2720       2730       2740       2750       2760 
TSPNYPNAYD SLTHCSSLLE APQGHTITLT FSDFDIEPHT TCAWDSVTVR NGGSPESPII 

      2770       2780       2790       2800       2810       2820 
GQYCGNSNPR TIQSGSNQLV VTFNSDHSLQ GGGFYATWNT QTLGCGGIFH SDNGTIRSPH 

      2830       2840       2850       2860       2870       2880 
WPQNFPENSR CSWTAITHKS KHLEISFDNN FLIPSGDGQC QNSFVKVWAG TEEVDKALLA 

      2890       2900       2910       2920       2930       2940 
TGCGNVAPGP VITPSNTFTA VFQSQEAPAQ GFSASFVSRC GSNFTGPSGY IISPNYPKQY 

      2950       2960       2970       2980       2990       3000 
DNNMNCTYVI EANPLSVVLL TFVSFHLEAR SAVTGSCVND GVHIIRGYSV MSTPFATVCG 

      3010       3020       3030       3040       3050       3060 
DEMPAPLTIA GPVLLNFYSN EQITDFGFKF SYRIISCGGV FNFSSGIITS PAYSYADYPN 

      3070       3080       3090       3100       3110       3120 
DMHCLYTITV SDDKVIELKF SDFDVVPSTS CSHDYLAIYD GANTSDPLLG KFCGSKRPPN 

      3130       3140       3150       3160       3170       3180 
VKSSNNSMLL VFKTDSFQTA KGWKMSFRQT LGPQQGCGGY LTGSNNTFAS PDSDSNGMYD 

      3190       3200       3210       3220       3230       3240 
KNLNCVWIII APVNKVIHLT FNTFALEAAS TRQRCLYDYV KLYDGDSENA NLAGTFCGST 

      3250       3260       3270       3280       3290       3300 
VPAPFISSGN FLTVQFISDL TLEREGFNAT YTIMDMPCGG TYNATWTPQN ISSPNSSDPD 

      3310       3320       3330       3340       3350       3360 
VPFSICTWVI DSPPHQQVKI TVWALQLTSQ DCTQNYLQLQ DSPQGHGNSR FQFCGRNASA 

      3370       3380       3390       3400       3410       3420 
VPVFYSSMST AMVIFKSGVV NRNSRMSFTY QIADCNRDYH KAFGNLRSPG WPDNYDNDKD 

      3430       3440       3450       3460       3470       3480 
CTVTLTAPQN HTISLFFHSL GIENSVECRN DFLEVRNGSN SNSPLLGKYC GTLLPNPVFS 

      3490       3500       3510       3520       3530       3540 
QNNELYLRFK SDSVTSDRGY EIIWTSSPSG CGGTLYGDRG SFTSPGYPGT YPNNTYCEWV 

      3550       3560       3570       3580       3590       3600 
LVAPAGRLVT INFYFISIDD PGDCVQNYLT LYDGPNASSP SSGPYCGGDT SIAPFVASSN 

