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Protein

E3 ubiquitin-protein ligase ZNF598

Gene

ZNF598

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

E3 ubiquitin-protein ligase that plays a key role in the ribosome quality control (RQC), a pathway that takes place when a ribosome has stalled during translation (PubMed:28065601, PubMed:28132843). Required for ribosomes to terminally stall during translation of poly(A) sequences by mediating monoubiquitination of 40S ribosomal protein RPS10/eS10, RPS20/uS10 and RPS3/uS3 (PubMed:28065601, PubMed:28132843). Stalling precludes synthesis of a long poly-lysine tail and initiates the RQC pathway to degrade the potentially detrimental aberrant nascent polypeptide (PubMed:28065601, PubMed:28132843). Also acts as a component of the 4EHP-GYF2 complex, a multiprotein complex that acts as a repressor of translation initiation (PubMed:22751931).3 Publications

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.2 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri29 – 69RING-typePROSITE-ProRule annotationAdd BLAST41
Zinc fingeri187 – 210C2H2-typePROSITE-ProRule annotationAdd BLAST24

GO - Molecular functioni

GO - Biological processi

  • protein monoubiquitination Source: UniProtKB
  • protein ubiquitination Source: UniProtKB
  • rescue of stalled ribosome Source: UniProtKB

Keywordsi

Molecular functionTransferase
Biological processTranslation regulation, Ubl conjugation pathway
LigandMetal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase ZNF598Curated (EC:2.3.2.272 Publications)
Alternative name(s):
Zinc finger protein 598Imported
Gene namesi
Name:ZNF598Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Unplaced

Organism-specific databases

EuPathDBiHostDB:ENSG00000167962.12
HGNCiHGNC:28079 ZNF598
MIMi617508 gene
neXtProtiNX_Q86UK7

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi29C → A: Abolishes E3 ubiquitin-protein ligase activity, leading to enhanced readthrough on the poly(A)-stall sequences. 1 Publication1

Organism-specific databases

PharmGKBiPA134944505

Polymorphism and mutation databases

DMDMi74727495

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002505681 – 904E3 ubiquitin-protein ligase ZNF598Add BLAST904

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei306PhosphotyrosineCombined sources1
Modified residuei437PhosphoserineCombined sources1
Isoform 2 (identifier: Q86UK7-2)
Modified residuei428PhosphoserineCombined sources1
Isoform 3 (identifier: Q86UK7-3)
Modified residuei431PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ86UK7
MaxQBiQ86UK7
PaxDbiQ86UK7
PeptideAtlasiQ86UK7
PRIDEiQ86UK7
ProteomicsDBi69826
69827 [Q86UK7-2]
69828 [Q86UK7-3]
69829 [Q86UK7-4]

PTM databases

iPTMnetiQ86UK7
PhosphoSitePlusiQ86UK7

Expressioni

Gene expression databases

BgeeiENSG00000167962 Expressed in 152 organ(s), highest expression level in adenohypophysis
CleanExiHS_ZNF598
GenevisibleiQ86UK7 HS

Organism-specific databases

HPAiHPA041760
HPA041896

Interactioni

Subunit structurei

Component of the 4EHP-GYF2 complex, at least composed of EIF4E2, GIGYF2 and ZNF598 (PubMed:22751931).1 Publication

Protein-protein interaction databases

BioGridi124771, 46 interactors
IntActiQ86UK7, 18 interactors
MINTiQ86UK7
STRINGi9606.ENSP00000411409

Structurei

3D structure databases

ProteinModelPortaliQ86UK7
SMRiQ86UK7
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi598 – 744Pro-richAdd BLAST147

Sequence similaritiesi

Belongs to the ZNF598 family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri29 – 69RING-typePROSITE-ProRule annotationAdd BLAST41
Zinc fingeri187 – 210C2H2-typePROSITE-ProRule annotationAdd BLAST24

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG2231 Eukaryota
COG5236 LUCA
HOGENOMiHOG000082533
HOVERGENiHBG055813
InParanoidiQ86UK7
KOiK22381
OrthoDBiEOG091G022A
PhylomeDBiQ86UK7
TreeFamiTF316196

