Reviewed, UniProtKB/Swiss-Prot Q01780 (EXOSX_HUMAN)

Names and origin

Protein names

Recommended name:
    Exosome component 10
Alternative name(s):
    Polymyositis/scleroderma autoantigen 2
    Autoantigen PM/Scl 2
    Polymyositis/scleroderma autoantigen 100 kDa
      Short name=PM/Scl-100
    P100 polymyositis-scleroderma overlap syndrome-associated autoantigen

Gene names

Name:	EXOSC10
Synonyms:	PMSCL, PMSCL2

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	885 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Part of a post-splicing multiprotein complex involved in both mRNA nuclear export and mRNA surveillance. Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons. Component of the exosome 3'->5' exoribonuclease complex, a complex that degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions. Required for the 3'processing of the 7S pre-RNA to the mature 5.8S rRNA. Could be an exonuclease By similarity. Mediates the association of MTR4, C1D and MPP6 wth the exosome and this complex is required for the maturation of 5.8S rRNA. Required for nucleolar localization of C1D.
Subunit structure	Component of the exosome multienzyme ribonuclease complex composed of at least 11 proteins: EXOSC1/CSL4, EXOSC2/RRP4, EXOSC3/RRP40, EXOSC4/RRP41, EXOSC5/RRP46, EXOSC6/MTR3, EXOSC7/RRP42, EXOSC8/RRP43, EXOSC9/Scl-75, DIS3/RRP44, and EXOSC10/Scl-100 (only in the nuclear complex). Found in a mRNA decay complex with RENT1, RENT2 and RENT3B. Also associated with the GTPase Ran By similarity. Interacts with PTGES2. Interacts with C1D. Forms a heterotrimeric complex with C1D and MPP6 in vitro.
Subcellular location	Cytoplasm. Nucleus › nucleolus. Ref.7 Ref.8 Ref.10
Involvement in disease	Antibodies against PM/SCL are found in patients with polymyositis and/or scleroderma.
Sequence similarities	Contains 1 3'-5' exonuclease domain. Contains 1 HRDC domain.

Ontologies

Keywords
Biological process	Nonsense-mediated mRNA decay rRNA processing
Cellular component	Cytoplasm Exosome Nucleus
Coding sequence diversity	Alternative splicing
Ligand	RNA-binding
Molecular function	Exonuclease Hydrolase Nuclease
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	nuclear-transcribed mRNA catabolic process, nonsense-mediated decay Inferred from electronic annotation. Source: UniProtKB-KW rRNA processing Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nuclear exosome (RNase complex) Inferred from electronic annotation. Source: InterPro nucleolus Ref.1 Traceable author statement. Source: ProtInc
Molecular function	3'-5' exonuclease activity Inferred from electronic annotation. Source: InterPro RNA binding Inferred from electronic annotation. Source: UniProtKB-KW identical protein binding Ref.9 Inferred from physical interaction. Source: IntAct protein serine/threonine kinase activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		1	EBI-358236,EBI-358236
B9D1	Q9UPM9	1	EBI-358236,EBI-372535
CHPF	Q8IZ52	1	EBI-358236,EBI-372500
CIB1	Q99828	1	EBI-358236,EBI-372594
DIS3	Q9Y2L1	1	EBI-358236,EBI-373539
dJ69B10.1	Q96KM8	1	EBI-358236,EBI-373200
DOM3Z	O77932	1	EBI-358236,EBI-372173
EXOSC4	Q9NPD3	1	EBI-358236,EBI-371823
EXOSC5	Q9NQT4	1	EBI-358236,EBI-371876
EXOSC7	Q15024	1	EBI-358236,EBI-371841
EXOSC8	Q96B26	1	EBI-358236,EBI-371922
FERMT3	Q86UX7	1	EBI-358236,EBI-373158
FOXRED1	Q96CU9	1	EBI-358236,EBI-372820
HIATL1	Q5SR56	1	EBI-358236,EBI-373355
LSM2	Q9Y333	1	EBI-358236,EBI-347416
LSM8	O95777	1	EBI-358236,EBI-347779
MPHOSPH6	Q99547	1	EBI-358236,EBI-373187
NOMO1	Q15155	1	EBI-358236,EBI-373107
PTGES2	Q9H7Z7	1	EBI-358236,EBI-681645
RPE	Q96AT9	1	EBI-358236,EBI-372480
RUVBL2	Q9Y230	1	EBI-358236,EBI-352939
SCRIB	Q14160	1	EBI-358236,EBI-357345
SKIV2L	Q15477	1	EBI-358236,EBI-373226
SSRP1	Q08945	1	EBI-358236,EBI-353771
TARDBP	Q13148	1	EBI-358236,EBI-372899
UPF2	Q9HAU5	1	EBI-358236,EBI-372073
USP21	Q9UK80	1	EBI-358236,EBI-373242
XRN2	Q9H0D6	1	EBI-358236,EBI-372110

