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Protein

Cubilin

Gene

CUBN

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.5 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi980Calcium 11
Metal bindingi988Calcium 11
Metal bindingi1027Calcium 11
Metal bindingi1029Calcium 11
Metal bindingi1030Calcium 1; via carbonyl oxygen1
Metal bindingi1096Calcium 21
Metal bindingi1105Calcium 21
Metal bindingi1146Calcium 21
Metal bindingi1148Calcium 2; via carbonyl oxygen1
Metal bindingi1149Calcium 2; via carbonyl oxygen1
Metal bindingi1213Calcium 31
Metal bindingi1221Calcium 31
Metal bindingi1262Calcium 31
Metal bindingi1264Calcium 3; via carbonyl oxygen1
Metal bindingi1265Calcium 3; via carbonyl oxygen1
Metal bindingi1328Calcium 41
Metal bindingi1336Calcium 41
Metal bindingi1373Calcium 41
Metal bindingi1375Calcium 4; via carbonyl oxygen1

GO - Molecular functioni

  • calcium ion binding Source: InterPro
  • cobalamin binding Source: UniProtKB-KW
  • protein homodimerization activity Source: UniProtKB
  • receptor activity Source: ProtInc
  • transporter activity Source: ProtInc

GO - Biological processi

  • cholesterol metabolic process Source: UniProtKB-KW
  • cobalamin metabolic process Source: Reactome
  • cobalamin transport Source: ProtInc
  • lipoprotein metabolic process Source: Reactome
  • lipoprotein transport Source: Ensembl
  • protein transport Source: UniProtKB-KW
  • receptor-mediated endocytosis Source: UniProtKB
  • tissue homeostasis Source: UniProtKB
  • vitamin D metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Cholesterol metabolism, Endocytosis, Lipid metabolism, Protein transport, Steroid metabolism, Sterol metabolism, Transport

Keywords - Ligandi

Calcium, Cobalamin, Cobalt, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000107611-MONOMER.
ReactomeiR-HSA-194223. HDL-mediated lipid transport.
R-HSA-196741. Cobalamin (Cbl, vitamin B12) transport and metabolism.
R-HSA-196791. Vitamin D (calciferol) metabolism.
R-HSA-3359462. Defective AMN causes hereditary megaloblastic anemia 1.
R-HSA-3359463. Defective CUBN causes hereditary megaloblastic anemia 1.

Names & Taxonomyi

Protein namesi
Recommended name:
Cubilin
Alternative name(s):
460 kDa receptor
Intestinal intrinsic factor receptor
Intrinsic factor-cobalamin receptor
Intrinsic factor-vitamin B12 receptor
Gene namesi
Name:CUBN
Synonyms:IFCR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:2548. CUBN.

Subcellular locationi

GO - Cellular componenti

  • apical plasma membrane Source: UniProtKB
  • brush border membrane Source: UniProtKB
  • clathrin-coated pit Source: UniProtKB-SubCell
  • cytosol Source: Reactome
  • endocytic vesicle Source: UniProtKB
  • endoplasmic reticulum Source: Ensembl
  • endosome membrane Source: Reactome
  • extracellular exosome Source: UniProtKB
  • extrinsic component of external side of plasma membrane Source: UniProtKB
  • Golgi apparatus Source: Ensembl
  • lysosomal lumen Source: Reactome
  • lysosomal membrane Source: UniProtKB-SubCell
  • membrane Source: ProtInc
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Coated pit, Endosome, Lysosome, Membrane

Pathology & Biotechi

Involvement in diseasei

Recessive hereditary megaloblastic anemia 1 (RH-MGA1)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionDue 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.
See also OMIM:261100
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0252881297P → L in RH-MGA1; decreases strongly the GIF binding affinity. 2 PublicationsCorresponds to variant rs28939699dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi8029.
MalaCardsiCUBN.
MIMi261100. phenotype.
OpenTargetsiENSG00000107611.
Orphaneti35858. Grasbeck-Imerslund disease.
PharmGKBiPA27044.

Chemistry databases

DrugBankiDB00115. Cyanocobalamin.
DB00200. Hydroxocobalamin.

Polymorphism and mutation databases

BioMutaiCUBN.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Sequence analysisAdd BLAST23
PropeptideiPRO_000004607224 – 35Removed in mature form1 PublicationAdd BLAST12
ChainiPRO_000004607336 – 3623CubilinAdd BLAST3588

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi105N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi136 ↔ 147By similarity
Disulfide bondi141 ↔ 156By similarity
Disulfide bondi158 ↔ 167By similarity
Disulfide bondi174 ↔ 190By similarity
Disulfide bondi184 ↔ 199By similarity
Disulfide bondi201 ↔ 210By similarity
Disulfide bondi267 ↔ 280By similarity
Disulfide bondi274 ↔ 289By similarity
Disulfide bondi292 ↔ 303By similarity
Disulfide bondi353 ↔ 366By similarity
Disulfide bondi360 ↔ 376By similarity
Disulfide bondi399 ↔ 409By similarity
Disulfide bondi404 ↔ 418By similarity
Disulfide bondi420 ↔ 429By similarity
Glycosylationi428N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi436 ↔ 447By similarity
Disulfide bondi441 ↔ 456By similarity
Disulfide bondi458 ↔ 467By similarity
Disulfide bondi474 ↔ 500By similarity
Glycosylationi482N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi527 ↔ 549By similarity
Disulfide bondi590 ↔ 616By similarity
Disulfide bondi643 ↔ 665By similarity
Disulfide bondi708 ↔ 734By similarity
Glycosylationi711N-linked (GlcNAc...)Sequence analysis1
Glycosylationi749N-linked (GlcNAc...)Sequence analysis1
Glycosylationi781N-linked (GlcNAc...)Sequence analysis1
Glycosylationi857N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi869 ↔ 891By similarity
Disulfide bondi932 ↔ 9581 Publication
Glycosylationi957N-linked (GlcNAc...)Sequence analysis1
Glycosylationi984N-linked (GlcNAc...)1 Publication1
Disulfide bondi985 ↔ 10051 Publication
Disulfide bondi1048 ↔ 10741 Publication
Glycosylationi1092N-linked (GlcNAc...)1 Publication1
Disulfide bondi1165 ↔ 11911 Publication
Glycosylationi1168N-linked (GlcNAc...)1 Publication1
Glycosylationi1217N-linked (GlcNAc...)1 Publication1
Disulfide bondi1218 ↔ 12401 Publication
Disulfide bondi1278 ↔ 13061 Publication
Glycosylationi1285N-linked (GlcNAc...)1 Publication1
Glycosylationi1307N-linked (GlcNAc...)1 Publication1
Glycosylationi1319N-linked (GlcNAc...)1 Publication1
Glycosylationi1332N-linked (GlcNAc...)1 Publication1
Disulfide bondi1333 ↔ 13511 Publication
Disulfide bondi1391 ↔ 1417By similarity
Disulfide bondi1444 ↔ 1466By similarity
Glycosylationi1500N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi1510 ↔ 1536By similarity
Glycosylationi1551N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi1563 ↔ 1581By similarity
Disulfide bondi1620 ↔ 1647By similarity
Glycosylationi1646N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi1675 ↔ 1697By similarity
Disulfide bondi1738 ↔ 1764By similarity
Disulfide bondi1791 ↔ 1812By similarity
Glycosylationi1802N-linked (GlcNAc...)Sequence analysis1
Glycosylationi1819N-linked (GlcNAc...)Sequence analysis1
Glycosylationi1885N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi1905 ↔ 1927By similarity
Disulfide bondi1978 ↔ 2006By similarity
Disulfide bondi2032 ↔ 2054By similarity
Glycosylationi2085N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi2092 ↔ 2118By similarity
Glycosylationi2117N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi2217 ↔ 2247By similarity
Glycosylationi2274N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi2275 ↔ 2297By similarity
Disulfide bondi2336 ↔ 2363By similarity
Glycosylationi2386N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi2390 ↔ 2411By similarity
Glycosylationi2400N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi2452 ↔ 2478By similarity
Disulfide bondi2505 ↔ 2527By similarity
Glycosylationi2531N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi2570 ↔ 2599By similarity
Glycosylationi2581N-linked (GlcNAc...)Sequence analysis1
Glycosylationi2592N-linked (GlcNAc...)Sequence analysis1
Glycosylationi2610N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi2628 ↔ 2649By similarity
Disulfide bondi2689 ↔ 2715By similarity
Disulfide bondi2742 ↔ 2764By similarity
Disulfide bondi2805 ↔ 2831By similarity
Glycosylationi2813N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi2860 ↔ 2883By similarity
Disulfide bondi2920 ↔ 2946By similarity
Glycosylationi2923N-linked (GlcNAc...)Sequence analysis1
Glycosylationi2945N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi2977 ↔ 2999By similarity
Modified residuei3008PhosphothreonineBy similarity1
Disulfide bondi3037 ↔ 3064By similarity
Glycosylationi3042N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi3091 ↔ 3113By similarity
Glycosylationi3103N-linked (GlcNAc...)Sequence analysis1
Glycosylationi3125N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi3157 ↔ 3185By similarity
Glycosylationi3165N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi3215 ↔ 3237By similarity
Glycosylationi3268N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi3278 ↔ 3306By similarity
Glycosylationi3283N-linked (GlcNAc...)Sequence analysis1
Glycosylationi3290N-linked (GlcNAc...)Sequence analysis1
Glycosylationi3295N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi3332 ↔ 3354By similarity
Glycosylationi3357N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi3395 ↔ 3421By similarity
Glycosylationi3430N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi3448 ↔ 3470By similarity
Glycosylationi3457N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi3511 ↔ 3537By similarity
Glycosylationi3533N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi3564 ↔ 3586By similarity
Glycosylationi3576N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

The precursor is cleaved by a trans-Golgi proteinase furin. The result is a propeptide cleaved off.1 Publication
N-glycosylated.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei35 – 36Cleavage; by furinSequence analysis2

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiO60494.
PeptideAtlasiO60494.
PRIDEiO60494.

PTM databases

iPTMnetiO60494.
PhosphoSitePlusiO60494.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000107611.
CleanExiHS_CUBN.
ExpressionAtlasiO60494. baseline and differential.
GenevisibleiO60494. HS.

Interactioni

Subunit structurei

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/PCLI1.6 Publications

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi113724. 10 interactors.
DIPiDIP-58583N.
IntActiO60494. 2 interactors.
STRINGi9606.ENSP00000367064.

Structurei

Secondary structure

13623
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi938 – 942Combined sources5
Beta strandi959 – 963Combined sources5
Beta strandi966 – 972Combined sources7
Beta strandi987 – 993Combined sources7
Beta strandi997 – 1004Combined sources8
Beta strandi1016 – 1025Combined sources10
Beta strandi1038 – 1046Combined sources9
Beta strandi1048 – 1052Combined sources5
Turni1062 – 1065Combined sources4
Beta strandi1073 – 1078Combined sources6
Beta strandi1087 – 1094Combined sources8
Beta strandi1104 – 1114Combined sources11
Beta strandi1119 – 1123Combined sources5
Beta strandi1125 – 1127Combined sources3
Beta strandi1135 – 1137Combined sources3
Beta strandi1139 – 1144Combined sources6
Beta strandi1153 – 1159Combined sources7
Beta strandi1171 – 1177Combined sources7
Turni1179 – 1182Combined sources4
Beta strandi1190 – 1195Combined sources6
Beta strandi1203 – 1209Combined sources7
Beta strandi1220 – 1230Combined sources11
Beta strandi1233 – 1239Combined sources7
Beta strandi1251 – 1253Combined sources3
Beta strandi1255 – 1260Combined sources6
Beta strandi1271 – 1276Combined sources6
Beta strandi1279 – 1283Combined sources5
Beta strandi1287 – 1292Combined sources6
Turni1294 – 1297Combined sources4
Beta strandi1305 – 1311Combined sources7
Beta strandi1319 – 1326Combined sources8
Turni1331 – 1334Combined sources4
Beta strandi1335 – 1342Combined sources8
Beta strandi1345 – 1350Combined sources6
Beta strandi1362 – 1371Combined sources10
Beta strandi1381 – 1386Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3KQ4X-ray3.30B/D/F932-1388[»]
ProteinModelPortaliO60494.
SMRiO60494.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO60494.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini132 – 168EGF-like 1PROSITE-ProRule annotationAdd BLAST37
Domaini170 – 211EGF-like 2; calcium-bindingPROSITE-ProRule annotationAdd BLAST42
Domaini263 – 304EGF-like 3; calcium-bindingPROSITE-ProRule annotationAdd BLAST42
Domaini305 – 348EGF-like 4; calcium-bindingPROSITE-ProRule annotationAdd BLAST44
Domaini349 – 385EGF-like 5PROSITE-ProRule annotationAdd BLAST37
Domaini395 – 430EGF-like 6PROSITE-ProRule annotationAdd BLAST36
Domaini432 – 468EGF-like 7; calcium-bindingPROSITE-ProRule annotationAdd BLAST37
Domaini474 – 586CUB 1PROSITE-ProRule annotationAdd BLAST113
Domaini590 – 702CUB 2PROSITE-ProRule annotationAdd BLAST113
Domaini708 – 816CUB 3PROSITE-ProRule annotationAdd BLAST109
Domaini816 – 928CUB 4PROSITE-ProRule annotationAdd BLAST113
Domaini932 – 1042CUB 5PROSITE-ProRule annotationAdd BLAST111
Domaini1048 – 1161CUB 6PROSITE-ProRule annotationAdd BLAST114
Domaini1165 – 1277CUB 7PROSITE-ProRule annotationAdd BLAST113
Domaini1278 – 1389CUB 8PROSITE-ProRule annotationAdd BLAST112
Domaini1391 – 1506CUB 9PROSITE-ProRule annotationAdd BLAST116
Domaini1510 – 1619CUB 10PROSITE-ProRule annotationAdd BLAST110
Domaini1620 – 1734CUB 11PROSITE-ProRule annotationAdd BLAST115
Domaini1738 – 1850CUB 12PROSITE-ProRule annotationAdd BLAST113
Domaini1852 – 1963CUB 13PROSITE-ProRule annotationAdd BLAST112
Domaini1978 – 2091CUB 14PROSITE-ProRule annotationAdd BLAST114
Domaini2092 – 2213CUB 15PROSITE-ProRule annotationAdd BLAST122
Domaini2217 – 2334CUB 16PROSITE-ProRule annotationAdd BLAST118
Domaini2336 – 2448CUB 17PROSITE-ProRule annotationAdd BLAST113
Domaini2452 – 2565CUB 18PROSITE-ProRule annotationAdd BLAST114
Domaini2570 – 2687CUB 19PROSITE-ProRule annotationAdd BLAST118
Domaini2689 – 2801CUB 20PROSITE-ProRule annotationAdd BLAST113
Domaini2805 – 2919CUB 21PROSITE-ProRule annotationAdd BLAST115
Domaini2920 – 3035CUB 22PROSITE-ProRule annotationAdd BLAST116
Domaini3037 – 3150CUB 23PROSITE-ProRule annotationAdd BLAST114
Domaini3157 – 3274CUB 24PROSITE-ProRule annotationAdd BLAST118
Domaini3278 – 3393CUB 25PROSITE-ProRule annotationAdd BLAST116
Domaini3395 – 3507CUB 26PROSITE-ProRule annotationAdd BLAST113
Domaini3511 – 3623CUB 27PROSITE-ProRule annotationAdd BLAST113

