WRIP1_HUMAN
ID WRIP1_HUMAN Reviewed; 665 AA.
AC Q96S55; B2RDB0; Q53EP6; Q59ET8; Q5W0E2; Q5W0E4; Q8WV26; Q9H681; Q9NRJ6;
DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2005, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=ATPase WRNIP1;
DE EC=3.6.1.- {ECO:0000269|PubMed:15670210};
DE AltName: Full=Werner helicase-interacting protein 1;
GN Name=WRNIP1 {ECO:0000312|HGNC:HGNC:20876};
GN Synonyms=WHIP {ECO:0000312|EMBL:BAB60709.1};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1] {ECO:0000305, ECO:0000312|EMBL:BAB60709.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Cervix carcinoma;
RX PubMed=11301316; DOI=10.1074/jbc.c100035200;
RA Kawabe Y., Branzei D., Hayashi T., Suzuki H., Masuko T., Onoda F.,
RA Heo S.-J., Ikeda H., Shimamoto A., Furuichi Y., Seki M., Enomoto T.;
RT "A novel protein interacts with the Werner's syndrome gene product
RT physically and functionally.";
RL J. Biol. Chem. 276:20364-20369(2001).
RN [2] {ECO:0000305, ECO:0000312|EMBL:BAB15383.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 303-665 (ISOFORM 1).
RC TISSUE=Kidney epithelium {ECO:0000312|EMBL:BAB15383.1};
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3] {ECO:0000305, ECO:0000312|EMBL:BAD97313.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain {ECO:0000312|EMBL:BAD92960.1}, and
RC Kidney {ECO:0000312|EMBL:BAD97313.1};
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000305, ECO:0000312|EMBL:AL139092}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5] {ECO:0000305, ECO:0000312|EMBL:BAD97313.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6] {ECO:0000305, ECO:0000312|EMBL:AAH18923.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Muscle {ECO:0000312|EMBL:AAH18923.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7] {ECO:0000305, ECO:0000312|EMBL:BAD97313.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 144-665 (ISOFORM 1).
RA Adamson A.W., Shannon M.E., Lamerdin J.E., Thelen M.P.;
RT "Characterization of RuvB homologs in human and mouse.";
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP FUNCTION, SUBUNIT, INTERACTION WITH POLD1; POLD2 AND POLD4, AND MUTAGENESIS
RP OF THR-294.
RX PubMed=15670210; DOI=10.1111/j.1365-2443.2004.00812.x;
RA Tsurimoto T., Shinozaki A., Yano M., Seki M., Enomoto T.;
RT "Human Werner helicase interacting protein 1 (WRNIP1) functions as a novel
RT modulator for DNA polymerase delta.";
RL Genes Cells 10:13-22(2005).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-534 AND TYR-562, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [11]
RP INTERACTION WITH POLYUBIQUITIN, SUMOYLATION, UBIQUITINATION AT LYS-81;
RP LYS-141; LYS-225; LYS-301; LYS-310; LYS-316; LYS-322; LYS-335; LYS-482;
RP LYS-627; LYS-633 AND LYS-636, AND DOMAIN UBZ-TYPE ZINC-FINGER.
RX PubMed=17550899; DOI=10.1074/jbc.m701042200;
RA Bish R.A., Myers M.P.;
RT "Werner helicase-interacting protein 1 binds polyubiquitin via its zinc
RT finger domain.";
RL J. Biol. Chem. 282:23184-23193(2007).
RN [12]
RP SUBCELLULAR LOCATION, INTERACTION WITH POLYUBIQUITIN, AND SUBUNIT.
RX PubMed=18842586; DOI=10.1074/jbc.m803219200;
RA Crosetto N., Bienko M., Hibbert R.G., Perica T., Ambrogio C., Kensche T.,
RA Hofmann K., Sixma T.K., Dikic I.;
RT "Human Wrnip1 is localized in replication factories in a ubiquitin-binding
RT zinc finger-dependent manner.";
RL J. Biol. Chem. 283:35173-35185(2008).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-75; THR-85; SER-91; SER-92
RP AND THR-116, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-85; SER-91 AND SER-92, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-633, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-75 AND SER-153, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-153, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-65; SER-75; SER-139 AND
RP SER-153, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-153, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [24]
RP FUNCTION, INTERACTION WITH TRIM14 AND PPP6C, AND SUBCELLULAR LOCATION.
