Q9H1J1 (REN3A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Regulator of nonsense transcripts 3A

Alternative name(s):
Nonsense mRNA reducing factor 3A
Up-frameshift suppressor 3 homolog A
Short name=hUpf3

Gene names

Name:	UPF3A
Synonyms:	RENT3A, UPF3

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

General annotation (Comments)

Function	Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by associating with the nuclear exon junction complex (EJC) and serving as link between the EJC core and NMD machinery. Recruits UPF2 at the cytoplasmic side of the nuclear envelope and the subsequent formation of an UPF1-UPF2-UPF3 surveillance complex (including UPF1 bound to release factors at the stalled ribosome) is believed to activate NMD. However, UPF3A is shown to be only marginally active in NMD as compared to UPF3B. Binds spliced mRNA upstream of exon-exon junctions. In vitro, weakly stimulates translation. Ref.1 Ref.9
Subunit structure	Found in a post-splicing messenger ribonucleoprotein (mRNP) complex. Associates with the exon junction complex (EJC). Interacts with UPF2 and RBM8A. Ref.1 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9
Subcellular location	Nucleus. Cytoplasm. Note: Shuttling between the nucleus and the cytoplasm. Ref.1 Ref.5
Tissue specificity	Isoform 1 is strongly expressed in testis, uterus, muscle, fetal brain and spinal cord. Isoform 2 is strongly expressed in fetal brain and spinal cord. Ref.5
Sequence similarities	Belongs to the RENT3 family.

Ontologies

Keywords
Biological process	Nonsense-mediated mRNA decay Transport mRNA transport
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	RNA-binding
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	gene expression Traceable author statement. Source: Reactome mRNA transport Inferred from electronic annotation. Source: UniProtKB-KW nuclear-transcribed mRNA catabolic process, nonsense-mediated decay Non-traceable author statement Ref.1. Source: UniProtKB positive regulation of translation Inferred from direct assay Ref.9. Source: UniProtKB
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleus Non-traceable author statement Ref.1. Source: UniProtKB plasma membrane Inferred from direct assay. Source: HPA
Molecular_function	RNA binding Inferred from electronic annotation. Source: UniProtKB-KW nucleocytoplasmic transporter activity Non-traceable author statement Ref.1. Source: UniProtKB nucleotide binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RBM8A	Q9Y5S9	4	EBI-521530,EBI-447231
UPF1	Q92900	4	EBI-521530,EBI-373471

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9H1J1-1)

Also known as: hUpf3p; hUPF3L;

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: Q9H1J1-2)

Also known as: hUpf3pdelta; hUPF3S;

The sequence of this isoform differs from the canonical sequence as follows:
     141-173: Missing.

Isoform 3 (identifier: Q9H1J1-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-325: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 476

476

Regulator of nonsense transcripts 3A

PRO_0000215296

Regions

Region

66 – 140

75

Required for interaction with UPF2

Region

421 – 434

14

Required for association with EIF4A3 and ECJ core components CASC3, MAGOH and RBM8A

Amino acid modifications

Modified residue

341

1

Phosphoserine Ref.10

Natural variations

Alternative sequence

1 – 325

325

Missing in isoform 3.

VSP_012961

Alternative sequence

141 – 173

33

Missing in isoform 2.

VSP_012962

Natural variant

64

1

R → K.
Corresponds to variant rs3752105 [ dbSNP | Ensembl ].

VAR_062143

Experimental info

Mutagenesis

432

1

A → R: Increases NMD activity and translation stimulation. Ref.9

Sequence conflict

25

1

K → M in AAG60690. Ref.5

Secondary structure

1

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.

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476

Helix Strand Turn

Details...

