P22692 (IBP4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Insulin-like growth factor-binding protein 4
Short name=IBP-4
Short name=IGF-binding protein 4
Short name=IGFBP-4

Gene names

Name:	IGFBP4
Synonyms:	IBP4

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	258 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.
Subunit structure	Binds IGF2 more than IGF1.
Subcellular location	Secreted.
Induction	By forskolin and N6,O2'dibutyryl adenosine 3',5'-cyclic monophosphate, but not by 1,9 dideoxyforskolin. Ref.11
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	DNA metabolic process Traceable author statement PubMed 1377672. Source: ProtInc cell proliferation Traceable author statement PubMed 1377672. Source: ProtInc cellular protein metabolic process Traceable author statement. Source: Reactome inflammatory response Inferred from electronic annotation. Source: Compara positive regulation of MAPK cascade Inferred from electronic annotation. Source: Compara positive regulation of insulin-like growth factor receptor signaling pathway Inferred from electronic annotation. Source: Compara regulation of cell growth Inferred from electronic annotation. Source: Compara regulation of glucose metabolic process Inferred from electronic annotation. Source: Compara signal transduction Traceable author statement PubMed 1377672. Source: ProtInc skeletal system development Traceable author statement PubMed 1377672. Source: ProtInc type B pancreatic cell proliferation Inferred from electronic annotation. Source: Compara
Cellular_component	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 – 21

21

Ref.3 Ref.10 Ref.11

Chain

22 – 258

237

Insulin-like growth factor-binding protein 4

PRO_0000014382

Regions

Domain

23 – 103

81

IGFBP N-terminal

Domain

171 – 249

79

Thyroglobulin type-1

Amino acid modifications

Glycosylation

125

1

N-linked (GlcNAc...) Potential Ref.3

Disulfide bond

27 ↔ 53

Ref.12 Ref.13

Disulfide bond

30 ↔ 55

Ref.12 Ref.13

Disulfide bond

38 ↔ 59

Ref.12 Ref.13

Disulfide bond

44 ↔ 56

Ref.12 Ref.13

Disulfide bond

67 ↔ 80

Ref.12 Ref.13

Disulfide bond

74 ↔ 100

Ref.12 Ref.13

Disulfide bond

131 ↔ 138

By similarity

Disulfide bond

174 ↔ 204

Ref.12 Ref.13

Disulfide bond

215 ↔ 226

Ref.12 Ref.13

Disulfide bond

228 ↔ 249

Ref.12 Ref.13

Natural variations

Natural variant

42

1

V → G.
Corresponds to variant rs599199 [ dbSNP | Ensembl ].

VAR_011906

Experimental info

Sequence conflict

51

1

P → A in M38177. Ref.2

Sequence conflict

51

1

P → A in AAA62670. Ref.4

Sequence conflict

51

1

P → A AA sequence Ref.10

Sequence conflict

160

1

G → E in AAV38694. Ref.6

Sequence conflict

198

1

I → F in M38177. Ref.2

Sequence conflict

198

1

I → F in AAA62670. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

258

Helix Strand Turn

Details...