Family and domain databases

InterProiView protein in InterPro
IPR013087 Znf_C2H2_type
IPR001841 Znf_RING
SMARTiView protein in SMART
SM00355 ZnF_C2H2, 5 hits
PROSITEiView protein in PROSITE
PS50089 ZF_RING_2, 1 hit
PS00028 ZINC_FINGER_C2H2_1, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q86UK7-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MAAAGGAEGR RAALEAAAAA APERGGGSCV LCCGDLEATA LGRCDHPVCY
60 70 80 90 100
RCSTKMRVLC EQRYCAVCRE ELRQVVFGKK LPAFATIPIH QLQHEKKYDI
110 120 130 140 150
YFADGKVYAL YRQLLQHECP RCPELPPFSL FGDLEQHMRR QHELFCCRLC
160 170 180 190 200
LQHLQIFTYE RKWYSRKDLA RHRMQGDPDD TSHRGHPLCK FCDERYLDND
210 220 230 240 250
ELLKHLRRDH YFCHFCDSDG AQDYYSDYAY LREHFREKHF LCEEGRCSTE
260 270 280 290 300
QFTHAFRTEI DLKAHRTACH SRSRAEARQN RHIDLQFSYA PRHSRRNEGV
310 320 330 340 350
VGGEDYEEVD RYSRQGRVAR AGTRGAQQSR RGSWRYKREE EDREVAAAVR
360 370 380 390 400
ASVAAQQQEE ARRSEDQEEG GRPKKEEAAA RGPEDPRGPR RSPRTQGEGP
410 420 430 440 450
GPKETSTNGP VSQEAFSVTG PAAPGCVGVP GALPPPSPKL KDEDFPSLSA
460 470 480 490 500
STSSSCSTAA TPGPVGLALP YAIPARGRSA FQEEDFPALV SSVPKPGTAP
510 520 530 540 550
TSLVSAWNSS SSSKKVAQPP LSAQATGSGQ PTRKAGKGSR GGRKGGPPFT
560 570 580 590 600
QEEEEDGGPA LQELLSTRPT GSVSSTLGLA SIQPSKVGKK KKVGSEKPGT
610 620 630 640 650
TLPQPPPATC PPGALQAPEA PASRAEGPVA VVVNGHTEGP APARSAPKEP
660 670 680 690 700
PGLPRPLGSF PCPTPQEDFP ALGGPCPPRM PPPPGFSAVV LLKGTPPPPP
710 720 730 740 750
PGLVPPISKP PPGFSGLLPS PHPACVPSPA TTTTTKAPRL LPAPRAYLVP
760 770 780 790 800
ENFRERNLQL IQSIRDFLQS DEARFSEFKS HSGEFRQGLI SAAQYYKSCR
810 820 830 840 850
DLLGENFQKV FNELLVLLPD TAKQQELLSA HTDFCNREKP LSTKSKKNKK
860 870 880 890 900
SAWQATTQQA GLDCRVCPTC QQVLAHGDAS SHQALHAARD DDFPSLQAIA

RIIT
Length:904
Mass (Da):98,637
Last modified:June 1, 2003 - v1
Checksum:i492F67EE4E334743
GO
Isoform 2 (identifier: Q86UK7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     335-337: Missing.
     424-429: Missing.
     551-551: Q → QE

Note: No experimental confirmation available.Combined sources
Show »
Length:896
Mass (Da):97,806
Checksum:i0524BC8755C1B28D
GO
Isoform 3 (identifier: Q86UK7-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     424-429: Missing.

Note: No experimental confirmation available.Combined sources
Show »
Length:898
Mass (Da):98,124
Checksum:i1C24E53E1A3573CF
GO
Isoform 4 (identifier: Q86UK7-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-397: Missing.
     398-431: EGPGPKETSTNGPVSQEAFSVTGPAAPGCVGVPG → MVGGCGQPQVGAGRAGMEPRGLIAVDQLCFPAPS
     551-551: Q → QE
     738-904: Missing.

Note: No experimental confirmation available.
Show »
Length:341
Mass (Da):34,010
Checksum:iABB2FDC981BB27EC
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H3BQQ2H3BQQ2_HUMAN
E3 ubiquitin-protein ligase ZNF598
ZNF598
849Annotation score:
H3BR87H3BR87_HUMAN
E3 ubiquitin-protein ligase ZNF598
ZNF598
203Annotation score:
H3BPF3H3BPF3_HUMAN
E3 ubiquitin-protein ligase ZNF598
ZNF598
90Annotation score:

Sequence cautioni

The sequence BAB15777 differs from that shown. Reason: Erroneous initiation.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_034470453S → Y2 PublicationsCorresponds to variant dbSNP:rs11556528Ensembl.1
Natural variantiVAR_059818608A → T2 PublicationsCorresponds to variant dbSNP:rs11248905Ensembl.1
Natural variantiVAR_052147637T → M2 PublicationsCorresponds to variant dbSNP:rs2286469Ensembl.1
Natural variantiVAR_034471725C → S1 PublicationCorresponds to variant dbSNP:rs2286468Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0206601 – 397Missing in isoform 4. 1 PublicationAdd BLAST397
Alternative sequenceiVSP_020661335 – 337Missing in isoform 2. 1 Publication3
Alternative sequenceiVSP_020662398 – 431EGPGP…VGVPG → MVGGCGQPQVGAGRAGMEPR GLIAVDQLCFPAPS in isoform 4. 1 PublicationAdd BLAST34
Alternative sequenceiVSP_020663424 – 429Missing in isoform 2 and isoform 3. 2 Publications6
Alternative sequenceiVSP_020664551Q → QE in isoform 2 and isoform 4. 2 Publications1
Alternative sequenceiVSP_020665738 – 904Missing in isoform 4. 1 PublicationAdd BLAST167

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK024487 mRNA Translation: BAB15777.1 Different initiation.
BC010990 mRNA Translation: AAH10990.2
BC041015 mRNA Translation: AAH41015.1
BC050477 mRNA Translation: AAH50477.1
AL834428 mRNA Translation: CAD39089.1
RefSeqiNP_835461.2, NM_178167.3
UniGeneiHs.343828

Genome annotation databases

EnsembliENST00000431526; ENSP00000411409; ENSG00000167962
GeneIDi90850
KEGGihsa:90850
UCSCiuc002cof.3 human [Q86UK7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK024487 mRNA Translation: BAB15777.1 Different initiation.
BC010990 mRNA Translation: AAH10990.2
BC041015 mRNA Translation: AAH41015.1
BC050477 mRNA Translation: AAH50477.1
AL834428 mRNA Translation: CAD39089.1
RefSeqiNP_835461.2, NM_178167.3
UniGeneiHs.343828

3D structure databases

ProteinModelPortaliQ86UK7
SMRiQ86UK7
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124771, 46 interactors
IntActiQ86UK7, 18 interactors
MINTiQ86UK7
STRINGi9606.ENSP00000411409

PTM databases

iPTMnetiQ86UK7
PhosphoSitePlusiQ86UK7

Polymorphism and mutation databases

DMDMi74727495

Proteomic databases

EPDiQ86UK7
MaxQBiQ86UK7
PaxDbiQ86UK7
PeptideAtlasiQ86UK7
PRIDEiQ86UK7
ProteomicsDBi69826
69827 [Q86UK7-2]
69828 [Q86UK7-3]
69829 [Q86UK7-4]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000431526; ENSP00000411409; ENSG00000167962
GeneIDi90850
KEGGihsa:90850
UCSCiuc002cof.3 human [Q86UK7-1]

Organism-specific databases

CTDi90850
EuPathDBiHostDB:ENSG00000167962.12
GeneCardsiZNF598
HGNCiHGNC:28079 ZNF598
HPAiHPA041760
HPA041896
MIMi617508 gene
neXtProtiNX_Q86UK7
PharmGKBiPA134944505
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2231 Eukaryota
COG5236 LUCA
HOGENOMiHOG000082533
HOVERGENiHBG055813
InParanoidiQ86UK7
KOiK22381
OrthoDBiEOG091G022A
PhylomeDBiQ86UK7
TreeFamiTF316196

Miscellaneous databases

GenomeRNAii90850
PROiPR:Q86UK7
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000167962 Expressed in 152 organ(s), highest expression level in adenohypophysis
CleanExiHS_ZNF598
GenevisibleiQ86UK7 HS

Family and domain databases

InterProiView protein in InterPro
IPR013087 Znf_C2H2_type
IPR001841 Znf_RING
SMARTiView protein in SMART
SM00355 ZnF_C2H2, 5 hits
PROSITEiView protein in PROSITE
PS50089 ZF_RING_2, 1 hit
PS00028 ZINC_FINGER_C2H2_1, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiZN598_HUMAN
AccessioniPrimary (citable) accession number: Q86UK7
Secondary accession number(s): Q8IW49
, Q8N3D9, Q96FG3, Q9H7J3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 3, 2006
Last sequence update: June 1, 2003
Last modified: November 7, 2018
This is version 126 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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