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Q8ND25

- ZNRF1_HUMAN

UniProt

Q8ND25 - ZNRF1_HUMAN

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Protein

E3 ubiquitin-protein ligase ZNRF1

Gene

ZNRF1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- 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

Pathwayi

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri184 – 22542RING-type; atypicalPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. ligase activity Source: UniProtKB-KW
  2. ubiquitin-protein transferase activity Source: UniProtKB
  3. zinc ion binding Source: InterPro

GO - Biological processi

  1. proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
  2. protein K48-linked ubiquitination Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:ZNRF1
Synonyms:NIN283
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 16

Organism-specific databases

HGNCiHGNC:18452. ZNRF1.

Subcellular locationi

Endosome. Lysosome. Membrane; Peripheral membrane protein. Cytoplasmic vesiclesecretory vesiclesynaptic vesicle membrane Curated; Peripheral membrane protein Curated
Note: Associated with synaptic vesicle membranes in neurons.

GO - Cellular componenti

  1. cell junction Source: UniProtKB-KW
  2. cytoplasmic vesicle Source: UniProtKB-KW
  3. cytosol Source: MGI
  4. endosome Source: LIFEdb
  5. lysosome Source: UniProtKB-KW
  6. membrane Source: MGI
  7. synapse Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi184 – 1841C → A: Loss of E3 activity. 1 Publication

Organism-specific databases

PharmGKBiPA134938288.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedCurated
Chaini2 – 227226E3 ubiquitin-protein ligase ZNRF1PRO_0000277799Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycine1 Publication
Modified residuei52 – 521Phosphoserine1 Publication
Modified residuei53 – 531Phosphoserine1 Publication

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

MaxQBiQ8ND25.
PaxDbiQ8ND25.
PRIDEiQ8ND25.

PTM databases

PhosphoSiteiQ8ND25.

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

BgeeiQ8ND25.
CleanExiHS_ZNRF1.
ExpressionAtlasiQ8ND25. baseline and differential.
GenevestigatoriQ8ND25.

Organism-specific databases

HPAiHPA027470.

Interactioni

Subunit structurei

Interacts with AKT1, GLUL and TUBB2A.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
UBE2D1P516684EBI-2129250,EBI-743540
UBE2D2P628374EBI-2129250,EBI-347677
UBE2D3P610773EBI-2129250,EBI-348268
UBE2D4Q9Y2X83EBI-2129250,EBI-745527
UBE2E1P519653EBI-2129250,EBI-348546
UBE2NP610883EBI-2129250,EBI-1052908
UBE2V1Q134042EBI-2129250,EBI-1050671

Protein-protein interaction databases

BioGridi124371. 23 interactions.
IntActiQ8ND25. 12 interactions.
MINTiMINT-4724320.
STRINGi9606.ENSP00000335091.

Structurei

3D structure databases

ProteinModelPortaliQ8ND25.
SMRiQ8ND25. Positions 183-222.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni2 – 109Required for endosomal and lysosomal localization and myristoylation

Domaini

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

Sequence similaritiesi

Contains 1 RING-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri184 – 22542RING-type; atypicalPROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiNOG314053.
GeneTreeiENSGT00390000013068.
HOGENOMiHOG000285998.
HOVERGENiHBG094200.
InParanoidiQ8ND25.
KOiK10694.
OMAiWRTECSW.
OrthoDBiEOG70W3FG.
PhylomeDBiQ8ND25.
TreeFamiTF317681.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF13639. zf-RING_2. 1 hit.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
[Graphical view]
PROSITEiPS50089. ZF_RING_2. 1 hit.
[Graphical view]

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. Align

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)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei173 – 1731N → NGRIQRSLRGAQPEKTWLSG RTLQEQPWRTECSWAPMAQM QSYPHCPVENRE in isoform 2. 1 PublicationVSP_023088

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]
UniGeneiHs.427284.

Genome annotation databases

EnsembliENST00000320619; ENSP00000323362; ENSG00000186187. [Q8ND25-2]
ENST00000335325; ENSP00000335091; ENSG00000186187. [Q8ND25-1]
ENST00000567962; ENSP00000455601; ENSG00000186187. [Q8ND25-1]
GeneIDi84937.
KEGGihsa:84937.
UCSCiuc002fdk.3. human. [Q8ND25-1]
uc010cgr.1. human. [Q8ND25-2]

Polymorphism databases

DMDMi126253846.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

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 .
CCDSi CCDS10912.1. [Q8ND25-1 ]
RefSeqi NP_115644.1. NM_032268.4. [Q8ND25-1 ]
UniGenei Hs.427284.

3D structure databases

ProteinModelPortali Q8ND25.
SMRi Q8ND25. Positions 183-222.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 124371. 23 interactions.
IntActi Q8ND25. 12 interactions.
MINTi MINT-4724320.
STRINGi 9606.ENSP00000335091.

PTM databases

PhosphoSitei Q8ND25.

Polymorphism databases

DMDMi 126253846.

Proteomic databases

MaxQBi Q8ND25.
PaxDbi Q8ND25.
PRIDEi Q8ND25.

Protocols and materials databases

DNASUi 84937.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000320619 ; ENSP00000323362 ; ENSG00000186187 . [Q8ND25-2 ]
ENST00000335325 ; ENSP00000335091 ; ENSG00000186187 . [Q8ND25-1 ]
ENST00000567962 ; ENSP00000455601 ; ENSG00000186187 . [Q8ND25-1 ]
GeneIDi 84937.
KEGGi hsa:84937.
UCSCi uc002fdk.3. human. [Q8ND25-1 ]
uc010cgr.1. human. [Q8ND25-2 ]

Organism-specific databases

CTDi 84937.
GeneCardsi GC16P075033.
HGNCi HGNC:18452. ZNRF1.
HPAi HPA027470.
MIMi 612060. gene.
neXtProti NX_Q8ND25.
PharmGKBi PA134938288.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG314053.
GeneTreei ENSGT00390000013068.
HOGENOMi HOG000285998.
HOVERGENi HBG094200.
InParanoidi Q8ND25.
KOi K10694.
OMAi WRTECSW.
OrthoDBi EOG70W3FG.
PhylomeDBi Q8ND25.
TreeFami TF317681.

Enzyme and pathway databases

UniPathwayi UPA00143 .

Miscellaneous databases

ChiTaRSi ZNRF1. human.
GeneWikii ZNRF1.
GenomeRNAii 84937.
NextBioi 75388.
PROi Q8ND25.
SOURCEi Search...

Gene expression databases

Bgeei Q8ND25.
CleanExi HS_ZNRF1.
ExpressionAtlasi Q8ND25. baseline and differential.
Genevestigatori Q8ND25.

Family and domain databases

Gene3Di 3.30.40.10. 1 hit.
InterProi IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view ]
Pfami PF13639. zf-RING_2. 1 hit.
[Graphical view ]
SMARTi SM00184. RING. 1 hit.
[Graphical view ]
PROSITEi PS50089. ZF_RING_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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.
    , 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. 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.

Entry informationi

Entry nameiZNRF1_HUMAN
AccessioniPrimary (citable) accession number: Q8ND25
Secondary accession number(s): D3DUJ9, Q9H083
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: February 20, 2007
Last modified: November 26, 2014
This is version 94 of the entry and version 2 of the sequence. [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. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3