Q92945 (FUBP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Far upstream element-binding protein 2
Short name=FUSE-binding protein 2

Alternative name(s):
KH type-splicing regulatory protein
Short name=KSRP
p75

Gene names

Name:	KHSRP
Synonyms:	FUBP2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	711 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Binds to the dendritic targeting element and may play a role in mRNA trafficking By similarity. Part of a ternary complex that binds to the downstream control sequence (DCS) of the pre-mRNA. Mediates exon inclusion in transcripts that are subject to tissue-specific alternative splicing. May interact with single-stranded DNA from the far-upstream element (FUSE). May activate gene expression. Also involved in degradation of inherently unstable mRNAs that contain AU-rich elements (AREs) in their 3'-UTR, possibly by recruiting degradation machinery to ARE-containing mRNAs. Ref.1 Ref.5 Ref.8
Subunit structure	Part of a ternary complex containing FUBP2, PTBP1, PTBP2 and HNRPH1. Interacts with PARN. Ref.8 Ref.9
Subcellular location	Nucleus. Cytoplasm. Note: A small proportion is also found in the cytoplasm of neuronal cell bodies and dendrites By similarity. Ref.21
Tissue specificity	Detected in neural and non-neural cell lines.
Domain	KH domains KH 3 and KH 4 behave as independent binding modules and can interact with different regions of the AU-rich RNA targets of degradation.
Post-translational modification	Phosphorylation at Ser-193 leads to the unfolding of the unstable KH domain 1, creating a site for 14-3-3 YWHAZ binding, which promotes nuclear localization and impairs the RNA degradation function.
Sequence similarities	Belongs to the KHSRP family. Contains 4 KH domains.
Sequence caution	The sequence AAC50892.1 differs from that shown. Reason: Frameshift at positions 304, 309, 466 and 473. The sequence AAH85004.1 differs from that shown. Reason: Aberrant splicing.

Ontologies

Keywords
Biological process	Transcription Transcription regulation Transport mRNA processing mRNA splicing mRNA transport
Cellular component	Cytoplasm Nucleus
Domain	Repeat
Ligand	DNA-binding RNA-binding
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	RNA splicing, via transesterification reactions Traceable author statement PubMed 10911989. Source: UniProtKB mRNA processing Traceable author statement Ref.1. Source: ProtInc mRNA transport Inferred from electronic annotation. Source: UniProtKB-KW regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasmic stress granule Inferred from electronic annotation. Source: Compara cytosol Traceable author statement. Source: Reactome nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW RNA binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 711

711

Far upstream element-binding protein 2

PRO_0000050137

Regions

Domain

144 – 208

65

KH 1

Domain

233 – 299

67

KH 2

Domain

322 – 386

65

KH 3

Domain

424 – 491

68

KH 4

Repeat

571 – 582

12

1

Repeat

617 – 628

12

2

Repeat

643 – 654

12

3

Repeat

673 – 684

12

4

Region

571 – 684

114

4 X 12 AA imperfect repeats

Compositional bias

7 – 67

61

Gly/Pro-rich

Compositional bias

68 – 496

429

Gly-rich

Compositional bias

498 – 612

115

Ala/Gly/Pro-rich

Amino acid modifications

Modified residue

100

1

Phosphothreonine Ref.14

Modified residue

181

1

Phosphoserine Ref.11 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.19

Modified residue

193

1

Phosphoserine Ref.21

Modified residue

274

1

Phosphoserine Ref.14 Ref.19

Modified residue

480

1

Phosphoserine Ref.10 Ref.17 Ref.19

Experimental info

Sequence conflict

46

1

G → C in AAB53222. Ref.1

Sequence conflict

46

1

G → C in AAD29861. Ref.4

Sequence conflict

96

1

V → G in AAC50892. Ref.5

Sequence conflict

406 – 407

2

MP → I in AAC50892. Ref.5

Sequence conflict

422

1

Missing in AAC50892. Ref.5

Sequence conflict

487 – 488

2

AK → CR in AAC50892. Ref.5

Sequence conflict

694 – 696

3

GPG → VP in AAC50892. Ref.5

Secondary structure

1

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711

Helix Strand Turn

Details...

