Reviewed, UniProtKB/Swiss-Prot P01344 (IGF2_HUMAN)

Names and origin

Protein names

Recommended name:
    Insulin-like growth factor II
      Short name=IGF-II
Alternative name(s):
    Somatomedin-A
Cleaved into the following chain:
    1- Recommended name:
            Insulin-like growth factor II Ala-25 Del

Gene names

Name:	IGF2
ORF Names:	PP1446

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	180 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 possess growth-promoting activity. In vitro, they are potent mitogens for cultured cells. IGF-II is influenced by placental lactogen and may play a role in fetal development.
Subcellular location	Secreted.
Sequence similarities	Belongs to the insulin family.
Mass spectrometry	Molecular weight is 7469.4 Da from positions 25 - 91. Determined by MALDI. Ref.20 Ref.21 Molecular weight is 7398.3 Da from positions 26 - 91. Determined by MALDI. Ref.20 Ref.21

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal
Molecular function	Growth factor Mitogen
PTM	Glycoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	cell proliferation Inferred from electronic annotation. Source: UniProtKB-KW genetic imprinting Traceable author statement. Source: ProtInc insulin receptor signaling pathway Traceable author statement. Source: ProtInc regulation of gene-specific transcription Non-traceable author statement. Source: UniProtKB skeletal system development Traceable author statement. Source: ProtInc
Cellular component	extracellular region Inferred from electronic annotation. Source: InterPro
Molecular function	growth factor activity Inferred from electronic annotation. Source: UniProtKB-KW hormone activity Inferred from electronic annotation. Source: InterPro insulin receptor binding Inferred from physical interaction. Source: UniProtKB insulin-like growth factor receptor binding Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: P01344-1)

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 2 (identifier: P01344-2)

The sequence of this isoform differs from the canonical sequence as follows:
     53-53: S → RLPG

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 24

24

Chain

25 – 91

67

Insulin-like growth factor II

PRO_0000015717

Chain

26 – 91

66

Insulin-like growth factor II Ala-25 Del

PRO_0000015718

Propeptide

92 – 180

89

E peptide

PRO_0000015719

Regions

Region

25 – 52

28

B

Region

53 – 64

12

C

Region

65 – 85

21

A

Region

86 – 91

6

D

Amino acid modifications

Glycosylation

99

1

O-linked (GalNAc...)

Disulfide bond

33 ↔ 71

Disulfide bond

45 ↔ 84

Disulfide bond

70 ↔ 75

Natural variations

Alternative sequence

53

1

S → RLPG in isoform 2.

VSP_002708

Natural variant

120

1

K → N: dbSNP rs14367.

VAR_011959

Natural variant

173

1

P → Q: dbSNP rs1050342.

VAR_011960

Natural variant

180

1

K → N: dbSNP rs12993.

VAR_011961

Experimental info

Sequence conflict

3

1

I → M in AAA52544. Ref.6

Sequence conflict

107 – 110

4

RYPV → EIPL in CAA27249. Ref.1

Sequence conflict

147

1

E → ELE Ref.5

Secondary structure

1

.

.

.

.

.

.

.

180

Helix Strand Turn

Details...