Domaini

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

Sequence similaritiesi

Contains 27 CUB domains.PROSITE-ProRule annotation
Contains 7 EGF-like domains.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Repeat, Signal

Phylogenomic databases

eggNOGiKOG3714. Eukaryota.
ENOG410ZPX7. LUCA.
GeneTreeiENSGT00760000119018.
HOGENOMiHOG000049236.
HOVERGENiHBG080357.
InParanoidiO60494.
KOiK14616.
OMAiYSFTDCG.
OrthoDBiEOG091G009U.
PhylomeDBiO60494.
TreeFamiTF316224.

Family and domain databases

CDDicd00041. CUB. 27 hits.
Gene3Di2.60.120.290. 27 hits.
InterProiIPR000859. CUB_dom.
IPR028876. Cubilin.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR024731. EGF_dom.
IPR009030. Growth_fac_rcpt_.
[Graphical view]
PANTHERiPTHR10127:SF645. PTHR10127:SF645. 5 hits.
PfamiPF00431. CUB. 27 hits.
PF00008. EGF. 3 hits.
PF12947. EGF_3. 1 hit.
PF07645. EGF_CA. 3 hits.
[Graphical view]
SMARTiSM00042. CUB. 27 hits.
SM00181. EGF. 8 hits.
SM00179. EGF_CA. 7 hits.
[Graphical view]
SUPFAMiSSF49854. SSF49854. 27 hits.
SSF57184. SSF57184. 1 hit.
PROSITEiPS00010. 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]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O60494-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MMNMSLPFLW SLLTLLIFAE VNGEAGELEL QRQKRSINLQ QPRMATERGN
60 70 80 90 100
LVFLTGSAQN IEFRTGSLGK IKLNDEDLSE CLHQIQKNKE DIIELKGSAI
110 120 130 140 150
GLPQNISSQI YQLNSKLVDL ERKFQGLQQT VDKKVCSSNP CQNGGTCLNL
160 170 180 190 200
HDSFFCICPP QWKGPLCSAD VNECEIYSGT PLSCQNGGTC VNTMGSYSCH
210 220 230 240 250
CPPETYGPQC ASKYDDCEGG SVARCVHGIC EDLMREQAGE PKYSCVCDAG
260 270 280 290 300
WMFSPNSPAC TLDRDECSFQ PGPCSTLVQC FNTQGSFYCG ACPTGWQGNG
310 320 330 340 350
YICEDINECE INNGGCSVAP PVECVNTPGS SHCQACPPGY QGDGRVCTLT
360 370 380 390 400
DICSVSNGGC HPDASCSSTL GSLPLCTCLP GYTGNGYGPN GCVQLSNICL
410 420 430 440 450
SHPCLNGQCI DTVSGYFCKC DSGWTGVNCT ENINECLSNP CLNGGTCVDG
460 470 480 490 500
VDSFSCECTR LWTGALCQVP QQVCGESLSG INGSFSYRSP DVGYVHDVNC
510 520 530 540 550
FWVIKTEMGK VLRITFTFFR LESMDNCPHE FLQVYDGDSS SAFQLGRFCG
560 570 580 590 600
SSLPHELLSS DNALYFHLYS EHLRNGRGFT VRWETQQPEC GGILTGPYGS
610 620 630 640 650
IKSPGYPGNY PPGRDCVWIV VTSPDLLVTF TFGTLSLEHH DDCNKDYLEI
660 670 680 690 700
RDGPLYQDPL LGKFCTTFSV PPLQTTGPFA RIHFHSDSQI SDQGFHITYL
710 720 730 740 750
TSPSDLRCGG NYTDPEGELF LPELSGPFTH TRQCVYMMKQ PQGEQIQINF
760 770 780 790 800
THVELQCQSD SSQNYIEVRD GETLLGKVCG NGTISHIKSI TNSVWIRFKI
810 820 830 840 850
DASVEKASFR AVYQVACGDE LTGEGVIRSP FFPNVYPGER TCRWTIHQPQ
860 870 880 890 900
SQVILLNFTV FEIGSSAHCE TDYVEIGSSS ILGSPENKKY CGTDIPSFIT
910 920 930 940 950
SVYNFLYVTF VKSSSTENHG FMAKFSAEDL ACGEILTEST GTIQSPGHPN
960 970 980 990 1000
VYPHGINCTW HILVQPNHLI HLMFETFHLE FHYNCTNDYL EVYDTDSETS
1010 1020 1030 1040 1050
LGRYCGKSIP PSLTSSGNSL MLVFVTDSDL AYEGFLINYE AISAATACLQ
1060 1070 1080 1090 1100
DYTDDLGTFT SPNFPNNYPN NWECIYRITV RTGQLIAVHF TNFSLEEAIG
1110 1120 1130 1140 1150
NYYTDFLEIR DGGYEKSPLL GIFYGSNLPP TIISHSNKLW LKFKSDQIDT
