P24592 (IBP6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Gene names

Name:	IGFBP6
Synonyms:	IBP6

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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. 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. Ref.10
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 Reference proteome
Gene Ontology (GO)
Biological_process	cellular protein metabolic process Traceable author statement. Source: Reactome negative regulation of cell proliferation Traceable author statement PubMed 7539002. Source: ProtInc regulation of cell growth Inferred from electronic annotation. Source: InterPro signal transduction Non-traceable author statement Ref.2. Source: ProtInc
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: Compara extracellular region Traceable author statement. Source: Reactome extracellular space Inferred from electronic annotation. Source: Compara
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...) Ref.10 Ref.12

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. Ref.3
Corresponds to variant rs9658616 [ dbSNP | Ensembl ].

VAR_018932

Natural variant

134

1

R → L.
Corresponds to variant rs34995393 [ dbSNP | Ensembl ].

VAR_049565

Natural variant

217

1

R → Q. Ref.3
Corresponds to variant rs6413498 [ dbSNP | Ensembl ].

VAR_018933

Natural variant

236

1

T → P.
Corresponds to variant rs1053134 [ dbSNP | Ensembl ].

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 [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] [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, MASS SPECTROMETRY. Tissue: Cerebrospinal fluid.
+	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. NM_002178.2.

UniGene

Hs.274313.

3D structure databases

PDBe
RCSB PDB
PDBj

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

DisProt

DP00211.

ProteinModelPortal

P24592.

ModBase

Search...

Protein-protein interaction databases

IntAct

P24592. 1 interaction.

MINT

MINT-2859943.

STRING

9606.ENSP00000301464.

Protein family/group databases

MEROPS

I31.952.

Polymorphism databases

DMDM

124068.

Proteomic databases

PaxDb

P24592.

PeptideAtlas

P24592.

PRIDE

P24592.

Protocols and materials databases

DNASU

3489.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000301464; ENSP00000301464; ENSG00000167779.

GeneID

3489.

KEGG

hsa:3489.

UCSC

uc001sbu.1. human.

Organism-specific databases

CTD

3489.

GeneCards

GC12P053491.

HGNC

HGNC:5475. IGFBP6.

HPA

HPA008005.

MIM

146735. gene.

neXtProt

NX_P24592.

PharmGKB

PA29708.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG47794.

HOGENOM

HOG000253012.

HOVERGEN

HBG002631.

InParanoid

P24592.

OMA

PNPGGVQ.

OrthoDB

EOG4W0XF4.

PhylomeDB

P24592.

Enzyme and pathway databases

Reactome

REACT_116125. Disease.

Gene expression databases

ArrayExpress

P24592.

Bgee

P24592.

CleanEx

HS_IGFBP6.

Genevestigator

P24592.

GermOnline

ENSG00000167779. Homo sapiens.

Family and domain databases

Gene3D

4.10.40.20. 1 hit.
4.10.800.10. 1 hit.

InterPro

IPR009030. Growth_fac_rcpt_N_dom.
IPR022326. IGFBP-6.
IPR000867. IGFBP-like.
IPR009168. IGFBP1-6.
IPR022321. IGFBP_1-6_chordata.
IPR000716. Thyroglobulin_1.
[Graphical view]

PANTHER

PTHR11551. PTHR11551. 1 hit.

Pfam

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

PRINTS

PR01976. IGFBPFAMILY.
PR01982. IGFBPFAMILY6.

SMART

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

SUPFAM

SSF57184. Grow_fac_recept. 1 hit.
SSF57610. Thyroglobulin_1. 1 hit.

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

BindingDB

P24592.

ChEMBL

CHEMBL2139.

EvolutionaryTrace

P24592.

GenomeRNAi

3489.

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:	May 29, 2013
This is version 140 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.