Helix

35 – 44

10

Helix

66 – 70

5

Helix

78 – 81

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: C1B0EB1E016BA37A	FASTA	180	20,140
	10 20 30 40 50 60 MGIPMGKSML VLLTFLAFAS CCIAAYRPSE TLCGGELVDT LQFVCGDRGF YFSRPASRVS 70 80 90 100 110 120 RRSRGIVEEC CFRSCDLALL ETYCATPAKS ERDVSTPPTV LPDNFPRYPV GKFFQYDTWK 130 140 150 160 170 180 QSTQRLRRGL PALLRARRGH VLAKELEAFR EAKRHRPLIA LPTQDPAHGG APPEMASNRK
	Isoform 2 [UniParc]. Checksum: A54CD97B56C2B96F		183	20,477
	10 20 30 40 50 60 MGIPMGKSML VLLTFLAFAS CCIAAYRPSE TLCGGELVDT LQFVCGDRGF YFRLPGRPAS 70 80 90 100 110 120 RVSRRSRGIV EECCFRSCDL ALLETYCATP AKSERDVSTP PTVLPDNFPR YPVGKFFQYD 130 140 150 160 170 180 TWKQSTQRLR RGLPALLRAR RGHVLAKELE AFREAKRHRP LIALPTQDPA HGGAPPEMAS NRK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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] (ISOFORM 1).
[2]	"Sequence of a cDNA clone encoding human preproinsulin-like growth factor II." Bell G.I., Merryweather J.P., Sanchez-Pescador R., Stempien M.M., Priestley L., Scott J., Rall L.B. Nature 310:775-777(1984) [PubMed: 6382021] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"Isolation of an insulin-like growth factor II cDNA with a unique 5' untranslated region from human placenta." Shen S.-J., Daimon M., Wang C.-Y., Jansen M., Ilan J. Proc. Natl. Acad. Sci. U.S.A. 85:1947-1951(1988) [PubMed: 2450353] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]	"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] (ISOFORM 1).
[5]	"Tissue-specific expression of insulin-like growth factor II mRNAs with distinct 5' untranslated regions." Irminger J.C., Rosen K.M., Humbel R.E., Villa-Komaroff L. Proc. Natl. Acad. Sci. U.S.A. 84:6330-6334(1987) [PubMed: 3476948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[6]	"Human insulin-like growth factor I and II messenger RNA: isolation of complementary DNA and analysis of expression." Rall L.B., Scott J., Bell G.I. Methods Enzymol. 146:239-248(1987) [PubMed: 3683205] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[7]	"Nucleotide sequences of cDNAs encoding precursors of human insulin-like growth factor II (IGF-II) and an IGF-II variant." Jansen M., van Schaik F.M.A., van Tol H., van den Brande J.L., Sussenbach J.S. FEBS Lett. 179:243-246(1985) [PubMed: 3881277] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
[8]	"Isolation of a cDNA for a growth factor of vascular endothelial cells from human lung cancer cells: its identity with insulin-like growth factor II." Hagiwara K., Kobayashi T., Tobita M., Kikyo N., Yazaki Y., Okabe T. Jpn. J. Cancer Res. 86:202-207(1995) [PubMed: 7730145] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[9]	"Imprinting of IGF2 P0 transcript and novel alternatively spliced INS-IGF2 isoforms show differences between mouse and human." Monk D., Sanches R., Arnaud P., Apostolidou S., Hills F.A., Abu-Amero S., Murrell A., Friess H., Reik W., Stanier P., Constancia M., Moore G.E. Hum. Mol. Genet. 15:1259-1269(2006) [PubMed: 16531418] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[10]	"Large-scale cDNA transfection screening for genes related to cancer development and progression." Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X. , Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J. Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004) [PubMed: 15498874] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[11]	"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 (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[12]	SeattleSNPs program for genomic applications Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [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] (ISOFORM 1). Tissue: Muscle.
[14]	"Differential expression of the human insulin-like growth factor II gene. Characterization of the IGF-II mRNAs and an mRNA encoding a putative IGF-II-associated protein." de Pagter-Holthuizen P., van der Kammen R.A., Jansen M., van Schaik F.M.A., Sussenbach J.S. Biochim. Biophys. Acta 950:282-295(1988) [PubMed: 3167054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 103-180.
[15]	"A new 5'-non-coding region for human placental insulin-like growth factor II mRNA expression." le Bouc Y., Noguiez P., Sondermeijer P., Dreyer D., Girard F., Binoux M. FEBS Lett. 222:181-185(1987) [PubMed: 3653397] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-161 (ISOFORM 2).
[16]	"Tissue-specific and developmentally regulated transcription of the insulin-like growth factor 2 gene." Gray A., Tam A.W., Dull T.J., Hayflick J.S., Pintar J., Cavenee W.K., Koufos A., Ullrich A. DNA 6:283-295(1987) [PubMed: 3652904] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-52. Tissue: Liver.
[17]	"Primary structure of human insulin-like growth factor II." Rinderknecht E., Humbel R.E. FEBS Lett. 89:283-286(1978) [PubMed: 658418] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-91.
[18]	"Structure and activity dependence of recombinant human insulin-like growth factor II on disulfide bond pairing." Smith M.C., Cook J.A., Furman T.C., Occolowitz J.L. J. Biol. Chem. 264:9314-9321(1989) [PubMed: 2722836] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, DISULFIDE BONDS.
[19]	"Purification and characterization of insulin-like growth factor II (IGF II) and an IGF II variant from human placenta." De Ceuninck F., Willeput J., Corvol M. J. Chromatogr. B 666:203-214(1995) [PubMed: 7633596] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-68.
[20]	"Detection of bound and free IGF-1 and IGF-2 in human plasma via biomolecular interaction analysis mass spectrometry." Nedelkov D., Nelson R.W., Kiernan U.A., Niederkofler E.E., Tubbs K.A. FEBS Lett. 536:130-134(2003) [PubMed: 12586351] [Abstract] Cited for: MASS SPECTROMETRY, PROTEOLYTIC PROCESSING.
[21]	"Quantitative mass spectrometric immunoassay of insulin like growth factor 1." Nelson R.W., Nedelkov D., Tubbs K.A., Kiernan U.A. J. Proteome Res. 3:851-855(2004) [PubMed: 15359740] [Abstract] Cited for: MASS SPECTROMETRY, PROTEOLYTIC PROCESSING.
[22]	"The identification of O-glycosylated precursors of insulin-like growth factor II." Hudgins W.R., Hampton B., Burgess W.H., Perdue J.F. J. Biol. Chem. 267:8153-8160(1992) [PubMed: 1569071] [Abstract] Cited for: GLYCOSYLATION AT THR-99.
[23]	"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.
[24]	"Solution structure of human insulin-like growth factor II; recognition sites for receptors and binding proteins." Terasawa H., Kohda D., Hatanaka H., Nagata K., Higashihashi N., Fujiwara H., Sakano K., Inagaki F. EMBO J. 13:5590-5597(1994) [PubMed: 7527339] [Abstract] Cited for: STRUCTURE BY NMR.
+	Additional computationally mapped references.