Beta strand

132 – 134

3

Helix

141 – 144

4

Beta strand

146 – 151

6

Helix

153 – 159

7

Turn

161 – 163

3

Helix

165 – 174

10

Beta strand

179 – 183

5

Beta strand

188 – 194

7

Helix

198 – 216

19

Beta strand

234 – 240

7

Turn

242 – 244

3

Turn

245 – 249

5

Turn

251 – 253

3

Helix

254 – 261

8

Beta strand

265 – 269

5

Beta strand

271 – 273

3

Beta strand

275 – 279

5

Beta strand

281 – 287

7

Helix

289 – 302

14

Beta strand

306 – 308

3

Turn

317 – 319

3

Beta strand

325 – 330

6

Turn

331 – 333

3

Helix

334 – 338

5

Beta strand

340 – 342

3

Helix

343 – 352

10

Beta strand

355 – 358

4

Beta strand

363 – 375

13

Helix

376 – 393

18

Beta strand

400 – 405

6

Turn

413 – 415

3

Beta strand

427 – 432

6

Helix

433 – 435

3

Turn

436 – 438

3

Turn

441 – 444

4

Helix

446 – 453

8

Beta strand

454 – 460

7

Beta strand

472 – 479

8

Helix

481 – 494

14

Sequences

	Sequence		Length	Mass (Da)
	Q92945 [UniParc]. Last modified November 30, 2010. Version 4. Checksum: AB0B7C0B5B938114	FASTA	711	73,115
	10 20 30 40 50 60 MSDYSTGGPP PGPPPPAGGG GGAGGAGGGP PPGPPGAGDR GGGGPGGGGP GGGSAGGPSQ 70 80 90 100 110 120 PPGGGGPGIR KDAFADAVQR ARQIAAKIGG DAATTVNNST PDFGFGGQKR QLEDGDQPES 130 140 150 160 170 180 KKLASQGDSI SSQLGPIHPP PRTSMTEEYR VPDGMVGLII GRGGEQINKI QQDSGCKVQI 190 200 210 220 230 240 SPDSGGLPER SVSLTGAPES VQKAKMMLDD IVSRGRGGPP GQFHDNANGG QNGTVQEIMI 250 260 270 280 290 300 PAGKAGLVIG KGGETIKQLQ ERAGVKMILI QDGSQNTNVD KPLRIIGDPY KVQQACEMVM 310 320 330 340 350 360 DILRERDQGG FGDRNEYGSR IGGGIDVPVP RHSVGVVIGR SGEMIKKIQN DAGVRIQFKQ 370 380 390 400 410 420 DDGTGPEKIA HIMGPPDRCE HAARIINDLL QSLRSGPPGP PGGPGMPPGG RGRGRGQGNW 430 440 450 460 470 480 GPPGGEMTFS IPTHKCGLVI GRGGENVKAI NQQTGAFVEI SRQLPPNGDP NFKLFIIRGS 490 500 510 520 530 540 PQQIDHAKQL IEEKIEGPLC PVGPGPGGPG PAGPMGPFNP GPFNQGPPGA PPHAGGPPPH 550 560 570 580 590 600 QYPPQGWGNT YPQWQPPAPH DPSKAAAAAA DPNAAWAAYY SHYYQQPPGP VPGPAPAPAA 610 620 630 640 650 660 PPAQGEPPQP PPTGQSDYTK AWEEYYKKIG QQPQQPGAPP QQDYTKAWEE YYKKQAQVAT 670 680 690 700 710 GGGPGAPPGS QPDYSAAWAE YYRQQAAYYG QTPGPGGPQP PPTQQGQQQA Q

