Reviewed, UniProtKB/Swiss-Prot O00425 (IF2B3_HUMAN)

Names and origin

Protein names

Recommended name:
    Insulin-like growth factor 2 mRNA-binding protein 3
      Short name=IGF2 mRNA-binding protein 3
Alternative name(s):
    IGF-II mRNA-binding protein 3
      Short name=IMP-3
    KH domain-containing protein overexpressed in cancer
      Short name=hKOC
    VICKZ family member 3

Gene names

Name:	IGF2BP3
Synonyms:	IMP3, KOC1, VICKZ3

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	579 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	RNA-binding protein that act as a regulator of mRNA translation and stability. Binds to the 5'-UTR of the insulin-like growth factor 2 (IGF2) mRNAs. Binds to sequences in the 3'-UTR of CD44 mRNA.
Subunit structure	Homodimer and multimer By similarity.
Subcellular location	Nucleus. Cytoplasm. Note= Found in lamellipodia of the leading edge, in the perinuclear region, and beneath the plasma membrane. The subcytoplasmic localization is cell specific and regulated by cell contact and growth. Localized at the connecting piece and the tail of the spermatozoa. Colocalized with CD44 mRNA in RNP granules.
Tissue specificity	Expressed in fetal liver, fetal lung, fetal kidney, fetal thymus, fetal placenta, fetal follicles of ovary and gonocytes of testis, growing oocytes, spermatogonia and semen (at protein level). Expressed in cervix adenocarcinoma, in testicular, pancreatic and renal-cell carcinomas (at protein level). Expressed ubiquitously during fetal development at 8 and 14 weeks of gestation. Expressed in ovary, testis, brain, placenta, pancreatic cancer tissues and pancreatic cancer cell lines.
Involvement in disease	Autoantibodies against IGF2BP3 are detected in sera from some patients with a variety of carcinomas.
Sequence similarities	Belongs to the RRM IMP/VICKZ family. Contains 4 KH domains. Contains 2 RRM (RNA recognition motif) domains.

Ontologies

Keywords
Biological process	Translation regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Domain	Repeat
Ligand	RNA-binding
Technical term	3D-structure
Gene Ontology (GO)
Biological process	anatomical structure morphogenesis Ref.5 Traceable author statement. Source: ProtInc negative regulation of translation Ref.5 Inferred from sequence or structural similarity. Source: UniProtKB regulation of cytokine biosynthetic process Ref.5 Inferred by curator. Source: UniProtKB
Cellular component	cytoplasm Ref.5 Traceable author statement. Source: ProtInc
Molecular function	mRNA 5'-UTR binding Ref.5 Inferred from direct assay. Source: UniProtKB translation regulator activity Ref.5 Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O00425-1)

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: O00425-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-381: Missing.

Isoform 3 (identifier: O00425-3)

The sequence of this isoform differs from the canonical sequence as follows:
     96-100: VLDSL → EMGQP
     101-579: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Chain

1 – 579

579

Insulin-like growth factor 2 mRNA-binding protein 3

Regions

Domain

2 – 75

74

RRM 1

Domain

81 – 156

76

RRM 2

Domain

195 – 260

66

KH 1

Domain

276 – 343

68

KH 2

Domain

405 – 470

66

KH 3

Domain

487 – 553

67

KH 4

Natural variations

Alternative sequence

1 – 381

381

Missing in isoform 2.

Alternative sequence

96 – 100

5

VLDSL → EMGQP in isoform 3.

Alternative sequence

101 – 579

479

Missing in isoform 3.

Experimental info

Sequence conflict

410

1

Q → L in CAH56186 and CAE45883. Ref.2

Sequence conflict

410

1

Q → L in AAH65269. Ref.3

Sequence conflict

494

1

V → A in CAH56186. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

579

Helix Strand Turn

Details...

