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Protein

E3 ubiquitin-protein ligase NEURL1

Gene

NEURL1

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

Functioni

Plays a role in hippocampal-dependent synaptic plasticity, learning and memory. Involved in the formation of spines and functional synaptic contacts by modulating the translational activity of the cytoplasmic polyadenylation element-binding protein CPEB3. Promotes ubiquitination of CPEB3, and hence induces CPEB3-dependent mRNA translation activation of glutamate receptor GRIA1 and GRIA2. Can function as an E3 ubiquitin-protein ligase to activate monoubiquitination of JAG1 (in vitro), thereby regulating the Notch pathway. Acts as a tumor suppressor; inhibits malignant cell transformation of medulloblastoma (MB) cells by inhibiting the Notch signaling pathway.1 Publication

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
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 fingeri520 – 56041RING-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Notch signaling pathway, Translation regulation, Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-2122948. Activated NOTCH1 Transmits Signal to the Nucleus.
R-HSA-2644606. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
R-HSA-2691232. Constitutive Signaling by NOTCH1 HD Domain Mutants.
R-HSA-2894862. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
R-HSA-2979096. NOTCH2 Activation and Transmission of Signal to the Nucleus.
SignaLinkiO76050.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase NEURL1 (EC:6.3.2.-)
Alternative name(s):
Neuralized-like protein 1A
Short name:
h-neu
Short name:
h-neuralized 1
RING finger protein 67
Gene namesi
Name:NEURL1
Synonyms:NEURL, NEURL1A, RNF67
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:7761. NEURL1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cytoplasm, Membrane, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Keywords - Diseasei

Tumor suppressor

Organism-specific databases

PharmGKBiPA31563.

Polymorphism and mutation databases

BioMutaiNEURL.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemoved
Chaini2 – 574573E3 ubiquitin-protein ligase NEURL1PRO_0000181255Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycineBy similarity

Post-translational modificationi

Myristoylation is a determinant of membrane targeting.By similarity

Keywords - PTMi

Lipoprotein, Myristate

Proteomic databases

MaxQBiO76050.
PaxDbiO76050.
PeptideAtlasiO76050.
PRIDEiO76050.

PTM databases

PhosphoSiteiO76050.

Expressioni

Tissue specificityi

Expressed in brain, testis, pituitary gland, pancreas and bone marrow. Also poorly expressed in an malignant astrocytomas and several neuroectodermal tumor cell lines. Weakly expressed in medulloblastoma (MB) compared with normal cerebellar tissues.2 Publications

Inductioni

Down-regulated in medulloblastoma (MB).

Gene expression databases

BgeeiO76050.
CleanExiHS_NEURL.
ExpressionAtlasiO76050. baseline and differential.
GenevisibleiO76050. HS.

Organism-specific databases

HPAiHPA044204.

Interactioni

Subunit structurei

Interacts with CPEB3 (via N-terminal domain); the interaction increases CPEB3 ubiquitination. Interacts with DLL1.By similarity

Protein-protein interaction databases

BioGridi114595. 8 interactions.
IntActiO76050. 2 interactions.
STRINGi9606.ENSP00000358795.

Structurei

3D structure databases

ProteinModelPortaliO76050.
SMRiO76050. Positions 62-218, 292-450, 519-565.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini61 – 217157NHR 1PROSITE-ProRule annotationAdd
BLAST
Domaini292 – 447156NHR 2PROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 2 NHR (neuralized homology repeat) domains.PROSITE-ProRule annotation
Contains 1 RING-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri520 – 56041RING-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG4172. Eukaryota.
KOG4625. Eukaryota.
ENOG410ZMNG. LUCA.
GeneTreeiENSGT00530000063117.
HOGENOMiHOG000233742.
InParanoidiO76050.
KOiK01931.
OMAiCPPVLPG.
OrthoDBiEOG7C2R0S.
PhylomeDBiO76050.
TreeFamiTF314368.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR006573. NHR_dom.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF07177. Neuralized. 2 hits.
[Graphical view]
SMARTiSM00588. NEUZ. 2 hits.
[Graphical view]
PROSITEiPS51065. NHR. 2 hits.
PS50089. 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. AlignAdd to basket

