Gene/Proteome Database (LMPD)

LMPD ID
LMP005600
Gene ID
8029
Species
Homo sapiens (Human)
Gene Name
cubilin (intrinsic factor-cobalamin receptor)
Gene Symbol
CUBN
Synonyms
IFCR; MGA1; gp280
Alternate Names
cubilin; 460 kDa receptor; cubilin precursor variant 1; cubilin precursor variant 2; intestinal intrinsic factor receptor; intrinsic factor-vitamin B12 receptor
Chromosome
10
Map Location
10p12.31
Summary
Cubilin (CUBN) acts as a receptor for intrinsic factor-vitamin B12 complexes. The role of receptor is supported by the presence of 27 CUB domains. Cubulin is located within the epithelium of intestine and kidney. Mutations in CUBN may play a role in autosomal recessive megaloblastic anemia. [provided by RefSeq, Jul 2008]
Orthologs
View orthologs and multiple alignments for CUBN

Proteins

cubilin precursor
Refseq ID NP_001072
Protein GI 126091152
UniProt ID O60494
mRNA ID NM_001081
Length 3623
RefSeq Status REVIEWED
MMNMSLPFLWSLLTLLIFAEVNGEAGELELQRQKRSINLQQPRMATERGNLVFLTGSAQNIEFRTGSLGKIKLNDEDLSECLHQIQKNKEDIIELKGSAIGLPQNISSQIYQLNSKLVDLERKFQGLQQTVDKKVCSSNPCQNGGTCLNLHDSFFCICPPQWKGPLCSADVNECEIYSGTPLSCQNGGTCVNTMGSYSCHCPPETYGPQCASKYDDCEGGSVARCVHGICEDLMREQAGEPKYSCVCDAGWMFSPNSPACTLDRDECSFQPGPCSTLVQCFNTQGSFYCGACPTGWQGNGYICEDINECEINNGGCSVAPPVECVNTPGSSHCQACPPGYQGDGRVCTLTDICSVSNGGCHPDASCSSTLGSLPLCTCLPGYTGNGYGPNGCVQLSNICLSHPCLNGQCIDTVSGYFCKCDSGWTGVNCTENINECLSNPCLNGGTCVDGVDSFSCECTRLWTGALCQVPQQVCGESLSGINGSFSYRSPDVGYVHDVNCFWVIKTEMGKVLRITFTFFRLESMDNCPHEFLQVYDGDSSSAFQLGRFCGSSLPHELLSSDNALYFHLYSEHLRNGRGFTVRWETQQPECGGILTGPYGSIKSPGYPGNYPPGRDCVWIVVTSPDLLVTFTFGTLSLEHHDDCNKDYLEIRDGPLYQDPLLGKFCTTFSVPPLQTTGPFARIHFHSDSQISDQGFHITYLTSPSDLRCGGNYTDPEGELFLPELSGPFTHTRQCVYMMKQPQGEQIQINFTHVELQCQSDSSQNYIEVRDGETLLGKVCGNGTISHIKSITNSVWIRFKIDASVEKASFRAVYQVACGDELTGEGVIRSPFFPNVYPGERTCRWTIHQPQSQVILLNFTVFEIGSSAHCETDYVEIGSSSILGSPENKKYCGTDIPSFITSVYNFLYVTFVKSSSTENHGFMAKFSAEDLACGEILTESTGTIQSPGHPNVYPHGINCTWHILVQPNHLIHLMFETFHLEFHYNCTNDYLEVYDTDSETSLGRYCGKSIPPSLTSSGNSLMLVFVTDSDLAYEGFLINYEAISAATACLQDYTDDLGTFTSPNFPNNYPNNWECIYRITVRTGQLIAVHFTNFSLEEAIGNYYTDFLEIRDGGYEKSPLLGIFYGSNLPPTIISHSNKLWLKFKSDQIDTRSGFSAYWDGSSTGCGGNLTTSSGTFISPNYPMPYYHSSECYWWLKSSHGSAFELEFKDFHLEHHPNCTLDYLAVYDGPSSNSHLLTQLCGDEKPPLIRSSGDSMFIKLRTDEGQQGRGFKAEYRQTCENVVIVNQTYGILESIGYPNPYSENQHCNWTIRATTGNTVNYTFLAFDLEHHINCSTDYLELYDGPRQMGRYCGVDLPPPGSTTSSKLQVLLLTDGVGRREKGFQMQWFVYGCGGELSGATGSFSSPGFPNRYPPNKECIWYIRTDPGSSIQLTIHDFDVEYHSRCNFDVLEIYGGPDFHSPRIAQLCTQRSPENPMQVSSTGNELAIRFKTDLSINGRGFNASWQAVTGGCGGIFQAPSGEIHSPNYPSPYRSNTDCSWVIRVDRNHRVLLNFTDFDLEPQDSCIMAYDGLSSTMSRLARTCGREQLANPIVSSGNSLFLRFQSGPSRQNRGFRAQFRQACGGHILTSSFDTVSSPRFPANYPNNQNCSWIIQAQPPLNHITLSFTHFELERSTTCARDFVEILDGGHEDAPLRGRYCGTDMPHPITSFSSALTLRFVSDSSISAGGFHTTVTASVSACGGTFYMAEGIFNSPGYPDIYPPNVECVWNIVSSPGNRLQLSFISFQLEDSQDCSRDFVEIREGNATGHLVGRYCGNSFPLNYSSIVGHTLWVRFISDGSGSGTGFQATFMKIFGNDNIVGTHGKVASPFWPENYPHNSNYQWTVNVNASHVVHGRILEMDIEEIQNCYYDKLRIYDGPSIHARLIGAYCGTQTESFSSTGNSLTFHFYSDSSISGKGFLLEWFAVDAPDGVLPTIAPGACGGFLRTGDAPVFLFSPGWPDSYSNRVDCTWLIQAPDSTVELNILSLDIESHRTCAYDSLVIRDGDNNLAQQLAVLCGREIPGPIRSTGEYMFIRFTSDSSVTRAGFNASFHKSCGGYLHADRGIITSPKYPETYPSNLNCSWHVLVQSGLTIAVHFEQPFQIPNGDSSCNQGDYLVLRNGPDICSPPLGPPGGNGHFCGSHASSTLFTSDNQMFVQFISDHSNEGQGFKIKYEAKSLACGGNVYIHDADSAGYVTSPNHPHNYPPHADCIWILAAPPETRIQLQFEDRFDIEVTPNCTSNYLELRDGVDSDAPILSKFCGTSLPSSQWSSGEVMYLRFRSDNSPTHVGFKAKYSIAQCGGRVPGQSGVVESIGHPTLPYRDNLFCEWHLQGLSGHYLTISFEDFNLQNSSGCEKDFVEIWDNHTSGNILGRYCGNTIPDSIDTSSNTAVVRFVTDGSVTASGFRLRFESSMEECGGDLQGSIGTFTSPNYPNPNPHGRICEWRITAPEGRRITLMFNNLRLATHPSCNNEHVIVFNGIRSNSPQLEKLCSSVNVSNEIKSSGNTMKVIFFTDGSRPYGGFTASYTSSEDAVCGGSLPNTPEGNFTSPGYDGVRNYSRNLNCEWTLSNPNQGNSSISIHFEDFYLESHQDCQFDVLEFRVGDADGPLMWRLCGPSKPTLPLVIPYSQVWIHFVTNERVEHIGFHAKYSFTDCGGIQIGDSGVITSPNYPNAYDSLTHCSSLLEAPQGHTITLTFSDFDIEPHTTCAWDSVTVRNGGSPESPIIGQYCGNSNPRTIQSGSNQLVVTFNSDHSLQGGGFYATWNTQTLGCGGIFHSDNGTIRSPHWPQNFPENSRCSWTAITHKSKHLEISFDNNFLIPSGDGQCQNSFVKVWAGTEEVDKALLATGCGNVAPGPVITPSNTFTAVFQSQEAPAQGFSASFVSRCGSNFTGPSGYIISPNYPKQYDNNMNCTYVIEANPLSVVLLTFVSFHLEARSAVTGSCVNDGVHIIRGYSVMSTPFATVCGDEMPAPLTIAGPVLLNFYSNEQITDFGFKFSYRIISCGGVFNFSSGIITSPAYSYADYPNDMHCLYTITVSDDKVIELKFSDFDVVPSTSCSHDYLAIYDGANTSDPLLGKFCGSKRPPNVKSSNNSMLLVFKTDSFQTAKGWKMSFRQTLGPQQGCGGYLTGSNNTFASPDSDSNGMYDKNLNCVWIIIAPVNKVIHLTFNTFALEAASTRQRCLYDYVKLYDGDSENANLAGTFCGSTVPAPFISSGNFLTVQFISDLTLEREGFNATYTIMDMPCGGTYNATWTPQNISSPNSSDPDVPFSICTWVIDSPPHQQVKITVWALQLTSQDCTQNYLQLQDSPQGHGNSRFQFCGRNASAVPVFYSSMSTAMVIFKSGVVNRNSRMSFTYQIADCNRDYHKAFGNLRSPGWPDNYDNDKDCTVTLTAPQNHTISLFFHSLGIENSVECRNDFLEVRNGSNSNSPLLGKYCGTLLPNPVFSQNNELYLRFKSDSVTSDRGYEIIWTSSPSGCGGTLYGDRGSFTSPGYPGTYPNNTYCEWVLVAPAGRLVTINFYFISIDDPGDCVQNYLTLYDGPNASSPSSGPYCGGDTSIAPFVASSNQVFIKFHADYARRPSAFRLTWDS
sig_peptide: 1..23 inference: COORDINATES: ab initio prediction:SignalP:4.0 calculated_mol_wt: 2641 peptide sequence: MMNMSLPFLWSLLTLLIFAEVNG

Gene Information

Entrez Gene ID
8029
Gene Name
cubilin (intrinsic factor-cobalamin receptor)
Gene Symbol
CUBN
Species
Homo sapiens

