Reviewed, UniProtKB/Swiss-Prot P22626 (ROA2_HUMAN)

Names and origin

Protein names

Recommended name:
    Heterogeneous nuclear ribonucleoproteins A2/B1
      Short name=hnRNP A2 / hnRNP B1

Gene names

Name:	HNRNPA2B1
Synonyms:	HNRPA2B1

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

General annotation (Comments)

Function	Involved with pre-mRNA processing. Forms complexes (ribonucleosomes) with at least 20 other different hnRNP and heterogeneous nuclear RNA in the nucleous.
Subunit structure	Identified in the spliceosome C complex, at least composed of AQR, ASCC3L1, C19orf29, CDC40, CDC5L, CRNKL1, DDX23, DDX41, DDX48, DDX5, DGCR14, DHX35, DHX38, DHX8, EFTUD2, FRG1, GPATC1, HNRNPA1, HNRNPA2B1, HNRPA3, HNRNPC, HNRPF, HNRPH1, HNRPK, HNRPM, HNRNPR, HNRNPU, KIAA1160, KIAA1604, LSM2, LSM3, MAGOH, MORG1, PABPC1, PLRG1, PNN, PPIE, PPIL1, PPIL3, PPWD1, PRPF19, PRPF4B, PRPF6, PRPF8, RALY, RBM22, RBM8A, RBMX, SART1, SF3A1, SF3A2, SF3A3, SF3B1, SF3B2, SF3B3, SFRS1, SKIV2L2, SNRPA1, SNRPB, SNRPB2, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, SNW1, SRRM1, SRRM2, SYF2, SYNCRIP, TFIP11, THOC4, U2AF1, WDR57, XAB2 and ZCCHC8.
Subcellular location	Nucleus › nucleoplasm. Cytoplasm By similarity. Note: Component of ribonucleosomes. Predominantly nucleoplasmic, however isoform A2 is also found in the cytoplasm of cells in some tissues. Not found in the nucleolus.
Sequence similarities	Contains 2 RRM (RNA recognition motif) domains.

Ontologies

Keywords
Biological process	mRNA processing mRNA splicing
Cellular component	Cytoplasm Nucleus Spliceosome
Coding sequence diversity	Alternative splicing
Domain	Repeat
Ligand	RNA-binding
Molecular function	Ribonucleoprotein
PTM	Methylation Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	RNA transport Inferred from direct assay. Source: HGNC nuclear mRNA splicing, via spliceosome Inferred by curator. Source: HGNC
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell heterogeneous nuclear ribonucleoprotein complex Ref.1 Inferred from direct assay. Source: HGNC nucleoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell spliceosome Inferred from direct assay. Source: HGNC
Molecular function	RNA binding Ref.3 Inferred from direct assay. Source: HGNC nucleotide binding Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction. Source: IntAct single-stranded telomeric DNA binding Inferred from direct assay. Source: HGNC
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Prnp	P04925	1	EBI-299649,EBI-768613	From a different organism.
TOB1	P50616	1	EBI-299649,EBI-723281

Alternative products

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

Isoform B1 (identifier: P22626-1)

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 A2 (identifier: P22626-2)

The sequence of this isoform differs from the canonical sequence as follows:
     3-14: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 353

353

Heterogeneous nuclear ribonucleoproteins A2/B1

PRO_0000081836

Regions

Domain

21 – 104

84

RRM 1

Domain

112 – 191

80

RRM 2

Region

308 – 347

40

Nuclear targeting sequence By similarity

Motif

9 – 15

7

Nuclear localization signal Potential

Compositional bias

202 – 353

152

Gly-rich

Amino acid modifications

Modified residue

104

1

N6,N6-dimethyllysine Ref.5

Modified residue

176

1

Phosphothreonine Ref.15

Modified residue

203

1

Dimethylated arginine; alternate Ref.5 Ref.11

Modified residue

203

1

Omega-N-methylarginine; alternate Ref.5 Ref.11

Modified residue

212

1

Phosphoserine Ref.15 Ref.18

Modified residue

213

1

Dimethylated arginine; alternate Ref.5

Modified residue

213

1

Omega-N-methylarginine; alternate Ref.5

Modified residue

225

1

Phosphoserine Ref.18

Modified residue

259

1

Phosphoserine Ref.15 Ref.18 Ref.13 Ref.14 Ref.16 Ref.17

Modified residue

324

1

Phosphoserine By similarity

Modified residue

341

1

Phosphoserine Ref.15 Ref.18 Ref.14 Ref.16

Modified residue

344

1

Phosphoserine Ref.15 Ref.18 Ref.12

Modified residue

347

1

Phosphotyrosine Ref.15

Natural variations

Alternative sequence

3 – 14

12

Missing in isoform A2.