      3610       3620 
QVFIKFHADY ARRPSAFRLT WDS 

« Hide

References

« Hide 'large scale' references
[1]"The human intrinsic factor-vitamin B12 receptor, cubilin: molecular characterization and chromosomal mapping of the gene to 10p within the autosomal recessive megaloblastic anemia (MGA1) region."
Kozyraki R., Kristiansen M., Silahtaroglu A., Hansen C., Jacobsen C., Tommerup N., Verroust P.J., Moestrup S.K.
Blood 91:3593-3600(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 36-41, FUNCTION, BINDING TO THE GIF-COBALAMIN COMPLEX, PROTEOLYTIC PROCESSING, VARIANTS SER-253; TYR-1545; ILE-1769; TYR-2162 AND TRP-2717.
[2]NHLBI resequencing and genotyping service (RS&G)
Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The intrinsic factor-vitamin B12 receptor, cubilin, is a high-affinity apolipoprotein A-I receptor facilitating endocytosis of high-density lipoprotein."
Kozyraki R., Fyfe J., Kristiansen M., Gerdes C., Jacobsen C., Cui S., Christensen E.I., Aminoff M., de la Chapelle A., Krahe R., Verroust P.J., Moestrup S.K.
Nat. Med. 5:656-661(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH APOA1, FUNCTION.
[5]"Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D(3)."
Nykjaer A., Fyfe J.C., Kozyraki R., Leheste J.-R., Jacobsen C., Nielsen M.S., Verroust P.J., Aminoff M., de la Chapelle A., Moestrup S.K., Ray R., Gliemann J., Willnow T.E., Christensen E.I.
Proc. Natl. Acad. Sci. U.S.A. 98:13895-13900(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GC, FUNCTION.
[6]"Megalin-dependent cubilin-mediated endocytosis is a major pathway for the apical uptake of transferrin in polarized epithelia."
Kozyraki R., Fyfe J., Verroust P.J., Jacobsen C., Dautry-Varsat A., Gburek J., Willnow T.E., Christensen E.I., Moestrup S.K.
Proc. Natl. Acad. Sci. U.S.A. 98:12491-12496(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TF, FUNCTION.
[7]"The functional cobalamin (vitamin B12)-intrinsic factor receptor is a novel complex of cubilin and amnionless."
Fyfe J.C., Madsen M., Hoejrup P., Christensen E.I., Tanner S.M., de la Chapelle A., He Q., Moestrup S.K.
Blood 103:1573-1579(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH AMN, GLYCOSYLATION, FUNCTION.
[8]"Identification of the ligands of protein interaction domains through a functional approach."
Caratu G., Allegra D., Bimonte M., Schiattarella G.G., D'Ambrosio C., Scaloni A., Napolitano M., Russo T., Zambrano N.
Mol. Cell. Proteomics 6:333-345(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH LRP1 AND PID1, INTERACTION WITH LRP1 AND PID1.
[9]"Structural basis for receptor recognition of vitamin-B(12)-intrinsic factor complexes."
Andersen C.B., Madsen M., Storm T., Moestrup S.K., Andersen G.R.
Nature 464:445-448(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 932-1388 IN COMPLEX WITH GIF AND CALCIUM IONS, INTERACTION WITH GIF, IDENTIFICATION IN CUBAM COMPLEX, SUBUNIT, DISULFIDE BONDS, GLYCOSYLATION AT ASN-984; ASN-1092; ASN-1168; ASN-1217; ASN-1285; ASN-1307; ASN-1319 AND ASN-1332.
[10]"Mutations in CUBN, encoding the intrinsic factor-vitamin B12 receptor, cubilin, cause hereditary megaloblastic anaemia 1."
Aminoff M., Carter J.E., Chadwick R.B., Johnson C., Graesbeck R., Abdelaal M.A., Broch H., Jenner L.B., Verroust P.J., Moestrup S.K., de la Chapelle A., Krahe R.
Nat. Genet. 21:309-313(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT RH-MGA1 LEU-1297, VARIANTS ILE-124; SER-253; THR-389; HIS-1032; TYR-1545; SER-1559; ILE-1769; PHE-2153; ARG-2575; ARG-2691; ILE-2879; VAL-2984; GLY-3002; ILE-3422 AND LYS-3552.
[11]"Cubilin P1297L mutation associated with hereditary megaloblastic anemia 1 causes impaired recognition of intrinsic factor-vitamin B(12) by cubilin."
Kristiansen M., Aminoff M., Jacobsen C., de La Chapelle A., Krahe R., Verroust P.J., Moestrup S.K.
Blood 96:405-409(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT RH-MGA1 LEU-1297.
[12]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLN-786; VAL-2252; VAL-2914 AND VAL-3189.
[13]"Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma."
Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H., Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J., Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M. expand/collapse author list , Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L., Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J., Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A., Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K., Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A.
Nature 469:539-542(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLY-3258.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF034611 mRNA. Translation: AAC82612.1.
EF444970 Genomic DNA. Translation: ACA05973.1.
EF444970 Genomic DNA. Translation: ACA05974.1.
AL596445 expand/collapse EMBL AC list , AL365215, AC067747, AL731551 Genomic DNA. Translation: CAH72450.1.
AL365215 expand/collapse EMBL AC list , AL596445, AC067747, AL731551 Genomic DNA. Translation: CAH73630.1.
AL731551 expand/collapse EMBL AC list , AL365215, AL596445, AC067747 Genomic DNA. Translation: CAI40246.1.
CCDSCCDS7113.1.
PIRT09456.
RefSeqNP_001072.2. NM_001081.3.
UniGeneHs.166206.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3KQ4X-ray3.30B/D/F932-1388[»]
ProteinModelPortalO60494.
SMRO60494. Positions 932-1388.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113724. 10 interactions.
DIPDIP-58583N.
IntActO60494. 1 interaction.
STRING9606.ENSP00000367064.

