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P18065 (IBP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 153. 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·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Insulin-like growth factor-binding protein 2

Short name=IBP-2
Short name=IGF-binding protein 2
Short name=IGFBP-2
Gene names
Name:IGFBP2
Synonyms:BP2, IBP2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length325 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Inhibits IGF-mediated growth and developmental rates. 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. Ref.11

Subunit structure

Binds IGF2 more than IGF1.

Subcellular location

Secreted.

Domain

The C-terminus is required for IGF-binding and growth inhibition. Ref.11

Post-translational modification

O-glycosylated. Ref.10

Sequence similarities

Contains 1 IGFBP N-terminal domain.

Contains 1 thyroglobulin type-1 domain.

Ontologies

Keywords
   Biological processGrowth regulation
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DomainSignal
   LigandGrowth factor binding
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processaging

Inferred from electronic annotation. Source: Ensembl

cellular protein metabolic process

Traceable author statement. Source: Reactome

cellular response to hormone stimulus

Inferred from electronic annotation. Source: Ensembl

female pregnancy

Inferred from electronic annotation. Source: Ensembl

positive regulation of activated T cell proliferation

Inferred from direct assay PubMed 15694994. Source: BHF-UCL

regulation of cell growth

Inferred from electronic annotation. Source: InterPro

regulation of insulin-like growth factor receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

response to drug

Inferred from electronic annotation. Source: Ensembl

response to estradiol

Inferred from electronic annotation. Source: Ensembl

response to glucocorticoid

Inferred from electronic annotation. Source: Ensembl

response to lithium ion

Inferred from electronic annotation. Source: Ensembl

response to mechanical stimulus

Inferred from electronic annotation. Source: Ensembl

response to nutrient

Inferred from electronic annotation. Source: Ensembl

response to retinoic acid

Inferred from electronic annotation. Source: Ensembl

signal transduction

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentapical plasma membrane

Inferred from electronic annotation. Source: Ensembl

cytoplasmic vesicle

Inferred from electronic annotation. Source: Ensembl

extracellular region

Inferred from sequence or structural similarity. Source: UniProtKB

extracellular space

Inferred from direct assay PubMed 15694994. Source: BHF-UCL

   Molecular_functioninsulin-like growth factor I binding

Inferred from direct assay Ref.11. Source: UniProtKB

insulin-like growth factor II binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

INO80BQ9C0864EBI-2504392,EBI-715611

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3535
Chain36 – 325290Insulin-like growth factor-binding protein 2
PRO_0000014370

Regions

Domain38 – 13497IGFBP N-terminal
Domain224 – 30683Thyroglobulin type-1
Motif301 – 3033Cell attachment site

Amino acid modifications

Disulfide bond227 ↔ 261 Ref.12
Disulfide bond272 ↔ 283 Ref.12
Disulfide bond285 ↔ 306 Ref.12

Natural variations

Natural variant1371A → D. Ref.7
Corresponds to variant rs9341096 [ dbSNP | Ensembl ].
VAR_018871

Experimental info

Mutagenesis216 – 2194KKLR → NNLA: Does not disrupt growth-inhibiting activity. Ref.11
Mutagenesis3031D → E: Does not disrupt growth-inhibiting activity. Ref.11
Sequence conflict151P → PPLL in CAA34373. Ref.1
Sequence conflict151P → PPLL in AAA36048. Ref.3
Sequence conflict151P → PPLL in AAA03246. Ref.4
Sequence conflict151P → PPLL in AAB22308. Ref.5
Sequence conflict151P → PPLL in AAQ87876. Ref.7
Sequence conflict151P → PPLL in AAH04312. Ref.9
Sequence conflict151P → PPLL in AAH09902. Ref.9
Sequence conflict151P → PPLL in AAH12769. Ref.9
Sequence conflict151P → PPLL in AAH71967. Ref.9
Sequence conflict571P → R in AAA36048. Ref.3
Sequence conflict3171R → C in CAA34373. Ref.1
Sequence conflict3201H → D in AAA36048. Ref.3

Secondary structure

.......... 325
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P18065 [UniParc].

Last modified March 2, 2010. Version 2.
Checksum: 9E1436DBCCC6EA2A

FASTA32534,814
        10         20         30         40         50         60 
MLPRVGCPAL PLPPPPLLPL LLLLLGASGG GGGARAEVLF RCPPCTPERL AACGPPPVAP 

        70         80         90        100        110        120 
PAAVAAVAGG ARMPCAELVR EPGCGCCSVC ARLEGEACGV YTPRCGQGLR CYPHPGSELP 

       130        140        150        160        170        180 
LQALVMGEGT CEKRRDAEYG ASPEQVADNG DDHSEGGLVE NHVDSTMNML GGGGSAGRKP 

       190        200        210        220        230        240 
LKSGMKELAV FREKVTEQHR QMGKGGKHHL GLEEPKKLRP PPARTPCQQE LDQVLERIST 

       250        260        270        280        290        300 
MRLPDERGPL EHLYSLHIPN CDKHGLYNLK QCKMSLNGQR GECWCVNPNT GKLIQGAPTI 