Isoform 1 (identifier: O76050-1) [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
MGNNFSSIPS LPRGNPSRAP RGHPQNLKDS IGGPFPVTSH RCHHKQKHCP
60 70 80 90 100
AVLPSGGLPA TPLLFHPHTK GSQILMDLSH KAVKRQASFC NAITFSNRPV
110 120 130 140 150
LIYEQVRLKI TKKQCCWSGA LRLGFTSKDP SRIHPDSLPK YACPDLVSQS
160 170 180 190 200
GFWAKALPEE FANEGNIIAF WVDKKGRVFH RINDSAVMLF FSGVRTADPL
210 220 230 240 250
WALVDVYGLT RGVQLLDSEL VLPDCLRPRS FTALRRPSLR READDARLSV
260 270 280 290 300
SLCDLNVPGA DGDEAAPAAG CPIPQNSLNS QHSRALPAQL DGDLRFHALR
310 320 330 340 350
AGAHVRILDE QTVARVEHGR DERALVFTSR PVRVAETIFV KVTRSGGARP
360 370 380 390 400
GALSFGVTTC DPGTLRPADL PFSPEALVDR KEFWAVCRVP GPLHSGDILG
410 420 430 440 450
LVVNADGELH LSHNGAAAGM QLCVDASQPL WMLFGLHGTI TQIRILGSTI
460 470 480 490 500
LAERGIPSLP CSPASTPTSP SALGSRLSDP LLSTCSSGPL GSSAGGTAPN
510 520 530 540 550
SPVSLPESPV TPGLGQWSDE CTICYEHAVD TVIYTCGHMC LCYACGLRLK
560 570
KALHACCPIC RRPIKDIIKT YRSS
Length:574
Mass (Da):61,860
Last modified:November 1, 1998 - v1
Checksum:iD9699F08F7443EBB
GO
Isoform 2 (identifier: O76050-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-28: MGNNFSSIPSLPRGNPSRAPRGHPQNLK → MGGQITRSTLH

Note: Gene prediction confirmed by EST data.
Show »
Length:557
Mass (Da):60,030
Checksum:i0983D61C1800F279
GO

Sequence cautioni

The sequence CAI13958.1 differs from that shown. Reason: Erroneous gene model prediction. Curated
The sequence CAI13959.1 differs from that shown. Reason: Erroneous gene model prediction. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti61 – 611T → A in AAH26336 (PubMed:15489334).Curated
Sequence conflicti270 – 2701G → S in AAH26336 (PubMed:15489334).Curated
Sequence conflicti476 – 4761R → G in AAH26336 (PubMed:15489334).Curated
Sequence conflicti566 – 5661D → G in AAH26336 (PubMed:15489334).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 2828MGNNF…PQNLK → MGGQITRSTLH in isoform 2. CuratedVSP_013151Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U87864 mRNA. Translation: AAC17474.1.
AF029729 mRNA. Translation: AAD01887.1.
AL121929 Genomic DNA. Translation: CAI13958.1. Sequence problems.
AL121929 Genomic DNA. Translation: CAI13959.1. Sequence problems.
AL121929, AL139339 Genomic DNA. Translation: CAI13960.1.
AL139339, AL121929 Genomic DNA. Translation: CAH71486.1.
BC026336 mRNA. Translation: AAH26336.1.
CCDSiCCDS7551.1. [O76050-1]
RefSeqiNP_004201.3. NM_004210.4. [O76050-1]
XP_005270326.1. XM_005270269.2. [O76050-2]
UniGeneiHs.594708.

Genome annotation databases

EnsembliENST00000369780; ENSP00000358795; ENSG00000107954. [O76050-1]
GeneIDi9148.
KEGGihsa:9148.
UCSCiuc001kxh.4. human. [O76050-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U87864 mRNA. Translation: AAC17474.1.
AF029729 mRNA. Translation: AAD01887.1.
AL121929 Genomic DNA. Translation: CAI13958.1. Sequence problems.
AL121929 Genomic DNA. Translation: CAI13959.1. Sequence problems.
AL121929, AL139339 Genomic DNA. Translation: CAI13960.1.
AL139339, AL121929 Genomic DNA. Translation: CAH71486.1.
BC026336 mRNA. Translation: AAH26336.1.
CCDSiCCDS7551.1. [O76050-1]
RefSeqiNP_004201.3. NM_004210.4. [O76050-1]
XP_005270326.1. XM_005270269.2. [O76050-2]
UniGeneiHs.594708.

