P18065 (IBP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Insulin-like growth factor-binding protein 2
Short name=IBP-2
Short name=IGF-binding protein 2
Short name=IGFBP-2

Gene names

Name:	IGFBP2
Synonyms:	BP2, IBP2

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	325 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	Inhibits IGF-mediated growth and developmental rates. 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. Ref.11
Subunit structure	Binds IGF2 more than IGF1.
Subcellular location	Secreted.
Domain	The C-terminus is required for IGF-binding and growth inhibition. Ref.11
Post-translational modification	O-glycosylated. Ref.10
Sequence similarities	Contains 1 IGFBP N-terminal domain. Contains 1 thyroglobulin type-1 domain.

Ontologies

Keywords
Biological process	Growth regulation
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	aging Inferred from electronic annotation. Source: Compara cellular protein metabolic process Traceable author statement. Source: Reactome cellular response to hormone stimulus Inferred from electronic annotation. Source: Compara female pregnancy Inferred from electronic annotation. Source: Compara positive regulation of activated T cell proliferation Inferred from direct assay PubMed 15694994. Source: BHF-UCL regulation of cell growth Inferred from electronic annotation. Source: InterPro regulation of insulin-like growth factor receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB response to drug Inferred from electronic annotation. Source: Compara response to estradiol stimulus Inferred from electronic annotation. Source: Compara response to glucocorticoid stimulus Inferred from electronic annotation. Source: Compara response to lithium ion Inferred from electronic annotation. Source: Compara response to mechanical stimulus Inferred from electronic annotation. Source: Compara response to nutrient Inferred from electronic annotation. Source: Compara response to retinoic acid Inferred from electronic annotation. Source: Compara response to stress Inferred from electronic annotation. Source: Compara signal transduction Inferred from electronic annotation. Source: Compara
Cellular_component	apical plasma membrane Inferred from electronic annotation. Source: Compara cytoplasmic vesicle Inferred from electronic annotation. Source: Compara extracellular space Inferred from direct assay PubMed 15694994. Source: BHF-UCL
Molecular_function	insulin-like growth factor I binding Inferred from direct assay Ref.11. Source: UniProtKB insulin-like growth factor II binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
INO80B	Q9C086	4	EBI-2504392,EBI-715611

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 35

35

Chain

36 – 325

290

Insulin-like growth factor-binding protein 2

PRO_0000014370

Regions

Domain

38 – 134

97

IGFBP N-terminal

Domain

224 – 306

83

Thyroglobulin type-1

Motif

301 – 303

3

Cell attachment site

Amino acid modifications

Disulfide bond

227 ↔ 261

Ref.12

Disulfide bond

272 ↔ 283

Ref.12

Disulfide bond

285 ↔ 306

Ref.12

Natural variations

Natural variant

137

1

A → D. Ref.7
Corresponds to variant rs9341096 [ dbSNP | Ensembl ].

VAR_018871

Experimental info

Mutagenesis

216 – 219

4

KKLR → NNLA: Does not disrupt growth-inhibiting activity. Ref.11

Mutagenesis

303

1

D → E: Does not disrupt growth-inhibiting activity. Ref.11

Sequence conflict

15

1

P → PPLL in CAA34373. Ref.1

Sequence conflict

15

1

P → PPLL in AAA36048. Ref.3

Sequence conflict

15

1

P → PPLL in AAA03246. Ref.4

Sequence conflict

15

1

P → PPLL in AAB22308. Ref.5

Sequence conflict

15

1

P → PPLL in AAQ87876. Ref.7

Sequence conflict

15

1

P → PPLL in AAH04312. Ref.9

Sequence conflict

15

1

P → PPLL in AAH09902. Ref.9

Sequence conflict

15

1

P → PPLL in AAH12769. Ref.9

Sequence conflict

15

1

P → PPLL in AAH71967. Ref.9

Sequence conflict

57

1

P → R in AAA36048. Ref.3

Sequence conflict

317

1

R → C in CAA34373. Ref.1

Sequence conflict

320

1

H → D in AAA36048. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

325

Helix Strand Turn

Details...

