O43395 (PRPF3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
U4/U6 small nuclear ribonucleoprotein Prp3

Alternative name(s):
Pre-mRNA-splicing factor 3
Short name=hPrp3
U4/U6 snRNP 90 kDa protein

Gene names

Name:	PRPF3
Synonyms:	HPRP3, PRP3

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	683 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Participates in pre-mRNA splicing. May play a role in the assembly of the U4/U5/U6 tri-snRNP complex.
Subunit structure	Interacts directly with PRPF4. Part of a heteromeric complex containing PPIH, PRPF3 and PRPF4 that is stable in the absence of RNA. This complex interacts with the U4/U5/U6 tri-snRNP complex. Ref.1 Ref.2
Subcellular location	Nucleus speckle. Note: Colocalizes with spliceosomal snRNPs.
Tissue specificity	Highly expressed in retina, liver, kidney and blood. Detected at lower levels in heart and brain. Ref.17
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14
Involvement in disease	Defects in PRPF3 are the cause of retinitis pigmentosa type 18 (RP18) [MIM:601414]. RP leads to degeneration of retinal photoreceptor cells. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP18 inheritance is autosomal dominant. Ref.17 Ref.18 Ref.19
Sequence similarities	Contains 1 PWI domain.

Ontologies

Keywords
Biological process	mRNA processing mRNA splicing
Cellular component	Nucleus Spliceosome
Coding sequence diversity	Polymorphism
Disease	Disease mutation Retinitis pigmentosa
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	nuclear mRNA splicing, via spliceosome Non-traceable author statement Ref.1. Source: UniProtKB
Cellular component	Cajal body Inferred from direct assay. Source: BHF-UCL cytoplasm Inferred from direct assay. Source: HPA nuclear speck Inferred from electronic annotation. Source: UniProtKB-SubCell spliceosomal complex Non-traceable author statement Ref.1. Source: UniProtKB
Molecular function	protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DVL3	Q92997	2	EBI-744322,EBI-739789

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 683

683

U4/U6 small nuclear ribonucleoprotein Prp3

PRO_0000097044

Regions

Domain

1 – 87

87

PWI

Compositional bias

579 – 584

6

Poly-Val

Amino acid modifications

Modified residue

133

1

Phosphoserine Ref.7 Ref.10

Modified residue

164

1

Phosphoserine Ref.11 Ref.13

Modified residue

167

1

Phosphothreonine Ref.11 Ref.13

Modified residue

356

1

Phosphoserine Ref.9

Modified residue

619

1

Phosphoserine Ref.6 Ref.8 Ref.10 Ref.11 Ref.12 Ref.14

Natural variations

Natural variant

12

1

K → N.
Corresponds to variant rs12736964 [ dbSNP | Ensembl ].

VAR_051286

Natural variant

493

1

P → S in RP18. Ref.17

VAR_046735

Natural variant

494

1

T → M in RP18; reduces phosphorylation; impairs binding to PRPF4; impairs self-association; affects interaction with the U4/U5/U6 tri-snRNP complex; does not affect global pre-mRNA splicing. Ref.17 Ref.18 Ref.19

VAR_016877

Experimental info

Sequence conflict

142

1

I → T in AAC09069. Ref.1

Sequence conflict

273 – 274

2

EL → SV in AAC09069. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

683

Helix Strand Turn

Details...

