NEUL1_HUMAN
ID NEUL1_HUMAN Reviewed; 574 AA.
AC O76050; Q5TDR2; Q5TDR3; Q8TAN0; Q9H463;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=E3 ubiquitin-protein ligase NEURL1;
DE EC=2.3.2.27;
DE AltName: Full=Neuralized-like protein 1A;
DE Short=h-neu;
DE Short=h-neuralized 1;
DE AltName: Full=RING finger protein 67;
DE AltName: Full=RING-type E3 ubiquitin transferase NEURL1 {ECO:0000305};
GN Name=NEURL1; Synonyms=NEURL, NEURL1A, RNF67;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Fetal brain;
RX PubMed=9519875; DOI=10.1038/sj.onc.1201618;
RA Nakamura H., Yoshida M., Tsuiki H., Ito K., Ueno M., Nakao M., Oka K.,
RA Tada M., Kochi M., Kuratsu J., Ushio Y., Saya H.;
RT "Identification of a human homolog of the Drosophila neuralized gene within
RT the 10q25.1 malignant astrocytoma deletion region.";
RL Oncogene 16:1009-1019(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Prinos P., Kilpatrick M.W., Tsipouras P.;
RL Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=11585928; DOI=10.1128/mcb.21.21.7481-7494.2001;
RA Vollrath B., Pudney J., Asa S., Leder P., Fitzgerald K.;
RT "Isolation of a murine homologue of the Drosophila neuralized gene, a gene
RT required for axonemal integrity in spermatozoa and terminal maturation of
RT the mammary gland.";
RL Mol. Cell. Biol. 21:7481-7494(2001).
RN [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=20847082; DOI=10.1093/neuonc/noq091;
RA Teider N., Scott D.K., Neiss A., Weeraratne S.D., Amani V.M., Wang Y.,
RA Marquez V.E., Cho Y.J., Pomeroy S.L.;
RT "Neuralized1 causes apoptosis and downregulates Notch target genes in
RT medulloblastoma.";
RL J. Neurooncol. 12:1244-1256(2010).
CC -!- FUNCTION: Plays a role in hippocampal-dependent synaptic plasticity,
CC learning and memory. Involved in the formation of spines and functional
CC synaptic contacts by modulating the translational activity of the
CC cytoplasmic polyadenylation element-binding protein CPEB3. Promotes
CC ubiquitination of CPEB3, and hence induces CPEB3-dependent mRNA
CC translation activation of glutamate receptor GRIA1 and GRIA2. Can
CC function as an E3 ubiquitin-protein ligase to activate
CC monoubiquitination of JAG1 (in vitro), thereby regulating the Notch
CC pathway. Acts as a tumor suppressor; inhibits malignant cell
CC transformation of medulloblastoma (MB) cells by inhibiting the Notch
CC signaling pathway. {ECO:0000269|PubMed:20847082}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with CPEB3 (via N-terminal domain); the interaction
CC increases CPEB3 ubiquitination. Interacts with DLL1.
CC {ECO:0000250|UniProtKB:Q923S6}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:11585928, ECO:0000269|PubMed:20847082}. Cell
CC membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}.
CC Perikaryon {ECO:0000250}. Cell projection, dendrite {ECO:0000250}.
CC Postsynaptic density {ECO:0000250}. Note=Localized in the cell bodies
CC of the pyramidal neurons and distributed along their apical dendrites.
CC Colocalized with PSD95 in postsynaptic sites. Colocalized with CPEB3 at
CC apical dendrites of CA1 neurons (By similarity). Colocalized with JAG1
CC at the cell surface. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O76050-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O76050-2; Sequence=VSP_013151;
CC -!- TISSUE SPECIFICITY: Expressed in brain, testis, pituitary gland,
CC pancreas and bone marrow. Also poorly expressed in malignant
CC astrocytomas and several neuroectodermal tumor cell lines. Weakly
CC expressed in medulloblastoma (MB) compared with normal cerebellar
CC tissues. {ECO:0000269|PubMed:11585928, ECO:0000269|PubMed:9519875}.
CC -!- INDUCTION: Down-regulated in medulloblastoma (MB).