       310        320 
RGDPECHLFY NEQQEARGVH TQRMQ 

« Hide

References

« Hide 'large scale' references
[1]"Cloning, sequence analysis and expression of a cDNA encoding a novel insulin-like growth factor binding protein (IGFBP-2)."
Binkert C., Landwehr J., Mary J.L., Schwander J., Heinrich G.
EMBO J. 8:2497-2502(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Fetal liver.
[2]"Isolation from adult human serum of four insulin-like growth factor (IGF) binding proteins and molecular cloning of one of them that is increased by IGF I administration and in extrapancreatic tumor hypoglycemia."
Zapf J., Kiefer M., Merryweather J., Musiarz F., Bauer D., Born W., Fischer J.A., Froesch E.R.
J. Biol. Chem. 265:14892-14898(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 37-74.
[3]"Structure and localization of the human insulin-like growth factor-binding protein 2 gene."
Ehrenborg E., Vilhelmsdotter S., Bajalica S., Larsson C., Sterm I., Koch J., Brondum-Nielsen K., Luthman H.
Biochem. Biophys. Res. Commun. 176:1250-1255(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Placenta.
[4]"Sequence analysis, expression and chromosomal localization of a gene, isolated from a subtracted human retina cDNA library, that encodes an insulin-like growth factor binding protein (IGFBP2)."
Agarwal N., Hsieh C.L., Sills D., Swaroop M., Desai B., Francke U., Swaroop A.
Exp. Eye Res. 52:549-561(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Retina.
[5]"Structure of the human insulin-like growth factor binding protein-2 gene."
Binkert C., Margot J.B., Landwehr J., Heinrich G., Schwander J.
Mol. Endocrinol. 6:826-836(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Placenta.
[6]"Full-length cDNA libraries and normalization."
Li W.B., Gruber C., Jessee J., Polayes D.
Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Placenta.
[7]NIEHS SNPs program
Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ASP-137.
[8]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
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: Brain, Ovary and Uterus.
[10]"Purification from human cerebrospinal fluid of insulin-like growth factor binding proteins (IGFBPs). Isolation of IGFBP-2, an altered form of IGFBP-3 and a new IGFBP species."
Roghani M., Segovia B., Whitechurch O., Binoux M.
Growth Regul. 1:125-130(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 40-58, INTERACTION WITH IGF2, GLYCOSYLATION.
Tissue: Cerebrospinal fluid.
[11]"Duplication of the IGFBP-2 gene in teleost fish: protein structure and functionality conservation and gene expression divergence."
Zhou J., Li W., Kamei H., Duan C.
PLoS ONE 3:E3926-E3926(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IGF1-BINDING, DOMAIN, MUTAGENESIS OF 216-LYS--ARG-219 AND ASP-303.
[12]"Structure, dynamics and heparin binding of the C-terminal domain of insulin-like growth factor-binding protein-2 (IGFBP-2)."
Kuang Z., Yao S., Keizer D.W., Wang C.C., Bach L.A., Forbes B.E., Wallace J.C., Norton R.S.
J. Mol. Biol. 364:690-704(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 220-325, DISULFIDE BONDS.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X16302 mRNA. Translation: CAA34373.1.
M69241 expand/collapse EMBL AC list , M69237, M69239, M69240 Genomic DNA. Translation: AAA36048.1.
M35410 mRNA. Translation: AAA03246.1.
S37730 expand/collapse EMBL AC list , S37712, S37722, S37726 Genomic DNA. Translation: AAB22308.1.
CR610845 mRNA. No translation available.
AY398667 Genomic DNA. Translation: AAQ87876.1.
AC073321 Genomic DNA. No translation available.
AC007563 Genomic DNA. No translation available.
BC004312 mRNA. Translation: AAH04312.1.
BC009902 mRNA. Translation: AAH09902.1.
BC012769 mRNA. Translation: AAH12769.1.
BC071967 mRNA. Translation: AAH71967.1.
PIRA41927.
RefSeqNP_000588.2. NM_000597.2.
UniGeneHs.438102.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2H7TNMR-A220-325[»]
ProteinModelPortalP18065.
SMRP18065. Positions 40-134, 220-325.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109706. 3 interactions.
IntActP18065. 3 interactions.
STRING9606.ENSP00000233809.

Chemistry

ChEMBLCHEMBL3088.

Protein family/group databases

MEROPSI31.953.

PTM databases

PhosphoSiteP18065.

Polymorphism databases

DMDM290457647.

Proteomic databases

PaxDbP18065.
PRIDEP18065.

Protocols and materials databases

DNASU3485.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000233809; ENSP00000233809; ENSG00000115457.
GeneID3485.
KEGGhsa:3485.
UCSCuc010zju.2. human.

Organism-specific databases

CTD3485.
GeneCardsGC02P217497.
HGNCHGNC:5471. IGFBP2.
MIM146731. gene.
neXtProtNX_P18065.
PharmGKBPA29704.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG47500.
HOGENOMHOG000253012.
HOVERGENHBG002631.
InParanoidP18065.
OMAGAGTCEK.
PhylomeDBP18065.
TreeFamTF331211.

Enzyme and pathway databases

ReactomeREACT_17015. Metabolism of proteins.

Gene expression databases

ArrayExpressP18065.
BgeeP18065.
CleanExHS_IGFBP2.
GenevestigatorP18065.

Family and domain databases

Gene3D4.10.40.20. 1 hit.
4.10.800.10. 1 hit.
InterProIPR009030. Growth_fac_rcpt_N_dom.
IPR012210. IGFBP-2.
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.
PTHR11551:SF5. PTHR11551:SF5. 1 hit.
PfamPF00219. IGFBP. 1 hit.
PF00086. Thyroglobulin_1. 1 hit.
[Graphical view]
PRINTSPR01976. IGFBPFAMILY.
PR01978. IGFBPFAMILY2.
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

EvolutionaryTraceP18065.
GeneWikiIGFBP2.
GenomeRNAi3485.
NextBio13704.
PMAP-CutDBP18065.
PROP18065.
SOURCESearch...

Entry information

Entry nameIBP2_HUMAN
AccessionPrimary (citable) accession number: P18065
Secondary accession number(s): Q14619, Q9UCL3
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: March 2, 2010
Last modified: April 16, 2014
This is version 153 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 2

Human chromosome 2: entries, gene names and cross-references to MIM