Beta strand

83 – 88

6

Beta strand

90 – 92

3

Helix

94 – 104

11

Beta strand

107 – 113

7

Beta strand

116 – 128

13

Helix

129 – 139

11

Beta strand

150 – 153

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 1, 1997. Version 1. Checksum: AE5C3A8EE3C135C5	FASTA	579	63,720
	10 20 30 40 50 60 MNKLYIGNLS ENAAPSDLES IFKDAKIPVS GPFLVKTGYA FVDCPDESWA LKAIEALSGK 70 80 90 100 110 120 IELHGKPIEV EHSVPKRQRI RKLQIRNIPP HLQWEVLDSL LVQYGVVESC EQVNTDSETA 130 140 150 160 170 180 VVNVTYSSKD QARQALDKLN GFQLENFTLK VAYIPDEMAA QQNPLQQPRG RRGLGQRGSS 190 200 210 220 230 240 RQGSPGSVSK QKPCDLPLRL LVPTQFVGAI IGKEGATIRN ITKQTQSKID VHRKENAGAA 250 260 270 280 290 300 EKSITILSTP EGTSAACKSI LEIMHKEAQD IKFTEEIPLK ILAHNNFVGR LIGKEGRNLK 310 320 330 340 350 360 KIEQDTDTKI TISPLQELTL YNPERTITVK GNVETCAKAE EEIMKKIRES YENDIASMNL 370 380 390 400 410 420 QAHLIPGLNL NALGLFPPTS GMPPPTSGPP SAMTPPYPQF EQSETETVHQ FIPALSVGAI 430 440 450 460 470 480 IGKQGQHIKQ LSRFAGASIK IAPAEAPDAK VRMVIITGPP EAQFKAQGRI YGKIKEENFV 490 500 510 520 530 540 SPKEEVKLEA HIRVPSFAAG RVIGKGGKTV NELQNLSSAE VVVPRDQTPD ENDQVVVKIT 550 560 570 GHFYACQVAQ RKIQEILTQV KQHQQQKALQ SGPPQSRRK
	Isoform 2 [UniParc]. Checksum: BF6AC21ADC2F82FC		198	21,645
	10 20 30 40 50 60 MPPPTSGPPS AMTPPYPQFE QSETETVHQF IPALSVGAII GKQGQHIKQL SRFAGASIKI 70 80 90 100 110 120 APAEAPDAKV RMVIITGPPE AQFKAQGRIY GKIKEENFVS PKEEVKLEAH IRVPSFAAGR 130 140 150 160 170 180 VIGKGGKTVN ELQNLSSAEV VVPRDQTPDE NDQVVVKITG HFYACQVAQR KIQEILTQVK 190 QHQQQKALQS GPPQSRRK
	Isoform 3 [UniParc]. Checksum: 39209C904FB31546		100	11,262
	10 20 30 40 50 60 MNKLYIGNLS ENAAPSDLES IFKDAKIPVS GPFLVKTGYA FVDCPDESWA LKAIEALSGK 70 80 90 100 IELHGKPIEV EHSVPKRQRI RKLQIRNIPP HLQWEEMGQP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of a gene highly overexpressed in cancer coding for a novel KH-domain containing protein." Mueller-Pillasch F., Lacher U., Wallrapp C., Micha A., Zimmerhackl F., Hameister H., Varga G., Friess H., Buechler M., Beger H.G., Vila M.R., Adler G., Gress T.M. Oncogene 14:2729-2733(1997) [PubMed: 9178771] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY. Tissue: Pancreas and Pancreatic cancer.
[2]	The German cDNA consortium Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Endometrial tumor.
[3]	"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] (ISOFORMS 1 AND 3). Tissue: Eye and Lymph.
[4]	"Expression of the highly conserved RNA binding protein KOC in embryogenesis." Mueller-Pillasch F., Pohl B., Wilda M., Lacher U., Beil M., Wallrapp C., Hameister H., Knoechel W., Adler G., Gress T.M. Mech. Dev. 88:95-99(1999) [PubMed: 10525192] [Abstract] Cited for: TISSUE SPECIFICITY.
[5]	"A family of insulin-like growth factor II mRNA-binding proteins represses translation in late development." Nielsen J., Christiansen J., Lykke-Andersen J., Johnsen A.H., Wewer U.M., Nielsen F.C. Mol. Cell. Biol. 19:1262-1270(1999) [PubMed: 9891060] [Abstract] Cited for: GENE FAMILY NOMENCLATURE, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, RNA-BINDING.
[6]	"Autoimmune responses to mRNA binding proteins p62 and Koc in diverse malignancies." Zhang J.-Y., Chan E.K., Peng X.-X., Lu M., Wang X., Mueller F., Tan E.M. Clin. Immunol. 100:149-156(2001) [PubMed: 11465943] [Abstract] Cited for: IDENTIFICATION AS A CARCINOMA ANTIGEN.
[7]	"Characterisation of the growth regulating gene IMP3, a candidate for Silver-Russell syndrome." Monk D., Bentley L., Beechey C., Hitchins M., Peters J., Preece M.A., Stanier P., Moore G.E. J. Med. Genet. 39:575-581(2002) [PubMed: 12161597] [Abstract] Cited for: TISSUE SPECIFICITY.
[8]	"Nuclear transit of human zipcode-binding protein IMP1." Nielsen J., Adolph S.K., Rajpert-De Meyts E., Lykke-Andersen J., Koch G., Christiansen J., Nielsen F.C. Biochem. J. 376:383-391(2003) [PubMed: 12921532] [Abstract] Cited for: SUBCELLULAR LOCATION.
[9]	"VICKZ proteins: a multi-talented family of regulatory RNA-binding proteins." Yisraeli J.K. Biol. Cell 97:87-96(2005) [PubMed: 15601260] [Abstract] Cited for: REVIEW.
[10]	"KOC (K homology domain containing protein overexpressed in cancer): a novel molecular marker that distinguishes between benign and malignant lesions of the pancreas." Yantiss R.K., Woda B.A., Fanger G.R., Kalos M., Whalen G.F., Tada H., Andersen D.K., Rock K.L., Dresser K. Diagn. Mol. Pathol. 29:188-195(2005) [PubMed: 15644775] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[11]	"Expression of IGF-II mRNA-binding proteins (IMPs) in gonads and testicular cancer." Hammer N.A., Hansen T.O., Byskov A.G., Rajpert-De Meyts E., Groendahl M.L., Bredkjaer H.E., Wewer U.M., Christiansen J., Nielsen F.C. Reproduction 130:203-212(2005) [PubMed: 16049158] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[12]	"RNA-binding IMPs promote cell adhesion and invadopodia formation." Vikesaa J., Hansen T.V., Joenson L., Borup R., Wewer U.M., Christiansen J., Nielsen F.C. EMBO J. 25:1456-1468(2006) [PubMed: 16541107] [Abstract] Cited for: FUNCTION, RNA-BINDING, SUBCELLULAR LOCATION.
[13]	"Analysis of RNA-binding protein IMP3 to predict metastasis and prognosis of renal-cell carcinoma: a retrospective study." Jiang Z., Chu P.G., Woda B.A., Rock K.L., Liu Q., Hsieh C.-C., Li C., Chen W., Duan H.O., McDougal S., Wu C.-L. Lancet Oncol. 7:556-564(2006) [PubMed: 16814207] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[14]	"IMP3 is a novel biomarker for adenocarcinoma in situ of the uterine cervix: an immunohistochemical study in comparison with p16(INK4a) expression." Li C., Rock K.L., Woda B.A., Jiang Z., Fraire A.E., Dresser K. Mod. Pathol. 20:242-247(2006) [PubMed: 17192788] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[15]	"Solution structure of RNA binding domain in insulin-like growth factor 2 mRNA-binding protein 3." RIKEN structural genomics initiative (RSGI) Submitted (JUN-2007) to the PDB data bank Cited for: STRUCTURE BY NMR OF 73-161.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

