Q9NS91 (RAD18_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
E3 ubiquitin-protein ligase RAD18
EC=6.3.2.-

Alternative name(s):
Postreplication repair protein RAD18
Short name=hHR18
Short name=hRAD18
RING finger protein 73

Gene names

Name:	RAD18
Synonyms:	RNF73

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

General annotation (Comments)

Function	E3 ubiquitin-protein ligase involved in postreplication repair of UV-damaged DNA. Postreplication repair functions in gap-filling of a daughter strand on replication of damaged DNA. Associates to the E2 ubiquitin conjugating enzyme UBE2B to form the UBE2B-RAD18 ubiquitin ligase complex involved in mono-ubiquitination of DNA-associated PCNA on 'Lys-164'. Has ssDNA binding activity. Ref.11 Ref.19
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Interacts with UBE2A and UBE2B. Interacts with HLTF and SHPRH. Interacts with SPRTN; leading to enhance chromatin association of RAD18 and RAD18-mediated PCNA ubiquitination and translesion DNA synthesis. Ref.9 Ref.11 Ref.14 Ref.15 Ref.21
Subcellular location	Nucleus By similarity.
Sequence similarities	Belongs to the RAD18 family. Contains 1 RING-type zinc finger. Contains 1 SAP domain. Contains 1 UBZ-type zinc finger.

Ontologies

Keywords
Biological process	DNA damage DNA repair Ubl conjugation pathway
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Ligase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA repair Non-traceable author statement Ref.1. Source: UniProtKB negative regulation of DNA recombination Inferred from electronic annotation. Source: Compara protein ubiquitination Inferred from electronic annotation. Source: UniProtKB-UniPathway response to UV Inferred from electronic annotation. Source: Compara spermatogenesis Inferred from electronic annotation. Source: Compara
Cellular_component	XY body Inferred from electronic annotation. Source: Compara chromatin Inferred from electronic annotation. Source: Compara nucleus Non-traceable author statement Ref.1. Source: UniProtKB replication fork Inferred from direct assay PubMed 18363965. Source: UniProtKB
Molecular_function	Y-form DNA binding Inferred from direct assay PubMed 18363965. Source: UniProtKB damaged DNA binding Non-traceable author statement Ref.1. Source: UniProtKB ligase activity Inferred from electronic annotation. Source: UniProtKB-KW polyubiquitin binding Inferred from direct assay Ref.20. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 495

495

E3 ubiquitin-protein ligase RAD18

PRO_0000056149

Regions

Domain

248 – 282

35

SAP

Zinc finger

25 – 64

40

RING-type

Zinc finger

201 – 224

24

UBZ-type

Motif

232 – 240

9

LR motif

Amino acid modifications

Modified residue

99

1

Phosphoserine Ref.8 Ref.12 Ref.13 Ref.16 Ref.17 Ref.18

Modified residue

103

1

Phosphoserine Ref.13 Ref.16

Modified residue

118

1

Phosphothreonine Ref.13

Modified residue

164

1

Phosphoserine Ref.13

Modified residue

471

1

Phosphoserine Ref.10 Ref.17 Ref.18

Natural variations

Natural variant

6

1

E → A. Ref.5
Corresponds to variant rs45520133 [ dbSNP | Ensembl ].

VAR_023423

Natural variant

302

1

R → Q. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.7
Corresponds to variant rs373572 [ dbSNP | Ensembl ].

VAR_023424

Natural variant

307

1

I → V. Ref.5
Corresponds to variant rs45569933 [ dbSNP | Ensembl ].

VAR_023425

Experimental info

Sequence conflict

191

1

P → L in AAF80856. Ref.2

Sequence conflict

482 – 484

3

ESA → GKC in AAF80856. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

495

Helix Strand Turn

Details...