RX PubMed=29053956; DOI=10.1016/j.molcel.2017.09.035;
RA Tan P., He L., Cui J., Qian C., Cao X., Lin M., Zhu Q., Li Y., Xing C.,
RA Yu X., Wang H.Y., Wang R.F.;
RT "Assembly of the WHIP-TRIM14-PPP6C mitochondrial complex promotes RIG-I-
RT mediated antiviral signaling.";
RL Mol. Cell 68:293-307(2017).
RN [25]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-482, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 17-40 IN COMPLEX WITH ZINC, AND
RP MUTAGENESIS OF VAL-18; PRO-21; VAL-22; ILE-32; ASN-33; LEU-36; ASP-37;
RP LEU-40; LEU-41; LEU-42 AND PRO-44.
RX PubMed=27062441; DOI=10.1111/febs.13734;
RA Suzuki N., Rohaim A., Kato R., Dikic I., Wakatsuki S., Kawasaki M.;
RT "A novel mode of ubiquitin recognition by the ubiquitin-binding zinc finger
RT domain of WRNIP1.";
RL FEBS J. 283:2004-2017(2016).
CC -!- FUNCTION: Functions as a modulator of initiation or reinitiation events
CC during DNA polymerase delta-mediated DNA synthesis. In the presence of
CC ATP, stimulation of DNA polymerase delta-mediated DNA synthesis is
CC decreased. Also plays a role in the innate immune defense against
CC viruses. Stabilizes the RIG-I/DDX58 dsRNA interaction and promotes RIG-
CC I/DDX58 'Lys-63'-linked polyubiquitination. In turn, RIG-I/DDX58
CC transmits the signal through mitochondrial MAVS.
CC {ECO:0000269|PubMed:15670210, ECO:0000269|PubMed:29053956}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:15670210};
CC -!- SUBUNIT: Forms homooligomers (PubMed:18842586), possibly octamers.
CC Directly interacts with POLD1, POLD2 and POLD4 (PubMed:15670210).
CC Interacts with the N-terminal domain of WRN (By similarity). Interacts
CC (via UBZ4-type zinc finger) with monoubiquitin and polyubiquitin
CC (PubMed:17550899, PubMed:18842586). Interacts with TRIM14 and PPP6C;
CC these interactions positively regulate the RIG-I/DDX58 signaling
CC pathway (PubMed:29053956). {ECO:0000250|UniProtKB:Q91XU0,
CC ECO:0000269|PubMed:15670210, ECO:0000269|PubMed:17550899,
CC ECO:0000269|PubMed:18842586, ECO:0000269|PubMed:29053956}.
CC -!- INTERACTION:
CC Q96S55; O95786: DDX58; NbExp=2; IntAct=EBI-2513471, EBI-995350;
CC Q96S55; P28340: POLD1; NbExp=2; IntAct=EBI-2513471, EBI-716569;
CC Q96S55; P49005: POLD2; NbExp=2; IntAct=EBI-2513471, EBI-372354;
CC Q96S55; Q9HCU8: POLD4; NbExp=2; IntAct=EBI-2513471, EBI-864968;
CC Q96S55; Q9H0E2: TOLLIP; NbExp=2; IntAct=EBI-2513471, EBI-74615;
CC Q96S55; Q96S55: WRNIP1; NbExp=2; IntAct=EBI-2513471, EBI-2513471;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:18842586}. Cytoplasm
CC {ECO:0000269|PubMed:29053956}. Note=Colocalizes with WRN in granular
CC structures in the nucleus. {ECO:0000269|PubMed:18842586,
CC ECO:0000269|PubMed:29053956}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1 {ECO:0000269|PubMed:11301316};
CC IsoId=Q96S55-1; Sequence=Displayed;
CC Name=2 {ECO:0000303|PubMed:14574404};
CC IsoId=Q96S55-2; Sequence=VSP_051783;
CC Name=3 {ECO:0000303|PubMed:14574404};
CC IsoId=Q96S55-3; Sequence=VSP_051781;
CC Name=4 {ECO:0000303|PubMed:14574404};
CC IsoId=Q96S55-4; Sequence=VSP_051782;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:11301316}.
CC -!- DOMAIN: The UBZ4-type zinc finger binds ubiquitin.
CC {ECO:0000269|PubMed:27062441}.
CC -!- PTM: Sumoylated with SUMO1 and SUMO2/3. {ECO:0000269|PubMed:17550899}.
CC -!- SIMILARITY: Belongs to the AAA ATPase family. RarA/MGS1/WRNIP1
CC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF80563.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAB15383.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AB056152; BAB60709.1; -; mRNA.
