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Protein

E3 ubiquitin-protein ligase ZNRF4

Gene

ZNRF4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

E3 ubiquitin-protein ligase which specifically induces ubiquitination and proteasomal degradation of CANX within the endoplasmic reticulum (PubMed:21205830). Could have a role in spermatogenesis (By similarity).By similarity1 Publication

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.1 Publication
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri309 – 35244RING-type; atypicalPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase ZNRF4Curated (EC:6.3.2.-1 Publication)
Alternative name(s):
Nixin1 Publication
RING finger protein 204Curated
Zinc/RING finger protein 4Curated
Gene namesi
Name:ZNRF4Imported
Synonyms:RNF204Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:17726. ZNRF4.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini28 – 250223Lumenal1 PublicationAdd
BLAST
Transmembranei251 – 27121HelicalSequence analysisAdd
BLAST
Topological domaini272 – 429158Cytoplasmic1 PublicationAdd
BLAST

GO - Cellular componenti

  • endoplasmic reticulum membrane Source: UniProtKB
  • integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi107 – 1071N → S: Abolishes glycosylation; when associated with S-152 and S-229. 1 Publication
Mutagenesisi152 – 1521N → S: Abolishes glycosylation; when associated with S-107 and S-229. 1 Publication
Mutagenesisi229 – 2291N → S: Abolishes glycosylation; when associated with S-107 and S-152. 1 Publication
Mutagenesisi329 – 3324HTYH → WTYW: Increased protein stability. No effect on interaction with CANX, but degradation of CANX is impaired.

Organism-specific databases

PharmGKBiPA134943871.

Polymorphism and mutation databases

BioMutaiZNRF4.
DMDMi126253848.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2727Sequence analysisAdd
BLAST
Chaini28 – 429402E3 ubiquitin-protein ligase ZNRF4PRO_0000277861Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi107 – 1071N-linked (GlcNAc...)1 Publication
Glycosylationi152 – 1521N-linked (GlcNAc...)1 Publication
Glycosylationi229 – 2291N-linked (GlcNAc...)1 Publication

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiQ8WWF5.
PaxDbiQ8WWF5.
PeptideAtlasiQ8WWF5.
PRIDEiQ8WWF5.

PTM databases

iPTMnetiQ8WWF5.

Expressioni

Gene expression databases

BgeeiQ8WWF5.
CleanExiHS_ZNRF4.
GenevisibleiQ8WWF5. HS.

Interactioni

Subunit structurei

Interacts with CANX.1 Publication

Protein-protein interaction databases

BioGridi127116. 80 interactions.
IntActiQ8WWF5. 9 interactions.
MINTiMINT-4658243.
STRINGi9606.ENSP00000222033.

Structurei

3D structure databases

ProteinModelPortaliQ8WWF5.
SMRiQ8WWF5. Positions 309-357.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini151 – 22373PASequence analysisAdd
BLAST

Domaini

The RING-type zinc finger is involved in CANX ubiquitination and degradation, but is not required for interaction with CANX.1 Publication

Sequence similaritiesi

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

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri309 – 35244RING-type; atypicalPROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix, Zinc-finger

Phylogenomic databases

eggNOGiKOG4628. Eukaryota.
ENOG410Z5DF. LUCA.
GeneTreeiENSGT00760000119057.
HOGENOMiHOG000013159.
HOVERGENiHBG063762.
InParanoidiQ8WWF5.
KOiK15715.
OMAiIDPWFSQ.
OrthoDBiEOG7NW68S.
PhylomeDBiQ8WWF5.
TreeFamiTF317486.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR003137. PA_domain.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF02225. PA. 1 hit.
PF13639. zf-RING_2. 1 hit.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
[Graphical view]
PROSITEiPS50089. ZF_RING_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q8WWF5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPLCRPEHLM PRASRVPVAA SLPLSHAVIP TQLPSRPGHR PPGRPRRCPK
60 70 80 90 100
ASCLPPPVGP SSTQTAKRVT MGWPRPGRAL VAVKALLVLS LLQVPAQAVV
110 120 130 140 150
RAVLEDNSSS VDFADLPALF GVPLAPEGIR GYLMEVKPAN ACHPIEAPRL
160 170 180 190 200
GNRSLGAIVL IRRYDCTFDL KVLNAQRAGF EAAIVHNVHS DDLVSMTHVY
210 220 230 240 250
EDLRGQIAIP SVFVSEAASQ DLRVILGCNK SAHALLLPDD PPCHDLGCHP
260 270 280 290 300
VLTVSWVLGC TLALVVSAFF VLNHLWLWAQ ACCSHRRPVK TSTCQKAQVR
310 320 330 340 350
TFTWHNDLCA ICLDEYEEGD QLKILPCSHT YHCKCIDPWF SQAPRRSCPV
360 370 380 390 400
CKQSVAATED SFDSTTYSFR DEDPSLPGHR PPIWAIQVQL RSRRLELLGR
410 420
ASPHCHCSTT SLEAEYTTVS SAPPEAPGQ
Length:429
Mass (Da):46,958
Last modified:February 20, 2007 - v3
Checksum:i9924ED37BC00644D
GO