Helix

226 – 240

15

Beta strand

247 – 249

3

Beta strand

269 – 276

8

Turn

277 – 279

3

Beta strand

282 – 285

4

Sequences

	Sequence		Length	Mass (Da)
	P18065 [UniParc]. Last modified March 2, 2010. Version 2. Checksum: 9E1436DBCCC6EA2A	FASTA	325	34,814
	10 20 30 40 50 60 MLPRVGCPAL PLPPPPLLPL LLLLLGASGG GGGARAEVLF RCPPCTPERL AACGPPPVAP 70 80 90 100 110 120 PAAVAAVAGG ARMPCAELVR EPGCGCCSVC ARLEGEACGV YTPRCGQGLR CYPHPGSELP 130 140 150 160 170 180 LQALVMGEGT CEKRRDAEYG ASPEQVADNG DDHSEGGLVE NHVDSTMNML GGGGSAGRKP 190 200 210 220 230 240 LKSGMKELAV FREKVTEQHR QMGKGGKHHL GLEEPKKLRP PPARTPCQQE LDQVLERIST 250 260 270 280 290 300 MRLPDERGPL EHLYSLHIPN CDKHGLYNLK QCKMSLNGQR GECWCVNPNT GKLIQGAPTI 310 320 RGDPECHLFY NEQQEARGVH TQRMQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning, sequence analysis and expression of a cDNA encoding a novel insulin-like growth factor binding protein (IGFBP-2)." Binkert C., Landwehr J., Mary J.L., Schwander J., Heinrich G. EMBO J. 8:2497-2502(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fetal liver.
[2]	"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: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 37-74.
[3]	"Structure and localization of the human insulin-like growth factor-binding protein 2 gene." Ehrenborg E., Vilhelmsdotter S., Bajalica S., Larsson C., Sterm I., Koch J., Brondum-Nielsen K., Luthman H. Biochem. Biophys. Res. Commun. 176:1250-1255(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Placenta.
[4]	"Sequence analysis, expression and chromosomal localization of a gene, isolated from a subtracted human retina cDNA library, that encodes an insulin-like growth factor binding protein (IGFBP2)." Agarwal N., Hsieh C.L., Sills D., Swaroop M., Desai B., Francke U., Swaroop A. Exp. Eye Res. 52:549-561(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Retina.
[5]	"Structure of the human insulin-like growth factor binding protein-2 gene." Binkert C., Margot J.B., Landwehr J., Heinrich G., Schwander J. Mol. Endocrinol. 6:826-836(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Placenta.
[6]	"Full-length cDNA libraries and normalization." Li W.B., Gruber C., Jessee J., Polayes D. Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[7]	NIEHS SNPs program Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ASP-137.
[8]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"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: Brain, Ovary and Uterus.
[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 40-58, INTERACTION WITH IGF2, GLYCOSYLATION. Tissue: Cerebrospinal fluid.
[11]	"Duplication of the IGFBP-2 gene in teleost fish: protein structure and functionality conservation and gene expression divergence." Zhou J., Li W., Kamei H., Duan C. PLoS ONE 3:E3926-E3926(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, IGF1-BINDING, DOMAIN, MUTAGENESIS OF 216-LYS--ARG-219 AND ASP-303.
[12]	"Structure, dynamics and heparin binding of the C-terminal domain of insulin-like growth factor-binding protein-2 (IGFBP-2)." Kuang Z., Yao S., Keizer D.W., Wang C.C., Bach L.A., Forbes B.E., Wallace J.C., Norton R.S. J. Mol. Biol. 364:690-704(2006) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 220-325, DISULFIDE BONDS.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X16302 mRNA. Translation: CAA34373.1.
M69241 , M69237, M69239, M69240 Genomic DNA. Translation: AAA36048.1.
M35410 mRNA. Translation: AAA03246.1.
S37730 , S37712, S37722, S37726 Genomic DNA. Translation: AAB22308.1.
CR610845 mRNA. No translation available.
AY398667 Genomic DNA. Translation: AAQ87876.1.
AC073321 Genomic DNA. No translation available.
AC007563 Genomic DNA. No translation available.
BC004312 mRNA. Translation: AAH04312.1.
BC009902 mRNA. Translation: AAH09902.1.
BC012769 mRNA. Translation: AAH12769.1.
BC071967 mRNA. Translation: AAH71967.1.

IPI

IPI00297284.

PIR

A41927.

RefSeq

NP_000588.2. NM_000597.2.

UniGene

Hs.438102.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2H7T	NMR	-	A	220-325	[»]

ProteinModelPortal

P18065.

SMR

P18065. Positions 42-138, 220-325.

ModBase

Search...

Protein-protein interaction databases

IntAct

P18065. 3 interactions.

STRING

9606.ENSP00000233809.

Protein family/group databases

MEROPS

I31.953.

PTM databases

PhosphoSite

P18065.

Polymorphism databases

DMDM

290457647.

Proteomic databases

PaxDb

P18065.

PRIDE

P18065.

Protocols and materials databases

DNASU

3485.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000233809; ENSP00000233809; ENSG00000115457.

GeneID

3485.

KEGG

hsa:3485.

UCSC

uc010zju.2. human.

Organism-specific databases

CTD

3485.

GeneCards

GC02P217497.

HGNC

HGNC:5471. IGFBP2.

MIM

146731. gene.

neXtProt

NX_P18065.

PharmGKB

PA29704.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG47500.

HOGENOM

HOG000253012.

HOVERGEN

HBG002631.

InParanoid

P18065.

OMA

GAGTCEK.

OrthoDB

EOG4TTGJD.

PhylomeDB

P18065.

Enzyme and pathway databases

Reactome

REACT_116125. Disease.

Gene expression databases

ArrayExpress

P18065.

Bgee

P18065.

CleanEx

HS_IGFBP2.

Genevestigator

P18065.

GermOnline

ENSG00000115457. 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.
IPR012210. IGFBP-2.
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:SF5. PTHR11551:SF5. 1 hit.

Pfam

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

PRINTS

PR01976. IGFBPFAMILY.
PR01978. IGFBPFAMILY2.

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

ChEMBL

CHEMBL3088.

EvolutionaryTrace

P18065.

GenomeRNAi

3485.

NextBio

13704.

PMAP-CutDB

P18065.

SOURCE

Search...

Entry information

Entry name

IBP2_HUMAN

Accession

Primary (citable) accession number: P18065
Secondary accession number(s): Q14619, Q9UCL3

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	March 2, 2010
Last modified:	May 29, 2013
This is version 144 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.