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Protein

Insulin-like growth factor-binding protein 3

Gene

IGFBP3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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. Also exhibits IGF-independent antiproliferative and apoptotic effects mediated by its receptor TMEM219/IGFBP-3R.1 Publication

GO - Molecular functioni

  • fibronectin binding Source: GO_Central
  • insulin-like growth factor binding Source: UniProtKB
  • insulin-like growth factor I binding Source: BHF-UCL
  • insulin-like growth factor II binding Source: GO_Central
  • metal ion binding Source: UniProtKB
  • protein tyrosine phosphatase activator activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Apoptosis

Keywords - Ligandi

Growth factor binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000146674-MONOMER.
ReactomeiR-HSA-381426. Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
R-HSA-6803211. TP53 Regulates Transcription of Death Receptors and Ligands.
SIGNORiP17936.

Protein family/group databases

MEROPSiI31.952.

Names & Taxonomyi

Protein namesi
Recommended name:
Insulin-like growth factor-binding protein 3
Short name:
IBP-3
Short name:
IGF-binding protein 3
Short name:
IGFBP-3
Gene namesi
Name:IGFBP3
Synonyms:IBP3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:5472. IGFBP3.

Subcellular locationi

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • extracellular region Source: UniProtKB
  • extracellular space Source: BHF-UCL
  • insulin-like growth factor binding protein complex Source: BHF-UCL
  • insulin-like growth factor ternary complex Source: BHF-UCL
  • nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi3486.
OpenTargetsiENSG00000146674.
PharmGKBiPA29705.

Chemistry databases

ChEMBLiCHEMBL3997.
DrugBankiDB01277. Mecasermin.

Polymorphism and mutation databases

BioMutaiIGFBP3.
DMDMi146327827.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 273 PublicationsAdd BLAST27
ChainiPRO_000001437828 – 291Insulin-like growth factor-binding protein 3Add BLAST264

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi116N-linked (GlcNAc...) (complex)1 Publication1
Glycosylationi136N-linked (GlcNAc...) (complex)4 Publications1
Modified residuei148Phosphoserine; by FAM20C1 Publication1
Glycosylationi199N-linked (GlcNAc...) (complex)2 Publications1
Modified residuei201Phosphoserine; by FAM20C1 Publication1
Disulfide bondi213 ↔ 240PROSITE-ProRule annotation
Disulfide bondi251 ↔ 262PROSITE-ProRule annotation
Disulfide bondi264 ↔ 285PROSITE-ProRule annotation

Post-translational modificationi

Phosphorylated by FAM20C in the extracellular medium.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP17936.
PaxDbiP17936.
PeptideAtlasiP17936.
PRIDEiP17936.

PTM databases

iPTMnetiP17936.
PhosphoSitePlusiP17936.

Miscellaneous databases

PMAP-CutDBP17936.

Expressioni

Tissue specificityi

Expressed by most tissues. Present in plasma.

Developmental stagei

IGFBP3 levels are higher during extrauterine life and peak during puberty.

Inductioni

Up-regulated in the presence of IGF1, insulin and other growth-stimulating factors such as growth hormone, EGF and phorbol esters.

Gene expression databases

BgeeiENSG00000146674.
CleanExiHS_IGFBP3.
ExpressionAtlasiP17936. baseline and differential.
GenevisibleiP17936. HS.

Organism-specific databases

HPAiCAB010360.
HPA013357.

Interactioni

Subunit structurei

Interacts with XLKD1 (By similarity). Binds IGF2 more than IGF1. Forms a ternary complex of about 140 to 150 kDa with IGF1 or IGF2 and a 85 kDa glycoprotein (ALS). Interacts with HN. Interacts with TMEM219.By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
EGFRP005333EBI-715709,EBI-297353
PRKDCP785272EBI-715709,EBI-352053

GO - Molecular functioni

  • fibronectin binding Source: GO_Central
  • insulin-like growth factor binding Source: UniProtKB
  • insulin-like growth factor I binding Source: BHF-UCL
  • insulin-like growth factor II binding Source: GO_Central

Protein-protein interaction databases

BioGridi109707. 18 interactors.
DIPiDIP-40786N.
IntActiP17936. 15 interactors.
MINTiMINT-142445.
STRINGi9606.ENSP00000370473.

Chemistry databases

BindingDBiP17936.