Helix

11 – 16

6

Helix

17 – 22

6

Turn

26 – 28

3

Beta strand

33 – 37

5

Turn

39 – 41

3

Beta strand

44 – 46

3

Helix

47 – 54

8

Turn

61 – 63

3

Helix

69 – 71

3

Helix

76 – 90

15

Helix

342 – 345

4

Helix

347 – 358

12

Sequences

	Sequence		Length	Mass (Da)
	Q9NS91 [UniParc]. Last modified November 30, 2010. Version 2. Checksum: 744A053A50C65DD7	FASTA	495	56,223
	10 20 30 40 50 60 MDSLAESRWP PGLAVMKTID DLLRCGICFE YFNIAMIIPQ CSHNYCSLCI RKFLSYKTQC 70 80 90 100 110 120 PTCCVTVTEP DLKNNRILDE LVKSLNFARN HLLQFALESP AKSPASSSSK NLAVKVYTPV 130 140 150 160 170 180 ASRQSLKQGS RLMDNFLIRE MSGSTSELLI KENKSKFSPQ KEASPAAKTK ETRSVEEIAP 190 200 210 220 230 240 DPSEAKRPEP PSTSTLKQVT KVDCPVCGVN IPESHINKHL DSCLSREEKK ESLRSSVHKR 250 260 270 280 290 300 KPLPKTVYNL LSDRDLKKKL KEHGLSIQGN KQQLIKRHQE FVHMYNAQCD ALHPKSAAEI 310 320 330 340 350 360 VREIENIEKT RMRLEASKLN ESVMVFTKDQ TEKEIDEIHS KYRKKHKSEF QLLVDQARKG 370 380 390 400 410 420 YKKIAGMSQK TVTITKEDES TEKLSSVCMG QEDNMTSVTN HFSQSKLDSP EELEPDREED 430 440 450 460 470 480 SSSCIDIQEV LSSSESDSCN SSSSDIIRDL LEEEEAWEAS HKNDLQDTEI SPRQNRRTRA 490 AESAEIEPRN KRNRN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Dysfunction of human Rad18 results in defective postreplication repair and hypersensitivity to multiple mutagens." Tateishi S., Sakuraba Y., Masuyama S., Inoue H., Yamaizumi M. Proc. Natl. Acad. Sci. U.S.A. 97:7927-7932(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLN-302. Tissue: Placenta.
[2]	"The human RAD18 gene product interacts with HHR6A and HHR6B." Xin H., Lin W., Sumanasekera W., Zhang Y., Wu X., Wang Z. Nucleic Acids Res. 28:2847-2854(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLN-302.
[3]	"Identification of human RAD18 (hHR18), a homolog of yeast RAD18." Jang Y., Chae S. Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLN-302.
[4]	"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], VARIANT GLN-302.
[5]	NIEHS SNPs program Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ALA-6; GLN-302 AND VAL-307.
[6]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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], VARIANT GLN-302. Tissue: Placenta.
[8]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-99, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"Human SHPRH suppresses genomic instability through proliferating cell nuclear antigen polyubiquitination." Motegi A., Sood R., Moinova H., Markowitz S.D., Liu P.P., Myung K. J. Cell Biol. 175:703-708(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SHPRH.
[10]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-471, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"Human SHPRH is a ubiquitin ligase for Mms2-Ubc13-dependent polyubiquitylation of proliferating cell nuclear antigen." Unk I., Hajdu I., Fatyol K., Szakal B., Blastyak A., Bermudez V., Hurwitz J., Prakash L., Prakash S., Haracska L. Proc. Natl. Acad. Sci. U.S.A. 103:18107-18112(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH SHPRH.
[12]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-99, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-99; SER-103; THR-118 AND SER-164, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"Human HLTF functions as a ubiquitin ligase for proliferating cell nuclear antigen polyubiquitination." Unk I., Hajdu I., Fatyol K., Hurwitz J., Yoon J.-H., Prakash L., Prakash S., Haracska L. Proc. Natl. Acad. Sci. U.S.A. 105:3768-3773(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HLTF.
[15]	"Polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH prevents genomic instability from stalled replication forks." Motegi A., Liaw H.-J., Lee K.-Y., Roest H.P., Maas A., Wu X., Moinova H., Markowitz S.D., Ding H., Hoeijmakers J.H.J., Myung K. Proc. Natl. Acad. Sci. U.S.A. 105:12411-12416(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HLTF.
[16]	"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-99 AND SER-103, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[17]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-99 AND SER-471, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[18]	"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-99 AND SER-471, MASS SPECTROMETRY.
[19]	"A DNA damage response screen identifies RHINO, a 9-1-1 and TopBP1 interacting protein required for ATR signaling." Cotta-Ramusino C., McDonald E.R. III, Hurov K., Sowa M.E., Harper J.W., Elledge S.J. Science 332:1313-1317(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY.
[20]	"Tandem protein interaction modules organize the ubiquitin-dependent response to DNA double-strand breaks." Panier S., Ichijima Y., Fradet-Turcotte A., Leung C.C., Kaustov L., Arrowsmith C.H., Durocher D. Mol. Cell 47:383-395(2012) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITIN-BINDING, LR MOTIF.
[21]	"Spartan/C1orf124, a reader of PCNA ubiquitylation and a regulator of UV-induced DNA damage response." Centore R.C., Yazinski S.A., Tse A., Zou L. Mol. Cell 46:625-635(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SPRTN.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB035274 mRNA. Translation: BAA99284.1.
AF169796 mRNA. Translation: AAF80856.1.
AY004333 mRNA. Translation: AAF86618.1.
AK023075 mRNA. Translation: BAB14392.1.
AY961989 Genomic DNA. Translation: AAX44049.1.
AC008151 Genomic DNA. No translation available.
AC034186 Genomic DNA. No translation available.
BC001302 mRNA. Translation: AAH01302.1.