Beta strand

70 – 73

4

Helix

81 – 84

4

Turn

85 – 88

4

Beta strand

92 – 96

5

Beta strand

104 – 106

3

Beta strand

115 – 119

5

Helix

121 – 130

10

Beta strand

134 – 137

4

Beta strand

143 – 150

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (hUpf3p) (hUPF3L) [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 023031890E47C4EB	FASTA	476	54,696
	10 20 30 40 50 60 MRSEKEGAGG LRAAVAARGP SGREKLSALE VQFHRDSQQQ EAETPPTSSS GCGGGAGKPR 70 80 90 100 110 120 EEKRTALSKV VIRRLPPGLT KEQLEEQLRP LPAHDYFEFF AADLSLYPHL YSRAYINFRN 130 140 150 160 170 180 PDDILLFRDR FDGYIFLDSK GLEYPAVVEF APFQKIAKKK LRKKDAKTGS IEDDPEYKKF 190 200 210 220 230 240 LETYCVEEEK TSANPETLLG EMEAKTRELI ARRTTPLLEY IKNRKLEKQR IREEKREERR 250 260 270 280 290 300 RRELEKKRLR EEEKRRRREE ERCKKKETDK QKKIAEKEVR IKLLKKPEKG EEPTTEKPKE 310 320 330 340 350 360 RGEEIDTGGG KQESCAPGAV VKARPMEGSL EEPQETSHSG SDKEHRDVER SQEQESEAQR 370 380 390 400 410 420 YHVDDGRRHR AHHEPERLSR RSEDEQRWGK GPGQDRGKKG SQDSGAPGEA MERLGRAQRC 430 440 450 460 470 DDSPAPRKER LANKDRPALQ LYDPGARFRA RECGGNRRIC KAEGSGTGPE KREEAE
	Isoform 2 (hUpf3pdelta) (hUPF3S) [UniParc]. Checksum: D2810FFFB457C889	FASTA	443	51,008
	10 20 30 40 50 60 MRSEKEGAGG LRAAVAARGP SGREKLSALE VQFHRDSQQQ EAETPPTSSS GCGGGAGKPR 70 80 90 100 110 120 EEKRTALSKV VIRRLPPGLT KEQLEEQLRP LPAHDYFEFF AADLSLYPHL YSRAYINFRN 130 140 150 160 170 180 PDDILLFRDR FDGYIFLDSK DPEYKKFLET YCVEEEKTSA NPETLLGEME AKTRELIARR 190 200 210 220 230 240 TTPLLEYIKN RKLEKQRIRE EKREERRRRE LEKKRLREEE KRRRREEERC KKKETDKQKK 250 260 270 280 290 300 IAEKEVRIKL LKKPEKGEEP TTEKPKERGE EIDTGGGKQE SCAPGAVVKA RPMEGSLEEP 310 320 330 340 350 360 QETSHSGSDK EHRDVERSQE QESEAQRYHV DDGRRHRAHH EPERLSRRSE DEQRWGKGPG 370 380 390 400 410 420 QDRGKKGSQD SGAPGEAMER LGRAQRCDDS PAPRKERLAN KDRPALQLYD PGARFRAREC 430 440 GGNRRICKAE GSGTGPEKRE EAE
	Isoform 3 [UniParc]. Checksum: A1CD017051B33DEA	FASTA	151	17,112
	10 20 30 40 50 60 MEGSLEEPQE TSHSGSDKEH RDVERSQEQE SEAQRYHVDD GRRHRAHHEP ERLSRRSEDE 70 80 90 100 110 120 QRWGKGPGQD RGKKGSQDSG APGEAMERLG RAQRCDDSPA PRKERLANKD RPALQLYDPG 130 140 150 ARFRARECGG NRRICKAEGS GTGPEKREEA E

