Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Insulin-like growth factor-binding protein 6

Gene

IGFBP6

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

GO - Biological processi

Complete GO annotation...

Keywords - Ligandi

Growth factor binding

Enzyme and pathway databases

ReactomeiREACT_15428. 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 6
Short name:
IBP-6
Short name:
IGF-binding protein 6
Short name:
IGFBP-6
Gene namesi
Name:IGFBP6
Synonyms:IBP6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:5475. IGFBP6.

Subcellular locationi

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • extracellular region Source: Reactome
  • extracellular space Source: GO_Central
  • Golgi apparatus Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA29708.

Polymorphism and mutation databases

BioMutaiIGFBP6.
DMDMi124068.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 27273 PublicationsAdd
BLAST
Chaini28 – 240213Insulin-like growth factor-binding protein 6PRO_0000014389Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi29 ↔ 32PROSITE-ProRule annotation1 Publication
Disulfide bondi40 ↔ 44PROSITE-ProRule annotation1 Publication
Disulfide bondi57 ↔ 63PROSITE-ProRule annotation1 Publication
Disulfide bondi71 ↔ 84PROSITE-ProRule annotation1 Publication
Disulfide bondi78 ↔ 104PROSITE-ProRule annotation1 Publication
Glycosylationi126 – 1261O-linked (HexNAc...)2 Publications
Glycosylationi144 – 1441O-linked (HexNAc...)By similarity
Glycosylationi145 – 1451O-linked (HexNAc...)By similarity
Glycosylationi146 – 1461O-linked (HexNAc...)By similarity
Glycosylationi152 – 1521O-linked (HexNAc...)By similarity
Disulfide bondi163 ↔ 190PROSITE-ProRule annotation1 Publication
Disulfide bondi201 ↔ 212PROSITE-ProRule annotation1 Publication
Disulfide bondi214 ↔ 234PROSITE-ProRule annotation1 Publication

Post-translational modificationi

O-linked glycans consist of hexose (probably Gal), N-acetylhexosamine (probably GalNAc) and sialic acid residues. O-glycosylated with core 1 or possibly core 8 glycans. O-glycosylated on one site only in the region AA 143-168 in cerebrospinal fluid.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiP24592.
PaxDbiP24592.
PeptideAtlasiP24592.
PRIDEiP24592.

Expressioni

Gene expression databases

BgeeiP24592.
CleanExiHS_IGFBP6.
ExpressionAtlasiP24592. baseline and differential.
GenevisibleiP24592. HS.

Organism-specific databases

HPAiHPA008005.

Interactioni

Protein-protein interaction databases

BioGridi109710. 2 interactions.
IntActiP24592. 1 interaction.
MINTiMINT-2859943.
STRINGi9606.ENSP00000301464.

Structurei

Secondary structure

1
240
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi162 – 17716Combined sources
Turni179 – 1813Combined sources
Beta strandi182 – 1887Combined sources
Beta strandi198 – 20811Combined sources
Beta strandi212 – 2154Combined sources
Turni226 – 2283Combined sources
Turni231 – 2333Combined sources
Beta strandi234 – 2363Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1RMJNMR-A161-240[»]
DisProtiDP00211.
ProteinModelPortaliP24592.
SMRiP24592. Positions 25-105, 161-240.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP24592.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini28 – 10780IGFBP N-terminalPROSITE-ProRule annotationAdd
BLAST
Domaini160 – 23475Thyroglobulin type-1PROSITE-ProRule annotationAdd
BLAST

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

eggNOGiNOG47794.
GeneTreeiENSGT00550000074457.
HOGENOMiHOG000253012.
HOVERGENiHBG002631.
InParanoidiP24592.
OMAiRDQQRNP.
PhylomeDBiP24592.
TreeFamiTF331211.

