Reviewed, UniProtKB/Swiss-Prot O43395 (PRPF3_HUMAN)

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.
Sequence processing	The displayed sequence is not processed.
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, HPRP3P 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.13
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11
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.13 Ref.14 Ref.15
Sequence similarities	Contains 1 PWI domain.

Ontologies

Keywords
Biological process	Sensory transduction Vision mRNA processing mRNA splicing
Cellular component	Nucleus Spliceosome
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Retinitis pigmentosa
PTM	Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	nuclear mRNA splicing, via spliceosome Ref.1 Non-traceable author statement. Source: UniProtKB response to stimulus Inferred from electronic annotation. Source: UniProtKB-KW visual perception Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nuclear speck Inferred from electronic annotation. Source: UniProtKB-SubCell spliceosome Ref.1 Non-traceable author statement. Source: UniProtKB
Molecular function	RNA splicing factor activity, transesterification mechanism Ref.1 Traceable author statement. Source: UniProtKB protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DVL3	Q92997	1	EBI-744322,EBI-739789
RNPS1	Q15287	1	EBI-744322,EBI-395959
SNRPN	P63162	1	EBI-744322,EBI-712493

Alternative products

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

Isoform 1 (identifier: O43395-1)

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: O43395-2)

The sequence of this isoform differs from the canonical sequence as follows:
     587-587: Missing.

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

Modified residue

164

1

Phosphoserine Ref.10

Modified residue

167

1

Phosphothreonine Ref.10

Modified residue

356

1

Phosphoserine Ref.9

Modified residue

619

1

Phosphoserine Ref.6 Ref.8 Ref.10 Ref.11

Natural variations

Alternative sequence

587

1

Missing in isoform 2.

VSP_008326

Natural variant

12

1

K → N: dbSNP rs12736964.

VAR_051286

Natural variant

493

1

P → S in RP18. Ref.13

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.13 Ref.14 Ref.15

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)
	Isoform 1 [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
	Isoform 2. Checksum: 556C74E7EADDF1D2		682	77,472
	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 VVVVEGPKAQ KKFKRLMLHR 610 620 630 640 650 660 IKWDEQTSNT KGDDDEESDE EAVKKTNKCV LVWEGTAKDR SFGEMKFKQC PTENMAREHF 670 680 KKHGAEHYWD LALSESVLES TD

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] (ISOFORM 2), 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] (ISOFORM 1), 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] (ISOFORM 1). 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: Epithelium.
[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: Epithelium.
[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.
[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.
[10]	"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.
[11]	"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.
[12]	"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.
[13]	"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.
[14]	"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.
[15]	"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

EMBLGenBankDDBJ

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.

PIR

T50839.
T50840.

RefSeq

NP_004689.1.

UniGene

Hs.11776

3D structure databases

PDBMSD

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

ModBase

Search...

Protein-protein interaction databases

IntAct

O43395. 7 interactions.

PTM databases

PhosphoSite

O43395.

Proteomic databases

PRIDE

O43395.

Genome annotation databases

Ensembl

ENSG00000117360. Homo sapiens. [Contig view]

GeneID

9129.

KEGG

hsa:9129.

Organism-specific databases

GeneCards

GC01P148560.

H-InvDB

HIX0001019.

HGNC

HGNC:17348. PRPF3.

MIM

601414. phenotype.
607301. gene.

Orphanet

791. Retinitis pigmentosa.

PharmGKB

PA134892509.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

O43395.

HOVERGEN

O43395.

Gene expression databases

ArrayExpress

O43395.

CleanEx

HS_PRPF3.

GermOnline

ENSG00000117360. Homo sapiens.

Family and domain databases

InterPro

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

Pfam

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 Resources

LinkHub

O43395.

NextBio

34221.

SOURCE

Search...

Entry information

Entry name	PRPF3_HUMAN
Accession	Primary (citable) accession number: O43395 Secondary accession number(s)