CC -!- PTM: Myristoylation is a determinant of membrane targeting.
CC {ECO:0000250}.
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DR EMBL; U87864; AAC17474.1; -; mRNA.
DR EMBL; AF029729; AAD01887.1; -; mRNA.
DR EMBL; AL121929; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL139339; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC026336; AAH26336.1; -; mRNA.
DR CCDS; CCDS7551.1; -. [O76050-1]
DR RefSeq; NP_004201.3; NM_004210.4. [O76050-1]
DR RefSeq; XP_005270326.1; XM_005270269.3. [O76050-2]
DR AlphaFoldDB; O76050; -.
DR SMR; O76050; -.
DR BioGRID; 114595; 16.
DR IntAct; O76050; 3.
DR STRING; 9606.ENSP00000358795; -.
DR iPTMnet; O76050; -.
DR PhosphoSitePlus; O76050; -.
DR BioMuta; NEURL1; -.
DR MassIVE; O76050; -.
DR MaxQB; O76050; -.
DR PaxDb; O76050; -.
DR PeptideAtlas; O76050; -.
DR PRIDE; O76050; -.
DR ProteomicsDB; 50363; -. [O76050-1]
DR ProteomicsDB; 50364; -. [O76050-2]
DR Antibodypedia; 46062; 222 antibodies from 29 providers.
DR DNASU; 9148; -.
DR Ensembl; ENST00000369780.9; ENSP00000358795.4; ENSG00000107954.11. [O76050-1]
DR GeneID; 9148; -.
DR KEGG; hsa:9148; -.
DR MANE-Select; ENST00000369780.9; ENSP00000358795.4; NM_004210.5; NP_004201.3.
DR UCSC; uc001kxh.4; human. [O76050-1]
DR CTD; 9148; -.
DR DisGeNET; 9148; -.
DR GeneCards; NEURL1; -.
DR HGNC; HGNC:7761; NEURL1.
DR HPA; ENSG00000107954; Tissue enhanced (skeletal muscle, tongue).
DR MIM; 603804; gene.
DR neXtProt; NX_O76050; -.
DR OpenTargets; ENSG00000107954; -.
DR PharmGKB; PA31563; -.
DR VEuPathDB; HostDB:ENSG00000107954; -.
DR eggNOG; KOG4172; Eukaryota.
DR eggNOG; KOG4625; Eukaryota.
DR GeneTree; ENSGT00940000156696; -.
DR HOGENOM; CLU_013230_1_0_1; -.
DR InParanoid; O76050; -.
DR OMA; AMCPIPQ; -.
DR OrthoDB; 1384219at2759; -.
DR PhylomeDB; O76050; -.
DR TreeFam; TF314368; -.
DR PathwayCommons; O76050; -.
DR Reactome; R-HSA-2122948; Activated NOTCH1 Transmits Signal to the Nucleus.
DR Reactome; R-HSA-2644606; Constitutive Signaling by NOTCH1 PEST Domain Mutants.
DR Reactome; R-HSA-2691232; Constitutive Signaling by NOTCH1 HD Domain Mutants.
DR Reactome; R-HSA-2894862; Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
DR Reactome; R-HSA-2979096; NOTCH2 Activation and Transmission of Signal to the Nucleus.
DR Reactome; R-HSA-9013507; NOTCH3 Activation and Transmission of Signal to the Nucleus.
DR SignaLink; O76050; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 9148; 14 hits in 1102 CRISPR screens.
DR ChiTaRS; NEURL1; human.
DR GeneWiki; NEURL; -.
DR GenomeRNAi; 9148; -.
DR Pharos; O76050; Tbio.
DR PRO; PR:O76050; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; O76050; protein.
DR Bgee; ENSG00000107954; Expressed in hindlimb stylopod muscle and 139 other tissues.
DR ExpressionAtlas; O76050; baseline and differential.
DR Genevisible; O76050; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0097440; C:apical dendrite; ISS:UniProtKB.
DR GO; GO:0043197; C:dendritic spine; ISS:UniProtKB.
DR GO; GO:0043204; C:perikaryon; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0045183; F:translation factor activity, non-nucleic acid binding; ISS:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; ISS:UniProtKB.
