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Protein

Insulin-like growth factor-binding protein 4

Gene

IGFBP4

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.

GO - Molecular functioni

  • insulin-like growth factor I binding Source: GO_Central
  • insulin-like growth factor II binding Source: GO_Central
  • receptor binding Source: ParkinsonsUK-UCL

GO - Biological processi

Complete GO annotation...

Keywords - Ligandi

Growth factor binding

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000141753-MONOMER.
ZFISH:ENSG00000141753-MONOMER.
ReactomeiR-HSA-381426. Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).

Protein family/group databases

MEROPSiI31.952.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:5473. IGFBP4.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi3487.
OpenTargetsiENSG00000141753.
PharmGKBiPA29706.

Chemistry databases

ChEMBLiCHEMBL2310.

Polymorphism and mutation databases

BioMutaiIGFBP4.
DMDMi124065.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 213 PublicationsAdd BLAST21
ChainiPRO_000001438222 – 258Insulin-like growth factor-binding protein 4Add BLAST237

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi27 ↔ 532 Publications
Disulfide bondi30 ↔ 552 Publications
Disulfide bondi38 ↔ 592 Publications
Disulfide bondi44 ↔ 562 Publications
Disulfide bondi67 ↔ 802 Publications
Disulfide bondi74 ↔ 1002 Publications
Glycosylationi125N-linked (GlcNAc...)1 PublicationSequence analysis1
Disulfide bondi131 ↔ 138PROSITE-ProRule annotation2 Publications
Disulfide bondi174 ↔ 2042 Publications
Disulfide bondi215 ↔ 2262 Publications
Disulfide bondi228 ↔ 2492 Publications
Modified residuei255Phosphoserine; by FAM20C1 Publication1

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP22692.
MaxQBiP22692.
PaxDbiP22692.
PeptideAtlasiP22692.
PRIDEiP22692.

PTM databases

iPTMnetiP22692.
PhosphoSitePlusiP22692.

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

BgeeiENSG00000141753.
CleanExiHS_IGFBP4.
ExpressionAtlasiP22692. baseline and differential.
GenevisibleiP22692. HS.

Organism-specific databases

HPAiHPA066240.

Interactioni

Subunit structurei

Binds IGF2 more than IGF1.2 Publications

GO - Molecular functioni

  • insulin-like growth factor I binding Source: GO_Central
  • insulin-like growth factor II binding Source: GO_Central
  • receptor binding Source: ParkinsonsUK-UCL

Protein-protein interaction databases

BioGridi109708. 6 interactors.
DIPiDIP-48432N.
IntActiP22692. 4 interactors.
MINTiMINT-6630380.
STRINGi9606.ENSP00000269593.

Chemistry databases

BindingDBiP22692.

Structurei

Secondary structure

1258
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi32 – 36Combined sources5
Beta strandi45 – 49Combined sources5
Beta strandi56 – 59Combined sources4
Beta strandi69 – 71Combined sources3
Beta strandi78 – 81Combined sources4
Helixi89 – 94Combined sources6
Beta strandi98 – 102Combined sources5
Helixi103 – 110Combined sources8
Helixi173 – 186Combined sources14
Helixi195 – 198Combined sources4
Beta strandi208 – 210Combined sources3
Beta strandi212 – 215Combined sources4
Beta strandi226 – 229Combined sources4
Turni231 – 233Combined sources3
Helixi244 – 246Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1WQJX-ray1.60B24-103[»]
2DSPX-ray2.50B22-113[»]
2DSQX-ray2.80A/B22-113[»]
2DSRX-ray2.10B24-103[»]
G172-253[»]
ProteinModelPortaliP22692.
SMRiP22692.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP22692.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini23 – 103IGFBP N-terminalPROSITE-ProRule annotationAdd BLAST81
Domaini171 – 249Thyroglobulin type-1PROSITE-ProRule annotationAdd BLAST79

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

eggNOGiENOG410IKZ1. Eukaryota.
ENOG4111HXV. LUCA.
GeneTreeiENSGT00550000074457.
HOGENOMiHOG000253012.
HOVERGENiHBG002631.
InParanoidiP22692.
OMAiLMHGQGI.
OrthoDBiEOG091G0EIN.
PhylomeDBiP22692.
TreeFamiTF331211.

Family and domain databases

Gene3Di4.10.800.10. 1 hit.
InterProiIPR009030. Growth_fac_rcpt_.
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]

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: P22692-1) [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
MLPLCLVAAL LLAAGPGPSL GDEAIHCPPC SEEKLARCRP PVGCEELVRE
60 70 80 90 100
PGCGCCATCA LGLGMPCGVY TPRCGSGLRC YPPRGVEKPL HTLMHGQGVC
110 120 130 140 150
MELAEIEAIQ ESLQPSDKDE GDHPNNSFSP CSAHDRRCLQ KHFAKIRDRS
160 170 180 190 200
TSGGKMKVNG APREDARPVP QGSCQSELHR ALERLAASQS RTHEDLYIIP
210 220 230 240 250
IPNCDRNGNF HPKQCHPALD GQRGKCWCVD RKTGVKLPGG LEPKGELDCH

QLADSFRE
Length:258
Mass (Da):27,934
Last modified:March 1, 1992 - v2
Checksum:i5E8F4638D99F0A94
GO
Isoform 2 (identifier: P22692-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-100: Missing.

