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 10-MAY-2017, entry version 118.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), AND VARIANTS
RP TYR-453; 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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
RP SEQUENCE [LARGE SCALE MRNA] OF 236-904 (ISOFORM 2), AND VARIANTS
RP TYR-453; THR-608 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
RT project: 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
RP VARIANT 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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., 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
RP 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
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-437, AND IDENTIFICATION
RP BY 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.,
RA Buerckstuemmer T., 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.,
RA Henderson V.C., Alain T., Fonseca B.D., Karashchuk G., Bennett C.F.,
RA Kabuta T., Higashi S., Larsson O., Topisirovic I., Smith R.J.,
RA 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.,
RA Wang L., Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT liver 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
RT site-specific ribosome ubiquitination.";
RL Mol. Cell 0:0-0(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.,
RA Bennett E.J.;
RT "ZNF598 and RACK1 regulate mammalian ribosome-associated quality
RT control function by mediating regulatory 40S ribosomal
RT ubiquitylation.";
RL Mol. Cell 0:0-0(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
CC during translation of poly(A) sequences by mediating
CC monoubiquitination of 40S ribosomal protein RPS10/eS10, RPS20/uS10
CC and RPS3/uS3 (PubMed:28065601, PubMed:28132843). Stalling
CC precludes synthesis of a long poly-lysine tail and initiates the
CC RQC pathway to degrade the potentially detrimental aberrant
CC nascent polypeptide (PubMed:28065601, PubMed:28132843). Also acts
CC as a component of the 4EHP-GYF2 complex, a multiprotein complex
CC 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: S-ubiquitinyl-[E2 ubiquitin-conjugating
CC enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-
CC conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor
CC protein]-L-lysine. {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 Note=No experimental confirmation available. Contains a
CC phosphoserine at position 428. {ECO:0000244|PubMed:19690332,
CC ECO:0000244|PubMed:24275569};
CC Name=3;
CC IsoId=Q86UK7-3; Sequence=VSP_020663;
CC Note=No experimental confirmation available. Contains a
CC phosphoserine at position 431. {ECO:0000244|PubMed:19690332,
CC ECO:0000244|PubMed:24275569};
CC Name=4;
CC IsoId=Q86UK7-4; Sequence=VSP_020660, VSP_020662, VSP_020664,
CC VSP_020665;
CC Note=No experimental confirmation available.;
CC -!- SIMILARITY: Belongs to the ZNF598 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB15777.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -----------------------------------------------------------------------
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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 UniGene; Hs.343828; -.
DR ProteinModelPortal; Q86UK7; -.
DR SMR; Q86UK7; -.
DR BioGrid; 124771; 31.
DR IntAct; Q86UK7; 17.
DR MINT; MINT-4776754; -.
DR STRING; 9606.ENSP00000411409; -.
DR iPTMnet; Q86UK7; -.
DR PhosphoSitePlus; Q86UK7; -.
DR DMDM; 74727495; -.
DR EPD; Q86UK7; -.
DR MaxQB; Q86UK7; -.
DR PaxDb; Q86UK7; -.
DR PeptideAtlas; Q86UK7; -.
DR PRIDE; Q86UK7; -.
DR Ensembl; ENST00000431526; ENSP00000411409; ENSG00000167962.
DR GeneID; 90850; -.
DR KEGG; hsa:90850; -.
DR UCSC; uc002cof.3; human. [Q86UK7-1]
DR CTD; 90850; -.
DR GeneCards; ZNF598; -.
DR HGNC; HGNC:28079; ZNF598.
DR HPA; HPA041760; -.
DR HPA; HPA041896; -.
DR neXtProt; NX_Q86UK7; -.
DR PharmGKB; PA134944505; -.
DR eggNOG; KOG2231; Eukaryota.
DR eggNOG; COG5236; LUCA.
DR HOGENOM; HOG000082533; -.
DR HOVERGEN; HBG055813; -.
DR InParanoid; Q86UK7; -.
DR OrthoDB; EOG091G022A; -.
DR PhylomeDB; Q86UK7; -.
DR TreeFam; TF316196; -.