Family and domain databases

Gene3Di4.10.40.20. 1 hit.
4.10.800.10. 1 hit.
InterProiIPR009030. Growth_fac_rcpt_N_dom.
IPR022326. IGFBP-6.
IPR000867. IGFBP-like.
IPR009168. IGFBP1-6.
IPR022321. IGFBP_1-6_chordata.
IPR000716. Thyroglobulin_1.
[Graphical view]
PANTHERiPTHR11551. PTHR11551. 1 hit.
PfamiPF00219. IGFBP. 1 hit.
PF00086. Thyroglobulin_1. 1 hit.
[Graphical view]
PRINTSiPR01976. IGFBPFAMILY.
PR01982. IGFBPFAMILY6.
SMARTiSM00121. IB. 1 hit.
SM00211. TY. 1 hit.
[Graphical view]
SUPFAMiSSF57184. SSF57184. 1 hit.
SSF57610. SSF57610. 1 hit.
PROSITEiPS51323. IGFBP_N_2. 1 hit.
PS00484. THYROGLOBULIN_1_1. 1 hit.
PS51162. THYROGLOBULIN_1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P24592-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTPHRLLPPL LLLLALLLAA SPGGALARCP GCGQGVQAGC PGGCVEEEDG
60 70 80 90 100
GSPAEGCAEA EGCLRREGQE CGVYTPNCAP GLQCHPPKDD EAPLRALLLG
110 120 130 140 150
RGRCLPARAP AVAEENPKES KPQAGTARPQ DVNRRDQQRN PGTSTTPSQP
160 170 180 190 200
NSAGVQDTEM GPCRRHLDSV LQQLQTEVYR GAQTLYVPNC DHRGFYRKRQ
210 220 230 240
CRSSQGQRRG PCWCVDRMGK SLPGSPDGNG SSSCPTGSSG
Length:240
Mass (Da):25,322
Last modified:March 1, 1992 - v1
Checksum:i285308231C025009
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti2 – 21T → C in AAA88070 (PubMed:1719383).Curated
Sequence conflicti28 – 292RC → AA AA sequence (PubMed:1697583).Curated
Sequence conflicti28 – 292RC → LA AA sequence (PubMed:2154495).Curated
Sequence conflicti32 – 321C → H AA sequence (PubMed:1697583).Curated
Sequence conflicti55 – 573EGC → QGG AA sequence (PubMed:1697583).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti128 – 1281R → G.1 Publication
Corresponds to variant rs9658616 [ dbSNP | Ensembl ].
VAR_018932
Natural varianti134 – 1341R → L.
Corresponds to variant rs34995393 [ dbSNP | Ensembl ].
VAR_049565
Natural varianti217 – 2171R → Q.1 Publication
Corresponds to variant rs6413498 [ dbSNP | Ensembl ].
VAR_018933
Natural varianti236 – 2361T → P.
Corresponds to variant rs1053134 [ dbSNP | Ensembl ].
VAR_011907

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M62402 mRNA. Translation: AAB06187.1.
AJ006952 Genomic DNA. Translation: CAA07346.1.
AY443494 Genomic DNA. Translation: AAR05445.1.
BC003507 mRNA. Translation: AAH03507.1.
BC005007 mRNA. Translation: AAH05007.1.
BC010162 mRNA. Translation: AAH10162.1.
BC011708 mRNA. Translation: AAH11708.1.
M69054 mRNA. Translation: AAA88070.1.
CCDSiCCDS8846.1.
PIRiA39842.
S05699.
RefSeqiNP_002169.1. NM_002178.2.
UniGeneiHs.274313.

Genome annotation databases

EnsembliENST00000301464; ENSP00000301464; ENSG00000167779.
GeneIDi3489.
KEGGihsa:3489.
UCSCiuc001sbu.1. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M62402 mRNA. Translation: AAB06187.1.
AJ006952 Genomic DNA. Translation: CAA07346.1.
AY443494 Genomic DNA. Translation: AAR05445.1.
BC003507 mRNA. Translation: AAH03507.1.
BC005007 mRNA. Translation: AAH05007.1.
BC010162 mRNA. Translation: AAH10162.1.
BC011708 mRNA. Translation: AAH11708.1.
M69054 mRNA. Translation: AAA88070.1.
CCDSiCCDS8846.1.
PIRiA39842.
S05699.
RefSeqiNP_002169.1. NM_002178.2.
UniGeneiHs.274313.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1RMJNMR-A161-240[»]
DisProtiDP00211.
ProteinModelPortaliP24592.
SMRiP24592. Positions 25-105, 161-240.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109710. 2 interactions.
IntActiP24592. 1 interaction.
MINTiMINT-2859943.
STRINGi9606.ENSP00000301464.

Chemistry

BindingDBiP24592.
ChEMBLiCHEMBL2139.

Protein family/group databases

MEROPSiI31.952.

Polymorphism and mutation databases

BioMutaiIGFBP6.
DMDMi124068.

Proteomic databases

MaxQBiP24592.
PaxDbiP24592.
PeptideAtlasiP24592.
PRIDEiP24592.

Protocols and materials databases

DNASUi3489.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000301464; ENSP00000301464; ENSG00000167779.
GeneIDi3489.
KEGGihsa:3489.
UCSCiuc001sbu.1. human.

Organism-specific databases

CTDi3489.
GeneCardsiGC12P053491.
HGNCiHGNC:5475. IGFBP6.
HPAiHPA008005.
MIMi146735. gene.
neXtProtiNX_P24592.
PharmGKBiPA29708.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG47794.
GeneTreeiENSGT00550000074457.
HOGENOMiHOG000253012.
HOVERGENiHBG002631.
InParanoidiP24592.
OMAiRDQQRNP.
PhylomeDBiP24592.
TreeFamiTF331211.

