P17936 (IBP3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Insulin-like growth factor-binding protein 3
Short name=IBP-3
Short name=IGF-binding protein 3
Short name=IGFBP-3

Gene names

Name:	IGFBP3
Synonyms:	IBP3

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	291 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. Also exhibits IGF-independent antiproliferative and apoptotic effects mediated by its receptor TMEM219/IGFBP-3R. Ref.16
Subunit structure	Interacts with XLKD1 By similarity. Binds IGF2 more than IGF1. Forms a ternary complex of about 140 to 150 kDa with IGF1 or IGF2 and a 85 kDa glycoprotein (ALS). Interacts with HN. Interacts with TMEM219. Ref.10 Ref.12 Ref.16
Subcellular location	Secreted Ref.16.
Tissue specificity	Expressed by most tissues. Present in plasma.
Developmental stage	IGFBP3 levels are higher during extrauterine life and peak during puberty.
Induction	Up-regulated in the presence of IGF1, insulin and other growth-stimulating factors such as growth hormone, EGF and phorbol esters.
Domain	The thyroglobulin type-1 domain mediates interaction with HN.
Post-translational modification	Phosphorylation sites are present in the extracellular medium.
Sequence similarities	Contains 1 IGFBP N-terminal domain. Contains 1 thyroglobulin type-1 domain.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Ligand	Growth factor binding
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of protein phosphorylation Inferred from direct assay PubMed 17591901. Source: MGI negative regulation of signal transduction Non-traceable author statement PubMed 11940579. Source: UniProtKB negative regulation of smooth muscle cell migration Inferred from direct assay PubMed 10766744. Source: BHF-UCL negative regulation of smooth muscle cell proliferation Inferred from direct assay PubMed 10766744. Source: BHF-UCL positive regulation of MAPK cascade Inferred from electronic annotation. Source: Compara positive regulation of apoptotic process Inferred from mutant phenotype PubMed 11971816. Source: UniProtKB positive regulation of insulin-like growth factor receptor signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of myoblast differentiation Inferred from direct assay PubMed 12599210. Source: UniProtKB protein phosphorylation Inferred from direct assay PubMed 17434920. Source: MGI regulation of cell growth Inferred from electronic annotation. Source: Compara regulation of glucose metabolic process Inferred from electronic annotation. Source: Compara type B pancreatic cell proliferation Inferred from electronic annotation. Source: Compara
Cellular_component	insulin-like growth factor binding protein complex Inferred by curator PubMed 10766744. Source: BHF-UCL nucleus Inferred from direct assay PubMed 17434920. Source: MGI
Molecular_function	insulin-like growth factor binding Non-traceable author statement PubMed 12599210. Source: UniProtKB metal ion binding Non-traceable author statement PubMed 14576163. Source: UniProtKB protein tyrosine phosphatase activator activity Inferred from direct assay PubMed 11940579. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 27	27	Ref.9 Ref.10 Ref.11
	Chain	28 – 291	264	Insulin-like growth factor-binding protein 3		PRO_0000014378
Regions
	Domain	36 – 117	82	IGFBP N-terminal
	Domain	210 – 285	76	Thyroglobulin type-1
	Region	28 – 134	107	IGF-binding Potential
	Compositional bias	138 – 161	24	Ser/Thr-rich
	Compositional bias	192 – 208	17	Ser/Thr-rich
Amino acid modifications
	Glycosylation	116	1	N-linked (GlcNAc...)
	Glycosylation	136	1	N-linked (GlcNAc...) Ref.13 Ref.14 Ref.15
	Glycosylation	199	1	N-linked (GlcNAc...) Ref.14
	Disulfide bond	213 ↔ 240		By similarity
	Disulfide bond	251 ↔ 262		By similarity
	Disulfide bond	264 ↔ 285		By similarity
Natural variations
	Natural variant	7	1	T → M in a colorectal cancer sample; somatic mutation. Ref.17		VAR_036279
	Natural variant	32	1	A → G. Ref.1 Ref.2 Ref.3 Ref.10 Corresponds to variant rs2854746 [ dbSNP | Ensembl ].		VAR_025262
	Natural variant	56	1	A → T. Ref.4 Corresponds to variant rs34257987 [ dbSNP | Ensembl ].		VAR_025263
	Natural variant	158	1	H → P. Corresponds to variant rs9282734 [ dbSNP | Ensembl ].		VAR_021974
	Natural variant	234	1	G → S. Ref.4 Corresponds to variant rs35712717 [ dbSNP | Ensembl ].		VAR_025264
	Natural variant	252	1	R → C in a colorectal cancer sample; somatic mutation. Ref.17		VAR_036280
Experimental info
	Sequence conflict	135	1	G → GEPPAPG in ABB96247. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P17936 [UniParc]. Last modified March 6, 2007. Version 2. Checksum: A9682065AB266586	FASTA	291	31,674
	10 20 30 40 50 60 MQRARPTLWA AALTLLVLLR GPPVARAGAS SAGLGPVVRC EPCDARALAQ CAPPPAVCAE 70 80 90 100 110 120 LVREPGCGCC LTCALSEGQP CGIYTERCGS GLRCQPSPDE ARPLQALLDG RGLCVNASAV 130 140 150 160 170 180 SRLRAYLLPA PPAPGNASES EEDRSAGSVE SPSVSSTHRV SDPKFHPLHS KIIIIKKGHA 190 200 210 220 230 240 KDSQRYKVDY ESQSTDTQNF SSESKRETEY GPCRREMEDT LNHLKFLNVL SPRGVHIPNC 250 260 270 280 290 DKKGFYKKKQ CRPSKGRKRG FCWCVDKYGQ PLPGYTTKGK EDVHCYSMQS K