Helix

5 – 23

19

Helix

28 – 39

12

Helix

44 – 51

8

Turn

52 – 55

4

Helix

56 – 58

3

Helix

60 – 73

14

Sequences

	Sequence		Length	Mass (Da)
	O43395 [UniParc]. Last modified September 26, 2003. Version 2. Checksum: 4AA6AA4C99110284	FASTA	683	77,529
	10 20 30 40 50 60 MALSKRELDE LKPWIEKTVK RVLGFSEPTV VTAALNCVGK GMDKKKAADH LKPFLDDSTL 70 80 90 100 110 120 RFVDKLFEAV EEGRSSRHSK SSSDRSRKRE LKEVFGDDSE ISKESSGVKK RRIPRFEEVE 130 140 150 160 170 180 EEPEVIPGPP SESPGMLTKL QIKQMMEAAT RQIEERKKQL SFISPPTPQP KTPSSSQPER 190 200 210 220 230 240 LPIGNTIQPS QAATFMNDAI EKARKAAELQ ARIQAQLALK PGLIGNANMV GLANLHAMGI 250 260 270 280 290 300 APPKVELKDQ TKPTPLILDE QGRTVDATGK EIELTHRMPT LKANIRAVKR EQFKQQLKEK 310 320 330 340 350 360 PSEDMESNTF FDPRVSIAPS QRQRRTFKFH DKGKFEKIAQ RLRTKAQLEK LQAEISQAAR 370 380 390 400 410 420 KTGIHTSTRL ALIAPKKELK EGDIPEIEWW DSYIIPNGFD LTEENPKRED YFGITNLVEH 430 440 450 460 470 480 PAQLNPPVDN DTPVTLGVYL TKKEQKKLRR QTRREAQKEL QEKVRLGLMP PPEPKVRISN 490 500 510 520 530 540 LMRVLGTEAV QDPTKVEAHV RAQMAKRQKA HEEANAARKL TAEQRKVKKI KKLKEDISQG 550 560 570 580 590 600 VHISVYRVRN LSNPAKKFKI EANAGQLYLT GVVVLHKDVN VVVVEGGPKA QKKFKRLMLH 610 620 630 640 650 660 RIKWDEQTSN TKGDDDEESD EEAVKKTNKC VLVWEGTAKD RSFGEMKFKQ CPTENMAREH 670 680 FKKHGAEHYW DLALSESVLE STD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and characterization of human genes encoding Hprp3p and Hprp4p, interacting components of the spliceosome." Wang A., Forman-Kay J., Luo Y., Luo M., Chow Y.-H., Plumb J., Friesen J.D., Tsui L.-C., Heng H.H.Q., Woolford J.L. Jr., Hu J. Hum. Mol. Genet. 6:2117-2126(1997) [PubMed: 9328476] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH PRPF4 AND U4/U5/U6 SNRNPS.
[2]	"A new cyclophilin and the human homologues of yeast Prp3 and Prp4 form a complex associated with U4/U6 snRNPs." Horowitz D.S., Kobayashi R., Krainer A.R. RNA 3:1374-1387(1997) [PubMed: 9404889] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 93-101; 253-267; 351-361; 409-428 AND 560-576, INTERACTION WITH PPIH; PRPF4 AND U4/U6 SNRNPS. Tissue: Neuroepithelium.
[3]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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]. Tissue: Eye and Skin.
[6]	"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: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-619, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[7]	"Phosphoproteome analysis of the human mitotic spindle." Nousiainen M., Sillje H.H.W., Sauer G., Nigg E.A., Koerner R. Proc. Natl. Acad. Sci. U.S.A. 103:5391-5396(2006) [PubMed: 16565220] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-133, MASS SPECTROMETRY. Tissue: Cervix adenocarcinoma.
[8]	"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 SER-619, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[9]	"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: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-356, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[10]	"Evaluation of the low-specificity protease elastase for large-scale phosphoproteome analysis." Wang B., Malik R., Nigg E.A., Korner R. Anal. Chem. 80:9526-9533(2008) [PubMed: 19007248] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-133 AND SER-619, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"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-164; THR-167 AND SER-619, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography." Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., Zou H., Gu J. Proteomics 8:1346-1361(2008) [PubMed: 18318008] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-619, MASS SPECTROMETRY. Tissue: Liver.
[13]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-164 AND THR-167, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[14]	"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: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-619, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[15]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]	"Solution structure of PWI domain in U4/U6 small nuclear ribonucleoprotein PRP3(HPRP3)." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 1-79.
[17]	"Mutations in HPRP3, a third member of pre-mRNA splicing factor genes, implicated in autosomal dominant retinitis pigmentosa." Chakarova C.F., Hims M.M., Bolz H., Abu-Safieh L., Patel R.J., Papaioannou M.G., Inglehearn C.F., Keen T.J., Willis C., Moore A.T., Rosenberg T., Webster A.R., Bird A.C., Gal A., Hunt D., Vithana E.N., Bhattacharya S.S. Hum. Mol. Genet. 11:87-92(2002) [PubMed: 11773002] [Abstract] Cited for: VARIANTS RP18 SER-493 AND MET-494, TISSUE SPECIFICITY.
[18]	"Mutations in the pre-mRNA splicing-factor genes PRPF3, PRPF8, and PRPF31 in Spanish families with autosomal dominant retinitis pigmentosa." Martinez-Gimeno M., Gamundi M.J., Hernan I., Maseras M., Milla E., Ayuso C., Garcia-Sandoval B., Beneyto M., Vilela C., Baiget M., Antinolo G., Carballo M. Invest. Ophthalmol. Vis. Sci. 44:2171-2177(2003) [PubMed: 12714658] [Abstract] Cited for: VARIANT RP18 MET-494.
[19]	"Mutation in the splicing factor Hprp3p linked to retinitis pigmentosa impairs interactions within the U4/U6 snRNP complex." Gonzalez-Santos J.M., Cao H., Duan R.C., Hu J. Hum. Mol. Genet. 17:225-239(2008) [PubMed: 17932117] [Abstract] Cited for: CHARACTERIZATION OF VARIANT RP18 MET-494.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF001947 mRNA. Translation: AAC09069.1.
AF016370 mRNA. Translation: AAC51926.1.
AL611942 Genomic DNA. Translation: CAH70312.1.
CH471121 Genomic DNA. Translation: EAW53556.1.
BC000184 mRNA. Translation: AAH00184.1.
BC001954 mRNA. Translation: AAH01954.1.

