ZN598_HUMAN
ID ZN598_HUMAN Reviewed; 904 AA.
AC Q86UK7; Q8IW49; Q8N3D9; Q96FG3; Q9H7J3;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=E3 ubiquitin-protein ligase ZNF598 {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000305|PubMed:28065601, ECO:0000305|PubMed:28132843};
DE AltName: Full=Zinc finger protein 598 {ECO:0000312|HGNC:HGNC:28079};
GN Name=ZNF598 {ECO:0000312|HGNC:HGNC:28079};
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), AND VARIANTS TYR-453;
RP THR-608 AND MET-637.
RC TISSUE=Spleen;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 236-904 (ISOFORM 2), AND VARIANTS TYR-453; THR-608
RP AND MET-637.
RC TISSUE=Lung, and Skin;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 376-904 (ISOFORM 3), AND VARIANT
RP SER-725.
RC TISSUE=Melanoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-306, AND IDENTIFICATION BY
RP 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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-437, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE 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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-428 (ISOFORM 2),
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-431 (ISOFORM 3), 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 [7]
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 [8]
RP IDENTIFICATION IN THE 4EHP-GYF2 COMPLEX.
RX PubMed=22751931; DOI=10.1128/mcb.00455-12;
RA Morita M., Ler L.W., Fabian M.R., Siddiqui N., Mullin M., Henderson V.C.,
RA Alain T., Fonseca B.D., Karashchuk G., Bennett C.F., Kabuta T., Higashi S.,
RA Larsson O., Topisirovic I., Smith R.J., Gingras A.C., Sonenberg N.;
RT "A novel 4EHP-GIGYF2 translational repressor complex is essential for
RT mammalian development.";
RL Mol. Cell. Biol. 32:3585-3593(2012).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-428 (ISOFORM 2),
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-431 (ISOFORM 3), AND
RP IDENTIFICATION BY 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 [10]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=28065601; DOI=10.1016/j.molcel.2016.11.039;
RA Juszkiewicz S., Hegde R.S.;
RT "Initiation of quality control during poly(A) translation requires site-
RT specific ribosome ubiquitination.";
RL Mol. Cell 65:743-750(2016).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF CYS-29.
RX PubMed=28132843; DOI=10.1016/j.molcel.2016.12.026;
RA Sundaramoorthy E., Leonard M., Mak R., Liao J., Fulzele A., Bennett E.J.;
RT "ZNF598 and RACK1 regulate mammalian ribosome-associated quality control
RT function by mediating regulatory 40S ribosomal ubiquitylation.";
RL Mol. Cell 65:751-760(2017).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that plays a key role in the
CC ribosome quality control (RQC), a pathway that takes place when a
CC ribosome has stalled during translation (PubMed:28065601,
CC PubMed:28132843). Required for ribosomes to terminally stall during
CC translation of poly(A) sequences by mediating monoubiquitination of 40S
CC ribosomal protein RPS10/eS10, RPS20/uS10 and RPS3/uS3 (PubMed:28065601,
CC PubMed:28132843). Stalling precludes synthesis of a long poly-lysine
CC tail and initiates the RQC pathway to degrade the potentially
CC detrimental aberrant nascent polypeptide (PubMed:28065601,
CC PubMed:28132843). Also acts as a component of the 4EHP-GYF2 complex, a
CC multiprotein complex that acts as a repressor of translation initiation
CC (PubMed:22751931). {ECO:0000269|PubMed:22751931,
CC ECO:0000269|PubMed:28065601, ECO:0000269|PubMed:28132843}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000305|PubMed:28065601,
CC ECO:0000305|PubMed:28132843};
CC -!- SUBUNIT: Component of the 4EHP-GYF2 complex, at least composed of
CC EIF4E2, GIGYF2 and ZNF598 (PubMed:22751931).