U76705 mRNA. Translation: AAD09223.1.
U97188 mRNA. Translation: AAC35208.1.
BX640800 mRNA. Translation: CAE45883.1.
BX648488 mRNA. Translation: CAH56186.1.
BC051296 mRNA. Translation: AAH51296.1.
BC065269 mRNA. Translation: AAH65269.1.

UniGene

Hs.700696

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2E44	NMR	-	A	73-161	[»]

ModBase

Search...

PTM databases

PhosphoSite

O00425.

Genome annotation databases

Ensembl

ENSG00000136231. Homo sapiens. [Contig view]

Organism-specific databases

HGNC

HGNC:28868. IGF2BP3.

HPA

HPA002037.

MIM

608259. gene.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOVERGEN

O00425.

Gene expression databases

ArrayExpress

O00425.

CleanEx

HS_IGF2BP3.
HS_IMP3.

Family and domain databases

InterPro

IPR012677. a_b_plait_nuc_bd.
IPR004087. KH.
IPR004088. KH_type_1.
IPR000504. RRM_RNP1.
[Graphical view]

Gene3D

G3DSA:3.30.70.330. a_b_plait_nuc_bd. 2 hits.

Pfam

PF00013. KH_1. 4 hits.
PF00076. RRM_1. 2 hits.
[Graphical view]

SMART

SM00322. KH. 4 hits.
SM00360. RRM. 2 hits.
[Graphical view]

PROSITE

PS50084. KH_TYPE_1. 4 hits.
PS50102. RRM. 2 hits.
[Graphical view]

ProDom

O00425.
[Graphical view] [Entries sharing at least one domain]

BLOCKS

Search...

Other Resources

SOURCE

Search...

ProtoNet

Search...

Entry information

Entry name

IF2B3_HUMAN

Accession

Primary (citable) accession number: O00425
Secondary accession number(s): A0A4Z5 , Q63HM0, Q6MZZ2, Q86VB1

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 3, 2007
Last sequence update:	July 1, 1997
Last modified:	July 22, 2008
This is version 63 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)