Alternative products

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

Isoform 1 (identifier: Q01780-1)

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: Q01780-2)

The sequence of this isoform differs from the canonical sequence as follows:
     695-719: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 885

885

Exosome component 10

PRO_0000087133

Regions

Domain

503 – 583

81

HRDC

Natural variations

Alternative sequence

695 – 719

25

Missing in isoform 2.

VSP_004362

Secondary structure

1

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885

Helix Strand Turn

Details...

Helix

492 – 495

4

Beta strand

497 – 500

4

Helix

504 – 523

20

Helix

528 – 531

4

Helix

534 – 543

10

Beta strand

546 – 548

3

Helix

549 – 553

5

Beta strand

555 – 557

3

Turn

560 – 565

6

Helix

566 – 578

13

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 1, 2000. Version 2. Checksum: A37BDC8F49BF2E57	FASTA	885	100,831
	10 20 30 40 50 60 MAPPSTREPR VLSATSATKS DGEMVLPGFP DADSFVKFAL GSVVAVTKAS GGLPQFGDEY 70 80 90 100 110 120 DFYRSFPGFQ AFCETQGDRL LQCMSRVMQY HGCRSNIKDR SKVTELEDKF DLLVDANDVI 130 140 150 160 170 180 LERVGILLDE ASGVNKNQQP VLPAGLQVPK TVVSSWNRKA AEYGKKAKSE TFRLLHAKNI 190 200 210 220 230 240 IRPQLKFREK IDNSNTPFLP KIFIKPNAQK PLPQALSKER RERPQDRPED LDVPPALADF 250 260 270 280 290 300 IHQQRTQQVE QDMFAHPYQY ELNHFTPADA VLQKPQPQLY RPIEETPCHF ISSLDELVEL 310 320 330 340 350 360 NEKLLNCQEF AVDLEHHSYR SFLGLTCLMQ ISTRTEDFII DTLELRSDMY ILNESLTDPA 370 380 390 400 410 420 IVKVFHGADS DIEWLQKDFG LYVVNMFDTH QAARLLNLGR HSLDHLLKLY CNVDSNKQYQ 430 440 450 460 470 480 LADWRIRPLP EEMLSYARDD THYLLYIYDK MRLEMWERGN GQPVQLQVVW QRSRDICLKK 490 500 510 520 530 540 FIKPIFTDES YLELYRKQKK HLNTQQLTAF QLLFAWRDKT ARREDESYGY VLPNHMMLKI 550 560 570 580 590 600 AEELPKEPQG IIACCNPVPP LVRQQINEMH LLIQQAREMP LLKSEVAAGV KKSGPLPSAE 610 620 630 640 650 660 RLENVLFGPH DCSHAPPDGY PIIPTSGSVP VQKQASLFPD EKEDNLLGTT CLIATAVITL 670 680 690 700 710 720 FNEPSAEDSK KGPLTVAQKK AQNIMESFEN PFRMFLPSLG HRAPVSQAAK FDPSTKIYEI 730 740 750 760 770 780 SNRWKLAQVQ VQKDSKEAVK KKAAEQTAAR EQAKEACKAA AEQAISVRQQ VVLENAAKKR 790 800 810 820 830 840 ERATSDPRTT EQKQEKKRLK ISKKPKDPEP PEKEFTPYDY SQSDFKAFAG NSKSKVSSQF 850 860 870 880 DPNKQTPSGK KCIAAKKIKQ SVGNKSMSFP TGKSDRGFRY NWPQR
	Isoform 2. Checksum: B7FBE8B15F28BFE2	FASTA	860	98,089
	10 20 30 40 50 60 MAPPSTREPR VLSATSATKS DGEMVLPGFP DADSFVKFAL GSVVAVTKAS GGLPQFGDEY 70 80 90 100 110 120 DFYRSFPGFQ AFCETQGDRL LQCMSRVMQY HGCRSNIKDR SKVTELEDKF DLLVDANDVI 130 140 150 160 170 180 LERVGILLDE ASGVNKNQQP VLPAGLQVPK TVVSSWNRKA AEYGKKAKSE TFRLLHAKNI 190 200 210 220 230 240 IRPQLKFREK IDNSNTPFLP KIFIKPNAQK PLPQALSKER RERPQDRPED LDVPPALADF 250 260 270 280 290 300 IHQQRTQQVE QDMFAHPYQY ELNHFTPADA VLQKPQPQLY RPIEETPCHF ISSLDELVEL 310 320 330 340 350 360 NEKLLNCQEF AVDLEHHSYR SFLGLTCLMQ ISTRTEDFII DTLELRSDMY ILNESLTDPA 370 380 390 400 410 420 IVKVFHGADS DIEWLQKDFG LYVVNMFDTH QAARLLNLGR HSLDHLLKLY CNVDSNKQYQ 430 440 450 460 470 480 LADWRIRPLP EEMLSYARDD THYLLYIYDK MRLEMWERGN GQPVQLQVVW QRSRDICLKK 490 500 510 520 530 540 FIKPIFTDES YLELYRKQKK HLNTQQLTAF QLLFAWRDKT ARREDESYGY VLPNHMMLKI 550 560 570 580 590 600 AEELPKEPQG IIACCNPVPP