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P22692

- IBP4_HUMAN

UniProt

P22692 - IBP4_HUMAN

Protein

Insulin-like growth factor-binding protein 4

Gene

IGFBP4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 151 (01 Oct 2014)
      Sequence version 2 (01 Mar 1992)
      Previous versions | rss
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    Functioni

    IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors.

    GO - Biological processi

    1. cell proliferation Source: ProtInc
    2. cellular protein metabolic process Source: Reactome
    3. DNA metabolic process Source: ProtInc
    4. inflammatory response Source: Ensembl
    5. positive regulation of insulin-like growth factor receptor signaling pathway Source: Ensembl
    6. positive regulation of MAPK cascade Source: Ensembl
    7. regulation of cell growth Source: Ensembl
    8. regulation of glucose metabolic process Source: Ensembl
    9. signal transduction Source: ProtInc
    10. skeletal system development Source: ProtInc
    11. type B pancreatic cell proliferation Source: Ensembl

    Keywords - Ligandi

    Growth factor binding

    Enzyme and pathway databases

    BioCyciMetaCyc:ENSG00000141753-MONOMER.
    ReactomeiREACT_15428. Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Insulin-like growth factor-binding protein 4
    Short name:
    IBP-4
    Short name:
    IGF-binding protein 4
    Short name:
    IGFBP-4
    Gene namesi
    Name:IGFBP4
    Synonyms:IBP4
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 17

    Organism-specific databases

    HGNCiHGNC:5473. IGFBP4.

    Subcellular locationi

    GO - Cellular componenti

    1. extracellular region Source: Reactome
    2. extracellular space Source: Ensembl

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA29706.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 21213 PublicationsAdd
    BLAST
    Chaini22 – 258237Insulin-like growth factor-binding protein 4PRO_0000014382Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi27 ↔ 53
    Disulfide bondi30 ↔ 55
    Disulfide bondi38 ↔ 59
    Disulfide bondi44 ↔ 56
    Disulfide bondi67 ↔ 80
    Disulfide bondi74 ↔ 100
    Glycosylationi125 – 1251N-linked (GlcNAc...)1 PublicationSequence Analysis
    Disulfide bondi131 ↔ 138PROSITE-ProRule annotation
    Disulfide bondi174 ↔ 204
    Disulfide bondi215 ↔ 226
    Disulfide bondi228 ↔ 249

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    MaxQBiP22692.
    PaxDbiP22692.
    PeptideAtlasiP22692.
    PRIDEiP22692.

    PTM databases

    PhosphoSiteiP22692.

    Miscellaneous databases

    PMAP-CutDBP22692.

    Expressioni

    Inductioni

    By forskolin and N6,O2'dibutyryl adenosine 3',5'-cyclic monophosphate, but not by 1,9 dideoxyforskolin.1 Publication

    Gene expression databases

    ArrayExpressiP22692.
    BgeeiP22692.
    CleanExiHS_IGFBP4.
    GenevestigatoriP22692.

    Interactioni

    Subunit structurei

    Binds IGF2 more than IGF1.2 Publications

    Protein-protein interaction databases

    BioGridi109708. 6 interactions.
    DIPiDIP-48432N.
    IntActiP22692. 3 interactions.
    MINTiMINT-6630380.
    STRINGi9606.ENSP00000269593.

    Structurei

    Secondary structure

    1
    258
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi32 – 365
    Beta strandi45 – 495
    Beta strandi56 – 594
    Beta strandi69 – 713
    Beta strandi78 – 814
    Helixi89 – 946
    Beta strandi98 – 1025
    Helixi103 – 1108
    Helixi173 – 18614
    Helixi195 – 1984
    Beta strandi208 – 2103
    Beta strandi212 – 2154
    Beta strandi226 – 2294
    Turni231 – 2333
    Helixi244 – 2463

