Reviewed, UniProtKB/Swiss-Prot Q9Y6M1 (IF2B2_HUMAN)

Names and origin

Protein names

Recommended name:
    Insulin-like growth factor 2 mRNA-binding protein 2
      Short name=IGF2 mRNA-binding protein 2
      Short name=IMP-2
Alternative name(s):
    IGF-II mRNA-binding protein 2
    Hepatocellular carcinoma autoantigen p62
    VICKZ family member 2

Gene names

Name:	IGF2BP2
Synonyms:	IMP2, VICKZ2

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	599 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Binds to the 5'-UTR of the insulin-like growth factor 2 (IGF2) mRNAs. Binding is isoform-specific. May regulate translation of target mRNAs. Ref.5
Subunit structure	Interacts with HNRPD. Ref.6
Subcellular location	Cytoplasm Probable. Note: Localizes at the connecting piece and the tail of the spermatozoa.
Tissue specificity	Expressed in oocytes, granulosa cells of small and growing follicles, Leydig cells, spermatogonia and semen (at protein level). Expressed in testicular cancer (at protein level). Expressed weakly in heart, placenta, skeletal muscle, bone marrow, colon, kidney, salivary glands, testis and pancreas. Detected in fetal liver, fetal ovary, gonocytes and interstitial cells of the testis. Ref.1 Ref.8
Involvement in disease	Autoantibodies against IGF2BP2 are detected in sera from some patients with hepatocellular carcinoma.
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
Coding sequence diversity	Alternative splicing
Domain	Repeat
Ligand	RNA-binding
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
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 Inferred from direct assay. Source: UniProtKB cytoskeletal part Inferred from direct assay. Source: UniProtKB nucleus Inferred from direct assay. Source: UniProtKB
Molecular function	mRNA 5'-UTR binding Ref.5 Inferred from direct assay. Source: UniProtKB nucleotide binding Inferred from electronic annotation. Source: InterPro protein binding Ref.6 Inferred from physical interaction. Source: IntAct translation regulator activity Ref.5 Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
HNRNPD	Q14103-4	4	EBI-1024419,EBI-432545
PUF60	Q9UHX1	1	EBI-1024419,EBI-1053259

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9Y6M1-2)

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: Q9Y6M1-1)

The sequence of this isoform differs from the canonical sequence as follows:
     358-400: Missing.

Isoform 3 (identifier: Q9Y6M1-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-80: MMNKLYIGNL...VDYSVSKKLR → MFSCPGHYHVDGFLNPG

Isoform 4 (identifier: Q9Y6M1-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-80: MMNKLYIGNL...VDYSVSKKLR → MFSCPGHYHVDGFLNPG
     113-113: Q → QVFAFSL

Isoform 5 (identifier: Q9Y6M1-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-80: MMNKLYIGNL...VDYSVSKKLR → MFSCPGHYHVDGFLNPG
     358-400: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 599

599

Insulin-like growth factor 2 mRNA-binding protein 2

PRO_0000244496

Regions

Domain

3 – 76

74

RRM 1

Domain

82 – 157

76

RRM 2

Domain

193 – 258

66

KH 1

Domain

274 – 341

68

KH 2

Domain

427 – 492

66

KH 3

Domain

509 – 575

67

KH 4

Amino acid modifications

Modified residue

162

1

Phosphoserine Ref.9

Modified residue

164

1

Phosphoserine Ref.9

Natural variations

Alternative sequence

1 – 80

80

MMNKL…SKKLR → MFSCPGHYHVDGFLNPG in isoform 3, isoform 4 and isoform 5.

VSP_036550

Alternative sequence

113

1

Q → QVFAFSL in isoform 4.

VSP_036552

Alternative sequence

358 – 400

43

Missing in isoform 2 and isoform 5.

VSP_036553

Secondary structure

1

.

.

.

.

.

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.

.

.

.

.

.

.

.

599

Helix Strand Turn

Details...