Enzyme and pathway databases

ReactomeiREACT_15428. Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).

Miscellaneous databases

EvolutionaryTraceiP24592.
GeneWikiiIGFBP6.
GenomeRNAii3489.
NextBioi13722.
PROiP24592.
SOURCEiSearch...

Gene expression databases

BgeeiP24592.
CleanExiHS_IGFBP6.
ExpressionAtlasiP24592. baseline and differential.
GenevisibleiP24592. HS.

Family and domain databases

Gene3Di4.10.40.20. 1 hit.
4.10.800.10. 1 hit.
InterProiIPR009030. Growth_fac_rcpt_N_dom.
IPR022326. IGFBP-6.
IPR000867. IGFBP-like.
IPR009168. IGFBP1-6.
IPR022321. IGFBP_1-6_chordata.
IPR000716. Thyroglobulin_1.
[Graphical view]
PANTHERiPTHR11551. PTHR11551. 1 hit.
PfamiPF00219. IGFBP. 1 hit.
PF00086. Thyroglobulin_1. 1 hit.
[Graphical view]
PRINTSiPR01976. IGFBPFAMILY.
PR01982. IGFBPFAMILY6.
SMARTiSM00121. IB. 1 hit.
SM00211. TY. 1 hit.
[Graphical view]
SUPFAMiSSF57184. SSF57184. 1 hit.
SSF57610. SSF57610. 1 hit.
PROSITEiPS51323. IGFBP_N_2. 1 hit.
PS00484. THYROGLOBULIN_1_1. 1 hit.
PS51162. THYROGLOBULIN_1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "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].
    Tissue: Osteosarcoma.
  2. "Characterization and chromosomal localization of the human insulin-like growth factor-binding protein 6 gene."
    Ehrenborg E., Zazzi H., Lagercrantz S., Granqvist M., Hillerbrand U., Allander S.V., Larsson C., Luthman H.
    Mamm. Genome 10:376-380(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. NIEHS SNPs program
    Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLY-128 AND GLN-217.
  4. "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: Pancreas.
  5. "Isolation and molecular cloning of insulin-like growth factor-binding protein-6."
    Shimasaki S., Gao L., Shimonaka M., Ling N.
    Mol. Endocrinol. 5:938-948(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 2-240.
    Tissue: Placenta.
  6. "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: PROTEIN SEQUENCE OF 28-57.
    Tissue: Serum.
  7. "Isolation from human cerebrospinal fluid of a new insulin-like growth factor-binding protein with a selective affinity for IGF-II."
    Roghani M., Hossenlopp P., Lepage P., Balland A., Binoux M.
    FEBS Lett. 255:253-258(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: PRELIMINARY PROTEIN SEQUENCE OF 28-42.
    Tissue: Cerebrospinal fluid.
  8. "Purification and properties of a novel insulin-like growth factor-II binding protein from transformed human fibroblasts."
    Martin J.L., Willetts K.E., Baxter R.C.
    J. Biol. Chem. 265:4124-4130(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 28-42.
    Tissue: Fibroblast.
  9. "A novel human insulin-like growth factor binding protein secreted by osteoblast-like cells."
    Andress D.L., Birnbaum R.S.
    Biochem. Biophys. Res. Commun. 176:213-218(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 28-42.
    Tissue: Osteosarcoma.
  10. "Identification of O-glycosylation sites and partial characterization of carbohydrate structure and disulfide linkages of human insulin-like growth factor binding protein 6."
    Neumann G.M., Marinaro J.A., Bach L.A.
    Biochemistry 37:6572-6585(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION AT THR-126; SER-144; THR-145; THR-146 AND SER-152.
  11. "The N-terminal disulfide linkages of human insulin-like growth factor-binding protein-6 (hIGFBP-6) and hIGFBP-1 are different as determined by mass spectrometry."
    Neumann G.M., Bach L.A.
    J. Biol. Chem. 274:14587-14594(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISULFIDE BONDS.
  12. "Enrichment of glycopeptides for glycan structure and attachment site identification."
    Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., Brinkmalm G., Larson G.
    Nat. Methods 6:809-811(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT THR-126, STRUCTURE OF CARBOHYDRATES.
    Tissue: Cerebrospinal fluid.

Entry informationi

Entry nameiIBP6_HUMAN
AccessioniPrimary (citable) accession number: P24592
Secondary accession number(s): Q14492
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: March 1, 1992
Last modified: June 24, 2015
This is version 160 of the entry and version 1 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 12
    Human chromosome 12: 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

External Data

Dasty 3

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 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.