CC {ECO:0000269|PubMed:22751931}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q86UK7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q86UK7-2; Sequence=VSP_020661, VSP_020663, VSP_020664;
CC Name=3;
CC IsoId=Q86UK7-3; Sequence=VSP_020663;
CC Name=4;
CC IsoId=Q86UK7-4; Sequence=VSP_020660, VSP_020662, VSP_020664,
CC VSP_020665;
CC -!- SIMILARITY: Belongs to the ZNF598 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB15777.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK024487; BAB15777.1; ALT_INIT; mRNA.
DR EMBL; BC010990; AAH10990.2; -; mRNA.
DR EMBL; BC041015; AAH41015.1; -; mRNA.
DR EMBL; BC050477; AAH50477.1; -; mRNA.
DR EMBL; AL834428; CAD39089.1; -; mRNA.
DR RefSeq; NP_835461.2; NM_178167.3.
DR AlphaFoldDB; Q86UK7; -.
DR BioGRID; 124771; 419.
DR IntAct; Q86UK7; 27.
DR MINT; Q86UK7; -.
DR STRING; 9606.ENSP00000411409; -.
DR GlyGen; Q86UK7; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q86UK7; -.
DR PhosphoSitePlus; Q86UK7; -.
DR SwissPalm; Q86UK7; -.
DR BioMuta; ZNF598; -.
DR DMDM; 74727495; -.
DR EPD; Q86UK7; -.
DR jPOST; Q86UK7; -.
DR MassIVE; Q86UK7; -.
DR MaxQB; Q86UK7; -.
DR PaxDb; Q86UK7; -.
DR PeptideAtlas; Q86UK7; -.
DR PRIDE; Q86UK7; -.
DR ProteomicsDB; 69826; -. [Q86UK7-1]
DR ProteomicsDB; 69827; -. [Q86UK7-2]
DR ProteomicsDB; 69828; -. [Q86UK7-3]
DR ProteomicsDB; 69829; -. [Q86UK7-4]
DR DNASU; 90850; -.
DR GeneID; 90850; -.
DR KEGG; hsa:90850; -.
DR UCSC; uc002cof.3; human. [Q86UK7-1]
DR CTD; 90850; -.
DR DisGeNET; 90850; -.
DR GeneCards; ZNF598; -.
DR HGNC; HGNC:28079; ZNF598.
DR MIM; 617508; gene.
DR neXtProt; NX_Q86UK7; -.
DR PharmGKB; PA134944505; -.
DR eggNOG; KOG2231; Eukaryota.
DR HOGENOM; CLU_015828_0_0_1; -.
DR InParanoid; Q86UK7; -.
DR OrthoDB; 1003372at2759; -.
DR PhylomeDB; Q86UK7; -.
DR TreeFam; TF316196; -.
DR PathwayCommons; Q86UK7; -.
DR SignaLink; Q86UK7; -.
DR BioGRID-ORCS; 90850; 32 hits in 337 CRISPR screens.
DR ChiTaRS; ZNF598; human.
DR GenomeRNAi; 90850; -.
DR Pharos; Q86UK7; Tbio.
DR PRO; PR:Q86UK7; -.
DR Proteomes; UP000005640; Unplaced.
DR RNAct; Q86UK7; protein.
DR Genevisible; Q86UK7; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0043022; F:ribosome binding; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB.
DR GO; GO:0006513; P:protein monoubiquitination; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IMP:UniProtKB.
DR GO; GO:0006417; P:regulation of translation; IEA:UniProtKB-KW.
DR GO; GO:0072344; P:rescue of stalled ribosome; IDA:UniProtKB.
DR GO; GO:1990116; P:ribosome-associated ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR CDD; cd16615; RING-HC_ZNF598; 1.
DR InterPro; IPR041888; RING-HC_ZNF598/Hel2.
DR InterPro; IPR044288; ZNF598/Hel2.
DR InterPro; IPR013087; Znf_C2H2_type.
DR InterPro; IPR001841; Znf_RING.
DR PANTHER; PTHR22938; PTHR22938; 1.
DR SMART; SM00355; ZnF_C2H2; 5.