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A new regulatory protein, KSRP, mediates exon inclusion through an intronic splicing enhancer." Min H., Turck C.W., Nikolic J.M., Black D.L. Genes Dev. 11:1023-1036(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 72-85; 123-128; 267-281; 283-291; 348-359; 474-488; 489-494; 621-627; 629-646 AND 647-653, FUNCTION. Tissue: Neuroblastoma and Retinoblastoma.
[2]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Ovary.
[4]	"Mapping of the KHSRP gene to a region of conserved synteny on human chromosome 19p13.3 and mouse chromosome 17." Ring H.Z., Vameghi-Meyers V., Nikolic J.M., Min H., Black D.L., Francke U. Genomics 56:350-352(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-115 AND 573-711.
[5]	"The far upstream element-binding proteins comprise an ancient family of single-strand DNA-binding transactivators." Davis-Smyth T., Duncan R.C., Zheng T., Michelotti G., Levens D. J. Biol. Chem. 271:31679-31687(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 60-711, FUNCTION. Tissue: B-cell lymphoma and Skeletal muscle.
[6]	Lubec G., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 151-162; 321-331 AND 385-394, MASS SPECTROMETRY. Tissue: Fetal brain cortex.
[7]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 183-566. Tissue: Brain.
[8]	"Cooperative assembly of an hnRNP complex induced by a tissue-specific homolog of polypyrimidine tract binding protein." Markovtsov V., Nikolic J.M., Goldman J.A., Turck C.W., Chou M.-Y., Black D.L. Mol. Cell. Biol. 20:7463-7479(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PTBP1; PTBP2 AND HNRPH1.
[9]	"A KH domain RNA binding protein, KSRP, promotes ARE-directed mRNA turnover by recruiting the degradation machinery." Gherzi R., Lee K.-Y., Briata P., Wegmueller D., Moroni C., Karin M., Chen C.-Y. Mol. Cell 14:571-583(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PARN.
[10]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-480, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Embryonic kidney.
[13]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-100; SER-181 AND SER-274, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[15]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181, MASS SPECTROMETRY.
[16]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[17]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181 AND SER-480, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[18]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[19]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181; SER-274 AND SER-480, MASS SPECTROMETRY.
[20]	"The structure of the C-terminal KH domains of KSRP reveals a noncanonical motif important for mRNA degradation." Garcia-Mayoral M.F., Hollingworth D., Masino L., Diaz-Moreno I., Kelly G., Gherzi R., Chou C.F., Chen C.Y., Ramos A. Structure 15:485-498(2007) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 218-418 AND 423-525.
[21]	"Phosphorylation-mediated unfolding of a KH domain regulates KSRP localization via 14-3-3 binding." Diaz-Moreno I., Hollingworth D., Frenkiel T.A., Kelly G., Martin S., Howell S., Garcia-Mayoral M., Gherzi R., Briata P., Ramos A. Nat. Struct. Mol. Biol. 16:238-246(2009) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 130-218 AND 221-305, PHOSPHORYLATION AT SER-193, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U94832 mRNA. Translation: AAB53222.1.
AC011491 Genomic DNA. No translation available.
AC011539 Genomic DNA. No translation available.
BC085004 mRNA. Translation: AAH85004.1. Sequence problems.
AF093747, AF093745 Genomic DNA. Translation: AAD29861.1.
AF093748 Genomic DNA. Translation: AAD29862.1.
U69126 mRNA. Translation: AAC50892.1. Frameshift.
AB209662 mRNA. Translation: BAD92899.1.

IPI

IPI00479786.
IPI00855957.

RefSeq

NP_003676.2. NM_003685.2.

UniGene

Hs.727344.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2HH2	NMR	-	A	423-525	[»]
2HH3	NMR	-	A	318-418	[»]
2JVZ	NMR	-	A	233-396	[»]
2OPU	NMR	-	A	130-218	[»]
2OPV	NMR	-	A	221-305	[»]
4B8T	NMR	-	A	317-418	[»]

ProteinModelPortal

Q92945.

SMR

Q92945. Positions 130-503.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-48484N.

IntAct

Q92945. 10 interactions.

STRING

9606.ENSP00000381216.

PTM databases

PhosphoSite

Q92945.

Polymorphism databases

DMDM

160380711.

2D gel databases

REPRODUCTION-2DPAGE

Q92945.

Proteomic databases

PaxDb

Q92945.

PRIDE

Q92945.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000398148; ENSP00000381216; ENSG00000088247.

GeneID

8570.

KEGG

hsa:8570.

UCSC

uc002mer.4. human.

Organism-specific databases

CTD

8570.

GeneCards

GC19M006413.

H-InvDB

HIX0040083.

HGNC

HGNC:6316. KHSRP.

HPA

HPA034739.

MIM

603445. gene.

neXtProt

NX_Q92945.

PharmGKB

PA30097.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG300923.

HOGENOM

HOG000231552.

HOVERGEN

HBG000625.

InParanoid

Q92945.

KO

K13210.

OMA

QASGNCH.

PhylomeDB

Q92945.

Enzyme and pathway databases

Reactome

REACT_21257. Metabolism of RNA.
REACT_71. Gene Expression.

Gene expression databases

Bgee

Q92945.

CleanEx

HS_KHSRP.

Genevestigator

Q92945.

GermOnline

ENSG00000088247. Homo sapiens.

Family and domain databases

InterPro

IPR015096. DUF1897.
IPR004087. KH_dom.
IPR004088. KH_dom_type_1.
[Graphical view]

Pfam

PF09005. DUF1897. 2 hits.
PF00013. KH_1. 4 hits.
[Graphical view]

SMART

SM00322. KH. 4 hits.
[Graphical view]

PROSITE

PS50084. KH_TYPE_1. 4 hits.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL1795105.

ChiTaRS

KHSRP. human.

EvolutionaryTrace

Q92945.

GenomeRNAi

8570.

NextBio

32149.

PMAP-CutDB

Q92945.

SOURCE

Search...

Entry information

Entry name

FUBP2_HUMAN

Accession

Primary (citable) accession number: Q92945
Secondary accession number(s): O00301 , Q59EZ9, Q5U4P6, Q9UNT5, Q9UQH5

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2003
Last sequence update:	November 30, 2010
Last modified:	May 1, 2013
This is version 125 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.