1160 1170 1180 1190 1200
RSGFSAYWDG SSTGCGGNLT TSSGTFISPN YPMPYYHSSE CYWWLKSSHG
1210 1220 1230 1240 1250
SAFELEFKDF HLEHHPNCTL DYLAVYDGPS SNSHLLTQLC GDEKPPLIRS
1260 1270 1280 1290 1300
SGDSMFIKLR TDEGQQGRGF KAEYRQTCEN VVIVNQTYGI LESIGYPNPY
1310 1320 1330 1340 1350
SENQHCNWTI RATTGNTVNY TFLAFDLEHH INCSTDYLEL YDGPRQMGRY
1360 1370 1380 1390 1400
CGVDLPPPGS TTSSKLQVLL LTDGVGRREK GFQMQWFVYG CGGELSGATG
1410 1420 1430 1440 1450
SFSSPGFPNR YPPNKECIWY IRTDPGSSIQ LTIHDFDVEY HSRCNFDVLE
1460 1470 1480 1490 1500
IYGGPDFHSP RIAQLCTQRS PENPMQVSST GNELAIRFKT DLSINGRGFN
1510 1520 1530 1540 1550
ASWQAVTGGC GGIFQAPSGE IHSPNYPSPY RSNTDCSWVI RVDRNHRVLL
1560 1570 1580 1590 1600
NFTDFDLEPQ DSCIMAYDGL SSTMSRLART CGREQLANPI VSSGNSLFLR
1610 1620 1630 1640 1650
FQSGPSRQNR GFRAQFRQAC GGHILTSSFD TVSSPRFPAN YPNNQNCSWI
1660 1670 1680 1690 1700
IQAQPPLNHI TLSFTHFELE RSTTCARDFV EILDGGHEDA PLRGRYCGTD
1710 1720 1730 1740 1750
MPHPITSFSS ALTLRFVSDS SISAGGFHTT VTASVSACGG TFYMAEGIFN
1760 1770 1780 1790 1800
SPGYPDIYPP NVECVWNIVS SPGNRLQLSF ISFQLEDSQD CSRDFVEIRE
1810 1820 1830 1840 1850
GNATGHLVGR YCGNSFPLNY SSIVGHTLWV RFISDGSGSG TGFQATFMKI
1860 1870 1880 1890 1900
FGNDNIVGTH GKVASPFWPE NYPHNSNYQW TVNVNASHVV HGRILEMDIE
1910 1920 1930 1940 1950
EIQNCYYDKL RIYDGPSIHA RLIGAYCGTQ TESFSSTGNS LTFHFYSDSS
1960 1970 1980 1990 2000
ISGKGFLLEW FAVDAPDGVL PTIAPGACGG FLRTGDAPVF LFSPGWPDSY
2010 2020 2030 2040 2050
SNRVDCTWLI QAPDSTVELN ILSLDIESHR TCAYDSLVIR DGDNNLAQQL
2060 2070 2080 2090 2100
AVLCGREIPG PIRSTGEYMF IRFTSDSSVT RAGFNASFHK SCGGYLHADR
2110 2120 2130 2140 2150
GIITSPKYPE TYPSNLNCSW HVLVQSGLTI AVHFEQPFQI PNGDSSCNQG
2160 2170 2180 2190 2200
DYLVLRNGPD ICSPPLGPPG GNGHFCGSHA SSTLFTSDNQ MFVQFISDHS
2210 2220 2230 2240 2250
NEGQGFKIKY EAKSLACGGN VYIHDADSAG YVTSPNHPHN YPPHADCIWI
2260 2270 2280 2290 2300
LAAPPETRIQ LQFEDRFDIE VTPNCTSNYL ELRDGVDSDA PILSKFCGTS
2310 2320 2330 2340 2350
LPSSQWSSGE VMYLRFRSDN SPTHVGFKAK YSIAQCGGRV PGQSGVVESI
2360 2370 2380 2390 2400
GHPTLPYRDN LFCEWHLQGL SGHYLTISFE DFNLQNSSGC EKDFVEIWDN
2410 2420 2430 2440 2450
HTSGNILGRY CGNTIPDSID TSSNTAVVRF VTDGSVTASG FRLRFESSME
2460 2470 2480 2490 2500
ECGGDLQGSI GTFTSPNYPN PNPHGRICEW RITAPEGRRI TLMFNNLRLA
2510 2520 2530 2540 2550
THPSCNNEHV IVFNGIRSNS PQLEKLCSSV NVSNEIKSSG NTMKVIFFTD
2560 2570 2580 2590 2600
GSRPYGGFTA SYTSSEDAVC GGSLPNTPEG NFTSPGYDGV RNYSRNLNCE
2610 2620 2630 2640 2650
WTLSNPNQGN SSISIHFEDF YLESHQDCQF DVLEFRVGDA DGPLMWRLCG
2660 2670 2680 2690 2700
PSKPTLPLVI PYSQVWIHFV TNERVEHIGF HAKYSFTDCG GIQIGDSGVI
2710 2720 2730 2740 2750
TSPNYPNAYD SLTHCSSLLE APQGHTITLT FSDFDIEPHT TCAWDSVTVR
2760 2770 2780 2790 2800
NGGSPESPII GQYCGNSNPR TIQSGSNQLV VTFNSDHSLQ GGGFYATWNT
2810 2820 2830 2840 2850
QTLGCGGIFH SDNGTIRSPH WPQNFPENSR CSWTAITHKS KHLEISFDNN
2860 2870 2880 2890 2900
FLIPSGDGQC QNSFVKVWAG TEEVDKALLA TGCGNVAPGP VITPSNTFTA
2910 2920 2930 2940 2950
VFQSQEAPAQ GFSASFVSRC GSNFTGPSGY IISPNYPKQY DNNMNCTYVI
2960 2970 2980 2990 3000