DR PROSITE; PS50089; ZF_RING_2; 1.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Metal-binding; Phosphoprotein; Reference proteome;
KW Transferase; Translation regulation; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT CHAIN 1..904
FT /note="E3 ubiquitin-protein ligase ZNF598"
FT /id="PRO_0000250568"
FT ZN_FING 29..69
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 187..210
FT /note="C2H2-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 312..469
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 490..656
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 332..347
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 359..392
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 399..415
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 446..461
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 495..533
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 565..582
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 600..614
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 306
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455"
FT MOD_RES 437
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT VAR_SEQ 1..397
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_020660"
FT VAR_SEQ 335..337
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_020661"
FT VAR_SEQ 398..431
FT /note="EGPGPKETSTNGPVSQEAFSVTGPAAPGCVGVPG -> MVGGCGQPQVGAGR
FT AGMEPRGLIAVDQLCFPAPS (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_020662"
FT VAR_SEQ 424..429
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_020663"
FT VAR_SEQ 551
FT /note="Q -> QE (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_020664"
FT VAR_SEQ 738..904
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_020665"
FT VARIANT 453
FT /note="S -> Y (in dbSNP:rs11556528)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_034470"
FT VARIANT 608
FT /note="A -> T (in dbSNP:rs11248905)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_059818"
FT VARIANT 637
FT /note="T -> M (in dbSNP:rs2286469)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_052147"
FT VARIANT 725
FT /note="C -> S (in dbSNP:rs2286468)"
FT /evidence="ECO:0000269|PubMed:17974005"
FT /id="VAR_034471"
FT MUTAGEN 29
FT /note="C->A: Abolishes E3 ubiquitin-protein ligase
FT activity, leading to enhanced readthrough on the poly(A)-
FT stall sequences."
FT /evidence="ECO:0000269|PubMed:28132843"
FT MOD_RES Q86UK7-2:428
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES Q86UK7-3:431
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:24275569"
SQ SEQUENCE 904 AA; 98637 MW; 492F67EE4E334743 CRC64;
MAAAGGAEGR RAALEAAAAA APERGGGSCV LCCGDLEATA LGRCDHPVCY RCSTKMRVLC
EQRYCAVCRE ELRQVVFGKK LPAFATIPIH QLQHEKKYDI YFADGKVYAL YRQLLQHECP
RCPELPPFSL FGDLEQHMRR QHELFCCRLC LQHLQIFTYE RKWYSRKDLA RHRMQGDPDD
TSHRGHPLCK FCDERYLDND ELLKHLRRDH YFCHFCDSDG AQDYYSDYAY LREHFREKHF
LCEEGRCSTE QFTHAFRTEI DLKAHRTACH SRSRAEARQN RHIDLQFSYA PRHSRRNEGV
VGGEDYEEVD RYSRQGRVAR AGTRGAQQSR RGSWRYKREE EDREVAAAVR ASVAAQQQEE
ARRSEDQEEG GRPKKEEAAA RGPEDPRGPR RSPRTQGEGP GPKETSTNGP VSQEAFSVTG
PAAPGCVGVP GALPPPSPKL KDEDFPSLSA STSSSCSTAA TPGPVGLALP YAIPARGRSA
FQEEDFPALV SSVPKPGTAP TSLVSAWNSS SSSKKVAQPP LSAQATGSGQ PTRKAGKGSR
GGRKGGPPFT QEEEEDGGPA LQELLSTRPT GSVSSTLGLA SIQPSKVGKK KKVGSEKPGT
TLPQPPPATC PPGALQAPEA PASRAEGPVA VVVNGHTEGP APARSAPKEP PGLPRPLGSF
PCPTPQEDFP ALGGPCPPRM PPPPGFSAVV LLKGTPPPPP PGLVPPISKP PPGFSGLLPS
PHPACVPSPA TTTTTKAPRL LPAPRAYLVP ENFRERNLQL IQSIRDFLQS DEARFSEFKS
HSGEFRQGLI SAAQYYKSCR DLLGENFQKV FNELLVLLPD TAKQQELLSA HTDFCNREKP
LSTKSKKNKK SAWQATTQQA GLDCRVCPTC QQVLAHGDAS SHQALHAARD DDFPSLQAIA
RIIT