Sequence cautioni

The sequence AAC62428.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti157 – 1593AIV → SIA in AAH17592 (PubMed:15489334).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti37 – 371P → S.1 Publication
Corresponds to variant rs2240743 [ dbSNP | Ensembl ].
VAR_030611
Natural varianti78 – 781R → Q.1 Publication
Corresponds to variant rs2240744 [ dbSNP | Ensembl ].
VAR_030612
Natural varianti100 – 1001V → I.
Corresponds to variant rs2240745 [ dbSNP | Ensembl ].
VAR_030613
Natural varianti157 – 1571A → S.
Corresponds to variant rs8103406 [ dbSNP | Ensembl ].
VAR_030614
Natural varianti159 – 1591V → A.
Corresponds to variant rs8107825 [ dbSNP | Ensembl ].
VAR_030615
Natural varianti163 – 1631R → C.
Corresponds to variant rs8104246 [ dbSNP | Ensembl ].
VAR_030616
Natural varianti163 – 1631R → H.1 Publication
Corresponds to variant rs17304380 [ dbSNP | Ensembl ].
VAR_030617
Natural varianti192 – 1921D → N.
Corresponds to variant rs16992985 [ dbSNP | Ensembl ].
VAR_030618

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK292251 mRNA. Translation: BAF84940.1.
AC005764 Genomic DNA. Translation: AAC62428.1. Different initiation.
CH471139 Genomic DNA. Translation: EAW69169.1.
BC017592 mRNA. Translation: AAH17592.2.
CCDSiCCDS42475.1.
RefSeqiNP_859061.3. NM_181710.3.
UniGeneiHs.126496.

Genome annotation databases

EnsembliENST00000222033; ENSP00000222033; ENSG00000105428.
GeneIDi148066.
KEGGihsa:148066.
UCSCiuc002mca.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK292251 mRNA. Translation: BAF84940.1.
AC005764 Genomic DNA. Translation: AAC62428.1. Different initiation.
CH471139 Genomic DNA. Translation: EAW69169.1.
BC017592 mRNA. Translation: AAH17592.2.
CCDSiCCDS42475.1.
RefSeqiNP_859061.3. NM_181710.3.
UniGeneiHs.126496.

3D structure databases

ProteinModelPortaliQ8WWF5.
SMRiQ8WWF5. Positions 309-357.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi127116. 80 interactions.
IntActiQ8WWF5. 9 interactions.
MINTiMINT-4658243.
STRINGi9606.ENSP00000222033.

PTM databases

iPTMnetiQ8WWF5.

Polymorphism and mutation databases

BioMutaiZNRF4.
DMDMi126253848.

Proteomic databases

EPDiQ8WWF5.
PaxDbiQ8WWF5.
PeptideAtlasiQ8WWF5.
PRIDEiQ8WWF5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000222033; ENSP00000222033; ENSG00000105428.
GeneIDi148066.
KEGGihsa:148066.
UCSCiuc002mca.5. human.

Organism-specific databases

CTDi148066.
GeneCardsiZNRF4.
HGNCiHGNC:17726. ZNRF4.
MIMi612063. gene.
neXtProtiNX_Q8WWF5.
PharmGKBiPA134943871.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4628. Eukaryota.
ENOG410Z5DF. LUCA.
GeneTreeiENSGT00760000119057.
HOGENOMiHOG000013159.
HOVERGENiHBG063762.
InParanoidiQ8WWF5.
KOiK15715.
OMAiIDPWFSQ.
OrthoDBiEOG7NW68S.
PhylomeDBiQ8WWF5.
TreeFamiTF317486.

Enzyme and pathway databases

UniPathwayiUPA00143.

Miscellaneous databases

GenomeRNAii148066.
PROiQ8WWF5.
SOURCEiSearch...

Gene expression databases

BgeeiQ8WWF5.
CleanExiHS_ZNRF4.
GenevisibleiQ8WWF5. HS.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR003137. PA_domain.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF02225. PA. 1 hit.
PF13639. zf-RING_2. 1 hit.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
[Graphical view]
PROSITEiPS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Testis.
  2. "The DNA sequence and biology of human chromosome 19."
    Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V.
    , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
    Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "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], VARIANTS SER-37 AND GLN-78 AND HIS-163.
    Tissue: Testis.
  5. "A systematic search for endoplasmic reticulum (ER) membrane-associated RING finger proteins identifies Nixin/ZNRF4 as a regulator of calnexin stability and ER homeostasis."
    Neutzner A., Neutzner M., Benischke A.S., Ryu S.W., Frank S., Youle R.J., Karbowski M.
    J. Biol. Chem. 286:8633-8643(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, PATHWAY, INTERACTION WITH CANX, SUBCELLULAR LOCATION, TOPOLOGY, DOMAIN, GLYCOSYLATION AT ASN-107; ASN-152 AND ASN-229, MUTAGENESIS OF ASN-107; ASN-152; ASN-229 AND 329-HIS--HIS-332.

Entry informationi

Entry nameiZNRF4_HUMAN
AccessioniPrimary (citable) accession number: Q8WWF5
Secondary accession number(s): A8K886, O75866
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: February 20, 2007
Last modified: July 6, 2016
This is version 107 of the entry and version 3 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 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.