Q8ND25 (ZNRF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	ZNRF1
Synonyms:	NIN283

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	227 AA.
Sequence status	Complete.
Protein existence	Evidence 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 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. 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.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cell junction Cytoplasmic vesicle Endosome Lysosome Membrane Synapse
Coding sequence diversity	Alternative splicing
Domain	Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
PTM	Lipoprotein Myristate Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	proteasomal ubiquitin-dependent protein catabolic process Inferred from sequence or structural similarity. Source: UniProtKB protein K48-linked ubiquitination Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW endosome Inferred from direct assay. Source: LIFEdb lysosome Inferred from electronic annotation. Source: UniProtKB-SubCell synaptic vesicle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ubiquitin-protein ligase activity Inferred from sequence or structural similarity. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
UBE2D1	P51668	4	EBI-2129250,EBI-743540
UBE2D2	P62837	4	EBI-2129250,EBI-347677
UBE2D3	P61077	3	EBI-2129250,EBI-348268
UBE2D4	Q9Y2X8	3	EBI-2129250,EBI-745527
UBE2E1	P51965	3	EBI-2129250,EBI-348546
UBE2N	P61088	3	EBI-2129250,EBI-1052908
UBE2V1	Q13404	2	EBI-2129250,EBI-1050671

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 227	227	E3 ubiquitin-protein ligase ZNRF1		PRO_0000277799
Regions
	Zinc finger	184 – 225	42	RING-type; atypical
	Region	1 – 10	10	Required for endosomal and lysosomal localization and myristoylation
Amino acid modifications
	Modified residue	52	1	Phosphoserine Ref.7
	Modified residue	53	1	Phosphoserine Ref.7
	Modified residue	123	1	Phosphoserine By similarity
	Lipidation	2	1	N-myristoyl glycine Probable
Natural variations
	Alternative sequence	173	1	N → NGRIQRSLRGAQPEKTWLSG RTLQEQPWRTECSWAPMAQM QSYPHCPVENRE in isoform 2.		VSP_023088
Experimental info
	Mutagenesis	184	1	C → A: Loss of E3 activity. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 20, 2007. Version 2. Checksum: 41BCF1AAEDD0C52C	FASTA	227	23,783
	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
	Isoform 2 [UniParc]. Checksum: 3BBC1E451429E13D	FASTA	278	29,777
	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 SYNGRIQRSL 190 200 210 220 230 240 RGAQPEKTWL SGRTLQEQPW RTECSWAPMA QMQSYPHCPV ENREDDVLTK DAGECVICLE 250 260 270 ELLQGDTIAR LPCLCIYHKS CIDSWFEVNR SCPEHPAD

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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, 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, MASS SPECTROMETRY. 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.
IPI	IPI00031059. IPI00168439.
RefSeq	NP_115644.1. NM_032268.4.
UniGene	Hs.427284.
3D structure databases
ProteinModelPortal	Q8ND25.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8ND25. 12 interactions.
STRING	9606.ENSP00000335091.
PTM databases
PhosphoSite	Q8ND25.
Polymorphism databases
DMDM	126253846.
Proteomic databases
PaxDb	Q8ND25.
PRIDE	Q8ND25.
Protocols and materials databases
DNASU	84937.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000320619; ENSP00000323362; ENSG00000186187. ENST00000335325; ENSP00000335091; ENSG00000186187. ENST00000567962; ENSP00000455601; ENSG00000186187.
GeneID	84937.
KEGG	hsa:84937.
UCSC	uc002fdk.3. human. uc010cgr.1. human.
Organism-specific databases
CTD	84937.
GeneCards	GC16P075033.
HGNC	HGNC:18452. ZNRF1.
HPA	HPA027470.
MIM	612060. gene.
neXtProt	NX_Q8ND25.
PharmGKB	PA134938288.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG314053.
HOGENOM	HOG000285998.
HOVERGEN	HBG094200.
KO	K10694.
OMA	FGHYRAG.
OrthoDB	EOG41C6XM.
Enzyme and pathway databases
UniPathway	UPA00143.
Gene expression databases
ArrayExpress	Q8ND25.
Bgee	Q8ND25.
CleanEx	HS_ZNRF1.
Genevestigator	Q8ND25.
Family and domain databases
Gene3D	3.30.40.10. 1 hit.
InterPro	IPR001841. Znf_RING. IPR013083. Znf_RING/FYVE/PHD. [Graphical view]
Pfam	PF13639. zf-RING_2. 1 hit. [Graphical view]
SMART	SM00184. RING. 1 hit. [Graphical view]
PROSITE	PS00518. ZF_RING_1. False negative. PS50089. ZF_RING_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	84937.
NextBio	75388.
SOURCE	Search...

Entry information

Entry name

ZNRF1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 78 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.