Beta strand

5 – 8

4

Helix

16 – 25

10

Beta strand

34 – 37

4

Beta strand

40 – 43

4

Helix

48 – 58

11

Turn

59 – 61

3

Beta strand

70 – 73

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 3, 2009. Version 2. Checksum: EA656F8733BBB39A	FASTA	599	66,121
	10 20 30 40 50 60 MMNKLYIGNL SPAVTADDLR QLFGDRKLPL AGQVLLKSGY AFVDYPDQNW AIRAIETLSG 70 80 90 100 110 120 KVELHGKIME VDYSVSKKLR SRKIQIRNIP PHLQWEVLDG LLAQYGTVEN VEQVNTDTET 130 140 150 160 170 180 AVVNVTYATR EEAKIAMEKL SGHQFENYSF KISYIPDEEV SSPSPPQRAQ RGDHSSREQG 190 200 210 220 230 240 HAPGGTSQAR QIDFPLRILV PTQFVGAIIG KEGLTIKNIT KQTQSRVDIH RKENSGAAEK 250 260 270 280 290 300 PVTIHATPEG TSEACRMILE IMQKEADETK LAEEIPLKIL AHNGLVGRLI GKEGRNLKKI 310 320 330 340 350 360 EHETGTKITI SSLQDLSIYN PERTITVKGT VEACASAEIE IMKKLREAFE NDMLAVNQQA 370 380 390 400 410 420 NLIPGLNLSA LGIFSTGLSV LSPPAGPRGA PPAAPYHPFT THSGYFSSLY PHHQFGPFPH 430 440 450 460 470 480 HHSYPEQEIV NLFIPTQAVG AIIGKKGAHI KQLARFAGAS IKIAPAEGPD VSERMVIITG 490 500 510 520 530 540 PPEAQFKAQG RIFGKLKEEN FFNPKEEVKL EAHIRVPSST AGRVIGKGGK TVNELQNLTS 550 560 570 580 590 AEVIVPRDQT PDENEEVIVR IIGHFFASQT AQRKIREIVQ QVKQQEQKYP QGVASQRSK
	Isoform 2. Checksum: 1EDEFB100443DDC4	FASTA	556	61,842
	10 20 30 40 50 60 MMNKLYIGNL SPAVTADDLR QLFGDRKLPL AGQVLLKSGY AFVDYPDQNW AIRAIETLSG 70 80 90 100 110 120 KVELHGKIME VDYSVSKKLR SRKIQIRNIP PHLQWEVLDG LLAQYGTVEN VEQVNTDTET 130 140 150 160 170 180 AVVNVTYATR EEAKIAMEKL SGHQFENYSF KISYIPDEEV SSPSPPQRAQ RGDHSSREQG 190 200 210 220 230 240 HAPGGTSQAR QIDFPLRILV PTQFVGAIIG KEGLTIKNIT KQTQSRVDIH RKENSGAAEK 250 260 270 280 290 300 PVTIHATPEG TSEACRMILE IMQKEADETK LAEEIPLKIL AHNGLVGRLI GKEGRNLKKI 310 320 330 340 350 360 EHETGTKITI SSLQDLSIYN PERTITVKGT VEACASAEIE IMKKLREAFE NDMLAVNTHS 370 380 390 400 410 420 GYFSSLYPHH QFGPFPHHHS YPEQEIVNLF IPTQAVGAII GKKGAHIKQL ARFAGASIKI 430 440 450 460 470 480 APAEGPDVSE RMVIITGPPE AQFKAQGRIF GKLKEENFFN PKEEVKLEAH IRVPSSTAGR 490 500 510 520 530 540 VIGKGGKTVN ELQNLTSAEV IVPRDQTPDE NEEVIVRIIG HFFASQTAQR KIREIVQQVK 550 QQEQKYPQGV ASQRSK
	Isoform 3. Checksum: 733536C7BDAD8AF5	FASTA	536	59,001
	10 20 30 40 50 60 MFSCPGHYHV DGFLNPGSRK IQIRNIPPHL QWEVLDGLLA QYGTVENVEQ VNTDTETAVV 70 80 90 100 110 120 NVTYATREEA KIAMEKLSGH QFENYSFKIS YIPDEEVSSP SPPQRAQRGD HSSREQGHAP 130 140 150 160 170 180 GGTSQARQID FPLRILVPTQ FVGAIIGKEG LTIKNITKQT QSRVDIHRKE NSGAAEKPVT 190 200 210 220 230 240 IHATPEGTSE ACRMILEIMQ KEADETKLAE EIPLKILAHN GLVGRLIGKE GRNLKKIEHE 250 260 270 280 290 300 TGTKITISSL QDLSIYNPER TITVKGTVEA CASAEIEIMK KLREAFENDM LAVNQQANLI 310 320 330 340 350 360 PGLNLSALGI FSTGLSVLSP PAGPRGAPPA APYHPFTTHS GYFSSLYPHH QFGPFPHHHS 370 380 390 400 410 420 YPEQEIVNLF IPTQAVGAII GKKGAHIKQL ARFAGASIKI APAEGPDVSE RMVIITGPPE 430 440 450 460 470 480 AQFKAQGRIF GKLKEENFFN PKEEVKLEAH IRVPSSTAGR VIGKGGKTVN ELQNLTSAEV 490 500 510 520 530 IVPRDQTPDE NEEVIVRIIG HFFASQTAQR KIREIVQQVK QQEQKYPQGV ASQRSK
	Isoform 4. Checksum: F1D98409DD8AE45D	FASTA	542	59,666
	10 20 30 40 50 60 MFSCPGHYHV DGFLNPGSRK IQIRNIPPHL QWEVLDGLLA QYGTVENVEQ VFAFSLVNTD 70 80 90 100 110 120 TETAVVNVTY ATREEAKIAM EKLSGHQFEN YSFKISYIPD EEVSSPSPPQ RAQRGDHSSR 130 140 150 160 170 180 EQGHAPGGTS QARQIDFPLR ILVPTQFVGA IIGKEGLTIK NITKQTQSRV DIHRKENSGA 190 200 210 220 230 240 AEKPVTIHAT PEGTSEACRM ILEIMQKEAD ETKLAEEIPL KILAHNGLVG RLIGKEGRNL 250 260 270 280 290 300 KKIEHETGTK ITISSLQDLS IYNPERTITV KGTVEACASA EIEIMKKLRE AFENDMLAVN 310 320 330 340 350 360 QQANLIPGLN LSALGIFSTG LSVLSPPAGP RGAPPAAPYH PFTTHSGYFS SLYPHHQFGP 370 380 390 400 410 420 FPHHHSYPEQ EIVNLFIPTQ AVGAIIGKKG AHIKQLARFA GASIKIAPAE GPDVSERMVI 430 440 450 460 470 480 ITGPPEAQFK AQGRIFGKLK EENFFNPKEE VKLEAHIRVP SSTAGRVIGK GGKTVNELQN 490 500 510 520 530 540 LTSAEVIVPR DQTPDENEEV IVRIIGHFFA SQTAQRKIRE IVQQVKQQEQ KYPQGVASQR SK
