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Protein

Zinc finger CCHC domain-containing protein 8

Gene

ZCCHC8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Scaffolding subunit of the trimeric nuclear exosome targeting (NEXT) complex, a complex that directs a subset of non-coding short-lived RNAs for exosomal degradation. The RNA exosome is fundamental for the degradation of RNA in eukaryotic nuclei. Substrate targeting is facilitated by its cofactor SKIV2L2/MTR4, which links to RNA-binding protein adapters (PubMed:27871484). May be involved in pre-mRNA splicing (Probable).1 Publication1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri227 – 244CCHC-typePROSITE-ProRule annotationAdd BLAST18

GO - Molecular functioni

  • RNA binding Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

  • mRNA splicing, via spliceosome Source: UniProtKB

Keywordsi

Biological processmRNA processing, mRNA splicing
LigandMetal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Zinc finger CCHC domain-containing protein 8
Alternative name(s):
TRAMP-like complex RNA-binding factor ZCCHC8
Gene namesi
Name:ZCCHC8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000033030.13.
HGNCiHGNC:25265. ZCCHC8.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus, Spliceosome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi295L → E: Impaired interaction with ZCCHC8; when associated with E-299. 1 Publication1
Mutagenesisi299L → E: Impaired interaction with ZCCHC8; when associated with E-295. 1 Publication1
Mutagenesisi309F → A: Reduced interaction with ZCCHC8; when associated with E-313. 1 Publication1
Mutagenesisi313M → E: Reduced interaction with ZCCHC8; when associated with A-309. 1 Publication1
Mutagenesisi492T → A: Impaired phosphorylation by GSK3. 1 Publication1

Organism-specific databases

DisGeNETi55596.
OpenTargetsiENSG00000033030.
PharmGKBiPA134889410.

Polymorphism and mutation databases

BioMutaiZCCHC8.
DMDMi66774213.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001509602 – 707Zinc finger CCHC domain-containing protein 8Add BLAST706

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei342PhosphothreonineCombined sources1
Cross-linki413Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei472PhosphothreonineCombined sources1
Modified residuei479PhosphothreonineCombined sources1
Modified residuei485PhosphothreonineCombined sources1
Modified residuei492Phosphothreonine; by GSK3Combined sources1 Publication1
Modified residuei577PhosphothreonineCombined sources1
Modified residuei598PhosphoserineCombined sources1
Modified residuei648PhosphothreonineCombined sources1
Modified residuei649PhosphoserineCombined sources1
Modified residuei658PhosphoserineCombined sources1
Modified residuei695PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylation at Thr-492 by GSK3 is triggered in cells entering mitosis; this phosphorylation is greatly enhanced by nocodazole treatment, but reduced by lithium.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ6NZY4.
MaxQBiQ6NZY4.
PaxDbiQ6NZY4.
PeptideAtlasiQ6NZY4.
PRIDEiQ6NZY4.

PTM databases

iPTMnetiQ6NZY4.
PhosphoSitePlusiQ6NZY4.

Miscellaneous databases

PMAP-CutDBiQ6NZY4.

Expressioni

Inductioni

Slight accumulation in cells entering S phase of the cell cycle.1 Publication

Gene expression databases

BgeeiENSG00000033030.
CleanExiHS_ZCCHC8.
ExpressionAtlasiQ6NZY4. baseline and differential.
GenevisibleiQ6NZY4. HS.

Organism-specific databases

HPAiHPA037483.
HPA037484.

Interactioni

Subunit structurei

Component of a nuclear TRAMP-like complex, an ATP-dependent exosome regulatory complex consisting of a helicase (SKIV2L2/MTR4), an oligadenylate polymerase (PAPD5 or PAPD7), and a substrate specific RNA-binding factor (ZCCHC7 or ZCCHC8). Several TRAMP-like complexes exist with specific compositions and are associated with nuclear, or nucleolar RNA exosomes. Identified in the spliceosome C complex. Component of the nuclear exosome targeting (NEXT) complex composed of SKIV2L2/MTR4, ZCCHC8, and RBM7 that directs a subset of non-coding short-lived RNAs for exosomal degradation (PubMed:27905398, PubMed:27871484). Interacts with proteins involved in RNA processing and degradation such as SKIV2L2/MTR4 and RBM7 (PubMed:16263084, PubMed:27905398, PubMed:27871484).5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BRCA1P383982EBI-1263058,EBI-349905

Protein-protein interaction databases

BioGridi120739. 58 interactors.
CORUMiQ6NZY4.
IntActiQ6NZY4. 24 interactors.
MINTiMINT-1187494.
STRINGi9606.ENSP00000337313.

Structurei

Secondary structure

1707
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi293 – 299Combined sources7
Helixi308 – 316Combined sources9
Helixi320 – 322Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5LXRX-ray2.00B285-324[»]
5LXYX-ray2.85C/D/F/H/J/L/N285-324[»]
ProteinModelPortaliQ6NZY4.
SMRiQ6NZY4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni286 – 299RBM7 bindingCombined sources1 PublicationAdd BLAST14
Regioni309 – 324RBM7 bindingCombined sources1 PublicationAdd BLAST16

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili45 – 80Sequence analysisAdd BLAST36
Coiled coili516 – 539Sequence analysisAdd BLAST24

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi466 – 501Pro-richPROSITE-ProRule annotationAdd BLAST36

Sequence similaritiesi

Belongs to the ZCCHC8 family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri227 – 244CCHC-typePROSITE-ProRule annotationAdd BLAST18

Keywords - Domaini

Coiled coil, Zinc-finger

Phylogenomic databases

eggNOGiKOG2673. Eukaryota.
ENOG410XPDY. LUCA.
GeneTreeiENSGT00390000011475.
HOGENOMiHOG000155769.
HOVERGENiHBG079371.
InParanoidiQ6NZY4.
KOiK13128.
OMAiVHTRFKD.
OrthoDBiEOG091G0KC3.
PhylomeDBiQ6NZY4.
TreeFamiTF321837.