VSP_005830

Experimental info

Sequence conflict

205

1

G → S in BAF82118. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

353

Helix Strand Turn

Details...

Helix

16 – 20

5

Beta strand

22 – 26

5

Helix

34 – 41

8

Beta strand

48 – 52

5

Turn

56 – 58

3

Beta strand

63 – 68

6

Helix

72 – 79

8

Beta strand

83 – 86

4

Beta strand

89 – 94

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform B1 [UniParc]. Last modified November 1, 1991. Version 2. Checksum: 4C2560A3D8E99D62	FASTA	353	37,430
	10 20 30 40 50 60 MEKTLETVPL ERKKREKEQF RKLFIGGLSF ETTEESLRNY YEQWGKLTDC VVMRDPASKR 70 80 90 100 110 120 SRGFGFVTFS SMAEVDAAMA ARPHSIDGRV VEPKRAVARE ESGKPGAHVT VKKLFVGGIK 130 140 150 160 170 180 EDTEEHHLRD YFEEYGKIDT IEIITDRQSG KKRGFGFVTF DDHDPVDKIV LQKYHTINGH 190 200 210 220 230 240 NAEVRKALSR QEMQEVQSSR SGRGGNFGFG DSRGGGGNFG PGPGSNFRGG SDGYGSGRGF 250 260 270 280 290 300 GDGYNGYGGG PGGGNFGGSP GYGGGRGGYG GGGPGYGNQG GGYGGGYDNY GGGNYGSGNY 310 320 330 340 350 NDFGNYNQQP SNYGPMKSGN FGGSRNMGGP YGGGNYGPGG SGGSGGYGGR SRY
	Isoform A2. Checksum: 39E8AB6ED874FA7C	FASTA	341	36,006
	10 20 30 40 50 60 MEREKEQFRK LFIGGLSFET TEESLRNYYE QWGKLTDCVV MRDPASKRSR GFGFVTFSSM 70 80 90 100 110 120 AEVDAAMAAR PHSIDGRVVE PKRAVAREES GKPGAHVTVK KLFVGGIKED TEEHHLRDYF 130 140 150 160 170 180 EEYGKIDTIE IITDRQSGKK RGFGFVTFDD HDPVDKIVLQ KYHTINGHNA EVRKALSRQE 190 200 210 220 230 240 MQEVQSSRSG RGGNFGFGDS RGGGGNFGPG PGSNFRGGSD GYGSGRGFGD GYNGYGGGPG 250 260 270 280 290 300 GGNFGGSPGY GGGRGGYGGG GPGYGNQGGG YGGGYDNYGG GNYGSGNYND FGNYNQQPSN 310 320 330 340 YGPMKSGNFG GSRNMGGPYG GGNYGPGGSG GSGGYGGRSR Y

