Human Gene ZNRF1 (uc002fdl.1) Description and Page Index
  Description: Homo sapiens zinc and ring finger 1, E3 ubiquitin protein ligase (ZNRF1), mRNA.
RefSeq Summary (NM_032268): This gene encodes an E3 ubiquitin-protein ligase that plays a role in neural-cell differentiation. Overexpression of this gene causes neurite-like elongation. The encoded protein contains both a zinc finger and a RING finger motif and is localized in the endosome/lysosome compartment, indicating that it may be involved in ubiquitin-mediated protein modification, and in synaptic vessicle membranes in neurons. [provided by RefSeq, Feb 2012]. Sequence Note: The RefSeq transcript and protein were derived from transcript and genomic sequence to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on alignments. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: AF378524.1, SRR1660803.161893.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA1965299, SAMEA1966682 [ECO:0000348] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000335325.9/ ENSP00000335091.4 RefSeq Select criteria :: based on conservation, expression, longest protein ##RefSeq-Attributes-END##
Transcript (Including UTRs)
   Position: hg19 chr16:75,032,915-75,144,892 Size: 111,978 Total Exon Count: 5 Strand: +
Coding Region
   Position: hg19 chr16:75,033,570-75,140,437 Size: 106,868 Coding Exon Count: 4 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-15

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr16:75,032,915-75,144,892)mRNA (may differ from genome)Protein (227 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
neXtProtOMIMPubMedReactomeStanford SOURCETreefam

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=E3 ubiquitin-protein ligase ZNRF1; EC=6.3.2.-; AltName: Full=Nerve injury-induced gene 283 protein; AltName: Full=Zinc/RING finger protein 1;
FUNCTION: 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).
PATHWAY: Protein modification; protein ubiquitination.
SUBUNIT: Interacts with AKT1, GLUL and TUBB2A (By similarity).
INTERACTION: P51668:UBE2D1; NbExp=4; IntAct=EBI-2129250, EBI-743540; P62837:UBE2D2; NbExp=4; IntAct=EBI-2129250, EBI-347677; P61077:UBE2D3; NbExp=3; IntAct=EBI-2129250, EBI-348268; Q9Y2X8:UBE2D4; NbExp=3; IntAct=EBI-2129250, EBI-745527; P51965:UBE2E1; NbExp=3; IntAct=EBI-2129250, EBI-348546; P61088:UBE2N; NbExp=3; IntAct=EBI-2129250, EBI-1052908; Q13404:UBE2V1; NbExp=2; IntAct=EBI-2129250, EBI-1050671;
SUBCELLULAR LOCATION: Endosome. Lysosome. Membrane; Peripheral membrane protein. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane; Peripheral membrane protein (Potential). Note=Associated with synaptic vesicle membranes in neurons.
TISSUE SPECIFICITY: Expressed primarily in the nervous system, with expression higher in developing brain relative to adult. Expressed at low levels in testis and thymus.
DOMAIN: The RING-type zinc finger domain is required for E3 ligase activity (By similarity).
SIMILARITY: Contains 1 RING-type zinc finger.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): ZNRF1
CDC HuGE Published Literature: ZNRF1

-  MalaCards Disease Associations
  MalaCards Gene Search: ZNRF1
Diseases sorted by gene-association score: b-cell adult acute lymphocytic leukemia (17)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 12.44 RPKM in Testis
Total median expression: 270.07 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -345.47655-0.527 Picture PostScript Text
3' UTR -1257.313294-0.382 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001841 - Znf_RING

Pfam Domains:
PF13639 - Ring finger domain

SCOP Domains:
57850 - RING/U-box

ModBase Predicted Comparative 3D Structure on Q8ND25
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
  Protein Sequence   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004842 ubiquitin-protein transferase activity
GO:0005515 protein binding
GO:0016740 transferase activity
GO:0046872 metal ion binding
GO:0061630 ubiquitin protein ligase activity

Biological Process:
GO:0000209 protein polyubiquitination
GO:0016567 protein ubiquitination
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
GO:0070936 protein K48-linked ubiquitination

Cellular Component:
GO:0005764 lysosome
GO:0005768 endosome
GO:0005829 cytosol
GO:0016020 membrane
GO:0030054 cell junction
GO:0030672 synaptic vesicle membrane
GO:0031410 cytoplasmic vesicle
GO:0045202 synapse