DR GO; GO:0007595; P:lactation; IEA:Ensembl.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; IDA:UniProtKB.
DR GO; GO:0007399; P:nervous system development; IBA:GO_Central.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0060999; P:positive regulation of dendritic spine development; ISS:UniProtKB.
DR GO; GO:0045741; P:positive regulation of epidermal growth factor-activated receptor activity; IEA:Ensembl.
DR GO; GO:0051491; P:positive regulation of filopodium assembly; ISS:UniProtKB.
DR GO; GO:0048170; P:positive regulation of long-term neuronal synaptic plasticity; ISS:UniProtKB.
DR GO; GO:0090129; P:positive regulation of synapse maturation; ISS:UniProtKB.
DR GO; GO:0006513; P:protein monoubiquitination; ISS:UniProtKB.
DR GO; GO:0007519; P:skeletal muscle tissue development; IEA:Ensembl.
DR GO; GO:0007288; P:sperm axoneme assembly; IEA:Ensembl.
DR Gene3D; 2.60.120.920; -; 2.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR043136; B30.2/SPRY_sf.
DR InterPro; IPR037962; Neuralized.
DR InterPro; IPR006573; NHR_dom.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR12429; PTHR12429; 1.
DR Pfam; PF07177; Neuralized; 2.
DR SMART; SM00588; NEUZ; 2.
DR PROSITE; PS51065; NHR; 2.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cell membrane; Cell projection; Cytoplasm;
KW Lipoprotein; Membrane; Metal-binding; Myristate; Notch signaling pathway;
KW Reference proteome; Repeat; Synapse; Transferase; Translation regulation;
KW Tumor suppressor; Ubl conjugation pathway; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..574
FT /note="E3 ubiquitin-protein ligase NEURL1"
FT /id="PRO_0000181255"
FT DOMAIN 61..217
FT /note="NHR 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00400"
FT DOMAIN 292..447
FT /note="NHR 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00400"
FT ZN_FING 520..560
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 1..41
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 491..511
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..28
FT /note="MGNNFSSIPSLPRGNPSRAPRGHPQNLK -> MGGQITRSTLH (in
FT isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_013151"
FT CONFLICT 61
FT /note="T -> A (in Ref. 4; AAH26336)"
FT /evidence="ECO:0000305"
FT CONFLICT 270
FT /note="G -> S (in Ref. 4; AAH26336)"
FT /evidence="ECO:0000305"
FT CONFLICT 476
FT /note="R -> G (in Ref. 4; AAH26336)"
FT /evidence="ECO:0000305"
FT CONFLICT 566
FT /note="D -> G (in Ref. 4; AAH26336)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 574 AA; 61860 MW; D9699F08F7443EBB CRC64;
MGNNFSSIPS LPRGNPSRAP RGHPQNLKDS IGGPFPVTSH RCHHKQKHCP AVLPSGGLPA
TPLLFHPHTK GSQILMDLSH KAVKRQASFC NAITFSNRPV LIYEQVRLKI TKKQCCWSGA
LRLGFTSKDP SRIHPDSLPK YACPDLVSQS GFWAKALPEE FANEGNIIAF WVDKKGRVFH
RINDSAVMLF FSGVRTADPL WALVDVYGLT RGVQLLDSEL VLPDCLRPRS FTALRRPSLR
READDARLSV SLCDLNVPGA DGDEAAPAAG CPIPQNSLNS QHSRALPAQL DGDLRFHALR
AGAHVRILDE QTVARVEHGR DERALVFTSR PVRVAETIFV KVTRSGGARP GALSFGVTTC
DPGTLRPADL PFSPEALVDR KEFWAVCRVP GPLHSGDILG LVVNADGELH LSHNGAAAGM
QLCVDASQPL WMLFGLHGTI TQIRILGSTI LAERGIPSLP CSPASTPTSP SALGSRLSDP
LLSTCSSGPL GSSAGGTAPN SPVSLPESPV TPGLGQWSDE CTICYEHAVD TVIYTCGHMC
LCYACGLRLK KALHACCPIC RRPIKDIIKT YRSS
