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Protein

E3 ubiquitin-protein ligase ZNRF1

Gene

ZNRF1

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

Functioni

E3 ubiquitin-protein ligase that mediates the ubiquitination of AKT1 and GLUL, thereby playing a role in neuron cells differentiation. Plays a role in the establishment and maintenance of neuronal transmission and plasticity. Regulates Schwann cells differentiation by mediating ubiquitination of GLUL. Promotes neurodegeneration by mediating 'Lys-48'-linked polyubiquitination and subsequent degradation of AKT1 in axons: degradation of AKT1 prevents AKT1-mediated phosphorylation of GSK3B, leading to GSK3B activation and phosphorylation of DPYSL2/CRMP2 followed by destabilization of microtubule assembly in axons (Probable).1 Publication

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.

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri184 – 225RING-type; atypicalPROSITE-ProRule annotationAdd BLAST42

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processUbl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
UniPathwayiUPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase ZNRF1 (EC:2.3.2.27)
Alternative name(s):
Nerve injury-induced gene 283 protein
RING-type E3 ubiquitin transferase ZNRF1
Zinc/RING finger protein 1
Gene namesi
Name:ZNRF1
Synonyms:NIN283
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000186187.11
HGNCiHGNC:18452 ZNRF1
MIMi612060 gene
neXtProtiNX_Q8ND25

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

Cell junction, Cytoplasmic vesicle, Endosome, Lysosome, Membrane, Synapse

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi184C → A: Loss of E3 activity. 1 Publication1

Organism-specific databases

DisGeNETi84937
OpenTargetsiENSG00000186187
PharmGKBiPA134938288

Polymorphism and mutation databases

BioMutaiZNRF1
DMDMi126253846

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCurated
ChainiPRO_00002777992 – 227E3 ubiquitin-protein ligase ZNRF1Add BLAST226

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycine1 Publication1
Modified residuei52PhosphoserineCombined sources1
Modified residuei53PhosphoserineCombined sources1
Modified residuei123PhosphoserineCombined sources1

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

EPDiQ8ND25
MaxQBiQ8ND25
PaxDbiQ8ND25
PeptideAtlasiQ8ND25
PRIDEiQ8ND25

PTM databases

iPTMnetiQ8ND25
PhosphoSitePlusiQ8ND25

Expressioni

Tissue specificityi

Expressed primarily in the nervous system, with expression higher in developing brain relative to adult. Expressed at low levels in testis and thymus.2 Publications

Gene expression databases

BgeeiENSG00000186187
CleanExiHS_ZNRF1
ExpressionAtlasiQ8ND25 baseline and differential
GenevisibleiQ8ND25 HS

Organism-specific databases

HPAiHPA027470

Interactioni

Subunit structurei

Interacts with AKT1, GLUL and TUBB2A.By similarity

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi124371, 28 interactors
IntActiQ8ND25, 13 interactors
STRINGi9606.ENSP00000335091

Structurei

3D structure databases

ProteinModelPortaliQ8ND25
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 10Required for endosomal and lysosomal localization and myristoylation9

Domaini

The RING-type zinc finger domain is required for E3 ligase activity.By similarity

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri184 – 225RING-type; atypicalPROSITE-ProRule annotationAdd BLAST42

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG0801 Eukaryota
ENOG4111V18 LUCA
GeneTreeiENSGT00390000013068
HOGENOMiHOG000285998
HOVERGENiHBG094200
InParanoidiQ8ND25
KOiK10694
OMAiAHSGFKC
OrthoDBiEOG091G0N7A
PhylomeDBiQ8ND25
TreeFamiTF317681

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
PfamiView protein in Pfam
PF13639 zf-RING_2, 1 hit
SMARTiView protein in SMART
SM00184 RING, 1 hit
PROSITEiView protein in PROSITE
PS50089 ZF_RING_2, 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: Q8ND25-1) [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
MGGKQSTAAR SRGPFPGVST DDSAVPPPGG APHFGHYRTG GGAMGLRSRS
60 70 80 90 100
VSSVAGMGMD PSTAGGVPFG LYTPASRGTG DSERAPGGGG SASDSTYAHG
110 120 130 140 150
NGYQETGGGH HRDGMLYLGS RASLADALPL HIAPRWFSSH SGFKCPICSK
160 170 180 190 200
SVASDEMEMH FIMCLSKPRL SYNDDVLTKD AGECVICLEE LLQGDTIARL
210 220
PCLCIYHKSC IDSWFEVNRS CPEHPAD
Length:227
Mass (Da):23,783
Last modified:February 20, 2007 - v2
Checksum:i41BCF1AAEDD0C52C
GO
Isoform 2 (identifier: Q8ND25-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     173-173: N → NGRIQRSLRGAQPEKTWLSGRTLQEQPWRTECSWAPMAQMQSYPHCPVENRE

Note: No experimental confirmation available.
Show »
Length:278
Mass (Da):29,777
Checksum:i3BBC1E451429E13D
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_023088173N → NGRIQRSLRGAQPEKTWLSG RTLQEQPWRTECSWAPMAQM QSYPHCPVENRE in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF378524 mRNA Translation: AAK69753.1
AL136903 mRNA Translation: CAB66837.1
AL834440 mRNA Translation: CAD39100.1
AC092383 Genomic DNA No translation available.
AC099508 Genomic DNA No translation available.
CH471114 Genomic DNA Translation: EAW95668.1
CH471114 Genomic DNA Translation: EAW95670.1
CH471114 Genomic DNA Translation: EAW95671.1
BC007235 mRNA Translation: AAH07235.1
CCDSiCCDS10912.1 [Q8ND25-1]
RefSeqiNP_115644.1, NM_032268.4 [Q8ND25-1]
XP_016879282.1, XM_017023793.1 [Q8ND25-1]
UniGeneiHs.427284

Genome annotation databases

EnsembliENST00000320619; ENSP00000323362; ENSG00000186187 [Q8ND25-2]
ENST00000335325; ENSP00000335091; ENSG00000186187 [Q8ND25-1]
ENST00000567962; ENSP00000455601; ENSG00000186187 [Q8ND25-1]
GeneIDi84937
KEGGihsa:84937
UCSCiuc002fdk.4 human [Q8ND25-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiZNRF1_HUMAN
AccessioniPrimary (citable) accession number: Q8ND25
Secondary accession number(s): D3DUJ9, Q9H083
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: February 20, 2007
Last modified: May 23, 2018
This is version 124 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

Complete proteome, Reference proteome

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