Reviewed, UniProtKB/Swiss-Prot P05019 (IGF1B_HUMAN)

Names and origin

Protein names

Recommended name:
    Insulin-like growth factor IB
      Short name=IGF-IB
Alternative name(s):
    Somatomedin-C
    Mechano growth factor
      Short name=MGF

Gene names

Name:	IGF1
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	195 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	The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity.
Subcellular location	Secreted.
Involvement in disease	Defects in IGF1 are the cause of insulin-like growth factor I deficiency (IGF1 deficiency) [MIM:608747]. IGF1 deficiency is an autosomal recessive disorder characterized by growth retardation, sensorineural deafness and mental retardation.
Sequence similarities	Belongs to the insulin family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Deafness
Domain	Signal
Molecular function	Growth factor
PTM	Disulfide bond
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	anti-apoptosis Inferred from direct assay. Source: UniProtKB muscle hypertrophy Inferred from mutant phenotype. Source: UniProtKB myoblast differentiation Inferred from direct assay. Source: UniProtKB myoblast proliferation Inferred from direct assay. Source: UniProtKB myotube cell development Inferred from direct assay. Source: UniProtKB negative regulation of smooth muscle cell apoptosis Inferred from direct assay. Source: UniProtKB phosphoinositide-mediated signaling Inferred from direct assay. Source: UniProtKB positive regulation of DNA replication Inferred from direct assay. Source: UniProtKB positive regulation of Ras protein signal transduction Inferred from direct assay. Source: UniProtKB positive regulation of epithelial cell proliferation Inferred from direct assay. Source: UniProtKB positive regulation of fibroblast proliferation Inferred from direct assay. Source: UniProtKB positive regulation of gene-specific transcription Inferred from direct assay. Source: UniProtKB positive regulation of glycolysis Inferred from direct assay. Source: UniProtKB positive regulation of insulin-like growth factor receptor signaling pathway Inferred from direct assay. Source: UniProtKB positive regulation of mitosis Inferred from direct assay. Source: UniProtKB positive regulation of phosphoinositide 3-kinase cascade Inferred from direct assay. Source: UniProtKB positive regulation of smooth muscle cell migration Inferred from direct assay. Source: UniProtKB positive regulation of smooth muscle cell proliferation Inferred from direct assay. Source: UniProtKB positive regulation of tyrosine phosphorylation of Stat5 protein Inferred from direct assay. Source: UniProtKB regulation of multicellular organism growth Inferred from expression pattern. Source: UniProtKB satellite cell maintenance involved in skeletal muscle regeneration Inferred from direct assay. Source: UniProtKB sensory perception of sound Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	insulin-like growth factor binding protein complex Inferred by curator. Source: UniProtKB platelet alpha granule lumen Inferred from Experiment. Source: Reactome
Molecular function	growth factor activity Inferred from electronic annotation. Source: UniProtKB-KW hormone activity Inferred from direct assay. Source: UniProtKB insulin receptor binding Inferred from physical interaction. Source: UniProtKB insulin-like growth factor receptor binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform IGF-IB (identifier: P05019-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform IGF-IA (identifier: P01343-1)

The sequence of this isoform can be found in the external entry P01343-1.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

21

Potential

Propeptide

22 – 48

27

Ref.6

PRO_0000015663

Chain

49 – 118

70

Insulin-like growth factor IB

PRO_0000015664

Propeptide

119 – 195

77

E peptide

PRO_0000015665

Regions

Region

49 – 77

29

B

Region

78 – 89

12

C

Region

90 – 110

21

A

Region

111 – 118

8

D

Amino acid modifications

Disulfide bond

54 ↔ 96

Ref.11

Disulfide bond

66 ↔ 109

Ref.11

Disulfide bond

95 ↔ 100

Ref.11

Natural variations

Natural variant

115

1

A → T: dbSNP rs17884626.

VAR_056113

Natural variant

187

1

A → D: dbSNP rs6213. Ref.12

VAR_013945

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

195

Helix Strand Turn

Details...

Helix

55 – 66

12

Helix

67 – 69

3

Beta strand

73 – 76

4

Beta strand

87 – 90

4

Helix

91 – 95

5

Turn

96 – 98

3

Helix

102 – 106

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform IGF-IB [UniParc]. Last modified August 13, 1987. Version 1. Checksum: E88A8CFBD1CD1873	FASTA	195	21,841
	10 20 30 40 50 60 MGKISSLPTQ LFKCCFCDFL KVKMHTMSSS HLFYLALCLL TFTSSATAGP ETLCGAELVD 70 80 90 100 110 120 ALQFVCGDRG FYFNKPTGYG SSSRRAPQTG IVDECCFRSC DLRRLEMYCA PLKPAKSARS 130 140 150 160 170 180 VRAQRHTDMP KTQKYQPPST NKNTKSQRRK GWPKTHPGGE QKEGTEASLQ IRGKKKEQRR 190 EIGSRNAECR GKKGK
	Isoform IGF-IA. See P01343.	FASTA	–	–