IPI

IPI00005861.

PIR

T50839.
T50840.

RefSeq

NP_004689.1. NM_004698.2.

UniGene

Hs.11776.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1X4Q	NMR	-	A	1-79	[»]

ProteinModelPortal

O43395.

SMR

O43395. Positions 1-73.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-34508N.

IntAct

O43395. 10 interactions.

MINT

MINT-1445186.

STRING

O43395.

PTM databases

PhosphoSite

O43395.

Proteomic databases

PRIDE

O43395.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000324862; ENSP00000315379; ENSG00000117360.

GeneID

9129.

KEGG

hsa:9129.

UCSC

uc001eum.2. human.

Organism-specific databases

CTD

9129.

GeneCards

GC01P150293.

H-InvDB

HIX0001019.

HGNC

HGNC:17348. PRPF3.

HPA

HPA027226.

MIM

601414. phenotype.
607301. gene.

neXtProt

NX_O43395.

Orphanet

791. Retinitis pigmentosa.

PharmGKB

PA134892509.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG07204.

HOGENOM

HBG562230.

HOVERGEN

HBG053699.

InParanoid

O43395.

OMA

GVHVSVY.

OrthoDB

EOG4G7BXZ.

PhylomeDB

O43395.

Gene expression databases

ArrayExpress

O43395.

Bgee

O43395.

CleanEx

HS_PRPF3.

Genevestigator

O43395.

GermOnline

ENSG00000117360. Homo sapiens.

Family and domain databases

InterPro

IPR010541. DUF1115.
IPR013881. Pre-mRNA_splic_Prp3.
IPR002483. PWI.
[Graphical view]

Gene3D

G3DSA:1.20.1390.10. PWI. 1 hit.

KO

K12843.

Pfam

PF06544. DUF1115. 1 hit.
PF08572. PRP3. 1 hit.
PF01480. PWI. 1 hit.
[Graphical view]

SMART

SM00311. PWI. 1 hit.
[Graphical view]

PROSITE

PS51025. PWI. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

34221.

PMAP-CutDB

O43395.

SOURCE

Search...

Entry information

Entry name

PRPF3_HUMAN

Accession

Primary (citable) accession number: O43395
Secondary accession number(s): O43446, Q5VT54

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2003
Last sequence update:	September 26, 2003
Last modified:	January 25, 2012
This is version 113 of the entry and version 2 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.