Structurei

3D structure databases

ProteinModelPortaliP17936.
SMRiP17936.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini36 – 117IGFBP N-terminalPROSITE-ProRule annotationAdd BLAST82
Domaini210 – 285Thyroglobulin type-1PROSITE-ProRule annotationAdd BLAST76

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni28 – 134IGF-bindingSequence analysisAdd BLAST107

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi138 – 161Ser/Thr-richAdd BLAST24
Compositional biasi192 – 208Ser/Thr-richAdd BLAST17

Domaini

The thyroglobulin type-1 domain mediates interaction with HN.

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

eggNOGiENOG410IHZU. Eukaryota.
ENOG4111MF3. LUCA.
GeneTreeiENSGT00550000074457.
HOGENOMiHOG000253012.
HOVERGENiHBG002631.
InParanoidiP17936.
KOiK10138.
OMAiRALEQCK.
OrthoDBiEOG091G0EIN.
PhylomeDBiP17936.
TreeFamiTF331211.

Family and domain databases

Gene3Di4.10.800.10. 1 hit.
InterProiIPR009030. Growth_fac_rcpt_.
IPR012211. IGFBP-3.
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.
PTHR11551:SF3. PTHR11551:SF3. 1 hit.
PfamiPF00219. IGFBP. 1 hit.
PF00086. Thyroglobulin_1. 1 hit.
[Graphical view]
PRINTSiPR01976. IGFBPFAMILY.
PR01979. IGFBPFAMILY3.
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]

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. AlignAdd to basket

Isoform 1 (identifier: P17936-1) [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

        10         20         30         40         50
MQRARPTLWA AALTLLVLLR GPPVARAGAS SAGLGPVVRC EPCDARALAQ
60 70 80 90 100
CAPPPAVCAE LVREPGCGCC LTCALSEGQP CGIYTERCGS GLRCQPSPDE
110 120 130 140 150
ARPLQALLDG RGLCVNASAV SRLRAYLLPA PPAPGNASES EEDRSAGSVE
160 170 180 190 200
SPSVSSTHRV SDPKFHPLHS KIIIIKKGHA KDSQRYKVDY ESQSTDTQNF
210 220 230 240 250
SSESKRETEY GPCRREMEDT LNHLKFLNVL SPRGVHIPNC DKKGFYKKKQ
260 270 280 290
CRPSKGRKRG FCWCVDKYGQ PLPGYTTKGK EDVHCYSMQS K
Length:291
Mass (Da):31,674
Last modified:March 6, 2007 - v2
Checksum:iA9682065AB266586
GO
Isoform 2 (identifier: P17936-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     135-135: G → GEPPAPG

Note: Gene prediction based on EST data.
Show »
Length:297
Mass (Da):32,223
Checksum:i8CCFAD16904D0DF4
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0362797T → M in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_02526232A → G.4 PublicationsCorresponds to variant rs2854746dbSNPEnsembl.1
Natural variantiVAR_02526356A → T.1 PublicationCorresponds to variant rs34257987dbSNPEnsembl.1
Natural variantiVAR_021974158H → P.Corresponds to variant rs9282734dbSNPEnsembl.1
Natural variantiVAR_025264234G → S.1 PublicationCorresponds to variant rs35712717dbSNPEnsembl.1
Natural variantiVAR_036280252R → C in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant rs538312081dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_047293135G → GEPPAPG in isoform 2. Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M31159 mRNA. Translation: AAA52541.1.
M35878 Genomic DNA. Translation: AAA52706.1.
X64875 mRNA. Translation: CAA46087.1.
DQ301819 Genomic DNA. Translation: ABB96247.1.
AC091524 Genomic DNA. Translation: AAS07554.1.
CH236958 Genomic DNA. Translation: EAL23801.1.
CH471128 Genomic DNA. Translation: EAW61028.1.
CH471128 Genomic DNA. Translation: EAW61029.1.
BC000013 mRNA. Translation: AAH00013.1.
BC018962 mRNA. Translation: AAH18962.1.
BC064987 mRNA. Translation: AAH64987.1.
CCDSiCCDS34632.1. [P17936-2]
CCDS5505.1. [P17936-1]
PIRiA36578. IOHU3.
RefSeqiNP_000589.2. NM_000598.4. [P17936-1]
NP_001013416.1. NM_001013398.1. [P17936-2]
XP_016867641.1. XM_017012152.1. [P17936-1]
UniGeneiHs.450230.

