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Q8ND25 (ZNRF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 87. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
E3 ubiquitin-protein ligase ZNRF1

EC=6.3.2.-
Alternative name(s):
Nerve injury-induced gene 283 protein
Zinc/RING finger protein 1
Gene names
Name:ZNRF1
Synonyms:NIN283
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length227 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.6

Pathway

Protein modification; protein ubiquitination.

Subunit structure

Interacts with AKT1, GLUL and TUBB2A By similarity.

Subcellular location

Endosome. Lysosome. Membrane; Peripheral membrane protein. Cytoplasmic vesiclesecretory vesiclesynaptic 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. Ref.1 Ref.6

Domain

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

Sequence similarities

Contains 1 RING-type zinc finger.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8ND25-1)

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.
Isoform 2 (identifier: Q8ND25-2)

The sequence of this isoform differs from the canonical sequence as follows:
     173-173: N → NGRIQRSLRGAQPEKTWLSGRTLQEQPWRTECSWAPMAQMQSYPHCPVENRE
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Probable
Chain2 – 227226E3 ubiquitin-protein ligase ZNRF1
PRO_0000277799

Regions

Zinc finger184 – 22542RING-type; atypical
Region2 – 109Required for endosomal and lysosomal localization and myristoylation

Amino acid modifications

Modified residue521Phosphoserine Ref.7
Modified residue531Phosphoserine Ref.7
Lipidation21N-myristoyl glycine Probable

Natural variations

Alternative sequence1731N → NGRIQRSLRGAQPEKTWLSG RTLQEQPWRTECSWAPMAQM QSYPHCPVENRE in isoform 2.
VSP_023088

Experimental info

Mutagenesis1841C → A: Loss of E3 activity. Ref.6

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 20, 2007. Version 2.
Checksum: 41BCF1AAEDD0C52C

FASTA22723,783
        10         20         30         40         50         60 
MGGKQSTAAR SRGPFPGVST DDSAVPPPGG APHFGHYRTG GGAMGLRSRS VSSVAGMGMD 

        70         80         90        100        110        120 
PSTAGGVPFG LYTPASRGTG DSERAPGGGG SASDSTYAHG NGYQETGGGH HRDGMLYLGS 

       130        140        150        160        170        180 
RASLADALPL HIAPRWFSSH SGFKCPICSK SVASDEMEMH FIMCLSKPRL SYNDDVLTKD 

       190        200        210        220 
AGECVICLEE LLQGDTIARL PCLCIYHKSC IDSWFEVNRS CPEHPAD 

« Hide

Isoform 2 [UniParc].

Checksum: 3BBC1E451429E13D
Show »

FASTA27829,777

References

« Hide 'large scale' references
[1]"Identification of genes induced in peripheral nerve after injury. Expression profiling and novel gene discovery."
Araki T., Nagarajan R., Milbrandt J.
J. Biol. Chem. 276:34131-34141(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
[2]"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs."
Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. expand/collapse author list , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A.
Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 8-278 (ISOFORM 2).
Tissue: Testis.
[3]"The sequence and analysis of duplication-rich human chromosome 16."
Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. expand/collapse author list , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Lung.
[6]"ZNRF proteins constitute a family of presynaptic E3 ubiquitin ligases."
Araki T., Milbrandt J.
J. Neurosci. 23:9385-9394(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, MYRISTOYLATION AT GLY-2, MUTAGENESIS OF CYS-184.
[7]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-52 AND SER-53, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_115644.1. NM_032268.4.
UniGeneHs.427284.

3D structure databases

ProteinModelPortalQ8ND25.
SMRQ8ND25. Positions 183-222.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid124371. 15 interactions.
IntActQ8ND25. 12 interactions.
MINTMINT-4724320.
STRING9606.ENSP00000335091.

PTM databases

PhosphoSiteQ8ND25.

Polymorphism databases

DMDM126253846.

Proteomic databases

PaxDbQ8ND25.
PRIDEQ8ND25.

Protocols and materials databases

DNASU84937.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000320619; ENSP00000323362; ENSG00000186187. [Q8ND25-2]
ENST00000335325; ENSP00000335091; ENSG00000186187. [Q8ND25-1]
ENST00000567962; ENSP00000455601; ENSG00000186187. [Q8ND25-1]
GeneID84937.
KEGGhsa:84937.
UCSCuc002fdk.3. human. [Q8ND25-1]
uc010cgr.1. human. [Q8ND25-2]

Organism-specific databases

CTD84937.
GeneCardsGC16P075033.
HGNCHGNC:18452. ZNRF1.
HPAHPA027470.
MIM612060. gene.
neXtProtNX_Q8ND25.
PharmGKBPA134938288.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG314053.
HOGENOMHOG000285998.
HOVERGENHBG094200.
KOK10694.
OMAWRTECSW.
OrthoDBEOG70W3FG.
PhylomeDBQ8ND25.
TreeFamTF317681.

Enzyme and pathway databases

UniPathwayUPA00143.

Gene expression databases

ArrayExpressQ8ND25.
BgeeQ8ND25.
CleanExHS_ZNRF1.
GenevestigatorQ8ND25.

Family and domain databases

Gene3D3.30.40.10. 1 hit.
InterProIPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamPF13639. zf-RING_2. 1 hit.
[Graphical view]
SMARTSM00184. RING. 1 hit.
[Graphical view]
PROSITEPS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiZNRF1.
GenomeRNAi84937.
NextBio75388.
PROQ8ND25.
SOURCESearch...

Entry information

Entry nameZNRF1_HUMAN
AccessionPrimary (citable) accession number: Q8ND25
Secondary accession number(s): D3DUJ9, Q9H083
Entry history
Integrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: February 20, 2007
Last modified: April 16, 2014
This is version 87 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM