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Protein

Gastric intrinsic factor

Gene

GIF

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

Functioni

Promotes absorption of the essential vitamin cobalamin (Cbl) in the ileum. After interaction with CUBN, the GIF-cobalamin complex is internalized via receptor-mediated endocytosis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei171Cobalamin2 Publications1
Binding sitei222Cobalamin2 Publications1
Binding sitei270Cobalamin2 Publications1

GO - Molecular functioni

  • cobalamin binding Source: UniProtKB

GO - Biological processi

  • cobalamin metabolic process Source: Reactome
  • cobalamin transport Source: UniProtKB
  • cobalt ion transport Source: UniProtKB-KW

Keywordsi

Biological processCobalt transport, Ion transport, Transport
LigandCobalt

Enzyme and pathway databases

ReactomeiR-HSA-196741 Cobalamin (Cbl, vitamin B12) transport and metabolism
R-HSA-3359457 Defective GIF causes intrinsic factor deficiency
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:
Gastric intrinsic factor
Alternative name(s):
Intrinsic factor
Short name:
IF
Short name:
INF
Gene namesi
Name:GIF
Synonyms:IFMH
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000134812.7
HGNCiHGNC:4268 GIF
MIMi609342 gene
neXtProtiNX_P27352

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Hereditary intrinsic factor deficiency (IFD)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAutosomal recessive disorder characterized by megaloblastic anemia.
See also OMIM:261000
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02274346S → L in IFD. 1 PublicationCorresponds to variant dbSNP:rs121434322EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi2694
MalaCardsiGIF
MIMi261000 phenotype
OpenTargetsiENSG00000134812
Orphaneti332 Congenital intrinsic factor deficiency
PharmGKBiPA28678

Chemistry databases

DrugBankiDB00115 Cyanocobalamin

Polymorphism and mutation databases

BioMutaiGIF
DMDMi62906845

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Sequence analysisAdd BLAST18
ChainiPRO_000000555819 – 417Gastric intrinsic factorAdd BLAST399

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi26 ↔ 246
Disulfide bondi103 ↔ 288
Disulfide bondi143 ↔ 182
Modified residuei191PhosphoserineBy similarity1
Glycosylationi311N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi330N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi334N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi413N-linked (GlcNAc...) asparagine2 Publications1

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP27352
PaxDbiP27352
PeptideAtlasiP27352
PRIDEiP27352
ProteomicsDBi54381
54382 [P27352-2]

PTM databases

iPTMnetiP27352
PhosphoSitePlusiP27352

Expressioni

Tissue specificityi

Gastric mucosa.

Gene expression databases

BgeeiENSG00000134812 Expressed in 73 organ(s), highest expression level in body of stomach
CleanExiHS_GIF
ExpressionAtlasiP27352 baseline and differential
GenevisibleiP27352 HS

Organism-specific databases

HPAiHPA039908
HPA040774

Interactioni

Subunit structurei

Interacts with CUBN (via CUB domains).2 Publications

Protein-protein interaction databases

BioGridi108961, 7 interactors
CORUMiP27352
DIPiDIP-46206N
IntActiP27352, 6 interactors
MINTiP27352
STRINGi9606.ENSP00000257248

Structurei

Secondary structure

1417
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP27352
SMRiP27352
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP27352

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni365 – 370Cobalamin binding6
Regioni386 – 395Cobalamin binding10

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IVBN Eukaryota
ENOG410XSU1 LUCA
GeneTreeiENSGT00530000063370
HOGENOMiHOG000013214
HOVERGENiHBG006133
InParanoidiP27352
KOiK14615
OMAiSVLIAMN
OrthoDBiEOG091G095C
PhylomeDBiP27352
TreeFamiTF333092

Family and domain databases

InterProiView protein in InterPro
IPR002157 Cbl-bd_prot
IPR027954 DUF4430
PfamiView protein in Pfam
PF01122 Cobalamin_bind, 1 hit
PF14478 DUF4430, 1 hit
PROSITEiView protein in PROSITE
PS00468 COBALAMIN_BINDING, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: P27352-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MAWFALYLLS LLWATAGTST QTQSSCSVPS AQEPLVNGIQ VLMENSVTSS
60 70 80 90 100
AYPNPSILIA MNLAGAYNLK AQKLLTYQLM SSDNNDLTIG QLGLTIMALT
110 120 130 140 150
SSCRDPGDKV SILQRQMENW APSSPNAEAS AFYGPSLAIL ALCQKNSEAT
160 170 180 190 200
LPIAVRFAKT LLANSSPFNV DTGAMATLAL TCMYNKIPVG SEEGYRSLFG
210 220 230 240 250
QVLKDIVEKI SMKIKDNGII GDIYSTGLAM QALSVTPEPS KKEWNCKKTT
260 270 280 290 300
DMILNEIKQG KFHNPMSIAQ ILPSLKGKTY LDVPQVTCSP DHEVQPTLPS
310 320 330 340 350
NPGPGPTSAS NITVIYTINN QLRGVELLFN ETINVSVKSG SVLLVVLEEA
360 370 380 390 400
QRKNPMFKFE TTMTSWGLVV SSINNIAENV NHKTYWQFLS GVTPLNEGVA
410
DYIPFNHEHI TANFTQY
Length:417
Mass (Da):45,416
Last modified:April 26, 2005 - v2
Checksum:iF8B376E03A3D0F3C
GO
Isoform 2 (identifier: P27352-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-27: MAWFALYLLSLLWATAGTSTQTQSSCS → MA

