Reviewed, UniProtKB/Swiss-Prot Q8ND25 (ZNRF1_HUMAN)

Names and origin

Protein names

Recommended name:
    E3 ubiquitin-protein ligase ZNRF1
    EC=6.3.2.-
Alternative name(s):
    Zinc/RING finger protein 1
    Nerve injury-induced gene 283 protein

Gene names

Name:	ZNRF1
Synonyms:	NIN283

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	227 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to substrates. May play a role in the establisment and maintenance of neuronal transmission and plasticity via its ubiquitin-protein ligase activity. Ref.4
Pathway	Protein modification; protein ubiquitination.
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.4 Ref.1
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
Gene Ontology (GO)
Biological process	modification-dependent protein catabolic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW cytoplasmic vesicle Inferred from electronic annotation. Source: UniProtKB-KW endosome Inferred from direct assay. Source: LIFEdb extrinsic to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell lysosome Inferred from electronic annotation. Source: UniProtKB-SubCell synapse Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	ligase activity Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDC34	P49427	1	EBI-2129250,EBI-975634
UBE2D1	P51668	1	EBI-2129250,EBI-743540
UBE2D2	P62837	1	EBI-2129250,EBI-347677
UBE2E1	P51965	1	EBI-2129250,EBI-348546

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
	Initiator methionine	1	1	Removed Probable
	Chain	2 – 227	226	E3 ubiquitin-protein ligase ZNRF1		PRO_0000277799
Regions
	Zinc finger	184 – 225	42	RING-type; atypical
	Region	2 – 10	9	Required for endosomal and lysosomal localization and myristoylation
Amino acid modifications
	Modified residue	52	1	Phosphoserine
	Modified residue	53	1	Phosphoserine
	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.4

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. 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: 11427537] [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: 11230166] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 8-278 (ISOFORM 2). Tissue: Testis.
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Lung.
[4]	"ZNRF proteins constitute a family of presynaptic E3 ubiquitin ligases." Araki T., Milbrandt J. J. Neurosci. 23:9385-9394(2003) [PubMed: 14561866] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, MYRISTOYLATION, MUTAGENESIS OF CYS-184.
[5]	"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: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-52 AND SER-53, MASS SPECTROMETRY. Tissue: T-cell.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF378524 mRNA. Translation: AAK69753.1. AL136903 mRNA. Translation: CAB66837.1. AL834440 mRNA. Translation: CAD39100.1. BC007235 mRNA. Translation: AAH07235.1.
IPI	IPI00031059. IPI00168439.
RefSeq	NP_115644.1.
UniGene	Hs.427284
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8ND25. 12 interactions.
STRING	Q8ND25.
PTM databases
PhosphoSite	Q8ND25.
Proteomic databases
PRIDE	Q8ND25.
Genome annotation databases
Ensembl	ENST00000335325; ENSP00000335091; ENSG00000186187; Homo sapiens. [Genome view]
GeneID	84937.
KEGG	hsa:84937.
UCSC	uc002fdk.1. human. uc010cgr.1. human.
Organism-specific databases
CTD	84937.
GeneCards	GC16P073590.
HGNC	HGNC:18452. ZNRF1.
MIM	612060. gene.
PharmGKB	PA134938288.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q8ND25.
OMA	NGYQETG
OrthoDB	EOG944P61
Gene expression databases
ArrayExpress	Q8ND25.
Bgee	Q8ND25.
CleanEx	HS_ZNRF1.
Genevestigator	Q8ND25.
Family and domain databases
InterPro	IPR018957. Znf_C3HC4_RING-type. IPR001841. Znf_RING. [Graphical view]
Pfam	PF00097. zf-C3HC4. 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 Resources
NextBio	75388.
SOURCE	Search...

Entry information

Entry name

ZNRF1_HUMAN

Accession

Primary (citable) accession number: Q8ND25
Secondary accession number(s): Q9H083

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 20, 2007
Last sequence update:	February 20, 2007
Last modified:	November 24, 2009
This is version 50 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.