3D structure databases

ProteinModelPortaliO76050.
SMRiO76050. Positions 62-218, 292-450, 519-565.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114595. 8 interactions.
IntActiO76050. 2 interactions.
STRINGi9606.ENSP00000358795.

PTM databases

PhosphoSiteiO76050.

Polymorphism and mutation databases

BioMutaiNEURL.

Proteomic databases

MaxQBiO76050.
PaxDbiO76050.
PeptideAtlasiO76050.
PRIDEiO76050.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000369780; ENSP00000358795; ENSG00000107954. [O76050-1]
GeneIDi9148.
KEGGihsa:9148.
UCSCiuc001kxh.4. human. [O76050-1]

Organism-specific databases

CTDi9148.
GeneCardsiNEURL1.
HGNCiHGNC:7761. NEURL1.
HPAiHPA044204.
MIMi603804. gene.
neXtProtiNX_O76050.
PharmGKBiPA31563.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4172. Eukaryota.
KOG4625. Eukaryota.
ENOG410ZMNG. LUCA.
GeneTreeiENSGT00530000063117.
HOGENOMiHOG000233742.
InParanoidiO76050.
KOiK01931.
OMAiCPPVLPG.
OrthoDBiEOG7C2R0S.
PhylomeDBiO76050.
TreeFamiTF314368.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiR-HSA-2122948. Activated NOTCH1 Transmits Signal to the Nucleus.
R-HSA-2644606. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
R-HSA-2691232. Constitutive Signaling by NOTCH1 HD Domain Mutants.
R-HSA-2894862. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
R-HSA-2979096. NOTCH2 Activation and Transmission of Signal to the Nucleus.
SignaLinkiO76050.

Miscellaneous databases

GeneWikiiNEURL.
GenomeRNAii9148.
PROiO76050.
SOURCEiSearch...

Gene expression databases

BgeeiO76050.
CleanExiHS_NEURL.
ExpressionAtlasiO76050. baseline and differential.
GenevisibleiO76050. HS.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR006573. NHR_dom.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF07177. Neuralized. 2 hits.
[Graphical view]
SMARTiSM00588. NEUZ. 2 hits.
[Graphical view]
PROSITEiPS51065. NHR. 2 hits.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Identification of a human homolog of the Drosophila neuralized gene within the 10q25.1 malignant astrocytoma deletion region."
    Nakamura H., Yoshida M., Tsuiki H., Ito K., Ueno M., Nakao M., Oka K., Tada M., Kochi M., Kuratsu J., Ushio Y., Saya H.
    Oncogene 16:1009-1019(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
    Tissue: Fetal brain.
  2. Prinos P., Kilpatrick M.W., Tsipouras P.
    Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  3. "The DNA sequence and comparative analysis of human chromosome 10."
    Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J.
    , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
    Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
    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] (ISOFORM 1).
    Tissue: Brain.
  5. "Isolation of a murine homologue of the Drosophila neuralized gene, a gene required for axonemal integrity in spermatozoa and terminal maturation of the mammary gland."
    Vollrath B., Pudney J., Asa S., Leder P., Fitzgerald K.
    Mol. Cell. Biol. 21:7481-7494(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
  6. "Neuralized1 causes apoptosis and downregulates Notch target genes in medulloblastoma."
    Teider N., Scott D.K., Neiss A., Weeraratne S.D., Amani V.M., Wang Y., Marquez V.E., Cho Y.J., Pomeroy S.L.
    J. Neurooncol. 12:1244-1256(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.

Entry informationi

Entry nameiNEUL1_HUMAN
AccessioniPrimary (citable) accession number: O76050
Secondary accession number(s): Q5TDR2
, Q5TDR3, Q8TAN0, Q9H463
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: November 1, 1998
Last modified: July 6, 2016
This is version 135 of the entry and version 1 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 10
    Human chromosome 10: 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

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.