	Isoform 5. Checksum: 36BF971E2C4296F7	FASTA	493	54,722
	10 20 30 40 50 60 MFSCPGHYHV DGFLNPGSRK IQIRNIPPHL QWEVLDGLLA QYGTVENVEQ VNTDTETAVV 70 80 90 100 110 120 NVTYATREEA KIAMEKLSGH QFENYSFKIS YIPDEEVSSP SPPQRAQRGD HSSREQGHAP 130 140 150 160 170 180 GGTSQARQID FPLRILVPTQ FVGAIIGKEG LTIKNITKQT QSRVDIHRKE NSGAAEKPVT 190 200 210 220 230 240 IHATPEGTSE ACRMILEIMQ KEADETKLAE EIPLKILAHN GLVGRLIGKE GRNLKKIEHE 250 260 270 280 290 300 TGTKITISSL QDLSIYNPER TITVKGTVEA CASAEIEIMK KLREAFENDM LAVNTHSGYF 310 320 330 340 350 360 SSLYPHHQFG PFPHHHSYPE QEIVNLFIPT QAVGAIIGKK GAHIKQLARF AGASIKIAPA 370 380 390 400 410 420 EGPDVSERMV IITGPPEAQF KAQGRIFGKL KEENFFNPKE EVKLEAHIRV PSSTAGRVIG 430 440 450 460 470 480 KGGKTVNELQ NLTSAEVIVP RDQTPDENEE VIVRIIGHFF ASQTAQRKIR EIVQQVKQQE 490 QKYPQGVASQ RSK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel cytoplasmic protein with RNA-binding motifs is an autoantigen in human hepatocellular carcinoma." Zhang J.-Y., Chan E.K.L., Peng X.-X., Tan E.M. J. Exp. Med. 189:1101-1110(1999) [PubMed: 10190901] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), IDENTIFICATION AS A HEPATOCELLULAR CARCINOMA ANTIGEN, TISSUE SPECIFICITY, SUBCELLULAR LOCATION. Tissue: Colon adenocarcinoma.
[2]	"A novel type 2 diabetes-associated variant of IGF2BP2 gene affects expression of a functional alternative splicing form." Prokunina-Olsson L., Hanisch J.J., Jackson A., Chines P.S., Erdos M.R., Bonnycastle L.L., Swift A., Narisu N., Scott L.J., Morken M., Mohlke K., Bergman R., Tuomilehto J., Boehnke M., Rotimi C.N., Watanabe R.N., Collins F.S. Submitted (JAN-2008) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3; 4 AND 5). Tissue: Pancreatic islet.
[3]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed: 16641997] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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: Pancreas.
[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: FUNCTION, SUBCELLULAR LOCATION.
[6]	"Identification and characterization of proteins that selectively interact with isoforms of the mRNA binding protein AUF1 (hnRNP D)." Moraes K.C., Quaresma A.J., Maehnss K., Kobarg J. Biol. Chem. 384:25-37(2003) [PubMed: 12674497] [Abstract] Cited for: INTERACTION WITH HNRPD.
[7]	"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.
[8]	"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.
[9]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-162 AND SER-164, MASS SPECTROMETRY.
[10]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[11]	"Solution structure of the RNA binding domain of IGF-II mRNA-binding protein 2." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 2-81.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF057352 mRNA. Translation: AAD31596.1.
EU408701 mRNA. Translation: ACB86625.1.
EU408702 mRNA. Translation: ACB86626.1.
EU408703 mRNA. Translation: ACB86627.1.
AC016961 Genomic DNA. No translation available.
AC108670 Genomic DNA. No translation available.
BC021290 mRNA. Translation: AAH21290.1. Different initiation.

IPI

IPI00179713.
IPI00180983.
IPI00743914.
IPI00922068.
IPI00922167.

RefSeq

NP_001007226.1.
NP_006539.3.

UniGene

Hs.35354

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2CQH	NMR	-	A	2-81	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9Y6M1. 11 interactions.

PTM databases

PhosphoSite

Q9Y6M1.

Proteomic databases

PRIDE

Q9Y6M1.

Genome annotation databases

Ensembl

ENSG00000073792. Homo sapiens. [Contig view]

GeneID

10644.

KEGG

hsa:10644.

UCSC

uc003fpp.1. human.

Organism-specific databases

GeneCards

GC03M186845.

HGNC

HGNC:28867. IGF2BP2.

HPA

CAB017126.

MIM

608289. gene.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

Q9Y6M1.

OMA

Q9Y6M1. KQQEQKH.

Gene expression databases

ArrayExpress

Q9Y6M1.

Bgee

Q9Y6M1.

CleanEx

HS_IGF2BP2.

GermOnline

ENSG00000073792. Homo sapiens.

Family and domain databases

InterPro

IPR012677. a_b_plait_nuc_bd.
IPR004087. KH.
IPR004088. KH_type_1.
IPR018111. KH_type_1_subgr.
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]

ProtoNet

Search...

Other Resources

NextBio

40455.

SOURCE

Search...

Entry information

Entry name

IF2B2_HUMAN

Accession

Primary (citable) accession number: Q9Y6M1
Secondary accession number(s): A0A4Z0 , B3FTN2, B3FTN3, B3FTN4

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 27, 2006
Last sequence update:	March 3, 2009
Last modified:	July 7, 2009
This is version 68 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)