EANPLSVVLL TFVSFHLEAR SAVTGSCVND GVHIIRGYSV MSTPFATVCG
3010 3020 3030 3040 3050
DEMPAPLTIA GPVLLNFYSN EQITDFGFKF SYRIISCGGV FNFSSGIITS
3060 3070 3080 3090 3100
PAYSYADYPN DMHCLYTITV SDDKVIELKF SDFDVVPSTS CSHDYLAIYD
3110 3120 3130 3140 3150
GANTSDPLLG KFCGSKRPPN VKSSNNSMLL VFKTDSFQTA KGWKMSFRQT
3160 3170 3180 3190 3200
LGPQQGCGGY LTGSNNTFAS PDSDSNGMYD KNLNCVWIII APVNKVIHLT
3210 3220 3230 3240 3250
FNTFALEAAS TRQRCLYDYV KLYDGDSENA NLAGTFCGST VPAPFISSGN
3260 3270 3280 3290 3300
FLTVQFISDL TLEREGFNAT YTIMDMPCGG TYNATWTPQN ISSPNSSDPD
3310 3320 3330 3340 3350
VPFSICTWVI DSPPHQQVKI TVWALQLTSQ DCTQNYLQLQ DSPQGHGNSR
3360 3370 3380 3390 3400
FQFCGRNASA VPVFYSSMST AMVIFKSGVV NRNSRMSFTY QIADCNRDYH
3410 3420 3430 3440 3450
KAFGNLRSPG WPDNYDNDKD CTVTLTAPQN HTISLFFHSL GIENSVECRN
3460 3470 3480 3490 3500
DFLEVRNGSN SNSPLLGKYC GTLLPNPVFS QNNELYLRFK SDSVTSDRGY
3510 3520 3530 3540 3550
EIIWTSSPSG CGGTLYGDRG SFTSPGYPGT YPNNTYCEWV LVAPAGRLVT
3560 3570 3580 3590 3600
INFYFISIDD PGDCVQNYLT LYDGPNASSP SSGPYCGGDT SIAPFVASSN
3610 3620
QVFIKFHADY ARRPSAFRLT WDS
Length:3,623
Mass (Da):398,736
Last modified:November 2, 2010 - v5
Checksum:i8D602663C6D4751F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti25A → R in AAC82612 (PubMed:9572993).Curated1
Sequence conflicti146T → N in AAC82612 (PubMed:9572993).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04744366G → R.Corresponds to variant rs12259370dbSNPEnsembl.1
Natural variantiVAR_025284124F → I.1 PublicationCorresponds to variant rs1801220dbSNPEnsembl.1
Natural variantiVAR_025285253F → S.2 PublicationsCorresponds to variant rs1801222dbSNPEnsembl.1
Natural variantiVAR_061154335A → T.Corresponds to variant rs57335729dbSNPEnsembl.1
Natural variantiVAR_025286389P → T.1 PublicationCorresponds to variant rs1801224dbSNPEnsembl.1
Natural variantiVAR_047444504I → M.Corresponds to variant rs2228053dbSNPEnsembl.1
Natural variantiVAR_047445730H → Y.Corresponds to variant rs7905349dbSNPEnsembl.1
Natural variantiVAR_035829786H → Q in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_047446969L → V.Corresponds to variant rs11254354dbSNPEnsembl.1
Natural variantiVAR_0252871032Y → H.1 PublicationCorresponds to variant rs1801227dbSNPEnsembl.1
Natural variantiVAR_0252881297P → L in RH-MGA1; decreases strongly the GIF binding affinity. 2 PublicationsCorresponds to variant rs28939699dbSNPEnsembl.1
Natural variantiVAR_0252891545N → Y.2 Publications1
Natural variantiVAR_0252901559P → S.1 PublicationCorresponds to variant rs1801231dbSNPEnsembl.1
Natural variantiVAR_0252911769V → I.2 PublicationsCorresponds to variant rs74116778dbSNPEnsembl.1
Natural variantiVAR_0474471775R → W.Corresponds to variant rs1276708dbSNPEnsembl.1
Natural variantiVAR_0474481840G → S.Corresponds to variant rs2271462dbSNPEnsembl.1
Natural variantiVAR_0474491935S → G.Corresponds to variant rs41289305dbSNPEnsembl.1
Natural variantiVAR_0474501971P → T.Corresponds to variant rs2356590dbSNPEnsembl.1
