Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

P27352

- IF_HUMAN

UniProt

P27352 - IF_HUMAN

Protein

Gastric intrinsic factor

Gene

GIF

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 132 (01 Oct 2014)
      Sequence version 2 (26 Apr 2005)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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

    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

    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

    ArrayExpressiP27352.
    BgeeiP27352.
    CleanExiHS_GIF.
    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.
    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

    MAWFALYLLS LLWATAGTST QTQSSCSVPS AQEPLVNGIQ VLMENSVTSS    50
    AYPNPSILIA MNLAGAYNLK AQKLLTYQLM SSDNNDLTIG QLGLTIMALT 100
    SSCRDPGDKV SILQRQMENW APSSPNAEAS AFYGPSLAIL ALCQKNSEAT 150
    LPIAVRFAKT LLANSSPFNV DTGAMATLAL TCMYNKIPVG SEEGYRSLFG 200
    QVLKDIVEKI SMKIKDNGII GDIYSTGLAM QALSVTPEPS KKEWNCKKTT 250
    DMILNEIKQG KFHNPMSIAQ ILPSLKGKTY LDVPQVTCSP DHEVQPTLPS 300
    NPGPGPTSAS NITVIYTINN QLRGVELLFN ETINVSVKSG SVLLVVLEEA 350
    QRKNPMFKFE TTMTSWGLVV SSINNIAENV NHKTYWQFLS GVTPLNEGVA 400
    DYIPFNHEHI TANFTQY 417
    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.

    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.
    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

    ArrayExpressi P27352.
    Bgeei P27352.
    CleanExi HS_GIF.
    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

    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 1, 2014
    This is version 132 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