LVRQQINEMH LLIQQAREMP LLKSEVAAGV KKSGPLPSAE 610 620 630 640 650 660 RLENVLFGPH DCSHAPPDGY PIIPTSGSVP VQKQASLFPD EKEDNLLGTT CLIATAVITL 670 680 690 700 710 720 FNEPSAEDSK KGPLTVAQKK AQNIMESFEN PFRMISNRWK LAQVQVQKDS KEAVKKKAAE 730 740 750 760 770 780 QTAAREQAKE ACKAAAEQAI SVRQQVVLEN AAKKRERATS DPRTTEQKQE KKRLKISKKP 790 800 810 820 830 840 KDPEPPEKEF TPYDYSQSDF KAFAGNSKSK VSSQFDPNKQ TPSGKKCIAA KKIKQSVGNK 850 860 SMSFPTGKSD RGFRYNWPQR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of the cDNA coding for a polymyositis-scleroderma overlap syndrome-related nucleolar 100-kD protein." Bluethner M., Bautz F.A. J. Exp. Med. 176:973-980(1992) [PubMed: 1383382] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Placenta.
[2]	"Cloning of a complementary DNA coding for the 100-kD antigenic protein of the PM-Scl autoantigen." Ge Q., Frank M.B., O'Brien C., Targoff I.N. J. Clin. Invest. 90:559-570(1992) [PubMed: 1644924] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Thymocyte.
[3]	"The human gene for mannan-binding lectin-associated serine protease-2 (MASP-2), the effector component of the lectin route of complement activation, is part of a tightly linked gene cluster on chromosome 1p36.2-3." Stover C., Endo Y., Takahashi M., Lynch N., Constantinescu C., Vorup-Jensen T., Thiel S., Friedl H., Hankeln T., Hall R., Gregory S., Fujita T., Schwaeble W. Genes Immun. 2:119-127(2001) [PubMed: 11426320] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2).
[4]	"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].
[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: Lymph and Skin.
[6]	"The yeast exosome and human PM-Scl are related complexes of 3'-->5' exonucleases." Allmang C., Petfalski E., Podtelejnikov A., Mann M., Tollervey D., Mitchell P. Genes Dev. 13:2148-2158(1999) [PubMed: 10465791] [Abstract] Cited for: CHARACTERIZATION.
[7]	"Functional proteomic analysis of human nucleolus." Scherl A., Coute Y., Deon C., Calle A., Kindbeiter K., Sanchez J.-C., Greco A., Hochstrasser D.F., Diaz J.-J. Mol. Biol. Cell 13:4100-4109(2002) [PubMed: 12429849] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
[8]	"Nonsense-mediated mRNA decay in mammalian cells involves decapping, deadenylating, and exonucleolytic activities." Lejeune F., Li X., Maquat L.E. Mol. Cell 12:675-687(2003) [PubMed: 14527413] [Abstract] Cited for: FUNCTION IN NONSENSE-MEDIATED MRNA DECAY, IDENTIFICATION IN A MRNA DECAY COMPLEX WITH RENT1; RENT2 AND RENT3B, SUBCELLULAR LOCATION.
[9]	"A protein interaction framework for human mRNA degradation." Lehner B., Sanderson C.M. Genome Res. 14:1315-1323(2004) [PubMed: 15231747] [Abstract] Cited for: INTERACTION WITH PTGES2.
[10]	"C1D and hMtr4p associate with the human exosome subunit PM/Scl-100 and are involved in pre-rRNA processing." Schilders G., van Dijk E., Pruijn G.J.M. Nucleic Acids Res. 35:2564-2572(2007) [PubMed: 17412707] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH C1D.
[11]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[12]	"Solution structure of the HRDC domain of human exosome component 10." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 483-593.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