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structures of the heterogeneous nuclear ribonucleoprotein A2, B1, and C2 proteins: a diversity of RNA binding proteins is generated by small peptide inserts." Burd C.G., Swanson M.S., Goerlach M., Dreyfuss G. Proc. Natl. Acad. Sci. U.S.A. 86:9788-9792(1989) [PubMed: 2557628] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS B1 AND A2).
[2]	"Two homologous genes, originated by duplication, encode the human hnRNP proteins A2 and A1." Biamonti G., Ruggiu M., Saccone S., Della Valle G., Riva S. Nucleic Acids Res. 22:1996-2002(1994) [PubMed: 8029005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Liver.
[3]	"Structure and expression of the gene (HNRPA2B1) encoding the human hnRNP protein A2/B1." Kozu T., Henrich B., Schaefer K.P. Genomics 25:365-371(1995) [PubMed: 7789969] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B1). Tissue: Glial tumor.
[5]	Bienvenut W.V., Lilla S., von Kriegsheim A., Lempens A., Kolch W. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 4-12; 22-59; 63-89; 100-147; 153-185; 201-266 AND 326-350, METHYLATION AT LYS-104; ARG-203 AND ARG-213, MASS SPECTROMETRY. Tissue: Ovarian carcinoma.
[6]	Lubec G., Vishwanath V., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 22-38; 154-168; 174-185; 214-228 AND 326-350, MASS SPECTROMETRY. Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[7]	"ADP-ribosylation of heterogeneous ribonucleoproteins in HeLa cells." Prasad S., Walent J., Dritschilo A. Biochem. Biophys. Res. Commun. 204:772-779(1994) [PubMed: 7980541] [Abstract] Cited for: PROTEIN SEQUENCE OF 80-100. Tissue: Cervix carcinoma.
[8]	"Purification and domain structure of core hnRNP proteins A1 and A2 and their relationship to single-stranded DNA-binding proteins." Kumar A., Willams K.R., Szer W. J. Biol. Chem. 261:11266-11273(1986) [PubMed: 3733753] [Abstract] Cited for: PROTEIN SEQUENCE OF 100-107; 121-128 AND 174-180.
[9]	"Two-dimensional gel electrophoresis, protein electroblotting and microsequencing: a direct link between proteins and genes." Bauw G., Rasmussen H.H., van den Bulcke M., van Damme J., Puype M., Gesser B., Celis J.E., Vandekerckhove J. Electrophoresis 11:528-536(1990) [PubMed: 1699755] [Abstract] Cited for: PROTEIN SEQUENCE OF 154-160; 204-212 AND 214-228.
[10]	"Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis." Jurica M.S., Licklider L.J., Gygi S.P., Grigorieff N., Moore M.J. RNA 8:426-439(2002) [PubMed: 11991638] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE SPICEOSOMAL C COMPLEX.
[11]	"Identifying and quantifying in vivo methylation sites by heavy methyl SILAC." Ong S.E., Mittler G., Mann M. Nat. Methods 1:119-126(2004) [PubMed: 15782174] [Abstract] Cited for: METHYLATION [LARGE SCALE ANALYSIS] AT ARG-203, MASS SPECTROMETRY.
[12]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-344, MASS SPECTROMETRY. Tissue: Epithelium.
[13]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-259, MASS SPECTROMETRY. Tissue: Epithelium.
[14]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-259 AND SER-341, MASS SPECTROMETRY. Tissue: Epithelium.
[15]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-176; SER-212; SER-259; SER-341; SER-344 AND TYR-347, MASS SPECTROMETRY.
[16]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-259 AND SER-341, MASS SPECTROMETRY.
[17]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-259, MASS SPECTROMETRY.
[18]	"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-212; SER-225; SER-259; SER-341 AND SER-344, MASS SPECTROMETRY.
[19]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[20]	"Solution structure of RRM domain in heterogeneous nuclear ribonucleaoproteins A2/B1." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 1-103.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M29064 mRNA. Translation: AAA60271.1.
M29065 mRNA. Translation: AAA36574.1.
U09123 , U09120, U09121, U09122 Genomic DNA. Translation: AAB60650.1.
D28877 Genomic DNA. Translation: BAA06031.1.
D28877 Genomic DNA. Translation: BAA06032.1.
AK289429 mRNA. Translation: BAF82118.1.

IPI

IPI00396378.
IPI00414696.

PIR

B34504. A56845.

RefSeq

NP_002128.1.
NP_112533.1.

UniGene

Hs.487774

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1X4B	NMR	-	A	1-103	[»]

SMR

P22626. Positions 15-193.

ModBase

Search...

Protein-protein interaction databases

IntAct

P22626. 9 interactions.

PTM databases

PhosphoSite

P22626.

2-D gel databases

SWISS-2DPAGE

P22626.

REPRODUCTION-2DPAGE

IPI00396378.
IPI00414696.
P22626.

Proteomic databases

PRIDE

P22626.

Genome annotation databases

Ensembl

ENSG00000122566. Homo sapiens. [Contig view]

GeneID

3181.

KEGG

hsa:3181.

Organism-specific databases

GeneCards

GC07M026197.

H-InvDB

HIX0006534.

HGNC

HGNC:5033. HNRNPA2B1.

HPA

CAB012403.

MIM

600124. gene.

PharmGKB

PA29356.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P22626.

HOVERGEN

P22626.

Enzyme and pathway databases

Reactome

REACT_1675. mRNA Processing.
REACT_6167. Influenza Infection.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

P22626.

Bgee

P22626.

CleanEx

HS_HNRNPA2B1.

GermOnline

ENSG00000122566. Homo sapiens.

Family and domain databases

InterPro

IPR012677. a_b_plait_nuc_bd.
IPR000504. RRM_RNP1.
[Graphical view]

Gene3D

G3DSA:3.30.70.330. a_b_plait_nuc_bd. 2 hits.

Pfam

PF00076. RRM_1. 2 hits.
[Graphical view]

SMART

SM00360. RRM. 2 hits.
[Graphical view]

PROSITE

PS50102. RRM. 2 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

12622.

PMAP-CutDB

P22626.

SOURCE

Search...

Entry information

Entry name

ROA2_HUMAN

Accession

Primary (citable) accession number: P22626
Secondary accession number(s): A8K064, P22627, Q9UC98

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	November 1, 1991
Last modified:	June 16, 2009
This is version 105 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)