DR GenomeRNAi; 90850; -.
DR PRO; PR:Q86UK7; -.
DR Proteomes; UP000005640; Unplaced.
DR Bgee; ENSG00000167962; -.
DR CleanEx; HS_ZNF598; -.
DR Genevisible; Q86UK7; HS.
DR GO; GO:0043022; F:ribosome binding; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IDA:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006513; P:protein monoubiquitination; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IMP:UniProtKB.
DR GO; GO:0072344; P:rescue of stalled ribosome; IDA:UniProtKB.
DR Gene3D; 3.30.40.10; -; 2.
DR InterPro; IPR013087; Znf_C2H2_type.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
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; Complete proteome; Metal-binding;
KW Phosphoprotein; Polymorphism; Reference proteome; Transferase;
KW Translation regulation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1 904 E3 ubiquitin-protein ligase ZNF598.
FT /FTId=PRO_0000250568.
FT ZN_FING 29 69 RING-type. {ECO:0000255|PROSITE-
FT ProRule:PRU00175}.
FT ZN_FING 187 210 C2H2-type. {ECO:0000255|PROSITE-
FT ProRule:PRU00042}.
FT COMPBIAS 598 744 Pro-rich.
FT MOD_RES 306 306 Phosphotyrosine.
FT {ECO:0000244|PubMed:15592455}.
FT MOD_RES 437 437 Phosphoserine.
FT {ECO:0000244|PubMed:18669648}.
FT VAR_SEQ 1 397 Missing (in isoform 4).
FT {ECO:0000303|PubMed:14702039}.
FT /FTId=VSP_020660.
FT VAR_SEQ 335 337 Missing (in isoform 2).
FT {ECO:0000303|PubMed:15489334}.
FT /FTId=VSP_020661.
FT VAR_SEQ 398 431 EGPGPKETSTNGPVSQEAFSVTGPAAPGCVGVPG -> MVG
FT GCGQPQVGAGRAGMEPRGLIAVDQLCFPAPS (in
FT isoform 4).
FT {ECO:0000303|PubMed:14702039}.
FT /FTId=VSP_020662.
FT VAR_SEQ 424 429 Missing (in isoform 2 and isoform 3).
FT {ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:17974005}.
FT /FTId=VSP_020663.
FT VAR_SEQ 551 551 Q -> QE (in isoform 2 and isoform 4).
FT {ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334}.
FT /FTId=VSP_020664.
FT VAR_SEQ 738 904 Missing (in isoform 4).
FT {ECO:0000303|PubMed:14702039}.
FT /FTId=VSP_020665.
FT VARIANT 453 453 S -> Y (in dbSNP:rs11556528).
FT {ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334}.
FT /FTId=VAR_034470.
FT VARIANT 608 608 A -> T (in dbSNP:rs11248905).
FT {ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334}.
FT /FTId=VAR_059818.
FT VARIANT 637 637 T -> M (in dbSNP:rs2286469).
FT {ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334}.
FT /FTId=VAR_052147.
FT VARIANT 725 725 C -> S (in dbSNP:rs2286468).
FT {ECO:0000269|PubMed:17974005}.
FT /FTId=VAR_034471.
FT MUTAGEN 29 29 C->A: Abolishes E3 ubiquitin-protein
FT ligase activity, leading to enhanced
FT readthrough on the poly(A)-stall
FT sequences. {ECO:0000269|PubMed:28132843}.
CC --------------------------------------------------------------------------
CC The following FT lines are automated annotations from the MyHits database.
CC --------------------------------------------------------------------------
FT MYHIT 117 142 ismart:ZnF_C2H2 [T]
FT MYHIT 240 270 ismart:ZnF_C2H2 [T]
FT MYHIT 29 69 iprf:ZF_RING_2 [T]
FT MYHIT 187 210 ismart:ZnF_C2H2 [T]
FT MYHIT 211 239 ismart:ZnF_C2H2 [T]
FT MYHIT 189 210 ipat:ZINC_FINGER_C2H2_1 [T]
FT MYHIT 865 886 ismart:ZnF_C2H2 [T]
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
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