Q2YD98 (UVSSA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
UV-stimulated scaffold protein A

Gene names

Name:	UVSSA
Synonyms:	KIAA1530

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

General annotation (Comments)

Function	Factor involved in transcription-coupled nucleotide excision repair (TC-NER) in response to UV damage. TC-NER allows RNA polymerase II-blocking lesions to be rapidly removed from the transcribed strand of active genes. Acts by promoting stabilization of ERCC6 by recruiting deubiquitinating enzyme USP7 to TC-NER complexes, preventing UV-induced degradation of ERCC6 by the proteasome. Interacts with the elongating form of RNA polymerase II (RNA pol IIo) and facilitates its ubiquitination at UV damage sites, leading to promote RNA pol IIo backtracking to allow access to the nucleotide excision repair machinery. Not involved in processing oxidative damage. Ref.7 Ref.8 Ref.9
Subunit structure	Interacts with the elongating form of RNA polymerase II (RNA pol IIo). Interacts with ERCC6, ERCC8 and USP7. Ref.8 Ref.9
Subcellular location	Chromosome. Note: Accumulates at UV DNA damage sites. Ref.8 Ref.9
Post-translational modification	Monoubiquitinated: ubiquitination does not increase in response to UV.
Involvement in disease	UV-sensitive syndrome 3 (UVSS3) [MIM:614640]: An autosomal recessive disorder characterized by cutaneous photosensitivity and slight dyspigmentation, without an increased risk of skin tumors. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.8 Ref.9
Sequence similarities	Belongs to the UVSSA family.
Sequence caution	The sequence BAA96054.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	DNA damage DNA repair
Cellular component	Chromosome
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Coiled coil
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	protein ubiquitination Inferred from mutant phenotype Ref.7. Source: UniProtKB response to UV Inferred from mutant phenotype Ref.7Ref.8Ref.9. Source: UniProtKB transcription-coupled nucleotide-excision repair Inferred from mutant phenotype Ref.7Ref.8Ref.9. Source: UniProtKB
Cellular_component	chromosomal part Inferred from direct assay Ref.8Ref.9. Source: UniProtKB
Molecular_function	RNA polymerase II core binding Inferred from direct assay Ref.8Ref.9. Source: UniProtKB
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q2YD98-1)