DR EMBL; AK026179; BAB15383.1; ALT_INIT; mRNA.
DR EMBL; AK315471; BAG37857.1; -; mRNA.
DR EMBL; AB209723; BAD92960.1; -; mRNA.
DR EMBL; AK223593; BAD97313.1; -; mRNA.
DR EMBL; AL139092; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471087; EAW55087.1; -; Genomic_DNA.
DR EMBL; BC018923; AAH18923.1; -; mRNA.
DR EMBL; AF218313; AAF80563.1; ALT_INIT; mRNA.
DR CCDS; CCDS4475.1; -. [Q96S55-1]
DR CCDS; CCDS4476.1; -. [Q96S55-2]
DR RefSeq; NP_064520.2; NM_020135.2. [Q96S55-1]
DR RefSeq; NP_569079.1; NM_130395.2. [Q96S55-2]
DR PDB; 3VHS; X-ray; 1.90 A; A/B=17-40.
DR PDB; 3VHT; X-ray; 2.40 A; B=9-46.
DR PDBsum; 3VHS; -.
DR PDBsum; 3VHT; -.
DR AlphaFoldDB; Q96S55; -.
DR SMR; Q96S55; -.
DR BioGRID; 121227; 93.
DR IntAct; Q96S55; 38.
DR MINT; Q96S55; -.
DR STRING; 9606.ENSP00000370150; -.
DR GlyGen; Q96S55; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q96S55; -.
DR PhosphoSitePlus; Q96S55; -.
DR BioMuta; WRNIP1; -.
DR DMDM; 73622085; -.
DR EPD; Q96S55; -.
DR jPOST; Q96S55; -.
DR MassIVE; Q96S55; -.
DR MaxQB; Q96S55; -.
DR PaxDb; Q96S55; -.
DR PeptideAtlas; Q96S55; -.
DR PRIDE; Q96S55; -.
DR ProteomicsDB; 78070; -. [Q96S55-1]
DR ProteomicsDB; 78071; -. [Q96S55-2]
DR ProteomicsDB; 78072; -. [Q96S55-3]
DR ProteomicsDB; 78073; -. [Q96S55-4]
DR Antibodypedia; 9254; 235 antibodies from 33 providers.
DR DNASU; 56897; -.
DR Ensembl; ENST00000380764.1; ENSP00000370141.1; ENSG00000124535.16. [Q96S55-4]
DR Ensembl; ENST00000380769.8; ENSP00000370146.3; ENSG00000124535.16. [Q96S55-3]
DR Ensembl; ENST00000380771.8; ENSP00000370148.4; ENSG00000124535.16. [Q96S55-2]
DR Ensembl; ENST00000380773.9; ENSP00000370150.4; ENSG00000124535.16. [Q96S55-1]
DR Ensembl; ENST00000618555.4; ENSP00000477551.1; ENSG00000124535.16. [Q96S55-1]
DR GeneID; 56897; -.
DR KEGG; hsa:56897; -.
DR MANE-Select; ENST00000380773.9; ENSP00000370150.4; NM_020135.3; NP_064520.2.
DR UCSC; uc003mtz.4; human. [Q96S55-1]
DR CTD; 56897; -.
DR DisGeNET; 56897; -.
DR GeneCards; WRNIP1; -.
DR HGNC; HGNC:20876; WRNIP1.
DR HPA; ENSG00000124535; Low tissue specificity.
DR MIM; 608196; gene.
DR neXtProt; NX_Q96S55; -.
DR OpenTargets; ENSG00000124535; -.
DR PharmGKB; PA134982239; -.
DR VEuPathDB; HostDB:ENSG00000124535; -.
DR eggNOG; KOG2028; Eukaryota.
DR GeneTree; ENSGT00390000008538; -.
DR HOGENOM; CLU_017985_0_2_1; -.
DR InParanoid; Q96S55; -.
DR OMA; ACEFVGM; -.
DR OrthoDB; 580439at2759; -.
DR PhylomeDB; Q96S55; -.
DR TreeFam; TF324547; -.
DR PathwayCommons; Q96S55; -.
DR SignaLink; Q96S55; -.
DR BioGRID-ORCS; 56897; 10 hits in 1082 CRISPR screens.
DR ChiTaRS; WRNIP1; human.
DR GeneWiki; WRNIP1; -.
DR GenomeRNAi; 56897; -.