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream of a termination codon." Lykke-Andersen J., Shu M.-D., Steitz J.A. Cell 103:1121-1131(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION IN NONSENSE-MEDIATED MRNA DECAY, INTERACTION WITH UPF1 AND UPF2, SUBCELLULAR LOCATION.
[2]	"The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T. Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3). Tissue: Brain and Eye.
[5]	"Identification and characterization of human orthologues to Saccharomyces cerevisiae Upf2 protein and Upf3 protein (Caenorhabditis elegans SMG-4)." Serin G., Gersappe A., Black J.D., Aronoff R., Maquat L.E. Mol. Cell. Biol. 21:209-223(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 25-476 (ISOFORM 1), INTERACTION WITH UPF2, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Cervix carcinoma.
[6]	"Role of the nonsense-mediated decay factor hUpf3 in the splicing-dependent exon-exon junction complex." Kim V.N., Kataoka N., Dreyfuss G. Science 293:1832-1836(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RBM8A, IDENTIFICATION IN A POST-SPLICING MRNP COMPLEX, ASSOCIATION WITH THE EJC COMPLEX, RNA-BINDING.
[7]	"Communication of the position of exon-exon junctions to the mRNA surveillance machinery by the protein RNPS1." Lykke-Andersen J., Shu M.-D., Steitz J.A. Science 293:1836-1839(2001) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A POST-SPLICING MRNP COMPLEX, ASSOCIATION WITH THE EJC COMPLEX.
[8]	"Characterization of human Smg5/7a: a protein with similarities to Caenorhabditis elegans SMG5 and SMG7 that functions in the dephosphorylation of Upf1." Chiu S.-Y., Serin G., Ohara O., Maquat L.E. RNA 9:77-87(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PROBABLE INTERACTION WITH SMG1.
[9]	"Functions of hUpf3a and hUpf3b in nonsense-mediated mRNA decay and translation." Kunz J.B., Neu-Yilik G., Hentze M.W., Kulozik A.E., Gehring N.H. RNA 12:1015-1022(2006) [PubMed] [Europe PMC] [Abstract] Cited for: LACK OF ACTIVITY IN NMD, FUNCTION IN TRANSLATION STIMULATION, PROTEIN INTERACTION, MUTAGENESIS OF ALA-432.
[10]	"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-341, MASS SPECTROMETRY.
[11]	"Solution NMR structure of nonsense mRNA reducing factor 3A from H. sapiens, northeast structural genomics consortium target HR4714B." Northeast structural genomics consortium (NESG) Submitted (AUG-2010) to the PDB data bank Cited for: STRUCTURE BY NMR OF 70-155.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AY013250 mRNA. Translation: AAG48510.1.
AL160396 Genomic DNA. Translation: CAM22288.1.
CH471085 Genomic DNA. Translation: EAX09252.1.
BC008694 mRNA. Translation: AAH08694.1.
BC023569 mRNA. Translation: AAH23569.1.
AF318575 mRNA. Translation: AAG60690.1.

IPI

IPI00011138.
IPI00082830.
IPI00552066.

RefSeq

NP_075387.1. NM_023011.3.
NP_542418.1. NM_080687.2.

UniGene

Hs.533855.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2L08	NMR	-	A	70-155	[»]

ProteinModelPortal

Q9H1J1.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31146N.

IntAct

Q9H1J1. 19 interactions.

MINT

MINT-1417517.

STRING

9606.ENSP00000364448.

PTM databases

PhosphoSite

Q9H1J1.

Polymorphism databases

DMDM

60390646.

Proteomic databases

PaxDb

Q9H1J1.

PRIDE

Q9H1J1.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000351487; ENSP00000329592; ENSG00000169062.
ENST00000375299; ENSP00000364448; ENSG00000169062.

GeneID

65110.

KEGG

hsa:65110.

UCSC

uc001vup.3. human.
uc001vuq.3. human.

Organism-specific databases

CTD

65110.

GeneCards

GC13P115047.

HGNC

HGNC:20332. UPF3A.

HPA

HPA018325.

MIM

605530. gene.

neXtProt

NX_Q9H1J1.

PharmGKB

PA134961553.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG251520.

HOVERGEN

HBG059714.

InParanoid

Q9H1J1.

KO

K14328.

OMA

PDRGKKG.

OrthoDB

EOG4DNF53.

PhylomeDB

Q9H1J1.

Enzyme and pathway databases

Reactome

REACT_21257. Metabolism of RNA.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

Q9H1J1.

Bgee

Q9H1J1.

CleanEx

HS_UPF3A.

Genevestigator

Q9H1J1.

GermOnline

ENSG00000169062. Homo sapiens.

Family and domain databases

Gene3D

3.30.70.330. 1 hit.

InterPro

IPR005120. Nonsense_mediated_decay_UPF3.
IPR012677. Nucleotide-bd_a/b_plait.
[Graphical view]

Pfam

PF03467. Smg4_UPF3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

UPF3A. human.

EvolutionaryTrace

Q9H1J1.

GenomeRNAi

65110.

NextBio

67308.

SOURCE

Search...

Entry information

Entry name

REN3A_HUMAN

Accession

Primary (citable) accession number: Q9H1J1
Secondary accession number(s): A2A366 , Q5T8C3, Q5T8C9, Q7Z6N3, Q86YK1, Q9BZI8

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 2005
Last sequence update:	March 1, 2001
Last modified:	May 1, 2013
This is version 100 of the entry and version 1 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.