Natural variantiVAR_0252922153L → F Higher frequency in West Africans than in individuals of European ancestry; occurs with variants V-2984 and G-3002 only in individuals of European ancestry. 2 PublicationsCorresponds to variant rs62619939dbSNPEnsembl.1
Natural variantiVAR_0252932162C → Y.1 PublicationCorresponds to variant rs1276712dbSNPEnsembl.1
Natural variantiVAR_0358302252A → V in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant rs529856485dbSNPEnsembl.1
Natural variantiVAR_0474512263F → C.Corresponds to variant rs2271460dbSNPEnsembl.1
Natural variantiVAR_0474522444R → Q.Corresponds to variant rs11254274dbSNPEnsembl.1
Natural variantiVAR_0252942575P → R.1 PublicationCorresponds to variant rs3740168dbSNPEnsembl.1
Natural variantiVAR_0252952691G → R.1 PublicationCorresponds to variant rs1801237dbSNPEnsembl.1
Natural variantiVAR_0252962717S → W.1 PublicationCorresponds to variant rs2796835dbSNPEnsembl.1
Natural variantiVAR_0252972879L → I.1 PublicationCorresponds to variant rs1801238dbSNPEnsembl.1
Natural variantiVAR_0358312914A → V in a breast cancer sample; somatic mutation. 1 PublicationCorresponds to variant rs45551835dbSNPEnsembl.1
Natural variantiVAR_0474532968E → Q.Corresponds to variant rs45569534dbSNPEnsembl.1
Natural variantiVAR_0252982984I → V Not found in West Africans; occurs with variants F-2153 and G-3002 only in individuals of European ancestry; associated with albuminuria in individuals of European ancestry and African Americans, both with and without diabetes; associated with 42% increased risk of developing persistent microalbuminuria in individuals with type I diabetes. 3 PublicationsCorresponds to variant rs1801239dbSNPEnsembl.1
Natural variantiVAR_0252993002E → G Higher frequency in West Africans than in individuals of European ancestry; occurs with variants F-2153 and V-2984 only in individuals of European ancestry. 2 PublicationsCorresponds to variant rs1801240dbSNPEnsembl.1
Natural variantiVAR_0358323189I → V in a breast cancer sample; somatic mutation. 1 PublicationCorresponds to variant rs111265129dbSNPEnsembl.1
Natural variantiVAR_0647043258S → G Found in a renal cell carcinoma case; somatic mutation. 1 Publication1
Natural variantiVAR_0253003422T → I.1 PublicationCorresponds to variant rs1801230dbSNPEnsembl.1
Natural variantiVAR_0557143432T → S.Corresponds to variant rs7898873dbSNPEnsembl.1
Natural variantiVAR_0253013552N → K.1 PublicationCorresponds to variant rs1801232dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF034611 mRNA. Translation: AAC82612.1.
EF444970 Genomic DNA. Translation: ACA05973.1.
EF444970 Genomic DNA. Translation: ACA05974.1.
AL596445
, AL365215, AC067747, AL731551 Genomic DNA. Translation: CAH72450.1.
AL365215
, AL596445, AC067747, AL731551 Genomic DNA. Translation: CAH73630.1.
AL731551
, AL365215, AL596445, AC067747 Genomic DNA. Translation: CAI40246.1.
CCDSiCCDS7113.1.
PIRiT09456.
RefSeqiNP_001072.2. NM_001081.3.
UniGeneiHs.166206.