DR Pharos; Q96S55; Tbio.
DR PRO; PR:Q96S55; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q96S55; protein.
DR Bgee; ENSG00000124535; Expressed in tendon of biceps brachii and 181 other tissues.
DR Genevisible; Q96S55; HS.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IMP:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:InterPro.
DR GO; GO:0008047; F:enzyme activator activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0017116; F:single-stranded DNA helicase activity; IBA:GO_Central.
DR GO; GO:0000731; P:DNA synthesis involved in DNA repair; IDA:UniProtKB.
DR GO; GO:0006261; P:DNA-templated DNA replication; IBA:GO_Central.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0006282; P:regulation of DNA repair; IBA:GO_Central.
DR GO; GO:0030174; P:regulation of DNA-templated DNA replication initiation; IDA:UniProtKB.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR032423; AAA_assoc_2.
DR InterPro; IPR003959; ATPase_AAA_core.
DR InterPro; IPR008921; DNA_pol3_clamp-load_cplx_C.
DR InterPro; IPR021886; MgsA_C.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR006642; Rad18_UBZ4.
DR InterPro; IPR040539; Znf-WRNIP1_ubi.
DR Pfam; PF00004; AAA; 1.
DR Pfam; PF16193; AAA_assoc_2; 1.
DR Pfam; PF12002; MgsA_C; 1.
DR Pfam; PF18279; zf-WRNIP1_ubi; 1.
DR SMART; SM00382; AAA; 1.
DR SMART; SM00734; ZnF_Rad18; 1.
DR SUPFAM; SSF48019; SSF48019; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS51908; ZF_UBZ4; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; Cytoplasm;
KW DNA damage; DNA repair; DNA replication; Hydrolase; Immunity;
KW Innate immunity; Isopeptide bond; Metal-binding; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1..665
FT /note="ATPase WRNIP1"
FT /id="PRO_0000084785"
FT ZN_FING 17..44
FT /note="UBZ4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT REGION 48..190
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 160..188
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 20
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256,
FT ECO:0000269|PubMed:27062441, ECO:0007744|PDB:3VHS,
FT ECO:0007744|PDB:3VHT"
FT BINDING 23
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256,
FT ECO:0000269|PubMed:27062441, ECO:0007744|PDB:3VHS,
FT ECO:0007744|PDB:3VHT"
FT BINDING 31
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:27062441,
FT ECO:0007744|PDB:3VHS"
FT BINDING 35
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256,
FT ECO:0000269|PubMed:27062441, ECO:0007744|PDB:3VHS,
FT ECO:0007744|PDB:3VHT"
FT BINDING 39
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256,
FT ECO:0000269|PubMed:27062441, ECO:0007744|PDB:3VHT"
FT BINDING 270..276
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P55072"
FT MOD_RES 65
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 75
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 85
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 91
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 92
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 116
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 139
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 153
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 534
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455"
FT MOD_RES 562
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455"
FT MOD_RES 633
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT CROSSLNK 81
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:17550899"
FT CROSSLNK 141
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:17550899"
FT CROSSLNK 225
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:17550899"
FT CROSSLNK 301
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:17550899"
FT CROSSLNK 310
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:17550899"
FT CROSSLNK 316
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:17550899"
FT CROSSLNK 322
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:17550899"
FT CROSSLNK 335
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:17550899"
FT CROSSLNK 482
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 482
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000269|PubMed:17550899"
FT CROSSLNK 627
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:17550899"
FT CROSSLNK 633
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000269|PubMed:17550899"
FT CROSSLNK 636
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:17550899"
FT VAR_SEQ 1..384
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14574404"
FT /id="VSP_051782"
FT VAR_SEQ 1..220
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14574404"
FT /id="VSP_051781"
FT VAR_SEQ 338..362
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14574404,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334"
FT /id="VSP_051783"
FT MUTAGEN 18
FT /note="V->A: Reduced affinity for ubiquitin."
FT /evidence="ECO:0000269|PubMed:27062441"
FT MUTAGEN 21
FT /note="P->A: Loss of affinity for ubiquitin."
FT /evidence="ECO:0000269|PubMed:27062441"
FT MUTAGEN 22
FT /note="V->A: Reduced affinity for ubiquitin."
FT /evidence="ECO:0000269|PubMed:27062441"
FT MUTAGEN 32
FT /note="I->A: Loss of affinity for ubiquitin."
FT /evidence="ECO:0000269|PubMed:27062441"
FT MUTAGEN 33
FT /note="N->A: Loss of affinity for ubiquitin."