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1WQJX-ray1.60B24-103[»]
    2DSPX-ray2.50B22-113[»]
    2DSQX-ray2.80A/B22-113[»]
    2DSRX-ray2.10B24-103[»]
    G172-253[»]
    ProteinModelPortaliP22692.
    SMRiP22692. Positions 24-103, 172-250.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP22692.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini23 – 10381IGFBP N-terminalPROSITE-ProRule annotationAdd
    BLAST
    Domaini171 – 24979Thyroglobulin type-1PROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 IGFBP N-terminal domain.PROSITE-ProRule annotation
    Contains 1 thyroglobulin type-1 domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG46496.
    HOGENOMiHOG000253012.
    HOVERGENiHBG002631.
    InParanoidiP22692.
    OMAiKGMPCGV.
    OrthoDBiEOG74N5HG.
    PhylomeDBiP22692.
    TreeFamiTF331211.

    Family and domain databases

    Gene3Di4.10.40.20. 1 hit.
    4.10.800.10. 1 hit.
    InterProiIPR009030. Growth_fac_rcpt_N_dom.
    IPR022327. IGFBP-4.
    IPR000867. IGFBP-like.
    IPR009168. IGFBP1-6.
    IPR022321. IGFBP_1-6_chordata.
    IPR017891. Insulin_GF-bd_Cys-rich_CS.
    IPR000716. Thyroglobulin_1.
    [Graphical view]
    PANTHERiPTHR11551. PTHR11551. 1 hit.
    PfamiPF00219. IGFBP. 1 hit.
    PF00086. Thyroglobulin_1. 1 hit.
    [Graphical view]
    PRINTSiPR01976. IGFBPFAMILY.
    PR01980. IGFBPFAMILY4.
    SMARTiSM00121. IB. 1 hit.
    SM00211. TY. 1 hit.
    [Graphical view]
    SUPFAMiSSF57184. SSF57184. 1 hit.
    SSF57610. SSF57610. 1 hit.
    PROSITEiPS00222. IGFBP_N_1. 1 hit.
    PS51323. IGFBP_N_2. 1 hit.
    PS00484. THYROGLOBULIN_1_1. 1 hit.
    PS51162. THYROGLOBULIN_1_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

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

    P22692-1 [UniParc]FASTAAdd to Basket

    « Hide

    MLPLCLVAAL LLAAGPGPSL GDEAIHCPPC SEEKLARCRP PVGCEELVRE    50
    PGCGCCATCA LGLGMPCGVY TPRCGSGLRC YPPRGVEKPL HTLMHGQGVC 100
    MELAEIEAIQ ESLQPSDKDE GDHPNNSFSP CSAHDRRCLQ KHFAKIRDRS 150
    TSGGKMKVNG APREDARPVP QGSCQSELHR ALERLAASQS RTHEDLYIIP 200
    IPNCDRNGNF HPKQCHPALD GQRGKCWCVD RKTGVKLPGG LEPKGELDCH 250
    QLADSFRE 258
    Length:258
    Mass (Da):27,934
    Last modified:March 1, 1992 - v2
    Checksum:i5E8F4638D99F0A94
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti51 – 511P → A in M38177. (PubMed:1707125)Curated
    Sequence conflicti51 – 511P → A in AAA62670. (PubMed:9048882)Curated
    Sequence conflicti51 – 511P → A AA sequence (PubMed:1709585)Curated
    Sequence conflicti160 – 1601G → E in AAV38694. 1 PublicationCurated
    Sequence conflicti198 – 1981I → F in M38177. (PubMed:1707125)Curated
    Sequence conflicti198 – 1981I → F in AAA62670. (PubMed:9048882)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti42 – 421V → G.
    Corresponds to variant rs599199 [ dbSNP | Ensembl ].
    VAR_011906

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M38177 mRNA. No translation available.
    M62403 mRNA. Translation: AAB06189.1.
    U20982 Genomic DNA. Translation: AAA62670.1.
    Y12508 Genomic DNA. Translation: CAA73110.1.
    BT019891 mRNA. Translation: AAV38694.1.
    BT019892 mRNA. Translation: AAV38695.1.
    AY442346 Genomic DNA. Translation: AAR05443.1.
    CH471152 Genomic DNA. Translation: EAW60664.1.
    BC016041 mRNA. Translation: AAH16041.1.
    CCDSiCCDS11367.1.
    PIRiG01662. B37252.
    RefSeqiNP_001543.2. NM_001552.2.
    UniGeneiHs.462998.

    Genome annotation databases

    EnsembliENST00000269593; ENSP00000269593; ENSG00000141753.
    GeneIDi3487.
    KEGGihsa:3487.
    UCSCiuc002hus.3. human.

    Polymorphism databases

    DMDMi124065.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M38177 mRNA. No translation available.
    M62403 mRNA. Translation: AAB06189.1 .
    U20982 Genomic DNA. Translation: AAA62670.1 .
    Y12508 Genomic DNA. Translation: CAA73110.1 .
    BT019891 mRNA. Translation: AAV38694.1 .
    BT019892 mRNA. Translation: AAV38695.1 .
    AY442346 Genomic DNA. Translation: AAR05443.1 .
    CH471152 Genomic DNA. Translation: EAW60664.1 .
    BC016041 mRNA. Translation: AAH16041.1 .
    CCDSi CCDS11367.1.
    PIRi G01662. B37252.
    RefSeqi NP_001543.2. NM_001552.2.
    UniGenei Hs.462998.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1WQJ X-ray 1.60 B 24-103 [» ]
    2DSP X-ray 2.50 B 22-113 [» ]
    2DSQ X-ray 2.80 A/B 22-113 [» ]
    2DSR X-ray 2.10 B 24-103 [» ]
    G 172-253 [» ]
    ProteinModelPortali P22692.
    SMRi P22692. Positions 24-103, 172-250.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109708. 6 interactions.
    DIPi DIP-48432N.
    IntActi P22692. 3 interactions.
    MINTi MINT-6630380.
    STRINGi 9606.ENSP00000269593.

    Chemistry

    BindingDBi P22692.
    ChEMBLi CHEMBL2310.

    PTM databases

    PhosphoSitei P22692.

    Polymorphism databases

    DMDMi 124065.

    Proteomic databases

    MaxQBi P22692.
    PaxDbi P22692.
    PeptideAtlasi P22692.
    PRIDEi P22692.

    Protocols and materials databases

    DNASUi 3487.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000269593 ; ENSP00000269593 ; ENSG00000141753 .
    GeneIDi 3487.
    KEGGi hsa:3487.
    UCSCi uc002hus.3. human.

    Organism-specific databases

    CTDi 3487.
    GeneCardsi GC17P038599.
    HGNCi HGNC:5473. IGFBP4.
    MIMi 146733. gene.
    neXtProti NX_P22692.
    PharmGKBi PA29706.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG46496.
    HOGENOMi HOG000253012.
    HOVERGENi HBG002631.
    InParanoidi P22692.
    OMAi KGMPCGV.
    OrthoDBi EOG74N5HG.
    PhylomeDBi P22692.
    TreeFami TF331211.

    Enzyme and pathway databases

    BioCyci MetaCyc:ENSG00000141753-MONOMER.
    Reactomei REACT_15428. Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).

    Miscellaneous databases

    ChiTaRSi IGFBP4. human.
    EvolutionaryTracei P22692.
    GeneWikii IGFBP4.
    GenomeRNAii 3487.
    NextBioi 13714.
    PMAP-CutDB P22692.
    PROi P22692.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P22692.
    Bgeei P22692.
    CleanExi HS_IGFBP4.
    Genevestigatori P22692.

    Family and domain databases

    Gene3Di 4.10.40.20. 1 hit.
    4.10.800.10. 1 hit.
    InterProi IPR009030. Growth_fac_rcpt_N_dom.
    IPR022327. IGFBP-4.
    IPR000867. IGFBP-like.
    IPR009168. IGFBP1-6.
    IPR022321. IGFBP_1-6_chordata.
    IPR017891. Insulin_GF-bd_Cys-rich_CS.
    IPR000716. Thyroglobulin_1.
    [Graphical view ]
    PANTHERi PTHR11551. PTHR11551. 1 hit.
    Pfami PF00219. IGFBP. 1 hit.
    PF00086. Thyroglobulin_1. 1 hit.
    [Graphical view ]
    PRINTSi PR01976. IGFBPFAMILY.
    PR01980. IGFBPFAMILY4.
    SMARTi SM00121. IB. 1 hit.
    SM00211. TY. 1 hit.
    [Graphical view ]
    SUPFAMi SSF57184. SSF57184. 1 hit.
    SSF57610. SSF57610. 1 hit.
    PROSITEi PS00222. IGFBP_N_1. 1 hit.
    PS51323. IGFBP_N_2. 1 hit.
    PS00484. THYROGLOBULIN_1_1. 1 hit.
    PS51162. THYROGLOBULIN_1_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Molecular cloning of the cDNAs encoding a novel insulin-like growth factor-binding protein from rat and human."
      Shimasaki S., Uchiyama F., Shimonaka M., Ling N.
      Mol. Endocrinol. 4:1451-1458(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Placenta.
    2. "Inhibitory insulin-like growth factor-binding protein: cloning, complete sequence, and physiological regulation."
      Latour D., Mohan S., Linkhart T.A., Baylink D.J., Strong D.D.
      Mol. Endocrinol. 4:1806-1814(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. "Identification and molecular cloning of two new 30-kDa insulin-like growth factor binding proteins isolated from adult human serum."
      Kiefer M.C., Masiarz F.R., Bauer D.M., Zapf J.
      J. Biol. Chem. 266:9043-9049(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 22-41.
      Tissue: Osteosarcoma.
    4. "Structural and functional analysis of the 5'-flanking region of the human insulin-like growth factor binding protein (IGFBP)-4 gene."
      Qin X., Morales S., Lee K.-W., Boonyaratanakornkit V., Baylink D.J., Mohan S., Strong D.D.
      Biochim. Biophys. Acta 1350:136-140(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Tissue: Placenta.
    5. "Structure and transcription regulation of the human insulin-like growth factor binding protein 4 gene (IGFBP4)."
      Zazzi H., Nikoshkov A., Hall K., Luthman H.
      Genomics 49:401-410(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    6. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
      Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
      Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    7. NIEHS SNPs program
      Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    8. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    9. "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].
      Tissue: Colon.
    10. "Purification of a colon cancer cell growth inhibitor and its identification as an insulin-like growth factor binding protein."
      Culouscou J.-M., Shoyab M.
      Cancer Res. 51:2813-2819(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 22-53.
      Tissue: Colon.
    11. "Evidence that the inhibition of TE85 human bone cell proliferation by agents which stimulate cAMP production may in part be mediated by changes in the IGF-II regulatory system."
      Mohan S., Baylink D.J.
      Growth Regul. 1:110-118(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 22-42, INDUCTION.
      Tissue: Osteosarcoma.
    12. "Structural basis for the regulation of insulin-like growth factors by IGF binding proteins."
      Siwanowicz I., Popowicz G.M., Wisniewska M., Huber R., Kuenkele K.-P., Lang K., Engh R.A., Holak T.A.
      Structure 13:155-167(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 24-103 IN COMPLEX WITH IGF1, DISULFIDE BONDS.
    13. "Structural basis for the inhibition of insulin-like growth factors by insulin-like growth factor-binding proteins."
      Sitar T., Popowicz G.M., Siwanowicz I., Huber R., Holak T.A.
      Proc. Natl. Acad. Sci. U.S.A. 103:13028-13033(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 22-253 IN COMPLEX WITH IGF1, DISULFIDE BONDS.

    Entry informationi

    Entry nameiIBP4_HUMAN
    AccessioniPrimary (citable) accession number: P22692
    Secondary accession number(s): A0N9W2, Q5U012, Q9UCL6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1991
    Last sequence update: March 1, 1992
    Last modified: October 1, 2014
    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, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 17
      Human chromosome 17: 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