Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Gastric intrinsic factor

Gene

GIF

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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
Complete GO annotation...

Keywords - Biological processi

Cobalt transport, Ion transport, Transport

Keywords - Ligandi

Cobalt

Enzyme and pathway databases

BioCyciZFISH:ENSG00000134812-MONOMER.
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

HGNCiHGNC:4268. GIF.

Subcellular locationi

GO - Cellular componenti

  • apical plasma membrane Source: UniProtKB
  • endosome Source: UniProtKB
  • extracellular region Source: Reactome
  • extracellular space Source: UniProtKB
  • lysosomal lumen Source: Reactome
  • microvillus Source: UniProtKB
Complete GO annotation...

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 rs121434322dbSNPEnsembl.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...)1 Publication1
Glycosylationi330N-linked (GlcNAc...)Sequence analysis1
Glycosylationi334N-linked (GlcNAc...)Sequence analysis1
Glycosylationi413N-linked (GlcNAc...)2 Publications1

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP27352.
PaxDbiP27352.
PeptideAtlasiP27352.
PRIDEiP27352.

PTM databases

iPTMnetiP27352.
PhosphoSitePlusiP27352.

Expressioni

Tissue specificityi

Gastric mucosa.

Gene expression databases

BgeeiENSG00000134812.
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. 5 interactors.
DIPiDIP-46206N.
IntActiP27352. 2 interactors.
STRINGi9606.ENSP00000257248.

Structurei

Secondary structure

1417
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni30 – 32Combined sources3
Helixi33 – 44Combined sources12
Beta strandi49 – 51Combined sources3
Helixi55 – 64Combined sources10
Helixi69 – 80Combined sources12
Helixi84 – 86Combined sources3
Helixi89 – 101Combined sources13
Helixi108 – 118Combined sources11
Helixi129 – 132Combined sources4
Helixi133 – 145Combined sources13
Helixi147 – 163Combined sources17
Helixi170 – 184Combined sources15
Helixi195 – 210Combined sources16
Beta strandi220 – 222Combined sources3
Helixi223 – 235Combined sources13
Helixi246 – 257Combined sources12
Turni258 – 262Combined sources5
Helixi265 – 275Combined sources11
Helixi280 – 285Combined sources6
Beta strandi311 – 319Combined sources9
Beta strandi333 – 339Combined sources7
Helixi343 – 352Combined sources10
Helixi355 – 357Combined sources3
Beta strandi359 – 364Combined sources6
Beta strandi367 – 375Combined sources9
Helixi380 – 382Combined sources3
Beta strandi384 – 390Combined sources7
Turni399 – 401Combined sources3
Beta strandi409 – 416Combined sources8

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...

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.
OMAiNLAGAYN.
OrthoDBiEOG091G095C.
PhylomeDBiP27352.
TreeFamiTF333092.

Family and domain databases

InterProiIPR002157. Cbl-bd_transpt_euk.
IPR027954. DUF4430.
[Graphical view]
PANTHERiPTHR10559. PTHR10559. 1 hit.
PfamiPF01122. Cobalamin_bind. 1 hit.
PF14478. DUF4430. 1 hit.
[Graphical view]
PROSITEiPS00468. COBALAMIN_BINDING. 1 hit.
[Graphical view]

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

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

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 → R.2 PublicationsCorresponds to variant rs35211634dbSNPEnsembl.1
Natural variantiVAR_02274346S → L in IFD. 1 PublicationCorresponds to variant rs121434322dbSNPEnsembl.1
Natural variantiVAR_04875365G → R.Corresponds to variant rs11825834dbSNPEnsembl.1
Natural variantiVAR_022744255N → S.1 PublicationCorresponds to variant rs35867471dbSNPEnsembl.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

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. 5 interactors.
DIPiDIP-46206N.
IntActiP27352. 2 interactors.
STRINGi9606.ENSP00000257248.

Chemistry databases

DrugBankiDB00115. Cyanocobalamin.

PTM databases

iPTMnetiP27352.
PhosphoSitePlusiP27352.

Polymorphism and mutation databases

BioMutaiGIF.
DMDMi62906845.

Proteomic databases

EPDiP27352.
PaxDbiP27352.
PeptideAtlasiP27352.
PRIDEiP27352.

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.
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.
OMAiNLAGAYN.
OrthoDBiEOG091G095C.
PhylomeDBiP27352.
TreeFamiTF333092.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000134812-MONOMER.
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.
PROiP27352.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000134812.
CleanExiHS_GIF.
ExpressionAtlasiP27352. baseline and differential.
GenevisibleiP27352. HS.

Family and domain databases

InterProiIPR002157. Cbl-bd_transpt_euk.
IPR027954. DUF4430.
[Graphical view]
PANTHERiPTHR10559. PTHR10559. 1 hit.
PfamiPF01122. Cobalamin_bind. 1 hit.
PF14478. DUF4430. 1 hit.
[Graphical view]
PROSITEiPS00468. COBALAMIN_BINDING. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiIF_HUMAN
AccessioniPrimary (citable) accession number: P27352
Secondary accession number(s): B2RAN8, B4DVZ1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: April 26, 2005
Last modified: November 2, 2016
This is version 151 of the entry and version 2 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, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: 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.