Helix

32 – 36

5

Beta strand

45 – 49

5

Beta strand

56 – 59

4

Beta strand

69 – 71

3

Beta strand

78 – 81

4

Helix

89 – 94

6

Beta strand

98 – 102

5

Helix

103 – 110

8

Sequences

	Sequence		Length	Mass (Da)
	P22692 [UniParc]. Last modified March 1, 1992. Version 2. Checksum: 5E8F4638D99F0A94	FASTA	258	27,934
	10 20 30 40 50 60 MLPLCLVAAL LLAAGPGPSL GDEAIHCPPC SEEKLARCRP PVGCEELVRE PGCGCCATCA 70 80 90 100 110 120 LGLGMPCGVY TPRCGSGLRC YPPRGVEKPL HTLMHGQGVC MELAEIEAIQ ESLQPSDKDE 130 140 150 160 170 180 GDHPNNSFSP CSAHDRRCLQ KHFAKIRDRS TSGGKMKVNG APREDARPVP QGSCQSELHR 190 200 210 220 230 240 ALERLAASQS RTHEDLYIIP IPNCDRNGNF HPKQCHPALD GQRGKCWCVD RKTGVKLPGG 250 LEPKGELDCH QLADSFRE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of the cDNAs encoding a novel insulin-like growth factor-binding protein from rat and human." Shimasaki S., Uchiyama F., Shimonaka M., Ling N. Mol. Endocrinol. 4:1451-1458(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[2]	"Inhibitory insulin-like growth factor-binding protein: cloning, complete sequence, and physiological regulation." Latour D., Mohan S., Linkhart T.A., Baylink D.J., Strong D.D. Mol. Endocrinol. 4:1806-1814(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"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], PROTEIN SEQUENCE OF 22-41. Tissue: Osteosarcoma.
[4]	"Structural and functional analysis of the 5'-flanking region of the human insulin-like growth factor binding protein (IGFBP)-4 gene." Qin X., Morales S., Lee K.-W., Boonyaratanakornkit V., Baylink D.J., Mohan S., Strong D.D. Biochim. Biophys. Acta 1350:136-140(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Placenta.
[5]	"Structure and transcription regulation of the human insulin-like growth factor binding protein 4 gene (IGFBP4)." Zazzi H., Nikoshkov A., Hall K., Luthman H. Genomics 49:401-410(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"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].
[7]	NIEHS SNPs program Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[8]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases 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: Colon.
[10]	"Purification of a colon cancer cell growth inhibitor and its identification as an insulin-like growth factor binding protein." Culouscou J.-M., Shoyab M. Cancer Res. 51:2813-2819(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 22-53. Tissue: Colon.
[11]	"Evidence that the inhibition of TE85 human bone cell proliferation by agents which stimulate cAMP production may in part be mediated by changes in the IGF-II regulatory system." Mohan S., Baylink D.J. Growth Regul. 1:110-118(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 22-42, INDUCTION. Tissue: Osteosarcoma.
[12]	"Structural basis for the regulation of insulin-like growth factors by IGF binding proteins." Siwanowicz I., Popowicz G.M., Wisniewska M., Huber R., Kuenkele K.-P., Lang K., Engh R.A., Holak T.A. Structure 13:155-167(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 24-103 IN COMPLEX WITH IGF1, DISULFIDE BONDS.
[13]	"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] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 22-253 IN COMPLEX WITH IGF1, DISULFIDE BONDS.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M38177 mRNA. No translation available.
M62403 mRNA. Translation: AAB06189.1.
U20982 Genomic DNA. Translation: AAA62670.1.
Y12508 Genomic DNA. Translation: CAA73110.1.
BT019891 mRNA. Translation: AAV38694.1.
BT019892 mRNA. Translation: AAV38695.1.
AY442346 Genomic DNA. Translation: AAR05443.1.
CH471152 Genomic DNA. Translation: EAW60664.1.
BC016041 mRNA. Translation: AAH16041.1.

IPI

IPI00305380.

PIR

B37252. G01662.

RefSeq

NP_001543.2. NM_001552.2.

UniGene

Hs.462998.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WQJ	X-ray	1.60	B	24-103	[»]
2DSP	X-ray	2.50	B	22-113	[»]
2DSQ	X-ray	2.80	A/B	22-113	[»]
2DSR	X-ray	2.10	B	24-103	[»]
			G	172-253	[»]

ProteinModelPortal

P22692.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-48432N.

IntAct

P22692. 1 interaction.

MINT

MINT-6630380.

STRING

9606.ENSP00000269593.

PTM databases

PhosphoSite

P22692.

Polymorphism databases

DMDM

124065.

Proteomic databases

PaxDb

P22692.

PeptideAtlas

P22692.

PRIDE

P22692.

Protocols and materials databases

DNASU

3487.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000269593; ENSP00000269593; ENSG00000141753.

GeneID

3487.

KEGG

hsa:3487.

UCSC

uc002hus.3. human.

Organism-specific databases

CTD

3487.

GeneCards

GC17P038599.

HGNC

HGNC:5473. IGFBP4.

MIM

146733. gene.

neXtProt

NX_P22692.

PharmGKB

PA29706.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG46496.

HOGENOM

HOG000253012.

HOVERGEN

HBG002631.

InParanoid

P22692.

OMA

KGMPCGV.

OrthoDB

EOG4FR0SF.

PhylomeDB

P22692.

Enzyme and pathway databases

BioCyc

MetaCyc:ENSG00000141753-MONOMER.

Reactome

REACT_116125. Disease.

Gene expression databases

ArrayExpress

P22692.

Bgee

P22692.

CleanEx

HS_IGFBP4.

Genevestigator

P22692.

GermOnline

ENSG00000141753. 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.
IPR022327. IGFBP-4.
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.

Pfam

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

PRINTS

PR01976. IGFBPFAMILY.
PR01980. IGFBPFAMILY4.

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

P22692.

ChEMBL

CHEMBL2310.

ChiTaRS

IGFBP4. human.

EvolutionaryTrace

P22692.

GenomeRNAi

3487.

NextBio

13714.

PMAP-CutDB

P22692.

SOURCE

Search...

Entry information

Entry name

IBP4_HUMAN

Accession

Primary (citable) accession number: P22692
Secondary accession number(s): A0N9W2, Q5U012, Q9UCL6

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	March 1, 1992
Last modified:	May 29, 2013
This is version 140 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.