IPI

IPI00024579.

RefSeq

NP_064550.3. NM_020165.3.

UniGene

Hs.375684.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2Y43	X-ray	1.80	A/B	1-99	[»]
2YBF	X-ray	2.00	B	340-366	[»]

ProteinModelPortal

Q9NS91.

SMR

Q9NS91. Positions 8-95.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29831N.

IntAct

Q9NS91. 10 interactions.

STRING

9606.ENSP00000264926.

PTM databases

PhosphoSite

Q9NS91.

Polymorphism databases

DMDM

21362876.

Proteomic databases

PaxDb

Q9NS91.

PeptideAtlas

Q9NS91.

PRIDE

Q9NS91.

Protocols and materials databases

DNASU

56852.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000264926; ENSP00000264926; ENSG00000070950.

GeneID

56852.

KEGG

hsa:56852.

UCSC

uc003brd.3. human.

Organism-specific databases

CTD

56852.

GeneCards

GC03M008896.

H-InvDB

HIX0003022.

HGNC

HGNC:18278. RAD18.

MIM

605256. gene.

neXtProt

NX_Q9NS91.

PharmGKB

PA134912253.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5432.

HOGENOM

HOG000234845.

HOVERGEN

HBG054721.

InParanoid

Q9NS91.

KO

K10627.

OMA

HSKYRKK.

PhylomeDB

Q9NS91.

Enzyme and pathway databases

UniPathway

UPA00143.

Gene expression databases

ArrayExpress

Q9NS91.

Bgee

Q9NS91.

CleanEx

HS_RAD18.

Genevestigator

Q9NS91.

GermOnline

ENSG00000070950. Homo sapiens.

Family and domain databases

Gene3D

1.10.720.30. 1 hit.
3.30.40.10. 2 hits.

InterPro

IPR003034. SAP_dom.
IPR006642. Znf_Rad18_put.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]

Pfam

PF02037. SAP. 1 hit.
[Graphical view]

SMART

SM00184. RING. 1 hit.
SM00513. SAP. 1 hit.
SM00734. ZnF_Rad18. 1 hit.
[Graphical view]

PROSITE

PS50800. SAP. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

GenomeRNAi

56852.

NextBio

62262.

SOURCE

Search...

Entry information

Entry name

RAD18_HUMAN

Accession

Primary (citable) accession number: Q9NS91
Secondary accession number(s): Q58F55, Q9NRT6

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 6, 2002
Last sequence update:	November 30, 2010
Last modified:	May 1, 2013
This is version 112 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.