P08833 (IBP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Insulin-like growth factor-binding protein 1
Short name=IBP-1
Short name=IGF-binding protein 1
Short name=IGFBP-1

Alternative name(s):
Placental protein 12
Short name=PP12

Gene names

Name:	IGFBP1
Synonyms:	IBP1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	259 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. Promotes cell migration. Ref.20
Subunit structure	Binds equally well IGF1 and IGF2.
Subcellular location	Secreted.
Post-translational modification	Phosphorylated; probably by casein kinase II. Phosphorylation alters the affinity of the protein for IGFs. In amniotic fluid, the unmodified protein is the most abundant form, while mono-, bi-, tri- and tetraphosphorylated forms are present in decreasing amounts. The phosphorylation state may influence the propensity to proteolysis. Ref.14 Ref.18 Ref.20
Sequence similarities	Contains 1 IGFBP N-terminal domain. Contains 1 thyroglobulin type-1 domain.
Sequence caution	The sequence AAA52540.1 differs from that shown. Reason: Frameshift at positions 55 and 71.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Ligand	Growth factor binding
PTM	Disulfide bond Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Cellular component	extracellular space Traceable author statement. Source: ProtInc
Molecular function	insulin-like growth factor binding 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 – 25

25

Ref.14 Ref.15 Ref.16

Chain

26 – 259

234

Insulin-like growth factor-binding protein 1

PRO_0000014365

Regions

Domain

26 – 107

82

IGFBP N-terminal

Domain

173 – 251

79

Thyroglobulin type-1

Motif

246 – 248

3

Cell attachment site

Amino acid modifications

Modified residue

120

1

Phosphoserine Ref.14

Modified residue

123

1

Phosphoserine Ref.14

Modified residue

126

1

Phosphoserine Ref.14 Ref.18

Modified residue

144

1

Phosphoserine Ref.14 Ref.18

Modified residue

194

1

Phosphoserine Ref.14 Ref.18

Disulfide bond

71 ↔ 84

Ref.19 Ref.20 Ref.21

Disulfide bond

78 ↔ 104

Ref.19 Ref.20 Ref.21

Disulfide bond

176 ↔ 206

Ref.19 Ref.20 Ref.21

Disulfide bond

217 ↔ 228

Ref.19 Ref.20 Ref.21

Disulfide bond

230 ↔ 251

Ref.19 Ref.20 Ref.21

Natural variations

Natural variant

114

1

H → D.
Corresponds to variant rs41258845 [ dbSNP | Ensembl ].

VAR_049564

Natural variant

183

1

V → I. Ref.10
Corresponds to variant rs1065782 [ dbSNP | Ensembl ].

VAR_011905

Natural variant

253

1

I → M. Ref.10 Ref.13
Corresponds to variant rs4619 [ dbSNP | Ensembl ].

VAR_003821

Experimental info

Sequence conflict

213

1

H → Q in AAA52540. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

259

Helix Strand Turn

Details...