Note: No experimental confirmation available.
Show »
Length:158
Mass (Da):17,635
Checksum:iF31375031D835A1E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti51P → A in M38177 (PubMed:1707125).Curated1
Sequence conflicti51P → A in AAA62670 (PubMed:9048882).Curated1
Sequence conflicti51P → A AA sequence (PubMed:1709585).Curated1
Sequence conflicti160G → E in AAV38694 (Ref. 7) Curated1
Sequence conflicti198I → F in M38177 (PubMed:1707125).Curated1
Sequence conflicti198I → F in AAA62670 (PubMed:9048882).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01190642V → G.Corresponds to variant rs599199dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0570341 – 100Missing in isoform 2. 1 PublicationAdd BLAST100

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M38177 mRNA. No translation available.
M62403 mRNA. Translation: AAB06189.1.
U20982 Genomic DNA. Translation: AAA62670.1.
Y12508 Genomic DNA. Translation: CAA73110.1.
AK304572 mRNA. Translation: BAG65363.1.
BT019891 mRNA. Translation: AAV38694.1.
BT019892 mRNA. Translation: AAV38695.1.
AY442346 Genomic DNA. Translation: AAR05443.1.
AC018629 Genomic DNA. No translation available.
CH471152 Genomic DNA. Translation: EAW60664.1.
BC016041 mRNA. Translation: AAH16041.1.
CCDSiCCDS11367.1. [P22692-1]
PIRiG01662. B37252.
RefSeqiNP_001543.2. NM_001552.2. [P22692-1]
UniGeneiHs.462998.

Genome annotation databases

EnsembliENST00000269593; ENSP00000269593; ENSG00000141753. [P22692-1]
GeneIDi3487.
KEGGihsa:3487.
UCSCiuc002hus.4. human. [P22692-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M38177 mRNA. No translation available.
M62403 mRNA. Translation: AAB06189.1.
U20982 Genomic DNA. Translation: AAA62670.1.
Y12508 Genomic DNA. Translation: CAA73110.1.
AK304572 mRNA. Translation: BAG65363.1.
BT019891 mRNA. Translation: AAV38694.1.
BT019892 mRNA. Translation: AAV38695.1.
AY442346 Genomic DNA. Translation: AAR05443.1.
AC018629 Genomic DNA. No translation available.
CH471152 Genomic DNA. Translation: EAW60664.1.
BC016041 mRNA. Translation: AAH16041.1.
CCDSiCCDS11367.1. [P22692-1]
PIRiG01662. B37252.
RefSeqiNP_001543.2. NM_001552.2. [P22692-1]
UniGeneiHs.462998.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1WQJX-ray1.60B24-103[»]
2DSPX-ray2.50B22-113[»]
2DSQX-ray2.80A/B22-113[»]
2DSRX-ray2.10B24-103[»]
G172-253[»]
ProteinModelPortaliP22692.
SMRiP22692.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109708. 6 interactors.
DIPiDIP-48432N.
IntActiP22692. 4 interactors.
MINTiMINT-6630380.
STRINGi9606.ENSP00000269593.

Chemistry databases

BindingDBiP22692.
ChEMBLiCHEMBL2310.

Protein family/group databases

MEROPSiI31.952.

PTM databases

iPTMnetiP22692.
PhosphoSitePlusiP22692.

Polymorphism and mutation databases

BioMutaiIGFBP4.
DMDMi124065.

Proteomic databases

EPDiP22692.
MaxQBiP22692.
PaxDbiP22692.
PeptideAtlasiP22692.
PRIDEiP22692.

Protocols and materials databases

DNASUi3487.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000269593; ENSP00000269593; ENSG00000141753. [P22692-1]
GeneIDi3487.
KEGGihsa:3487.
UCSCiuc002hus.4. human. [P22692-1]

Organism-specific databases

CTDi3487.
DisGeNETi3487.
GeneCardsiIGFBP4.
HGNCiHGNC:5473. IGFBP4.
HPAiHPA066240.
MIMi146733. gene.
neXtProtiNX_P22692.
OpenTargetsiENSG00000141753.
PharmGKBiPA29706.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IKZ1. Eukaryota.
ENOG4111HXV. LUCA.
GeneTreeiENSGT00550000074457.
HOGENOMiHOG000253012.
HOVERGENiHBG002631.
InParanoidiP22692.
OMAiLMHGQGI.
OrthoDBiEOG091G0EIN.
PhylomeDBiP22692.
TreeFamiTF331211.

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000141753-MONOMER.
ZFISH:ENSG00000141753-MONOMER.
ReactomeiR-HSA-381426. Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).

Miscellaneous databases

ChiTaRSiIGFBP4. human.
EvolutionaryTraceiP22692.
GeneWikiiIGFBP4.
GenomeRNAii3487.
PMAP-CutDBP22692.
PROiP22692.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000141753.
CleanExiHS_IGFBP4.
ExpressionAtlasiP22692. baseline and differential.
GenevisibleiP22692. HS.

Family and domain databases

Gene3Di4.10.800.10. 1 hit.
InterProiIPR009030. Growth_fac_rcpt_.
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]
ProtoNetiSearch...

Entry informationi

Entry nameiIBP4_HUMAN
AccessioniPrimary (citable) accession number: P22692
Secondary accession number(s): A0N9W2
, B4E351, Q5U012, Q9UCL6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: March 1, 1992
Last modified: November 2, 2016
This is version 171 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

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.