Genome annotation databases

EnsembliENST00000275521; ENSP00000275521; ENSG00000146674. [P17936-1]
ENST00000381083; ENSP00000370473; ENSG00000146674. [P17936-2]
GeneIDi3486.
KEGGihsa:3486.
UCSCiuc003tnr.4. human. [P17936-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs
SHMPD

The Singapore human mutation and polymorphism database

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M31159 mRNA. Translation: AAA52541.1.
M35878 Genomic DNA. Translation: AAA52706.1.
X64875 mRNA. Translation: CAA46087.1.
DQ301819 Genomic DNA. Translation: ABB96247.1.
AC091524 Genomic DNA. Translation: AAS07554.1.
CH236958 Genomic DNA. Translation: EAL23801.1.
CH471128 Genomic DNA. Translation: EAW61028.1.
CH471128 Genomic DNA. Translation: EAW61029.1.
BC000013 mRNA. Translation: AAH00013.1.
BC018962 mRNA. Translation: AAH18962.1.
BC064987 mRNA. Translation: AAH64987.1.
CCDSiCCDS34632.1. [P17936-2]
CCDS5505.1. [P17936-1]
PIRiA36578. IOHU3.
RefSeqiNP_000589.2. NM_000598.4. [P17936-1]
NP_001013416.1. NM_001013398.1. [P17936-2]
XP_016867641.1. XM_017012152.1. [P17936-1]
UniGeneiHs.450230.

3D structure databases

ProteinModelPortaliP17936.
SMRiP17936.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109707. 18 interactors.
DIPiDIP-40786N.
IntActiP17936. 15 interactors.
MINTiMINT-142445.
STRINGi9606.ENSP00000370473.

Chemistry databases

BindingDBiP17936.
ChEMBLiCHEMBL3997.
DrugBankiDB01277. Mecasermin.

Protein family/group databases

MEROPSiI31.952.

PTM databases

iPTMnetiP17936.
PhosphoSitePlusiP17936.

Polymorphism and mutation databases

BioMutaiIGFBP3.
DMDMi146327827.

Proteomic databases

MaxQBiP17936.
PaxDbiP17936.
PeptideAtlasiP17936.
PRIDEiP17936.

Protocols and materials databases

DNASUi3486.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000275521; ENSP00000275521; ENSG00000146674. [P17936-1]
ENST00000381083; ENSP00000370473; ENSG00000146674. [P17936-2]
GeneIDi3486.
KEGGihsa:3486.
UCSCiuc003tnr.4. human. [P17936-1]

Organism-specific databases

CTDi3486.
DisGeNETi3486.
GeneCardsiIGFBP3.
HGNCiHGNC:5472. IGFBP3.
HPAiCAB010360.
HPA013357.
MIMi146732. gene.
neXtProtiNX_P17936.
OpenTargetsiENSG00000146674.
PharmGKBiPA29705.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IHZU. Eukaryota.
ENOG4111MF3. LUCA.
GeneTreeiENSGT00550000074457.
HOGENOMiHOG000253012.
HOVERGENiHBG002631.
InParanoidiP17936.
KOiK10138.
OMAiRALEQCK.
OrthoDBiEOG091G0EIN.
PhylomeDBiP17936.
TreeFamiTF331211.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000146674-MONOMER.
ReactomeiR-HSA-381426. Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
R-HSA-6803211. TP53 Regulates Transcription of Death Receptors and Ligands.
SIGNORiP17936.

Miscellaneous databases

ChiTaRSiIGFBP3. human.
GeneWikiiIGFBP3.
GenomeRNAii3486.
PMAP-CutDBP17936.
PROiP17936.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000146674.
CleanExiHS_IGFBP3.
ExpressionAtlasiP17936. baseline and differential.
GenevisibleiP17936. HS.

Family and domain databases

Gene3Di4.10.800.10. 1 hit.
InterProiIPR009030. Growth_fac_rcpt_.
IPR012211. IGFBP-3.
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.
PTHR11551:SF3. PTHR11551:SF3. 1 hit.
PfamiPF00219. IGFBP. 1 hit.
PF00086. Thyroglobulin_1. 1 hit.
[Graphical view]
PRINTSiPR01976. IGFBPFAMILY.
PR01979. IGFBPFAMILY3.
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]
ProtoNetiSearch...

Entry informationi

Entry nameiIBP3_HUMAN
AccessioniPrimary (citable) accession number: P17936
Secondary accession number(s): A4D2F5
, D3DVM0, Q2V509, Q6P1M6, Q9UCL4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: March 6, 2007
Last modified: November 2, 2016
This is version 193 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

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: 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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.