Helix

175 – 193

19

Beta strand

199 – 201

3

Beta strand

210 – 212

3

Beta strand

214 – 217

4

Beta strand

222 – 224

3

Beta strand

228 – 231

4

Turn

233 – 235

3

Beta strand

245 – 247

3

Sequences

	Sequence		Length	Mass (Da)
	P08833 [UniParc]. Last modified November 1, 1988. Version 1. Checksum: 8AA75AF7DC966012	FASTA	259	27,904
	10 20 30 40 50 60 MSEVPVARVW LVLLLLTVQV GVTAGAPWQC APCSAEKLAL CPPVSASCSE VTRSAGCGCC 70 80 90 100 110 120 PMCALPLGAA CGVATARCAR GLSCRALPGE QQPLHALTRG QGACVQESDA SAPHAAEAGS 130 140 150 160 170 180 PESPESTEIT EEELLDNFHL MAPSEEDHSI LWDAISTYDG SKALHVTNIK KWKEPCRIEL 190 200 210 220 230 240 YRVVESLAKA QETSGEEISK FYLPNCNKNG FYHSRQCETS MDGEAGLCWC VYPWNGKRIP 250 GSPEIRGDPN CQIYFNVQN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of a cDNA encoding the low molecular weight insulin-like growth factor binding protein (IBP-1)." Brinkman A., Groffen C., Kortleve D.J., Geurts A., Drop S.L.S. EMBO J. 7:2417-2423(1988) [PubMed: 2461294] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[2]	"Cloning, characterization, and expression of a human insulin-like growth factor binding protein." Brewer M.T., Stetler G.L., Squires C.H., Thompson R.C., Busby W.H. Jr., Clemmons D.R. Biochem. Biophys. Res. Commun. 152:1289-1297(1988) [PubMed: 2454104] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Decidua.
[3]	"Cloning of cDNA encoding human placental protein 12 (PP12): binding protein for IGF I and somatomedin." Grundmann U., Nerlich C., Bohn H., Rein T. Nucleic Acids Res. 16:8711-8711(1988) [PubMed: 3419931] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[4]	"Primary structure of human insulin-like growth factor-binding protein/placental protein 12 and tissue-specific expression of its mRNA." Julkunen M., Koistinen R., Aalto-Setala K., Seppala M., Janne O.A., Kontula K. FEBS Lett. 236:295-302(1988) [PubMed: 2457513] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Decidua.
[5]	"Insulin-like growth factor (IGF) binding protein complementary deoxyribonucleic acid from human HEP G2 hepatoma cells: predicted protein sequence suggests an IGF binding domain different from those of the IGF-I and IGF-II receptors." Lee Y.-L., Hintz R.L., James P.M., Lee P.D.K., Shively J.E., Powell D.R. Mol. Endocrinol. 2:404-411(1988) [PubMed: 2458522] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]	"Structure of the human chromosomal gene for the 25 kilodalton insulin-like growth factor binding protein." Cubbage M.L., Suwanichkul A., Powell D.R. Mol. Endocrinol. 3:846-851(1989) [PubMed: 2474129] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]	"Organization of the gene encoding the insulin-like growth factor binding protein IBP-1." Brinkman A., Groffen C.A., Kortleve D.J., Drop S.L. Biochem. Biophys. Res. Commun. 157:898-907(1988) [PubMed: 2849945] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[8]	"Contiguous localization of the genes encoding human insulin-like growth factor binding proteins 1 (IGBP1) and 3 (IGBP3) on chromosome 7." Ehrenborg E., Larsson C., Stern I., Janson M., Powell D.R., Luthman H. Genomics 12:497-502(1992) [PubMed: 1373120] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Liver.
[9]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[10]	NIEHS SNPs program Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ILE-183 AND MET-253.
[11]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed: 12690205] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[12]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[13]	"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], VARIANT MET-253. Tissue: Skin.
[14]	"Identification of the amniotic fluid insulin-like growth factor binding protein-1 phosphorylation sites and propensity to proteolysis of the isoforms." Dolcini L., Sala A., Campagnoli M., Labo S., Valli M., Visai L., Minchiotti L., Monaco H.L., Galliano M. FEBS J. 276:6033-6046(2009) [PubMed: 19765076] [Abstract] Cited for: PROTEIN SEQUENCE OF 26-53; 95-152 AND 182-208, CLEAVAGE OF INITIATOR METHIONINE, PHOSPHORYLATION AT SER-120; SER-123; SER-126; SER-144 AND SER-194, MASS SPECTROMETRY. Tissue: Amniotic fluid.
[15]	"Human insulin-like growth-factor-binding protein. Low-molecular-mass form: protein sequence and cDNA cloning." Luthman H., Soederling-Barros J., Persson B., Engberg C., Stern I., Lake M., Franzen S.A., Israelsson M., Raden B., Lindgren B., Hjelmqvist L., Enerbaeck S., Carlsson P., Bjursell G., Povoa G., Hall K., Joernvall H. Eur. J. Biochem. 180:259-265(1989) [PubMed: 2466665] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 141-259, PROTEIN SEQUENCE OF 26-259. Tissue: Amniotic fluid.
[16]	"Purification of a 31,000-dalton insulin-like growth factor binding protein from human amniotic fluid. Isolation of two forms with different biologic actions." Busby W.H. Jr., Klapper D.G., Clemmons D.R. J. Biol. Chem. 263:14203-14210(1988) [PubMed: 2971653] [Abstract] Cited for: PROTEIN SEQUENCE OF 26-53.
[17]	"Site-directed mutagenesis of the N-terminal region of IGF binding protein 1; analysis of IGF binding capability." Brinkman A., Kortlrve D.J., Schuller A.G.P., Zwarthoff E.C., Drop S.L.S. FEBS Lett. 291:264-268(1991) [PubMed: 1718783] [Abstract] Cited for: MUTAGENESIS.
[18]	"Identification of the sites of phosphorylation in insulin-like growth factor binding protein-1. Regulation of its affinity by phosphorylation of serine 101." Jones J.I., Busby W.H. Jr., Wright G., Smith C.E., Kimack N.M., Clemmons D.R. J. Biol. Chem. 268:1125-1131(1993) [PubMed: 7678248] [Abstract] Cited for: PHOSPHORYLATION AT SER-126; SER-144 AND SER-194, PARTIAL PROTEIN SEQUENCE.
[19]	"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.
[20]	"Structure and properties of the C-terminal domain of insulin-like growth factor-binding protein-1 isolated from human amniotic fluid." Sala A., Capaldi S., Campagnoli M., Faggion B., Labo S., Perduca M., Romano A., Carrizo M.E., Valli M., Visai L., Minchiotti L., Galliano M., Monaco H.L. J. Biol. Chem. 280:29812-29819(2005) [PubMed: 15972819] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 172-251, PARTIAL PROTEIN SEQUENCE, FUNCTION, PHOSPHORYLATION, DISULFIDE BONDS.
[21]	"Structural basis for the inhibition of insulin-like growth factors by insulin-like growth factor-binding proteins." Sitar T., Popowicz G.M., Siwanowicz I., Huber R., Holak T.A. Proc. Natl. Acad. Sci. U.S.A. 103:13028-13033(2006) [PubMed: 16924115] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 166-259 IN COMPLEX WITH IGFBP4 AND IGF1, DISULFIDE BONDS.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Y00856 mRNA. Translation: CAA68770.1.
M20841 mRNA. Translation: AAA52540.1. Frameshift.
X12385 mRNA. Translation: CAA30942.1.
X13405 mRNA. Translation: CAA31771.1.
M31145 mRNA. Translation: AAA52542.1.
M59316 Genomic DNA. Translation: AAA52783.1.
M23595 , M23592, M23593, M23594 Genomic DNA. Translation: AAA52785.1.
M74587 Genomic DNA. Translation: AAA52784.1.
BT019685 mRNA. Translation: AAV38491.1.
AY434089 Genomic DNA. Translation: AAQ96599.1.
CH236958 Genomic DNA. Translation: EAL23800.1.
CH471128 Genomic DNA. Translation: EAW61030.1.
CH471128 Genomic DNA. Translation: EAW61031.1.
BC035263 mRNA. Translation: AAH35263.2.
X15002 mRNA. Translation: CAA33110.1.