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression of the growth hormone-dependent insulin-like growth factor-binding protein." Wood W.I., Cachianes G., Henzel W.J., Winslow G.A., Spencer S.A., Hellmiss R., Martin J.L., Baxter R.C. Mol. Endocrinol. 2:1176-1185(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLY-32.
[2]	"Insulin-like growth factor binding protein-3. Organization of the human chromosomal gene and demonstration of promoter activity." Cubbage M.L., Suwanichkul A., Powell D.R. J. Biol. Chem. 265:12642-12649(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLY-32.
[3]	"Analysis of the primary structure of insulin-like growth factor binding protein-3 cDNA from Werner syndrome fibroblasts." Thweatt R., Fleischmann R., Goldstein S. DNA Seq. 4:43-46(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLY-32. Tissue: Skin.
[4]	NIEHS SNPs program Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-56 AND SER-234.
[5]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	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].
[8]	"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: Kidney and Spleen.
[9]	"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 28-65.
[10]	"Purification from human cerebrospinal fluid of insulin-like growth factor binding proteins (IGFBPs). Isolation of IGFBP-2, an altered form of IGFBP-3 and a new IGFBP species." Roghani M., Segovia B., Whitechurch O., Binoux M. Growth Regul. 1:125-130(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 28-45, INTERACTION WITH IGF2, VARIANT GLY-32. Tissue: Cerebrospinal fluid.
[11]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 28-42.
[12]	"Interaction between the Alzheimer's survival peptide humanin and insulin-like growth factor-binding protein 3 regulates cell survival and apoptosis." Ikonen M., Liu B., Hashimoto Y., Ma L., Lee K.W., Niikura T., Nishimoto I., Cohen P. Proc. Natl. Acad. Sci. U.S.A. 100:13042-13047(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HN.
[13]	"Screening for N-glycosylated proteins by liquid chromatography mass spectrometry." Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R. Proteomics 4:454-465(2004) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-136, MASS SPECTROMETRY. Tissue: Plasma.
[14]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-136 AND ASN-199, MASS SPECTROMETRY. Tissue: Plasma.
[15]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-136, MASS SPECTROMETRY. Tissue: Liver.
[16]	"Identification of a novel cell death receptor mediating IGFBP-3-induced anti-tumor effects in breast and prostate cancer." Ingermann A.R., Yang Y.F., Han J., Mikami A., Garza A.E., Mohanraj L., Fan L., Idowu M., Ware J.L., Kim H.S., Lee D.Y., Oh Y. J. Biol. Chem. 285:30233-30246(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH TMEM219.
[17]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] MET-7 AND CYS-252.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