References

[1]	"Organization and sequence of the human insulin-like growth factor I gene. Alternative RNA processing produces two insulin-like growth factor I precursor peptides." Rotwein P., Pollock K.M., Didier D.K., Krivi G.G. J. Biol. Chem. 261:4828-4832(1986) [PubMed: 2937782] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Two insulin-like growth factor I messenger RNAs are expressed in human liver." Rotwein P. Proc. Natl. Acad. Sci. U.S.A. 83:77-81(1986) [PubMed: 3455760] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Organization of the human genes for insulin-like growth factors I and II." de Pagter-Holthuizen P., van Schaik F.M.A., Verduijn G.M., van Ommen G.J.B., Bouma B.N., Jansen M., Sussenbach J.S. FEBS Lett. 195:179-184(1986) [PubMed: 3002851] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Characterization of insulin-like growth factor 1 in human primary brain tumors." Sandberg-Nordqvist A.-C., Staehlbom P.-A., Reinecke M., Collins V.P., von Holst H., Sara V. Cancer Res. 53:2475-2478(1993) [PubMed: 8495408] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[5]	"Insulin-like growth factor II precursor gene organization in relation to insulin gene family." Dull T.J., Gray A., Hayflick J.S., Ullrich A. Nature 310:777-781(1984) [PubMed: 6382022] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 22-50.
[6]	"The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin." Rinderknecht E., Humbel R.E. J. Biol. Chem. 253:2769-2776(1978) [PubMed: 632300] [Abstract] Cited for: PROTEIN SEQUENCE OF 49-118.
[7]	"Tertiary structures, receptor binding, and antigenicity of insulinlike growth factors." Blundell T.L., Bedarkar S., Humbel R.E. Fed. Proc. 42:2592-2597(1983) [PubMed: 6189745] [Abstract] Cited for: 3D-STRUCTURE MODELING.
[8]	"Solution structure of human insulin-like growth factor 1: a nuclear magnetic resonance and restrained molecular dynamics study." Cooke R.M., Harvey T.S., Campbell I.D. Biochemistry 30:5484-5491(1991) [PubMed: 2036417] [Abstract] Cited for: STRUCTURE BY NMR.
[9]	"1H-NMR assignment and secondary structure of human insulin-like growth factor-I (IGF-I) in solution." Sato A., Nishimura S., Ohkubo T., Kyogoku Y., Koyama S., Kobayashi M., Yasuda T., Kobayashi Y. J. Biochem. 111:529-536(1992) [PubMed: 1319992] [Abstract] Cited for: STRUCTURE BY NMR.
[10]	"Intrauterine growth retardation and postnatal growth failure associated with deletion of the insulin-like growth factor I gene." Woods K.A., Camacho-Hubner C., Savage M.O., Clark A.J. N. Engl. J. Med. 335:1363-1367(1996) [PubMed: 8857020] [Abstract] Cited for: INVOLVEMENT IN IGF1 DEFICIENCY.
[11]	"Location of disulphide bonds in human insulin-like growth factors (IGFs) synthesized by recombinant DNA technology." Raschdorf F., Dahinden R., Maerki W., Richter W.J., Merryweather J.P. Biomed. Environ. Mass Spectrom. 16:3-8(1988) [PubMed: 3242681] [Abstract] Cited for: DISULFIDE BONDS.
[12]	"Characterization of single-nucleotide polymorphisms in coding regions of human genes." Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S. Nat. Genet. 22:231-238(1999) [PubMed: 10391209] [Abstract] Cited for: VARIANT ASP-187.
[13]	Erratum Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S. Nat. Genet. 23:373-373(1999)
+	Additional computationally mapped references.

Web resources

SHMPD

The Singapore human mutation and polymorphism database

Cross-references

Sequence databases

EMBLGenBankDDBJ

M14155 , M12659, M14153, M14154 Genomic DNA. Translation: AAA52537.1.
M11568 mRNA. Translation: AAA52539.1.
X56774 mRNA. Translation: CAA40093.1.
X03563 Genomic DNA. Translation: CAA27250.1. Sequence problems.
X03420 Genomic DNA. Translation: CAA27152.1.
X03421 Genomic DNA. Translation: CAA27153.1.
X03422 Genomic DNA. Translation: CAA27154.1.

IPI

IPI00433029.

PIR

IGHU1B. A01611.

RefSeq

NP_001104755.1.

UniGene

Hs.160562

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BQT	NMR	-	A	49-118	[»]
1GF1	model	-	A	49-118	[»]
1PMX	NMR	-	A	49-118	[»]
1WQJ	X-ray	1.60	I	49-118	[»]
2DSP	X-ray	2.50	I	49-118	[»]
2DSQ	X-ray	2.80	C/I	49-118	[»]
2DSR	X-ray	2.10	I	49-118	[»]
3LRI	NMR	-	A	49-118	[»]

ModBase

Search...

Proteomic databases

PRIDE

P05019.

Genome annotation databases

Ensembl

ENSG00000017427. Homo sapiens. [Contig view]

GeneID

3479.

Organism-specific databases

GeneCards

GC12M101292.

HGNC

HGNC:5464. IGF1.

MIM

147440. gene.
608747. phenotype.

Orphanet

73272. Growth delay due to insulin-like growth factor I deficiency.
633. Short stature due to growth hormone resistance.

PharmGKB

PA29697.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P05019.

HOVERGEN

P05019.

OMA

P05019. KAQKEVH.

Enzyme and pathway databases

Reactome

REACT_604. Hemostasis.

Gene expression databases

ArrayExpress

P05019.

Bgee

P05019.

CleanEx

HS_IGF1.

GermOnline

ENSG00000017427. Homo sapiens.

Family and domain databases

InterPro

IPR004825. Ins/IGF/relaxin.
[Graphical view]

Gene3D

G3DSA:1.10.100.10. Ins/IGF/relaxin. 1 hit.

Pfam

PF00049. Insulin. 1 hit.
[Graphical view]

PRINTS

PR00277. INSULINB.

ProDom

PD001048. Bombyxin. 1 hit.
PD015667. Mollusc_ins. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00078. IlGF. 1 hit.
[Graphical view]

PROSITE

PS00262. INSULIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

13678.

SOURCE

Search...

Entry information

Entry name

IGF1B_HUMAN

Accession

Primary (citable) accession number: P05019

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	August 13, 1987
Last modified:	June 16, 2009
This is version 118 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)