Reviewed, UniProtKB/Swiss-Prot P24592 (IBP6_HUMAN)

Names and origin

Protein names

Recommended name:
    Insulin-like growth factor-binding protein 6
      Short name=IGF-binding protein 6
      Short name=IGFBP-6
      Short name=IBP-6

Gene names

Name:	IGFBP6
Synonyms:	IBP6

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	240 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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.
Subcellular location	Secreted.
Post-translational modification	O-linked glycans consist of hexose (probably Gal), N-acetylhexosamine (probably GalNAc) and sialic acid residues. Major glycoforms consist of 8-16 monosaccharides (by homology to IGFBP6 expressed recombinantly in CHO cells).
Sequence similarities	Contains 1 IGFBP N-terminal domain. Contains 1 thyroglobulin type-1 domain.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Ligand	Growth factor binding
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	negative regulation of cell proliferation Traceable author statement. Source: ProtInc regulation of cell growth Inferred from electronic annotation. Source: InterPro signal transduction Ref.2 Non-traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 27

27

Probable

Chain

28 – 240

213

Insulin-like growth factor-binding protein 6

PRO_0000014389

Regions

Domain

28 – 107

80

IGFBP N-terminal

Domain

160 – 234

75

Thyroglobulin type-1

Amino acid modifications

Glycosylation

126

1

O-linked (HexNAc...) By similarity

Glycosylation

144

1

O-linked (HexNAc...) By similarity

Glycosylation

145

1

O-linked (HexNAc...) By similarity

Glycosylation

146

1

O-linked (HexNAc...) By similarity

Glycosylation

152

1

O-linked (HexNAc...) By similarity

Disulfide bond

29 ↔ 32

Ref.11

Disulfide bond

40 ↔ 44

Ref.11

Disulfide bond

57 ↔ 63

Ref.11

Disulfide bond

71 ↔ 84

Ref.11

Disulfide bond

78 ↔ 104

Ref.11

Disulfide bond

163 ↔ 190

Ref.11

Disulfide bond

201 ↔ 212

Ref.11

Disulfide bond

214 ↔ 234

Ref.11

Natural variations

Natural variant

128

1

R → G: dbSNP rs9658616. Ref.3

VAR_018932

Natural variant

134

1

R → L: dbSNP rs34995393.

VAR_049565

Natural variant

217

1

R → L: dbSNP rs6413498.

VAR_020159

Natural variant

217

1

R → Q: dbSNP rs6413498. Ref.3

VAR_018933

Natural variant

236

1

T → P: dbSNP rs1053134.

VAR_011907

Experimental info

Sequence conflict

2

1

T → C in AAA88070. Ref.5

Sequence conflict

28 – 29

2

RC → AA AA sequence Ref.6

Sequence conflict

28 – 29

2

RC → LA AA sequence Ref.8

Sequence conflict

32

1

C → H AA sequence Ref.6

Sequence conflict

55 – 57

3

EGC → QGG AA sequence Ref.6

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

240

Helix Strand Turn

Details...

Helix

162 – 177

16

Turn

179 – 181

3

Beta strand

182 – 188

7

Beta strand

198 – 208

11

Beta strand

212 – 215

4

Turn

226 – 228

3

Turn

231 – 233

3

Beta strand

234 – 236

3

Sequences

	Sequence		Length	Mass (Da)
	P24592-1 [UniParc]. Last modified March 1, 1992. Version 1. Checksum: 285308231C025009	FASTA	240	25,322
	10 20 30 40 50 60 MTPHRLLPPL LLLLALLLAA SPGGALARCP GCGQGVQAGC PGGCVEEEDG GSPAEGCAEA 70 80 90 100 110 120 EGCLRREGQE CGVYTPNCAP GLQCHPPKDD EAPLRALLLG RGRCLPARAP AVAEENPKES 130 140 150 160 170 180 KPQAGTARPQ DVNRRDQQRN PGTSTTPSQP NSAGVQDTEM GPCRRHLDSV LQQLQTEVYR 190 200 210 220 230 240 GAQTLYVPNC DHRGFYRKRQ CRSSQGQRRG PCWCVDRMGK SLPGSPDGNG SSSCPTGSSG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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: 1709161] [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: 10087296] [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: 15489334] [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: 1719383] [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: 1697583] [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: 2551732] [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: 2154495] [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: 1850257] [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: 9572875] [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: 10329650] [Abstract] Cited for: DISULFIDE BONDS.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00029235.

PIR

A39842.
S05699.

RefSeq

NP_002169.1.

UniGene

Hs.274313

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1RMJ	NMR	-	A	161-240	[»]

SMR

P24592. Positions 25-69, 27-106, 67-109.

DisProt

DP00211.

ModBase

Search...

Protein-protein interaction databases

IntAct

P24592. 1 interaction.

STRING

P24592.

Protein family/group databases

MEROPS

I31.952.

Proteomic databases

PeptideAtlas

P24592.

PRIDE

P24592.

Genome annotation databases

Ensembl

ENST00000301464; ENSP00000301464; ENSG00000167779; Homo sapiens. [Genome view]

GeneID

3489.

KEGG

hsa:3489.

UCSC

uc001sbu.1. human.

Organism-specific databases

CTD

3489.

GeneCards

GC12P051777.

H-InvDB

HIX0010665.

HGNC

HGNC:5475. IGFBP6.

HPA

HPA008005.

MIM

146735. gene.

PharmGKB

PA29708.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG20502.

HOGENOM

HBG443735.

HOVERGEN

P24592.

InParanoid

P24592.

OMA

GCVEEED.

OrthoDB

EOG97Q0RN.

PhylomeDB

P24592.

Enzyme and pathway databases

Reactome

REACT_15380. Diabetes pathways.

Gene expression databases

ArrayExpress

P24592.

Bgee

P24592.

CleanEx

HS_IGFBP6.

Genevestigator

P24592.

GermOnline

ENSG00000167779. Homo sapiens.

Family and domain databases

InterPro

IPR009030. Growth_fac_rcpt.
IPR000867. IGFBP-like.
IPR009168. IGFBP1-6.
IPR000716. Thyroglobulin_1.
[Graphical view]

Gene3D

G3DSA:4.10.800.10. Thyroglobulin_1. 1 hit.

PANTHER

PTHR11551. IGFBP1-6. 1 hit.

Pfam

PF00219. IGFBP. 1 hit.
PF00086. Thyroglobulin_1. 1 hit.
[Graphical view]

SMART

SM00121. IB. 1 hit.
SM00211. TY. 1 hit.
[Graphical view]

PROSITE

PS00222. IGFBP_N_1. False negative.
PS51323. IGFBP_N_2. 1 hit.
PS00484. THYROGLOBULIN_1_1. 1 hit.
PS51162. THYROGLOBULIN_1_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

13722.

SOURCE

Search...

Entry information

Entry name

IBP6_HUMAN

Accession

Primary (citable) accession number: P24592
Secondary accession number(s): Q14492

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 1992
Last sequence update:	March 1, 1992
Last modified:	January 19, 2010
This is version 114 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.