FT /evidence="ECO:0000269|PubMed:27062441"
FT MUTAGEN 36
FT /note="L->A: Loss of affinity for ubiquitin."
FT /evidence="ECO:0000269|PubMed:27062441"
FT MUTAGEN 37
FT /note="D->A: Loss of affinity for ubiquitin."
FT /evidence="ECO:0000269|PubMed:27062441"
FT MUTAGEN 40
FT /note="L->A: Loss of affinity for ubiquitin."
FT /evidence="ECO:0000269|PubMed:27062441"
FT MUTAGEN 41
FT /note="L->A: Normal affinity for ubiquitin."
FT /evidence="ECO:0000269|PubMed:27062441"
FT MUTAGEN 42
FT /note="L->A: Normal affinity for ubiquitin."
FT /evidence="ECO:0000269|PubMed:27062441"
FT MUTAGEN 44
FT /note="P->A: Normal affinity for ubiquitin."
FT /evidence="ECO:0000269|PubMed:27062441"
FT MUTAGEN 294
FT /note="T->A: Loss of ATPase activity."
FT /evidence="ECO:0000269|PubMed:15670210"
FT CONFLICT 144
FT /note="A -> V (in Ref. 1; BAB60709)"
FT /evidence="ECO:0000305"
FT CONFLICT 170..173
FT /note="Missing (in Ref. 3; BAD92960)"
FT /evidence="ECO:0000305"
FT CONFLICT 265
FT /note="I -> N (in Ref. 1; BAB60709)"
FT /evidence="ECO:0000305"
FT CONFLICT 377
FT /note="L -> F (in Ref. 2; BAB15383)"
FT /evidence="ECO:0000305"
FT CONFLICT 499
FT /note="H -> Y (in Ref. 3; BAD97313)"
FT /evidence="ECO:0000305"
FT CONFLICT 545
FT /note="E -> G (in Ref. 2; BAB15383)"
FT /evidence="ECO:0000305"
FT CONFLICT 568
FT /note="I -> M (in Ref. 1; BAB60709)"
FT /evidence="ECO:0000305"
FT CONFLICT 576
FT /note="L -> F (in Ref. 1; BAB60709)"
FT /evidence="ECO:0000305"
FT STRAND 17..19
FT /evidence="ECO:0007829|PDB:3VHS"
FT TURN 21..23
FT /evidence="ECO:0007829|PDB:3VHS"
FT STRAND 26..28
FT /evidence="ECO:0007829|PDB:3VHS"
FT HELIX 29..31
FT /evidence="ECO:0007829|PDB:3VHS"
FT HELIX 32..39
FT /evidence="ECO:0007829|PDB:3VHS"
SQ SEQUENCE 665 AA; 72133 MW; DE43D8E59C4B29E8 CRC64;
MEVSGPEDDP FLSQLHQVQC PVCQQMMPAA HINSHLDRCL LLHPAGHAEP AAGSHRAGER
AKGPSPPGAK RRRLSESSAL KQPATPTAAE SSEGEGEEGD DGGETESRES YDAPPTPSGA
RLIPDFPVAR SSSPGRKGSG KRPAAAAAAG SASPRSWDEA EAQEEEEAVG DGDGDGDADA
DGEDDPGHWD ADAAEAATAF GASGGGRPHP RALAAEEIRQ MLQGKPLADT MRPDTLQDYF
GQSKAVGQDT LLRSLLETNE IPSLILWGPP GCGKTTLAHI IASNSKKHSI RFVTLSATNA
KTNDVRDVIK QAQNEKSFFK RKTILFIDEI HRFNKSQQDT FLPHVECGTI TLIGATTENP
SFQVNAALLS RCRVIVLEKL PVEAMVTILM RAINSLGIHV LDSSRPTDPL SHSSNSSSEP
AMFIEDKAVD TLAYLSDGDA RAGLNGLQLA VLARLSSRKM FCKKSGQSYS PSRVLITEND
VKEGLQRSHI LYDRAGEEHY NCISALHKSM RGSDQNASLY WLARMLEGGE DPLYVARRLV
RFASEDIGLA DPSALTQAVA AYQGCHFIGM PECEVLLAQC VVYFARAPKS IEVYSAYNNV
KACLRNHQGP LPPVPLHLRN APTRLMKDLG YGKGYKYNPM YSEPVDQEYL PEELRGVDFF
KQRRC