Show »
Length:392
Mass (Da):42,698
Checksum:iF86FC9448C15FDFC
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PM21E9PM21_HUMAN
Gastric intrinsic factor
GIF
48Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti11L → P in BAG36935 (PubMed:14702039).Curated1
Sequence conflicti91Q → H in AAA66354 (PubMed:2071148).Curated1
Sequence conflicti96I → V in BAG62853 (PubMed:14702039).Curated1
Sequence conflicti264N → D in BAG36935 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02274223Q → R2 PublicationsCorresponds to variant dbSNP:rs35211634EnsemblClinVar.1
Natural variantiVAR_02274346S → L in IFD. 1 PublicationCorresponds to variant dbSNP:rs121434322EnsemblClinVar.1
Natural variantiVAR_04875365G → R. Corresponds to variant dbSNP:rs11825834Ensembl.1
Natural variantiVAR_022744255N → S1 PublicationCorresponds to variant dbSNP:rs35867471EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0415851 – 27MAWFA…QSSCS → MA in isoform 2. 1 PublicationAdd BLAST27

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M63154 mRNA Translation: AAA66354.1
X76562 mRNA Translation: CAA54061.1
AK314275 mRNA Translation: BAG36935.1
AK301295 mRNA Translation: BAG62853.1
AP002347 Genomic DNA No translation available.
BC037958 mRNA Translation: AAH37958.1
CCDSiCCDS7977.1 [P27352-1]
PIRiA39904
RefSeqiNP_005133.2, NM_005142.2 [P27352-1]
UniGeneiHs.110014

Genome annotation databases

EnsembliENST00000257248; ENSP00000257248; ENSG00000134812 [P27352-1]
GeneIDi2694
KEGGihsa:2694
UCSCiuc001noi.4 human [P27352-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Wikipedia

Intrinsic factor entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M63154 mRNA Translation: AAA66354.1
X76562 mRNA Translation: CAA54061.1
AK314275 mRNA Translation: BAG36935.1
AK301295 mRNA Translation: BAG62853.1
AP002347 Genomic DNA No translation available.
BC037958 mRNA Translation: AAH37958.1
CCDSiCCDS7977.1 [P27352-1]
PIRiA39904
RefSeqiNP_005133.2, NM_005142.2 [P27352-1]
UniGeneiHs.110014

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2CKTmodel-X19-417[»]
2PMVX-ray2.60A/B/C/D19-417[»]
3KQ4X-ray3.30A/C/E25-417[»]
ProteinModelPortaliP27352
SMRiP27352
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108961, 7 interactors
CORUMiP27352
DIPiDIP-46206N
IntActiP27352, 6 interactors
MINTiP27352
STRINGi9606.ENSP00000257248

Chemistry databases

DrugBankiDB00115 Cyanocobalamin

PTM databases

iPTMnetiP27352
PhosphoSitePlusiP27352

Polymorphism and mutation databases

BioMutaiGIF
DMDMi62906845

Proteomic databases

EPDiP27352
PaxDbiP27352
PeptideAtlasiP27352
PRIDEiP27352
ProteomicsDBi54381
54382 [P27352-2]

Protocols and materials databases

DNASUi2694
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000257248; ENSP00000257248; ENSG00000134812 [P27352-1]
GeneIDi2694
KEGGihsa:2694
UCSCiuc001noi.4 human [P27352-1]

Organism-specific databases

CTDi2694
DisGeNETi2694
EuPathDBiHostDB:ENSG00000134812.7
GeneCardsiGIF
HGNCiHGNC:4268 GIF
HPAiHPA039908
HPA040774
MalaCardsiGIF
MIMi261000 phenotype
609342 gene
neXtProtiNX_P27352
OpenTargetsiENSG00000134812
Orphaneti332 Congenital intrinsic factor deficiency
PharmGKBiPA28678
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IVBN Eukaryota
ENOG410XSU1 LUCA
GeneTreeiENSGT00530000063370
HOGENOMiHOG000013214
HOVERGENiHBG006133
InParanoidiP27352
KOiK14615
OMAiSVLIAMN
OrthoDBiEOG091G095C
PhylomeDBiP27352
TreeFamiTF333092

Enzyme and pathway databases

ReactomeiR-HSA-196741 Cobalamin (Cbl, vitamin B12) transport and metabolism
R-HSA-3359457 Defective GIF causes intrinsic factor deficiency
R-HSA-3359462 Defective AMN causes hereditary megaloblastic anemia 1
R-HSA-3359463 Defective CUBN causes hereditary megaloblastic anemia 1

Miscellaneous databases

ChiTaRSiGIF human
EvolutionaryTraceiP27352
GeneWikiiIntrinsic_factor
GenomeRNAii2694
PROiPR:P27352
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000134812 Expressed in 73 organ(s), highest expression level in body of stomach
CleanExiHS_GIF
ExpressionAtlasiP27352 baseline and differential
GenevisibleiP27352 HS

Family and domain databases

InterProiView protein in InterPro
IPR002157 Cbl-bd_prot
IPR027954 DUF4430
PfamiView protein in Pfam
PF01122 Cobalamin_bind, 1 hit
PF14478 DUF4430, 1 hit
PROSITEiView protein in PROSITE
PS00468 COBALAMIN_BINDING, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiIF_HUMAN
AccessioniPrimary (citable) accession number: P27352
Secondary accession number(s): B2RAN8, B4DVZ1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: April 26, 2005
Last modified: November 7, 2018
This is version 164 of the entry and version 2 of the sequence. See 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, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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