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P27352 (IF_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 128. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Gastric intrinsic factor
Alternative name(s):
Intrinsic factor
Short name=IF
Short name=INF
Gene names
Name:GIF
Synonyms:IFMH
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length417 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

Interacts with CUBN (via CUB domains). Ref.7

Subcellular location

Secreted.

Tissue specificity

Gastric mucosa.

Involvement in disease

Hereditary intrinsic factor deficiency (IFD) [MIM:261000]: Autosomal recessive disorder characterized by megaloblastic anemia.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9

Sequence similarities

Belongs to the eukaryotic cobalamin transport proteins family.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P27352-1)

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.
Isoform 2 (identifier: P27352-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Potential
Chain19 – 417399Gastric intrinsic factor
PRO_0000005558

Regions

Region365 – 3706Cobalamin binding
Region386 – 39510Cobalamin binding

Sites

Binding site1711Cobalamin
Binding site2221Cobalamin
Binding site2701Cobalamin

Amino acid modifications

Glycosylation3111N-linked (GlcNAc...) Ref.7
Glycosylation3301N-linked (GlcNAc...) Potential
Glycosylation3341N-linked (GlcNAc...) Potential
Glycosylation4131N-linked (GlcNAc...) Ref.6 Ref.7
Disulfide bond26 ↔ 246 Ref.6 Ref.7
Disulfide bond103 ↔ 288 Ref.6 Ref.7
Disulfide bond143 ↔ 182 Ref.6 Ref.7

Natural variations

Alternative sequence1 – 2727MAWFA…QSSCS → MA in isoform 2.
VSP_041585
Natural variant231Q → R. Ref.8 Ref.9
Corresponds to variant rs35211634 [ dbSNP | Ensembl ].
VAR_022742
Natural variant461S → L in IFD. Ref.9
VAR_022743
Natural variant651G → R.
Corresponds to variant rs11825834 [ dbSNP | Ensembl ].
VAR_048753
Natural variant2551N → S. Ref.9
Corresponds to variant rs35867471 [ dbSNP | Ensembl ].
VAR_022744

Experimental info

Sequence conflict111L → P in BAG36935. Ref.3
Sequence conflict911Q → H in AAA66354. Ref.1
Sequence conflict961I → V in BAG62853. Ref.3
Sequence conflict2641N → D in BAG36935. Ref.3

Secondary structure

....................................................... 417
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified April 26, 2005. Version 2.
Checksum: F8B376E03A3D0F3C

FASTA41745,416
        10         20         30         40         50         60 
MAWFALYLLS LLWATAGTST QTQSSCSVPS AQEPLVNGIQ VLMENSVTSS AYPNPSILIA 

        70         80         90        100        110        120 
MNLAGAYNLK AQKLLTYQLM SSDNNDLTIG QLGLTIMALT SSCRDPGDKV SILQRQMENW 

       130        140        150        160        170        180 
APSSPNAEAS AFYGPSLAIL ALCQKNSEAT LPIAVRFAKT LLANSSPFNV DTGAMATLAL 

       190        200        210        220        230        240 
TCMYNKIPVG SEEGYRSLFG QVLKDIVEKI SMKIKDNGII GDIYSTGLAM QALSVTPEPS 

       250        260        270        280        290        300 
KKEWNCKKTT DMILNEIKQG KFHNPMSIAQ ILPSLKGKTY LDVPQVTCSP DHEVQPTLPS 

       310        320        330        340        350        360 
NPGPGPTSAS NITVIYTINN QLRGVELLFN ETINVSVKSG SVLLVVLEEA QRKNPMFKFE 

       370        380        390        400        410 
TTMTSWGLVV SSINNIAENV NHKTYWQFLS GVTPLNEGVA DYIPFNHEHI TANFTQY 

« Hide

Isoform 2 [UniParc].

Checksum: F86FC9448C15FDFC
Show »

FASTA39242,698

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
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]"Hereditary juvenile cobalamin deficiency caused by mutations in the intrinsic factor gene."
Tanner S.M., Li Z., Perko J.D., Oener C., Cetin M., Altay C., Yurtsever Z., David K.L., Faivre L., Ismail E.A., Graesbeck R., de la Chapelle A.
Proc. Natl. Acad. Sci. U.S.A. 102:4130-4133(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT IFD LEU-46, VARIANTS ARG-23 AND SER-255.
+Additional computationally mapped references.

Web resources

GeneReviews
Wikipedia

Intrinsic factor entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRA39904.
RefSeqNP_005133.2. NM_005142.2.
XP_005273967.1. XM_005273910.2.
UniGeneHs.110014.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2CKTmodel-X19-417[»]
2PMVX-ray2.60A/B/C/D19-417[»]
3KQ4X-ray3.30A/C/E25-417[»]
ProteinModelPortalP27352.
SMRP27352. Positions 25-417.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108961. 3 interactions.
DIPDIP-46206N.
IntActP27352. 1 interaction.
STRING9606.ENSP00000257248.

PTM databases

PhosphoSiteP27352.

Polymorphism databases

DMDM62906845.

Proteomic databases

PaxDbP27352.
PRIDEP27352.

Protocols and materials databases

DNASU2694.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000257248; ENSP00000257248; ENSG00000134812. [P27352-1]
ENST00000541311; ENSP00000440427; ENSG00000134812. [P27352-2]
GeneID2694.
KEGGhsa:2694.
UCSCuc001noi.3. human. [P27352-1]

Organism-specific databases

CTD2694.
GeneCardsGC11M059596.
HGNCHGNC:4268. GIF.
HPAHPA039908.
HPA040774.
MIM261000. phenotype.
609342. gene.
neXtProtNX_P27352.
Orphanet332. Congenital intrinsic factor deficiency.
PharmGKBPA28678.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG45775.
HOGENOMHOG000013214.
HOVERGENHBG006133.
InParanoidP27352.
KOK14615.
OMANLAGAYN.
OrthoDBEOG7H1JKX.
PhylomeDBP27352.
TreeFamTF333092.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.

Gene expression databases

ArrayExpressP27352.
BgeeP27352.
CleanExHS_GIF.
GenevestigatorP27352.

Family and domain databases

InterProIPR002157. Cbl-bd_transpt_euk.
[Graphical view]
PANTHERPTHR10559. PTHR10559. 1 hit.
PfamPF01122. Cobalamin_bind. 1 hit.
[Graphical view]
PROSITEPS00468. COBALAMIN_BINDING. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSGIF. human.
EvolutionaryTraceP27352.
GeneWikiIntrinsic_factor.
GenomeRNAi2694.
NextBio10656.
PROP27352.
SOURCESearch...

Entry information

Entry nameIF_HUMAN
AccessionPrimary (citable) accession number: P27352
Secondary accession number(s): B2RAN8, B4DVZ1
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: April 26, 2005
Last modified: April 16, 2014
This is version 128 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM