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P22692 (IBP4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 149. 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·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Insulin-like growth factor-binding protein 4

Short name=IBP-4
Short name=IGF-binding protein 4
Short name=IGFBP-4
Gene names
Name:IGFBP4
Synonyms:IBP4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length258 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

Binds IGF2 more than IGF1.

Subcellular location

Secreted.

Induction

By forskolin and N6,O2'dibutyryl adenosine 3',5'-cyclic monophosphate, but not by 1,9 dideoxyforskolin. Ref.11

Sequence similarities

Contains 1 IGFBP N-terminal domain.

Contains 1 thyroglobulin type-1 domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Ref.3 Ref.10 Ref.11
Chain22 – 258237Insulin-like growth factor-binding protein 4
PRO_0000014382

Regions

Domain23 – 10381IGFBP N-terminal
Domain171 – 24979Thyroglobulin type-1

Amino acid modifications

Glycosylation1251N-linked (GlcNAc...) Potential Ref.3
Disulfide bond27 ↔ 53 Ref.12 Ref.13
Disulfide bond30 ↔ 55 Ref.12 Ref.13
Disulfide bond38 ↔ 59 Ref.12 Ref.13
Disulfide bond44 ↔ 56 Ref.12 Ref.13
Disulfide bond67 ↔ 80 Ref.12 Ref.13
Disulfide bond74 ↔ 100 Ref.12 Ref.13
Disulfide bond131 ↔ 138 By similarity
Disulfide bond174 ↔ 204 Ref.12 Ref.13
Disulfide bond215 ↔ 226 Ref.12 Ref.13
Disulfide bond228 ↔ 249 Ref.12 Ref.13

Natural variations

Natural variant421V → G.
Corresponds to variant rs599199 [ dbSNP | Ensembl ].
VAR_011906

Experimental info

Sequence conflict511P → A in M38177. Ref.2
Sequence conflict511P → A in AAA62670. Ref.4
Sequence conflict511P → A AA sequence Ref.10
Sequence conflict1601G → E in AAV38694. Ref.6
Sequence conflict1981I → F in M38177. Ref.2
Sequence conflict1981I → F in AAA62670. Ref.4

Secondary structure

.............................. 258
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P22692 [UniParc].

Last modified March 1, 1992. Version 2.
Checksum: 5E8F4638D99F0A94

FASTA25827,934
        10         20         30         40         50         60 
MLPLCLVAAL LLAAGPGPSL GDEAIHCPPC SEEKLARCRP PVGCEELVRE PGCGCCATCA 

        70         80         90        100        110        120 
LGLGMPCGVY TPRCGSGLRC YPPRGVEKPL HTLMHGQGVC MELAEIEAIQ ESLQPSDKDE 

       130        140        150        160        170        180 
GDHPNNSFSP CSAHDRRCLQ KHFAKIRDRS TSGGKMKVNG APREDARPVP QGSCQSELHR 

       190        200        210        220        230        240 
ALERLAASQS RTHEDLYIIP IPNCDRNGNF HPKQCHPALD GQRGKCWCVD RKTGVKLPGG 

       250 
LEPKGELDCH QLADSFRE 

« Hide

References

« Hide 'large scale' references
[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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS11367.1.
PIRB37252. G01662.
RefSeqNP_001543.2. NM_001552.2.
UniGeneHs.462998.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1WQJX-ray1.60B24-103[»]
2DSPX-ray2.50B22-113[»]
2DSQX-ray2.80A/B22-113[»]
2DSRX-ray2.10B24-103[»]
G172-253[»]
ProteinModelPortalP22692.
SMRP22692. Positions 24-103, 172-250.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109708. 6 interactions.
DIPDIP-48432N.
IntActP22692. 3 interactions.
MINTMINT-6630380.
STRING9606.ENSP00000269593.

Chemistry

BindingDBP22692.
ChEMBLCHEMBL2310.

PTM databases

PhosphoSiteP22692.

Polymorphism databases

DMDM124065.

Proteomic databases

MaxQBP22692.
PaxDbP22692.
PeptideAtlasP22692.
PRIDEP22692.

Protocols and materials databases

DNASU3487.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000269593; ENSP00000269593; ENSG00000141753.
GeneID3487.
KEGGhsa:3487.
UCSCuc002hus.3. human.

Organism-specific databases

CTD3487.
GeneCardsGC17P038599.
HGNCHGNC:5473. IGFBP4.
MIM146733. gene.
neXtProtNX_P22692.
PharmGKBPA29706.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG46496.
HOGENOMHOG000253012.
HOVERGENHBG002631.
InParanoidP22692.
OMAKGMPCGV.
OrthoDBEOG74N5HG.
PhylomeDBP22692.
TreeFamTF331211.

Enzyme and pathway databases

BioCycMetaCyc:ENSG00000141753-MONOMER.
ReactomeREACT_17015. Metabolism of proteins.

Gene expression databases

ArrayExpressP22692.
BgeeP22692.
CleanExHS_IGFBP4.
GenevestigatorP22692.

Family and domain databases

Gene3D4.10.40.20. 1 hit.
4.10.800.10. 1 hit.
InterProIPR009030. 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]
PANTHERPTHR11551. PTHR11551. 1 hit.
PfamPF00219. IGFBP. 1 hit.
PF00086. Thyroglobulin_1. 1 hit.
[Graphical view]
PRINTSPR01976. IGFBPFAMILY.
PR01980. IGFBPFAMILY4.
SMARTSM00121. IB. 1 hit.
SM00211. TY. 1 hit.
[Graphical view]
SUPFAMSSF57184. SSF57184. 1 hit.
SSF57610. SSF57610. 1 hit.
PROSITEPS00222. 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]
ProtoNetSearch...

Other

ChiTaRSIGFBP4. human.
EvolutionaryTraceP22692.
GeneWikiIGFBP4.
GenomeRNAi3487.
NextBio13714.
PMAP-CutDBP22692.
PROP22692.
SOURCESearch...

Entry information

Entry nameIBP4_HUMAN
AccessionPrimary (citable) accession number: P22692
Secondary accession number(s): A0N9W2, Q5U012, Q9UCL6
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: March 1, 1992
Last modified: July 9, 2014
This is version 149 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 17

Human chromosome 17: entries, gene names and cross-references to MIM