SHMPD

The Singapore human mutation and polymorphism database

Cross-references

Sequence databases
EMBL GenBank DDBJ	M31159 mRNA. Translation: AAA52541.1. M35878 Genomic DNA. Translation: AAA52706.1. X64875 mRNA. Translation: CAA46087.1. DQ301819 Genomic DNA. Translation: ABB96247.1. AC091524 Genomic DNA. Translation: AAS07554.1. CH236958 Genomic DNA. Translation: EAL23801.1. CH471128 Genomic DNA. Translation: EAW61028.1. CH471128 Genomic DNA. Translation: EAW61029.1. BC000013 mRNA. Translation: AAH00013.1. BC018962 mRNA. Translation: AAH18962.1. BC064987 mRNA. Translation: AAH64987.1.
IPI	IPI00018305.
PIR	IOHU3. A36578.
RefSeq	NP_000589.2. NM_000598.4. NP_001013416.1. NM_001013398.1.
UniGene	Hs.450230.
3D structure databases
ProteinModelPortal	P17936.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-40786N.
IntAct	P17936. 4 interactions.
MINT	MINT-142445.
STRING	9606.ENSP00000370473.
Protein family/group databases
MEROPS	I31.952.
PTM databases
PhosphoSite	P17936.
Polymorphism databases
DMDM	146327827.
Proteomic databases
PaxDb	P17936.
PeptideAtlas	P17936.
PRIDE	P17936.
Protocols and materials databases
DNASU	3486.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000275521; ENSP00000275521; ENSG00000146674. ENST00000381083; ENSP00000370473; ENSG00000146674.
GeneID	3486.
KEGG	hsa:3486.
UCSC	uc003tnr.3. human.
Organism-specific databases
CTD	3486.
GeneCards	GC07M045918.
HGNC	HGNC:5472. IGFBP3.
HPA	CAB010360. HPA013357.
MIM	146732. gene.
neXtProt	NX_P17936.
PharmGKB	PA29705.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG38980.
HOGENOM	HOG000253012.
HOVERGEN	HBG002631.
KO	K10138.
OrthoDB	EOG46144F.
PhylomeDB	P17936.
Enzyme and pathway databases
Reactome	REACT_116125. Disease.
Gene expression databases
ArrayExpress	P17936.
Bgee	P17936.
CleanEx	HS_IGFBP3.
Genevestigator	P17936.
GermOnline	ENSG00000146674. Homo sapiens.
Family and domain databases
Gene3D	4.10.800.10. 1 hit.
InterPro	IPR009030. Growth_fac_rcpt. IPR012211. IGFBP-3. IPR000867. IGFBP-like. IPR009168. IGFBP1-6. IPR022321. IGFBP_1-6_chordata. IPR017891. Insulin_GF-bd_Cys-rich_CS. IPR000716. Thyroglobulin_1. [Graphical view]
PANTHER	PTHR11551. PTHR11551. 1 hit. PTHR11551:SF3. PTHR11551:SF3. 1 hit.
Pfam	PF00219. IGFBP. 1 hit. PF00086. Thyroglobulin_1. 1 hit. [Graphical view]
PRINTS	PR01976. IGFBPFAMILY. PR01979. IGFBPFAMILY3.
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
BindingDB	P17936.
ChEMBL	CHEMBL3997.
ChiTaRS	IGFBP3. human.
DrugBank	DB01277. Mecasermin.
GenomeRNAi	3486.
NextBio	13708.
PMAP-CutDB	P17936.
SOURCE	Search...

Entry information

Entry name

IBP3_HUMAN

Accession

Primary (citable) accession number: P17936
Secondary accession number(s): A4D2F5 , D3DVM0, Q2V509, Q6P1M6, Q9UCL4

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	March 6, 2007
Last modified:	May 1, 2013
This is version 157 of the entry and version 2 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.