Web resources

GeneReviews

Wikipedia

Insulin-like growth factor 2 entry

SeattleSNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

X03562 Genomic DNA. Translation: CAA27249.1.
X00910 mRNA. Translation: CAA25426.1.
J03242 mRNA. Translation: AAA52545.1.
X03425 Genomic DNA. Translation: CAA27155.1.
X03426 Genomic DNA. Translation: CAA27156.1.
X03427 Genomic DNA. Translation: CAA27157.1.
M17426 mRNA. Translation: AAA60088.1.
M29645 mRNA. Translation: AAA52544.1.
M17863 mRNA. Translation: AAA52443.1. Sequence problems.
S77035 mRNA. Translation: AAB34155.1.
DQ104203 mRNA. Translation: ABD93451.1.
AF217977 mRNA. Translation: AAG17220.1.
BT007013 mRNA. Translation: AAP35659.1.
AF517226 Genomic DNA. Translation: AAM51825.1.
BC000531 mRNA. Translation: AAH00531.1.
X07868 Genomic DNA. Translation: CAA30717.1.
X06159 mRNA. Translation: CAA29516.1.
X06160 Other RNA. Translation: CAA29517.1.
X06161 mRNA. Translation: CAA29518.1.
M22373 Genomic DNA. Translation: AAA52536.1.

PIR

IGHU2. B23614.
I67610.
S02423.

RefSeq

NP_000603.1.
NP_001007140.2.

UniGene

Hs.523414
Hs.654579
Hs.700350
Hs.700789

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1GF2	model	-	A	25-91	[»]
1IGL	NMR	-	A	25-91	[»]
2V5P	X-ray	4.10	C/D	25-91	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:6026N.

PTM databases

PhosphoSite

P01344.

Genome annotation databases

Ensembl

ENSG00000167244. Homo sapiens. [Contig view]

GeneID

3481.

KEGG

hsa:3481.

Organism-specific databases

H-InvDB

HIX0009345.
HIX0036355.
HIX0092841.

HGNC

HGNC:5466. IGF2.

HPA

HPA007993.

MIM

147470. gene+phenotype.

Orphanet

116. Beckwith-Wiedemann syndrome.
813. Silver-Russell dwarfism.

PharmGKB

PA29699.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOVERGEN

P01344.

Gene expression databases

ArrayExpress

P01344.

CleanEx

HS_IGF2.

GermOnline

ENSG00000167244. Homo sapiens.

Family and domain databases

InterPro

IPR013576. IGF2_C.
IPR004825. Ins/IGF/relaxin.
[Graphical view]

Gene3D

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

Pfam

PF08365. IGF2_C. 1 hit.
PF00049. Insulin. 1 hit.
[Graphical view]

PRINTS

PR00277. INSULINB.

ProDom

PD001048. Bombyxin. 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

LinkHub

P01344.

NextBio

13686.

SOURCE

Search...

Entry information

Entry name

IGF2_HUMAN

Accession

Primary (citable) accession number: P01344
Secondary accession number(s): P78449 , Q14299, Q1WM26, Q9UC68, Q9UC69

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	November 25, 2008
This is version 124 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)