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P27352

- IF_HUMAN

UniProt

P27352 - IF_HUMAN

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Protein

Gastric intrinsic factor

Gene

GIF

Organism
Homo sapiens (Human)
Status
Reviewed - 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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei171 – 1711Cobalamin2 Publications
Binding sitei222 – 2221Cobalamin2 Publications
Binding sitei270 – 2701Cobalamin2 Publications

GO - Molecular functioni

  1. cobalamin binding Source: UniProtKB

GO - Biological processi

  1. cobalamin metabolic process Source: RefGenome
  2. cobalamin transport Source: UniProtKB
  3. cobalt ion transport Source: UniProtKB-KW
  4. small molecule metabolic process Source: Reactome
  5. vitamin metabolic process Source: Reactome
  6. water-soluble vitamin metabolic process Source: Reactome
Complete GO annotation...

Keywords - Biological processi

Cobalt transport, Ion transport, Transport

Keywords - Ligandi

Cobalt

Enzyme and pathway databases

ReactomeiREACT_163862. Cobalamin (Cbl, vitamin B12) transport and metabolism.
REACT_169132. Defective CUBN causes hereditary megaloblastic anemia 1.
REACT_169280. Defective AMN causes hereditary megaloblastic anemia 1.
REACT_169415. Defective GIF causes intrinsic factor deficiency.

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
ProteomesiUP000005640: Chromosome 11

Organism-specific databases

HGNCiHGNC:4268. GIF.

Subcellular locationi

GO - Cellular componenti

  1. apical plasma membrane Source: UniProtKB
  2. endosome Source: UniProtKB
  3. extracellular region Source: Reactome
  4. extracellular space Source: UniProtKB
  5. lysosomal lumen Source: Reactome
  6. microvillus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Hereditary intrinsic factor deficiency (IFD) [MIM:261000]: Autosomal recessive disorder characterized by megaloblastic anemia.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti46 – 461S → L in IFD. 1 Publication
VAR_022743

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi261000. phenotype.
Orphaneti332. Congenital intrinsic factor deficiency.
PharmGKBiPA28678.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1818Sequence AnalysisAdd
BLAST
Chaini19 – 417399Gastric intrinsic factorPRO_0000005558Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi26 ↔ 246
Disulfide bondi103 ↔ 288
Disulfide bondi143 ↔ 182
Glycosylationi311 – 3111N-linked (GlcNAc...)1 Publication
Glycosylationi330 – 3301N-linked (GlcNAc...)Sequence Analysis
Glycosylationi334 – 3341N-linked (GlcNAc...)Sequence Analysis
Glycosylationi413 – 4131N-linked (GlcNAc...)2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP27352.
PRIDEiP27352.

PTM databases

PhosphoSiteiP27352.

Expressioni

Tissue specificityi

Gastric mucosa.

Gene expression databases

BgeeiP27352.
CleanExiHS_GIF.
ExpressionAtlasiP27352. baseline and differential.
GenevestigatoriP27352.

Organism-specific databases

HPAiHPA039908.
HPA040774.

Interactioni

Subunit structurei

Interacts with CUBN (via CUB domains).2 Publications

Protein-protein interaction databases

BioGridi108961. 3 interactions.
DIPiDIP-46206N.
IntActiP27352. 1 interaction.
STRINGi9606.ENSP00000257248.

Structurei

Secondary structure

1
417
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni30 – 323
Helixi33 – 4412
Beta strandi49 – 513
Helixi55 – 6410
Helixi69 – 8012
Helixi84 – 863
Helixi89 – 10113
Helixi108 – 11811
Helixi129 – 1324
Helixi133 – 14513
Helixi147 – 16317
Helixi170 – 18415
Helixi195 – 21016
Beta strandi220 – 2223
Helixi223 – 23513
Helixi246 – 25712
Turni258 – 2625
Helixi265 – 27511
Helixi280 – 2856
Beta strandi311 – 3199
Beta strandi333 – 3397
Helixi343 – 35210
Helixi355 – 3573
Beta strandi359 – 3646
Beta strandi367 – 3759
Helixi380 – 3823
Beta strandi384 – 3907
Turni399 – 4013
Beta strandi409 – 4168

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2CKTmodel-X19-417[»]
2PMVX-ray2.60A/B/C/D19-417[»]
3KQ4X-ray3.30A/C/E25-417[»]
ProteinModelPortaliP27352.
SMRiP27352. Positions 25-417.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP27352.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni365 – 3706Cobalamin binding
Regioni386 – 39510Cobalamin binding

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG45775.
GeneTreeiENSGT00530000063370.
HOGENOMiHOG000013214.
HOVERGENiHBG006133.
InParanoidiP27352.
KOiK14615.
OMAiNLAGAYN.
OrthoDBiEOG7H1JKX.
PhylomeDBiP27352.
TreeFamiTF333092.

Family and domain databases

InterProiIPR002157. Cbl-bd_transpt_euk.
[Graphical view]
PANTHERiPTHR10559. PTHR10559. 1 hit.
PfamiPF01122. Cobalamin_bind. 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. Align

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti11 – 111L → P in BAG36935. (PubMed:14702039)Curated
Sequence conflicti91 – 911Q → H in AAA66354. (PubMed:2071148)Curated
Sequence conflicti96 – 961I → V in BAG62853. (PubMed:14702039)Curated
Sequence conflicti264 – 2641N → D in BAG36935. (PubMed:14702039)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti23 – 231Q → R.2 Publications
Corresponds to variant rs35211634 [ dbSNP | Ensembl ].
VAR_022742
Natural varianti46 – 461S → L in IFD. 1 Publication
VAR_022743
Natural varianti65 – 651G → R.
Corresponds to variant rs11825834 [ dbSNP | Ensembl ].
VAR_048753
Natural varianti255 – 2551N → S.1 Publication
Corresponds to variant rs35867471 [ dbSNP | Ensembl ].
VAR_022744

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 2727MAWFA…QSSCS → MA in isoform 2. 1 PublicationVSP_041585Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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]
XP_005273967.1. XM_005273910.2. [P27352-2]
UniGeneiHs.110014.

Genome annotation databases

EnsembliENST00000257248; ENSP00000257248; ENSG00000134812. [P27352-1]
GeneIDi2694.
KEGGihsa:2694.
UCSCiuc001noi.3. human. [P27352-1]

Polymorphism databases

DMDMi62906845.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

Intrinsic factor entry

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS7977.1. [P27352-1 ]
PIRi A39904.
RefSeqi NP_005133.2. NM_005142.2. [P27352-1 ]
XP_005273967.1. XM_005273910.2. [P27352-2 ]
UniGenei Hs.110014.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2CKT model - X 19-417 [» ]
2PMV X-ray 2.60 A/B/C/D 19-417 [» ]
3KQ4 X-ray 3.30 A/C/E 25-417 [» ]
ProteinModelPortali P27352.
SMRi P27352. Positions 25-417.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 108961. 3 interactions.
DIPi DIP-46206N.
IntActi P27352. 1 interaction.
STRINGi 9606.ENSP00000257248.

Chemistry

DrugBanki DB00115. Cyanocobalamin.

PTM databases

PhosphoSitei P27352.

Polymorphism databases

DMDMi 62906845.

Proteomic databases

PaxDbi P27352.
PRIDEi P27352.

Protocols and materials databases

DNASUi 2694.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000257248 ; ENSP00000257248 ; ENSG00000134812 . [P27352-1 ]
GeneIDi 2694.
KEGGi hsa:2694.
UCSCi uc001noi.3. human. [P27352-1 ]

Organism-specific databases

CTDi 2694.
GeneCardsi GC11M059596.
HGNCi HGNC:4268. GIF.
HPAi HPA039908.
HPA040774.
MIMi 261000. phenotype.
609342. gene.
neXtProti NX_P27352.
Orphaneti 332. Congenital intrinsic factor deficiency.
PharmGKBi PA28678.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG45775.
GeneTreei ENSGT00530000063370.
HOGENOMi HOG000013214.
HOVERGENi HBG006133.
InParanoidi P27352.
KOi K14615.
OMAi NLAGAYN.
OrthoDBi EOG7H1JKX.
PhylomeDBi P27352.
TreeFami TF333092.

Enzyme and pathway databases

Reactomei REACT_163862. Cobalamin (Cbl, vitamin B12) transport and metabolism.
REACT_169132. Defective CUBN causes hereditary megaloblastic anemia 1.
REACT_169280. Defective AMN causes hereditary megaloblastic anemia 1.
REACT_169415. Defective GIF causes intrinsic factor deficiency.

Miscellaneous databases

ChiTaRSi GIF. human.
EvolutionaryTracei P27352.
GeneWikii Intrinsic_factor.
GenomeRNAii 2694.
NextBioi 10656.
PROi P27352.
SOURCEi Search...

Gene expression databases

Bgeei P27352.
CleanExi HS_GIF.
ExpressionAtlasi P27352. baseline and differential.
Genevestigatori P27352.

Family and domain databases

InterProi IPR002157. Cbl-bd_transpt_euk.
[Graphical view ]
PANTHERi PTHR10559. PTHR10559. 1 hit.
Pfami PF01122. Cobalamin_bind. 1 hit.
[Graphical view ]
PROSITEi PS00468. COBALAMIN_BINDING. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Human gastric intrinsic factor: characterization of cDNA and genomic clones and localization to human chromosome 11."
    Hewitt J.E., Gordon M.M., Taggart R.T., Mohandas T.K., Alpers D.H.
    Genomics 10:432-440(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  2. "A cDNA sequence of the human intrinsic factor."
    Hannappel M., Kehl M., Winnacker E.L.
    Submitted (APR-1994) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Stomach.
  3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Tissue: Stomach.
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Colon.
  6. "Crystal structure of human intrinsic factor: cobalamin complex at 2.6-A resolution."
    Mathews F.S., Gordon M.M., Chen Z., Rajashankar K.R., Ealick S.E., Alpers D.H., Sukumar N.
    Proc. Natl. Acad. Sci. U.S.A. 104:17311-17316(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 19-417 IN COMPLEX WITH COBALAMIN, DISULFIDE BONDS, GLYCOSYLATION AT ASN-413.
  7. "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 25-417 IN COMPLEX WITH COBALAMIN AND CUBN, INTERACTION WITH CUBN, DISULFIDE BONDS, GLYCOSYLATION AT ASN-311 AND ASN-413.
  8. "A genetic polymorphism in the coding region of the gastric intrinsic factor gene (GIF) is associated with congenital intrinsic factor deficiency."
    Gordon M.M., Brada N., Remacha A., Badell I., del Rio E., Baiget M., Santer R., Quadros E.V., Rothenberg S.P., Alpers D.H.
    Hum. Mutat. 23:85-91(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT ARG-23.
  9. Cited for: VARIANT IFD LEU-46, VARIANTS ARG-23 AND SER-255.

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: October 29, 2014
This is version 133 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

External Data

Dasty 3