X66113 mRNA. Translation: CAA46904.1.
L01457 mRNA. Translation: AAB59352.1.
AJ300188 Genomic DNA. Translation: CAC15569.1.
AL109811 Genomic DNA. Translation: CAI22106.1.
BC039901 mRNA. Translation: AAH39901.1.
BC073788 mRNA. Translation: AAH73788.1.

IPI

IPI00009464.
IPI00220336.

PIR

A43920.
JH0796.

RefSeq

NP_001001998.1.

UniGene

Hs.632368

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2CPR	NMR	-	A	483-593	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q01780. 29 interactions.

PTM databases

PhosphoSite

Q01780.

2-D gel databases

SWISS-2DPAGE

Q01780.

Proteomic databases

PRIDE

Q01780.

Genome annotation databases

Ensembl

ENSG00000171824. Homo sapiens. [Contig view]

GeneID

5394.

KEGG

hsa:5394.

UCSC

uc001asa.1. human.
uc001asb.1. human.

Organism-specific databases

GeneCards

GC01M011060.

H-InvDB

HIX0000121.

HGNC

HGNC:9138. EXOSC10.

MIM

605960. gene.

PharmGKB

PA33464.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q01780.

HOVERGEN

Q01780.

OMA

Q01780. YEISNRW.

Gene expression databases

ArrayExpress

Q01780.

Bgee

Q01780.

CleanEx

HS_EXOSC10.

GermOnline

ENSG00000171824. Homo sapiens.

Family and domain databases

InterPro

IPR002562. 3_5_exonuclease.
IPR012588. Exosome-assoc_fac_Rrp6_N.
IPR002121. HRDC.
[Graphical view]

Pfam

PF01612. 3_5_exonuc. 1 hit.
PF00570. HRDC. 1 hit.
PF08066. PMC2NT. 1 hit.
[Graphical view]

SMART

SM00474. 35EXOc. 1 hit.
SM00341. HRDC. 1 hit.
[Graphical view]

PROSITE

PS50967. HRDC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

20912.

SOURCE

Search...

Entry information

Entry name

EXOSX_HUMAN

Accession

Primary (citable) accession number: Q01780
Secondary accession number(s): B1AKQ1, Q15158

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1993
Last sequence update:	December 1, 2000
Last modified:	July 7, 2009
This is version 102 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)