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Protein

Insulin-like growth factor-binding protein 3

Gene

IGFBP3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionGrowth factor binding
Biological processApoptosis

Enzyme and pathway databases

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
R-HSA-8957275 Post-translational protein phosphorylation
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

EuPathDBiHostDB:ENSG00000146674.14
HGNCiHGNC:5472 IGFBP3
MIMi146732 gene
neXtProtiNX_P17936

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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) asparagine1 Publication1
Glycosylationi136N-linked (GlcNAc...) (complex) asparagine4 Publications1
Modified residuei148Phosphoserine; by FAM20C1 Publication1
Glycosylationi199N-linked (GlcNAc...) (complex) asparagine2 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

EPDiP17936
MaxQBiP17936
PaxDbiP17936
PeptideAtlasiP17936
PRIDEiP17936
ProteomicsDBi53527

PTM databases

iPTMnetiP17936
PhosphoSitePlusiP17936

Miscellaneous databases

PMAP-CutDBiP17936

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 Expressed in 229 organ(s), highest expression level in decidua
CleanExiHS_IGFBP3
ExpressionAtlasiP17936 baseline and differential
GenevisibleiP17936 HS

Organism-specific databases

HPAiCAB010360

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109707, 18 interactors
CORUMiP17936
DIPiDIP-40786N
IntActiP17936, 18 interactors
MINTiP17936
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.

Keywords - Domaini

Signal

Phylogenomic databases

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

Family and domain databases

CDDicd00191 TY, 1 hit
Gene3Di4.10.800.10, 1 hit
InterProiView protein in InterPro
IPR009030 Growth_fac_rcpt_cys_sf
IPR012211 IGFBP-3
IPR000867 IGFBP-like
IPR009168 IGFBP1-6
IPR022321 IGFBP_1-6_chordata
IPR017891 Insulin_GF-bd_Cys-rich_CS
IPR000716 Thyroglobulin_1
IPR036857 Thyroglobulin_1_sf
PANTHERiPTHR11551 PTHR11551, 1 hit
PTHR11551:SF3 PTHR11551:SF3, 1 hit
PfamiView protein in Pfam
PF00219 IGFBP, 1 hit
PF00086 Thyroglobulin_1, 1 hit
PRINTSiPR01976 IGFBPFAMILY
PR01979 IGFBPFAMILY3
SMARTiView protein in SMART
SM00121 IB, 1 hit
SM00211 TY, 1 hit
SUPFAMiSSF57184 SSF57184, 1 hit
SSF57610 SSF57610, 1 hit
PROSITEiView protein in PROSITE
PS00222 IGFBP_N_1, 1 hit
PS51323 IGFBP_N_2, 1 hit
PS00484 THYROGLOBULIN_1_1, 1 hit
PS51162 THYROGLOBULIN_1_2, 1 hit

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

This entry has 2 described isoforms and 6 potential isoforms that are computationally mapped.iShow all

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

Computationally mapped potential isoform sequencesi

There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A6XND0A6XND0_HUMAN
Insulin-like growth factor-binding ...
IGFBP3
270Annotation score:
A6XND1A6XND1_HUMAN
Insulin-like growth factor binding ...
IGFBP3
263Annotation score:
B3KWK7B3KWK7_HUMAN
Insulin-like growth factor binding ...
IGFBP3 hCG_1735376
194Annotation score:
H0Y5K2H0Y5K2_HUMAN
Insulin-like growth factor-binding ...
IGFBP3
153Annotation score:
H0Y485H0Y485_HUMAN
Insulin-like growth factor-binding ...
IGFBP3
143Annotation score:
C9JMX4C9JMX4_HUMAN
Insulin-like growth factor-binding ...
IGFBP3
132Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0362797T → M in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_02526232A → G4 PublicationsCorresponds to variant dbSNP:rs2854746Ensembl.1
Natural variantiVAR_02526356A → T1 PublicationCorresponds to variant dbSNP:rs34257987Ensembl.1
Natural variantiVAR_021974158H → P. Corresponds to variant dbSNP:rs9282734Ensembl.1
Natural variantiVAR_025264234G → S1 PublicationCorresponds to variant dbSNP:rs35712717Ensembl.1
Natural variantiVAR_036280252R → C in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs538312081Ensembl.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

Similar proteinsi

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
CORUMiP17936
DIPiDIP-40786N
IntActiP17936, 18 interactors
MINTiP17936
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

EPDiP17936
MaxQBiP17936
PaxDbiP17936
PeptideAtlasiP17936
PRIDEiP17936
ProteomicsDBi53527

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
EuPathDBiHostDB:ENSG00000146674.14
GeneCardsiIGFBP3
HGNCiHGNC:5472 IGFBP3
HPAiCAB010360
MIMi146732 gene
neXtProtiNX_P17936
OpenTargetsiENSG00000146674
PharmGKBiPA29705
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

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
R-HSA-8957275 Post-translational protein phosphorylation
SIGNORiP17936

Miscellaneous databases

ChiTaRSiIGFBP3 human
GeneWikiiIGFBP3
GenomeRNAii3486
PMAP-CutDBiP17936
PROiPR:P17936
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000146674 Expressed in 229 organ(s), highest expression level in decidua
CleanExiHS_IGFBP3
ExpressionAtlasiP17936 baseline and differential
GenevisibleiP17936 HS

Family and domain databases

CDDicd00191 TY, 1 hit
Gene3Di4.10.800.10, 1 hit
InterProiView protein in InterPro
IPR009030 Growth_fac_rcpt_cys_sf
IPR012211 IGFBP-3
IPR000867 IGFBP-like
IPR009168 IGFBP1-6
IPR022321 IGFBP_1-6_chordata
IPR017891 Insulin_GF-bd_Cys-rich_CS
IPR000716 Thyroglobulin_1
IPR036857 Thyroglobulin_1_sf
PANTHERiPTHR11551 PTHR11551, 1 hit
PTHR11551:SF3 PTHR11551:SF3, 1 hit
PfamiView protein in Pfam
PF00219 IGFBP, 1 hit
PF00086 Thyroglobulin_1, 1 hit
PRINTSiPR01976 IGFBPFAMILY
PR01979 IGFBPFAMILY3
SMARTiView protein in SMART
SM00121 IB, 1 hit
SM00211 TY, 1 hit
SUPFAMiSSF57184 SSF57184, 1 hit
SSF57610 SSF57610, 1 hit
PROSITEiView protein in PROSITE
PS00222 IGFBP_N_1, 1 hit
PS51323 IGFBP_N_2, 1 hit
PS00484 THYROGLOBULIN_1_1, 1 hit
PS51162 THYROGLOBULIN_1_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiIBP3_HUMAN
AccessioniPrimary (citable) accession number: P17936
Secondary accession number(s): A4D2F5
, D3DVM0, Q2V509, Q6P1M6, Q9UCL4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: March 6, 2007
Last modified: September 12, 2018
This is version 207 of the entry and version 2 of the sequence. See 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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