-  Descriptions from all associated GenBank mRNAs
  AK294434 - Homo sapiens cDNA FLJ58842 complete cds, highly similar to Homo sapiens zinc and ring finger 1 (ZNRF1), mRNA.
BC007235 - Homo sapiens zinc and ring finger 1, mRNA (cDNA clone MGC:15430 IMAGE:2823677), complete cds.
AF378524 - Homo sapiens nin283 mRNA, complete cds.
AL136903 - Homo sapiens mRNA; cDNA DKFZp434E229 (from clone DKFZp434E229); complete cds.
BC027686 - Homo sapiens cDNA clone IMAGE:3833114, **** WARNING: chimeric clone ****.
CU675577 - Synthetic construct Homo sapiens gateway clone IMAGE:100023282 5' read ZNRF1 mRNA.
AB463358 - Synthetic construct DNA, clone: pF1KB8399, Homo sapiens ZNRF1 gene for zinc and ring finger protein 1, without stop codon, in Flexi system.
AM392788 - Synthetic construct Homo sapiens clone IMAGE:100001657 for hypothetical protein (ZNRF1 gene).
EU446548 - Synthetic construct Homo sapiens clone IMAGE:100070087; IMAGE:100011757; FLH257499.01L zinc and ring finger 1 (ZNRF1) gene, encodes complete protein.
KJ895056 - Synthetic construct Homo sapiens clone ccsbBroadEn_04450 ZNRF1 gene, encodes complete protein.
AL834440 - Homo sapiens mRNA; cDNA DKFZp434E1228 (from clone DKFZp434E1228).
JD493535 - Sequence 474559 from Patent EP1572962.
JD303656 - Sequence 284680 from Patent EP1572962.
JD128829 - Sequence 109853 from Patent EP1572962.
JD566647 - Sequence 547671 from Patent EP1572962.
JD228548 - Sequence 209572 from Patent EP1572962.
JD354606 - Sequence 335630 from Patent EP1572962.
JD456961 - Sequence 437985 from Patent EP1572962.
JD142457 - Sequence 123481 from Patent EP1572962.
AK128349 - Homo sapiens cDNA FLJ46491 fis, clone THYMU3027655.
AK094870 - Homo sapiens cDNA FLJ37551 fis, clone BRCAN2028040.
AL390144 - Homo sapiens mRNA; cDNA DKFZp547N084 (from clone DKFZp547N084).
LF208320 - JP 2014500723-A/15823: Polycomb-Associated Non-Coding RNAs.
JD279621 - Sequence 260645 from Patent EP1572962.
JD176695 - Sequence 157719 from Patent EP1572962.
JD197446 - Sequence 178470 from Patent EP1572962.
JD365736 - Sequence 346760 from Patent EP1572962.
JD564050 - Sequence 545074 from Patent EP1572962.
JD316790 - Sequence 297814 from Patent EP1572962.
JD300809 - Sequence 281833 from Patent EP1572962.
JD267483 - Sequence 248507 from Patent EP1572962.
JD376910 - Sequence 357934 from Patent EP1572962.
JD154565 - Sequence 135589 from Patent EP1572962.
JD300033 - Sequence 281057 from Patent EP1572962.
JD061745 - Sequence 42769 from Patent EP1572962.
AK027752 - Homo sapiens cDNA FLJ14846 fis, clone PLACE1000347.
JD548859 - Sequence 529883 from Patent EP1572962.
JD349466 - Sequence 330490 from Patent EP1572962.
JD046579 - Sequence 27603 from Patent EP1572962.
JD041000 - Sequence 22024 from Patent EP1572962.
JD187882 - Sequence 168906 from Patent EP1572962.
JD043849 - Sequence 24873 from Patent EP1572962.
JD408652 - Sequence 389676 from Patent EP1572962.
JD176993 - Sequence 158017 from Patent EP1572962.
JD398846 - Sequence 379870 from Patent EP1572962.
JD132883 - Sequence 113907 from Patent EP1572962.
JD259570 - Sequence 240594 from Patent EP1572962.
JD261243 - Sequence 242267 from Patent EP1572962.
JD532164 - Sequence 513188 from Patent EP1572962.
JD499909 - Sequence 480933 from Patent EP1572962.
JD372466 - Sequence 353490 from Patent EP1572962.
JD535945 - Sequence 516969 from Patent EP1572962.
JD289792 - Sequence 270816 from Patent EP1572962.
JD285095 - Sequence 266119 from Patent EP1572962.
JD460815 - Sequence 441839 from Patent EP1572962.
JD332539 - Sequence 313563 from Patent EP1572962.
JD448652 - Sequence 429676 from Patent EP1572962.
JD124906 - Sequence 105930 from Patent EP1572962.
JD194059 - Sequence 175083 from Patent EP1572962.
JD162228 - Sequence 143252 from Patent EP1572962.
JD281549 - Sequence 262573 from Patent EP1572962.
JD475209 - Sequence 456233 from Patent EP1572962.
JD387685 - Sequence 368709 from Patent EP1572962.
JD455171 - Sequence 436195 from Patent EP1572962.
JD315661 - Sequence 296685 from Patent EP1572962.
JD544210 - Sequence 525234 from Patent EP1572962.
JD162000 - Sequence 143024 from Patent EP1572962.
JD482353 - Sequence 463377 from Patent EP1572962.
JD207333 - Sequence 188357 from Patent EP1572962.
JD477915 - Sequence 458939 from Patent EP1572962.
JD455320 - Sequence 436344 from Patent EP1572962.
JD037778 - Sequence 18802 from Patent EP1572962.
JD226949 - Sequence 207973 from Patent EP1572962.
JD411519 - Sequence 392543 from Patent EP1572962.
JD465741 - Sequence 446765 from Patent EP1572962.
JD228618 - Sequence 209642 from Patent EP1572962.
JD140245 - Sequence 121269 from Patent EP1572962.
JD176600 - Sequence 157624 from Patent EP1572962.
JD271629 - Sequence 252653 from Patent EP1572962.
MA443897 - JP 2018138019-A/15823: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q8ND25 (Reactome details) participates in the following event(s):

R-HSA-983157 Interaction of E3 with substrate and E2-Ub complex
R-HSA-983147 Release of E3 from polyubiquitinated substrate
R-HSA-983140 Transfer of Ub from E2 to substrate and release of E2
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-983169 Class I MHC mediated antigen processing & presentation
R-HSA-1280218 Adaptive Immune System
R-HSA-168256 Immune System

-  Other Names for This Gene
  Alternate Gene Symbols: D3DUJ9, NIN283, NM_032268, NP_115644, Q8ND25, Q9H083, ZNRF1_HUMAN
UCSC ID: uc002fdl.1
RefSeq Accession: NM_032268
Protein: Q8ND25 (aka ZNRF1_HUMAN)
CCDS: CCDS10912.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_032268.4
exon count: 5CDS single in 3' UTR: no RNA size: 4633
ORF size: 684CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 1511.00frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.