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0005794 IEA:Ensembl C Golgi apparatus
GO:0016324 IDA:UniProt C apical plasma membrane
GO:0031526 NAS:UniProtKB C brush border membrane
GO:0005905 IEA:Ensembl C coated pit
GO:0005829 TAS:Reactome C cytosol
GO:0030139 IDA:UniProt C endocytic vesicle
GO:0005783 IEA:Ensembl C endoplasmic reticulum
GO:0010008 TAS:Reactome C endosome membrane
GO:0070062 IDA:UniProtKB C extracellular vesicular exosome
GO:0031232 NAS:UniProtKB C extrinsic component of external side of plasma membrane
GO:0043202 TAS:Reactome C lysosomal lumen
GO:0016020 TAS:ProtInc C membrane
GO:0005886 TAS:Reactome C plasma membrane
GO:0005509 IEA:InterPro F calcium ion binding
GO:0031419 IEA:UniProtKB-KW F cobalamin binding
GO:0042803 IDA:UniProtKB F protein homodimerization activity
GO:0004872 TAS:ProtInc F receptor activity
GO:0005215 TAS:ProtInc F transporter activity
GO:0008203 IEA:UniProtKB-KW P cholesterol metabolic process
GO:0009235 TAS:Reactome P cobalamin metabolic process
GO:0015889 TAS:ProtInc P cobalamin transport
GO:0042157 TAS:Reactome P lipoprotein metabolic process
GO:0042953 IEA:Ensembl P lipoprotein transport
GO:0006898 NAS:UniProtKB P receptor-mediated endocytosis
GO:0044281 TAS:Reactome P small molecule metabolic process
GO:0008202 TAS:Reactome P steroid metabolic process
GO:0001894 NAS:UniProtKB P tissue homeostasis
GO:0042359 TAS:Reactome P vitamin D metabolic process
GO:0006766 TAS:Reactome P vitamin metabolic process
GO:0006767 TAS:Reactome P water-soluble vitamin metabolic process

KEGG Pathway Links

KEGG Pathway ID Description
hsa04977 Vitamin digestion and absorption

REACTOME Pathway Links

REACTOME Pathway ID Description
REACT_163862 Cobalamin (Cbl, vitamin B12) transport and metabolism
REACT_13621 HDL-mediated lipid transport
REACT_13523 Vitamin D (calciferol) metabolism

Domain Information

InterPro Annotations

Accession Description
IPR000859 CUB domain
IPR028876 Cubilin
IPR024731 EGF domain, merozoite surface protein 1-like
IPR001881 EGF-like calcium-binding domain
IPR018097 EGF-like calcium-binding, conserved site
IPR013032 EGF-like, conserved site
IPR000152 EGF-type aspartate/asparagine hydroxylation site
IPR000742 Epidermal growth factor-like domain
IPR009030 Insulin-like growth factor binding protein, N-terminal

UniProt Annotations

Entry Information

Gene Name
cubilin (intrinsic factor-cobalamin receptor)
Protein Entry
CUBN_HUMAN
UniProt ID
O60494
Species
Human

Comments

Comment Type Description
Disease Recessive hereditary megaloblastic anemia 1 (RH-MGA1) [MIM
Domain The CUB domains 5 to 8 mediate binding to GIF and ALB. CUB domains 1 and 2 mediate interaction with LRP2.
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. {ECO
Ptm N-glycosylated. {ECO
Ptm The precursor is cleaved by a trans-Golgi proteinase furin. The result is a propeptide cleaved off.
Similarity Contains 27 CUB domains. {ECO
Similarity Contains 7 EGF-like domains. {ECO
Subcellular Location Endosome membrane ; Peripheral membrane protein {ECO
Subunit 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. {ECO
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.

Identical and Related Proteins

Unique RefSeq proteins for LMP005600 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
126091152 RefSeq NP_001072 3623 cubilin precursor

Identical Sequences to LMP005600 proteins

Reference Database Accession Length Protein Name
GI:126091152 GenBank ACA05973.1 3623 cubilin precursor variant 1 [Homo sapiens]
GI:126091152 GenBank ACA05974.1 3623 cubilin precursor variant 2 [Homo sapiens]
GI:126091152 SwissProt O60494.5 3623 RecName: Full=Cubilin; AltName: Full=460 kDa receptor; AltName: Full=Intestinal intrinsic factor receptor; AltName: Full=Intrinsic factor-cobalamin receptor; AltName: Full=Intrinsic factor-vitamin B12 receptor; Flags: Precursor [Homo sapiens]

Related Sequences to LMP005600 proteins

Reference Database Accession Length Protein Name
GI:126091152 GenBank EAW86221.1 3623 cubilin (intrinsic factor-cobalamin receptor) [Homo sapiens]
GI:126091152 GenBank ABY14960.1 3623 Sequence 335 from patent US 7306913
GI:126091152 GenBank ACP56883.1 3623 Sequence 1012 from patent US 7482117
GI:126091152 GenBank ADA18230.1 3623 Sequence 54 from patent US 7608413
GI:126091152 GenBank ADS30480.1 3623 Sequence 1012 from patent US 7781168
GI:126091152 GenBank AEN34126.1 3623 Sequence 54 from patent US 7998689