Family and domain databases

Gene3Di4.10.60.10. 1 hit.
InterProiView protein in InterPro
IPR006568. PSP_pro-rich.
IPR001878. Znf_CCHC.
IPR036875. Znf_CCHC_sf.
PfamiView protein in Pfam
PF04046. PSP. 1 hit.
PF00098. zf-CCHC. 1 hit.
SMARTiView protein in SMART
SM00581. PSP. 1 hit.
SM00343. ZnF_C2HC. 1 hit.
PROSITEiView protein in PROSITE
PS50158. ZF_CCHC. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q6NZY4-1) [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
MAAEVYFGDL ELFEPFDHPE ESIPKPVHTR FKDDDGDEED ENGVGDAELR
60 70 80 90 100
ERLRQCEETI EQLRAENQEL KRKLNILTRP SGILVNDTKL DGPILQILFM
110 120 130 140 150
NNAISKQYHQ EIEEFVSNLV KRFEEQQKND VEKTSFNLLP QPSSIVLEED
160 170 180 190 200
HKVEESCAIK NNKEAFSVVG SVLYFTNFCL DKLGQPLLNE NPQLSEGWEI
210 220 230 240 250
PKYHQVFSHI VSLEGQEIQV KAKRPKPHCF NCGSEEHQMK DCPMPRNAAR
260 270 280 290 300
ISEKRKEYMD ACGEANNQNF QQRYHAEEVE ERFGRFKPGV ISEELQDALG
310 320 330 340 350
VTDKSLPPFI YRMRQLGYPP GWLKEAELEN SGLALYDGKD GTDGETEVGE
360 370 380 390 400
IQQNKSVTYD LSKLVNYPGF NISTPRGIPD EWRIFGSIPM QACQQKDVFA
410 420 430 440 450
NYLTSNFQAP GVKSGNKRSS SHSSPGSPKK QKNESNSAGS PADMELDSDM
460 470 480 490 500
EVPHGSQSSE SFQFQPPLPP DTPPLPRGTP PPVFTPPLPK GTPPLTPSDS
510 520 530 540 550
PQTRTASGAV DEDALTLEEL EEQQRRIWAA LEQAESVNSD SDVPVDTPLT
560 570 580 590 600
GNSVASSPCP NELDLPVPEG KTSEKQTLDE PEVPEIFTKK SEAGHASSPD
610 620 630 640 650
SEVTSLCQKE KAELAPVNTE GALLDNGSVV PNCDISNGGS QKLFPADTSP
660 670 680 690 700
STATKIHSPI PDMSKFATGI TPFEFENMAE STGMYLRIRS LLKNSPRNQQ

KNKKASE
Length:707
Mass (Da):78,577
Last modified:May 10, 2005 - v2
Checksum:i7BE6E30F919A4771
GO
Isoform 2 (identifier: Q6NZY4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-238: Missing.

Note: No experimental confirmation available.
Show »
Length:469
Mass (Da):51,130
Checksum:i891FCBBB70026D4C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti20E → G in BAB55308 (PubMed:14702039).Curated1
Sequence conflicti216 – 219QEIQ → DAWV in AAH17704 (PubMed:15489334).Curated4
Sequence conflicti326A → V in AAH65918 (PubMed:15489334).Curated1
Sequence conflicti461S → G in BAB55308 (PubMed:14702039).Curated1
Sequence conflicti582E → G in BAC11105 (PubMed:14702039).Curated1
Sequence conflicti663M → V in CAB75658 (PubMed:17974005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_034585672P → A. Corresponds to variant dbSNP:rs1063155Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0137171 – 238Missing in isoform 2. 1 PublicationAdd BLAST238

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK027702 mRNA. Translation: BAB55308.1.
AK074638 mRNA. Translation: BAC11105.1.
AL157433 mRNA. Translation: CAB75657.1.
AL157434 mRNA. Translation: CAB75658.1.
BC017704 mRNA. Translation: AAH17704.2.
BC065918 mRNA. Translation: AAH65918.1.
PIRiT46929.
T46930.
RefSeqiNP_060082.2. NM_017612.4. [Q6NZY4-1]
UniGeneiHs.37706.

Genome annotation databases

EnsembliENST00000536306; ENSP00000441423; ENSG00000033030. [Q6NZY4-2]
ENST00000543897; ENSP00000438993; ENSG00000033030. [Q6NZY4-2]
ENST00000633063; ENSP00000488055; ENSG00000033030. [Q6NZY4-1]
GeneIDi55596.
KEGGihsa:55596.
UCSCiuc009zxp.4. human. [Q6NZY4-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiZCHC8_HUMAN
AccessioniPrimary (citable) accession number: Q6NZY4
Secondary accession number(s): Q7L2P6
, Q8N2K5, Q96SK7, Q9NSS2, Q9NSS3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 10, 2005
Last sequence update: May 10, 2005
Last modified: October 25, 2017
This is version 139 of the entry and version 2 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families