IPI

IPI00031086.

PIR

IOHU1. A31867.

RefSeq

NP_000587.1. NM_000596.2.

UniGene

Hs.642938.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ZT3	X-ray	1.80	A	172-251	[»]
1ZT5	X-ray	1.82	A	172-251	[»]
2DSQ	X-ray	2.80	G/H	166-259	[»]

ProteinModelPortal

P08833.

SMR

P08833. Positions 25-115, 172-251.

ModBase

Search...

Protein-protein interaction databases

STRING

P08833.

Protein family/group databases

MEROPS

I31.951.

PTM databases

PhosphoSite

P08833.

Polymorphism databases

DMDM

124055.

2D gel databases

Siena-2DPAGE

P08833.

Proteomic databases

PeptideAtlas

P08833.

PRIDE

P08833.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000275525; ENSP00000275525; ENSG00000146678.

GeneID

3484.

KEGG

hsa:3484.

UCSC

uc003tnp.1. human.

Organism-specific databases

CTD

3484.

GeneCards

GC07P045894.

H-InvDB

HIX0033527.

HGNC

HGNC:5469. IGFBP1.

HPA

CAB004445.

MIM

146730. gene.

neXtProt

NX_P08833.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HBG443735.

HOVERGEN

HBG002631.

InParanoid

P08833.

OMA

RCARGLS.

OrthoDB

EOG4W9J4F.

PhylomeDB

P08833.

Enzyme and pathway databases

Pathway_Interaction_DB

hnf3bpathway. FOXA2 and FOXA3 transcription factor networks.
hif1_tfpathway. HIF-1-alpha transcription factor network.

Reactome

REACT_15380. Diabetes pathways.

Gene expression databases

ArrayExpress

P08833.

Bgee

P08833.

CleanEx

HS_IGFBP1.

Genevestigator

P08833.

GermOnline

ENSG00000146678. Homo sapiens.

Family and domain databases

InterPro

IPR009030. Growth_fac_rcpt.
IPR000867. IGFBP-like.
IPR022322. IGFBP1.
IPR009168. IGFBP1-6.
IPR022321. IGFBP_1-6_chordata.
IPR017891. Insulin_GF-bd_Cys-rich_CS.
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]

PRINTS

PR01976. IGFBPFAMILY.
PR01977. IGFBPFAMILY1.

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. 1 hit.
PS51323. IGFBP_N_2. 1 hit.
PS00484. THYROGLOBULIN_1_1. 1 hit.
PS51162. THYROGLOBULIN_1_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

13700.

PMAP-CutDB

P08833.

SOURCE

Search...

Entry information

Entry name

IBP1_HUMAN

Accession

Primary (citable) accession number: P08833
Secondary accession number(s): A4D2F4, D3DVL9, Q8IYP5

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1988
Last sequence update:	November 1, 1988
Last modified:	January 25, 2012
This is version 142 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.