Genome annotation databases

EnsembliENST00000377833; ENSP00000367064; ENSG00000107611.
GeneIDi8029.
KEGGihsa:8029.
UCSCiuc001ioo.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF034611 mRNA. Translation: AAC82612.1.
EF444970 Genomic DNA. Translation: ACA05973.1.
EF444970 Genomic DNA. Translation: ACA05974.1.
AL596445
, AL365215, AC067747, AL731551 Genomic DNA. Translation: CAH72450.1.
AL365215
, AL596445, AC067747, AL731551 Genomic DNA. Translation: CAH73630.1.
AL731551
, AL365215, AL596445, AC067747 Genomic DNA. Translation: CAI40246.1.
CCDSiCCDS7113.1.
PIRiT09456.
RefSeqiNP_001072.2. NM_001081.3.
UniGeneiHs.166206.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3KQ4X-ray3.30B/D/F932-1388[»]
ProteinModelPortaliO60494.
SMRiO60494.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113724. 10 interactors.
DIPiDIP-58583N.
IntActiO60494. 2 interactors.
STRINGi9606.ENSP00000367064.

Chemistry databases

DrugBankiDB00115. Cyanocobalamin.
DB00200. Hydroxocobalamin.

PTM databases

iPTMnetiO60494.
PhosphoSitePlusiO60494.

Polymorphism and mutation databases

BioMutaiCUBN.

Proteomic databases

PaxDbiO60494.
PeptideAtlasiO60494.
PRIDEiO60494.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000377833; ENSP00000367064; ENSG00000107611.
GeneIDi8029.
KEGGihsa:8029.
UCSCiuc001ioo.4. human.

Organism-specific databases

CTDi8029.
DisGeNETi8029.
GeneCardsiCUBN.
H-InvDBHIX0035313.
HIX0035577.
HGNCiHGNC:2548. CUBN.
MalaCardsiCUBN.
MIMi261100. phenotype.
602997. gene.
neXtProtiNX_O60494.
OpenTargetsiENSG00000107611.
Orphaneti35858. Grasbeck-Imerslund disease.
PharmGKBiPA27044.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3714. Eukaryota.
ENOG410ZPX7. LUCA.
GeneTreeiENSGT00760000119018.
HOGENOMiHOG000049236.
HOVERGENiHBG080357.
InParanoidiO60494.
KOiK14616.
OMAiYSFTDCG.
OrthoDBiEOG091G009U.
PhylomeDBiO60494.
TreeFamiTF316224.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000107611-MONOMER.
ReactomeiR-HSA-194223. HDL-mediated lipid transport.
R-HSA-196741. Cobalamin (Cbl, vitamin B12) transport and metabolism.
R-HSA-196791. Vitamin D (calciferol) metabolism.
R-HSA-3359462. Defective AMN causes hereditary megaloblastic anemia 1.
R-HSA-3359463. Defective CUBN causes hereditary megaloblastic anemia 1.

Miscellaneous databases

ChiTaRSiCUBN. human.
EvolutionaryTraceiO60494.
GeneWikiiCubilin.
GenomeRNAii8029.
PROiO60494.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000107611.
CleanExiHS_CUBN.
ExpressionAtlasiO60494. baseline and differential.
GenevisibleiO60494. HS.

Family and domain databases

CDDicd00041. CUB. 27 hits.
Gene3Di2.60.120.290. 27 hits.
InterProiIPR000859. CUB_dom.
IPR028876. Cubilin.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR024731. EGF_dom.
IPR009030. Growth_fac_rcpt_.
[Graphical view]
PANTHERiPTHR10127:SF645. PTHR10127:SF645. 5 hits.
PfamiPF00431. CUB. 27 hits.
PF00008. EGF. 3 hits.
PF12947. EGF_3. 1 hit.
PF07645. EGF_CA. 3 hits.
[Graphical view]
SMARTiSM00042. CUB. 27 hits.
SM00181. EGF. 8 hits.
SM00179. EGF_CA. 7 hits.
[Graphical view]
SUPFAMiSSF49854. SSF49854. 27 hits.
SSF57184. SSF57184. 1 hit.
PROSITEiPS00010. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiCUBN_HUMAN
AccessioniPrimary (citable) accession number: O60494
Secondary accession number(s): B0YIZ4, Q5VTA6, Q96RU9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 7, 2006
Last sequence update: November 2, 2010
Last modified: November 30, 2016
This is version 154 of the entry and version 5 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.