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: Q2YD98-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-449: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 709	709	UV-stimulated scaffold protein A		PRO_0000317282
Regions
	Region	2 – 145	144	VHS-like
	Coiled coil	165 – 199	35	Potential
Amino acid modifications
	Modified residue	281	1	Phosphoserine Ref.6
	Modified residue	287	1	Phosphoserine Ref.6
Natural variations
	Alternative sequence	1 – 449	449	Missing in isoform 2.		VSP_030932
	Natural variant	32	1	C → R in UVSS3; mild phenotype; impairs transcription-coupled nucleotide excision repair ability. Ref.7		VAR_067798
	Natural variant	391	1	R → H. Corresponds to variant rs2276904 [ dbSNP | Ensembl ].		VAR_038499
	Natural variant	620	1	P → L. Ref.1 Ref.2 Ref.4 Corresponds to variant rs28522910 [ dbSNP | Ensembl ].		VAR_038500
Experimental info
	Mutagenesis	120	1	W → A: Impairs transcription-coupled nucleotide excision repair ability. Ref.7
	Mutagenesis	157 – 159	3	RKR → EEE: Impairs transcription-coupled nucleotide excision repair ability. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 18, 2010. Version 2. Checksum: 34698BE37A43BF2F	FASTA	709	80,591
	10 20 30 40 50 60 MDQKLSKLVE ELTTSGEPRL NPEKMKELKK ICKSSEEQLS RAYRLLIAQL TQEHAEIRLS 70 80 90 100 110 120 AFQIVEELFV RSHQFRMLVV SNFQEFLELT LGTDPAQPLP PPREAAQRLR QATTRAVEGW 130 140 150 160 170 180 NEKFGEAYKK LALGYHFLRH NKKVDFQDTN ARSLAERKRE EEKQKHLDKI YQERASQAER 190 200 210 220 230 240 EMQEMSGEIE SCLTEVESCF RLLVPFDFDP NPETESLGMA SGMSDALRSS CAGQVGPCRS 250 260 270 280 290 300 GTPDPRDGEQ PCCSRDLPAS AGHPRAGGGA QPSQTATGDP SDEDEDSDLE EFVRSHGLGS 310 320 330 340 350 360 HKYTLDVELC SEGLKVQENE DNLALIHAAR DTLKLIRNKF LPAVCSWIQR FTRVGTHGGC 370 380 390 400 410 420 LKRAIDLKAE LELVLRKYKE LDIEPEGGER RRTEALGDAE EDEDDEDFVE VPEKEGYEPH 430 440 450 460 470 480 IPDHLRPEYG LEAAPEKDTV VRCLRTRTRM DEEVSDPTSA AAQLRQLRDH LPPPSSASPS 490 500 510 520 530 540 RALPEPQEAQ KLAAERARAP VVPYGVDLHY WGQELPTAGK IVKSDSQHRF WKPSEVEEEV 550 560 570 580 590 600 VNADISEMLR SRHITFAGKF EPVQHWCRAP RPDGRLCERQ DRLKCPFHGK IVPRDDEGRP 610 620 630 640 650 660 LDPEDRAREQ RRQLQKQERP EWQDPELMRD VEAATGQDLG SSRYSGKGRG KKRRYPSLTN 670 680 690 700 LKAQADTARA RIGRKVFAKA AVRRVVAAMN RMDQKKHEKF SNQFNYALN
	Isoform 2 [UniParc]. Checksum: 5A72163E1A43CE42	FASTA	260	29,763
	10 20 30 40 50 60 MDEEVSDPTS AAAQLRQLRD HLPPPSSASP SRALPEPQEA QKLAAERARA PVVPYGVDLH 70 80 90 100 110 120 YWGQELPTAG KIVKSDSQHR FWKPSEVEEE VVNADISEML RSRHITFAGK FEPVQHWCRA 130 140 150 160 170 180 PRPDGRLCER QDRLKCPFHG KIVPRDDEGR PLDPEDRARE QRRQLQKQER PEWQDPELMR 190 200 210 220 230 240 DVEAATGQDL GSSRYSGKGR GKKRRYPSLT NLKAQADTAR ARIGRKVFAK AAVRRVVAAM 250 260 NRMDQKKHEK FSNQFNYALN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O. DNA Res. 7:143-150(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT LEU-620. Tissue: Brain.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT LEU-620. Tissue: Thymus.
[3]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] 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 1 AND 2), VARIANT LEU-620. Tissue: Duodenum, Lung and Skin.
[5]	"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[6]	"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-281 AND SER-287, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[7]	"Mutations in UVSSA cause UV-sensitive syndrome and impair RNA polymerase IIo processing in transcription-coupled nucleotide-excision repair." Nakazawa Y., Sasaki K., Mitsutake N., Matsuse M., Shimada M., Nardo T., Takahashi Y., Ohyama K., Ito K., Mishima H., Nomura M., Kinoshita A., Ono S., Takenaka K., Masuyama R., Kudo T., Slor H., Utani A. , Tateishi S., Yamashita S., Stefanini M., Lehmann A.R., Yoshiura K.I., Ogi T. Nat. Genet. 44:586-592(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INVOLVEMENT IN UVSS3, MUTAGENESIS OF TRP-120 AND 157-ARG--ARG-159, VARIANT UVSS3 ARG-32, CHARACTERIZATION OF VARIANT UVSS3 ARG-32.
[8]	"UV-sensitive syndrome protein UVSSA recruits USP7 to regulate transcription-coupled repair." Schwertman P., Lagarou A., Dekkers D.H., Raams A., van der Hoek A.C., Laffeber C., Hoeijmakers J.H., Demmers J.A., Fousteri M., Vermeulen W., Marteijn J.A. Nat. Genet. 44:598-602(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INVOLVEMENT IN UVSS3, SUBCELLULAR LOCATION, UBIQUITINATION, INTERACTION WITH USP7.
[9]	"Mutations in UVSSA cause UV-sensitive syndrome and destabilize ERCC6 in transcription-coupled DNA repair." Zhang X., Horibata K., Saijo M., Ishigami C., Ukai A., Kanno S.I., Tahara H., Neilan E.G., Honma M., Nohmi T., Yasui A., Tanaka K. Nat. Genet. 44:593-597(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INVOLVEMENT IN UVSS3, SUBCELLULAR LOCATION, INTERACTION WITH ERCC6; ERCC8 AND USP7.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB040963 mRNA. Translation: BAA96054.1. Different initiation. AK292661 mRNA. Translation: BAF85350.1. AC078852 Genomic DNA. No translation available. AC118281 Genomic DNA. No translation available. BC021930 mRNA. Translation: AAH21930.1. BC110331 mRNA. Translation: AAI10332.1. BC140901 mRNA. Translation: AAI40902.1.
IPI	IPI00001849. IPI00885147.
RefSeq	NP_065945.2. NM_020894.2.
UniGene	Hs.380475.
3D structure databases
ProteinModelPortal	Q2YD98.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000374501.
PTM databases
PhosphoSite	Q2YD98.
Polymorphism databases
DMDM	296434546.
Proteomic databases
PaxDb	Q2YD98.
PRIDE	Q2YD98.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000389851; ENSP00000374501; ENSG00000163945. ENST00000507531; ENSP00000421741; ENSG00000163945. ENST00000511216; ENSP00000425130; ENSG00000163945. ENST00000511563; ENSP00000423340; ENSG00000163945. ENST00000512728; ENSP00000427701; ENSG00000163945.
GeneID	57654.
KEGG	hsa:57654.
UCSC	uc003gde.4. human. uc010ibv.3. human.
Organism-specific databases
CTD	57654.
GeneCards	GC04P001341.
HGNC	HGNC:29304. UVSSA.
HPA	HPA050824.
MIM	614632. gene. 614640. phenotype.
neXtProt	NX_Q2YD98.
Orphanet	178338. UV-sensitive syndrome.
PharmGKB	PA162393105.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG313134.
HOGENOM	HOG000060117.
HOVERGEN	HBG076421.
InParanoid	Q2YD98.
OMA	YEPHIPD.
OrthoDB	EOG4TQM8W.
Gene expression databases
ArrayExpress	Q2YD98.
Bgee	Q2YD98.
CleanEx	HS_KIAA1530.
Genevestigator	Q2YD98.
Family and domain databases
InterPro	IPR018610. DUF2043. [Graphical view]
Pfam	PF09740. DUF2043. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	57654.
NextBio	64404.
SOURCE	Search...

Entry information

Entry name

UVSSA_HUMAN

Accession

Primary (citable) accession number: Q2YD98
Secondary accession number(s): A8K9E6 , B2RU11, Q8WTX4, Q9P1Z8

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 5, 2008
Last sequence update:	May 18, 2010
Last modified:	May 1, 2013
This is version 57 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.