Chemistry

DrugBankDB00115. Cyanocobalamin.
DB00200. Hydroxocobalamin.

PTM databases

PhosphoSiteO60494.

Proteomic databases

PaxDbO60494.
PRIDEO60494.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000377833; ENSP00000367064; ENSG00000107611.
GeneID8029.
KEGGhsa:8029.
UCSCuc001ioo.3. human.

Organism-specific databases

CTD8029.
GeneCardsGC10M016906.
H-InvDBHIX0035313.
HIX0035577.
HGNCHGNC:2548. CUBN.
MIM261100. phenotype.
602997. gene.
neXtProtNX_O60494.
Orphanet35858. Grasbeck-Imerslund disease.
PharmGKBPA27044.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG287752.
HOGENOMHOG000049236.
HOVERGENHBG080357.
InParanoidO60494.
KOK14616.
OMASIQLTIH.
OrthoDBEOG741Z18.
PhylomeDBO60494.
TreeFamTF316224.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.
REACT_15493. Steroid hormones.

Gene expression databases

ArrayExpressO60494.
BgeeO60494.
CleanExHS_CUBN.
GenevestigatorO60494.

Family and domain databases

Gene3D2.60.120.290. 27 hits.
InterProIPR000859. CUB_dom.
IPR028876. Cubilin.
IPR000742. EG-like_dom.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR024731. EGF_dom_MSP1-like.
IPR009030. Growth_fac_rcpt_N_dom.
[Graphical view]
PANTHERPTHR10127:SF561. PTHR10127:SF561. 1 hit.
PfamPF00431. CUB. 27 hits.
PF00008. EGF. 3 hits.
PF12947. EGF_3. 1 hit.
PF07645. EGF_CA. 3 hits.
[Graphical view]
SMARTSM00042. CUB. 27 hits.
SM00181. EGF. 5 hits.
SM00179. EGF_CA. 3 hits.
[Graphical view]
SUPFAMSSF49854. SSF49854. 27 hits.
SSF57184. SSF57184. 1 hit.
PROSITEPS00010. ASX_HYDROXYL. 4 hits.
PS01180. CUB. 27 hits.
PS00022. EGF_1. 4 hits.
PS01186. EGF_2. 2 hits.
PS50026. EGF_3. 6 hits.
PS01187. EGF_CA. 3 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO60494.
GeneWikiCubilin.
GenomeRNAi8029.
NextBio30607.
PROO60494.
SOURCESearch...

Entry information

Entry nameCUBN_HUMAN
AccessionPrimary (citable) accession number: O60494
Secondary accession number(s): B0YIZ4, Q5VTA6, Q96RU9
Entry history
Integrated into UniProtKB/Swiss-Prot: February 7, 2006
Last sequence update: November 2, 2010
Last modified: July 9, 2014
This is version 130 of the entry and version 5 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM