ID   NEU1B_HUMAN             Reviewed;         555 AA.
AC   A8MQ27; C9DQJ5; C9DQJ6; C9DQJ7;
DT   02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT   04-DEC-2007, sequence version 1.
DT   27-MAR-2024, entry version 122.
DE   RecName: Full=E3 ubiquitin-protein ligase NEURL1B;
DE            EC=2.3.2.27;
DE   AltName: Full=Neuralized-2;
DE            Short=NEUR2;
DE   AltName: Full=Neuralized-like protein 1B;
DE   AltName: Full=Neuralized-like protein 3;
DE   AltName: Full=RING-type E3 ubiquitin transferase NEURL1B {ECO:0000305};
GN   Name=NEURL1B; Synonyms=NEURL3;
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] (ISOFORMS 1; 2 AND 3), FUNCTION, SUBCELLULAR
RP   LOCATION, ALTERNATIVE SPLICING, INTERACTION WITH DLL1 AND DLL4, AND TISSUE
RP   SPECIFICITY.
RX   PubMed=19723503; DOI=10.1016/j.bbrc.2009.08.147;
RA   Rullinkov G., Tamme R., Sarapuu A., Lauren J., Sepp M., Palm K.,
RA   Timmusk T.;
RT   "Neuralized-2: Expression in human and rodents and interaction with Delta-
RT   like ligands.";
RL   Biochem. Biophys. Res. Commun. 389:420-425(2009).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15372022; DOI=10.1038/nature02919;
RA   Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA   Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA   She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA   Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA   Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA   Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA   Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA   Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA   Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA   Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA   Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA   Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA   Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT   "The DNA sequence and comparative analysis of human chromosome 5.";
RL   Nature 431:268-274(2004).
RN   [3]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-199, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
CC   -!- FUNCTION: E3 ubiquitin-protein ligase involved in regulation of the
CC       Notch pathway through influencing the stability and activity of several
CC       Notch ligands. {ECO:0000269|PubMed:19723503}.
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 JAG1, DLL1 and DLL4.
CC       {ECO:0000269|PubMed:19723503}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19723503}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=A8MQ27-1; Sequence=Displayed;
CC       Name=2; Synonyms=delta-NHR1;
CC         IsoId=A8MQ27-2; Sequence=VSP_044404;
CC       Name=3; Synonyms=delta-NHR2;
CC         IsoId=A8MQ27-3; Sequence=VSP_044405;
CC   -!- TISSUE SPECIFICITY: Highest expression in brain, prostate and small
CC       intestine. In the brain the levels are higher in fetal than in adult
CC       stage. In the adult brain the highest levels are detected in the
CC       olfactory system, cerebellar cortex, optic nerve and the frontal lobe.
CC       {ECO:0000269|PubMed:19723503}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; GQ414757; ACV53563.1; -; mRNA.
DR   EMBL; GQ414758; ACV53564.1; -; mRNA.
DR   EMBL; GQ414759; ACV53565.1; -; mRNA.
DR   EMBL; AC027309; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS47342.1; -. [A8MQ27-1]
DR   CCDS; CCDS78085.1; -. [A8MQ27-3]
DR   CCDS; CCDS83042.1; -. [A8MQ27-2]
DR   RefSeq; NP_001136123.1; NM_001142651.2. [A8MQ27-1]
DR   RefSeq; NP_001295106.1; NM_001308177.1. [A8MQ27-2]
DR   RefSeq; NP_001295107.1; NM_001308178.1. [A8MQ27-3]
DR   AlphaFoldDB; A8MQ27; -.
DR   SMR; A8MQ27; -.
DR   BioGRID; 119989; 5.
DR   STRING; 9606.ENSP00000358815; -.
DR   iPTMnet; A8MQ27; -.
DR   PhosphoSitePlus; A8MQ27; -.
DR   BioMuta; NEURL1B; -.
DR   jPOST; A8MQ27; -.
DR   MassIVE; A8MQ27; -.
DR   PaxDb; 9606-ENSP00000358815; -.
DR   PeptideAtlas; A8MQ27; -.
DR   ProteomicsDB; 1935; -. [A8MQ27-1]
DR   ProteomicsDB; 7613; -.
DR   Antibodypedia; 49674; 65 antibodies from 11 providers.
DR   DNASU; 54492; -.
DR   Ensembl; ENST00000369800.6; ENSP00000358815.5; ENSG00000214357.9. [A8MQ27-1]
DR   Ensembl; ENST00000520919.5; ENSP00000429797.1; ENSG00000214357.9. [A8MQ27-3]
DR   Ensembl; ENST00000522853.5; ENSP00000430001.1; ENSG00000214357.9. [A8MQ27-2]
DR   GeneID; 54492; -.
DR   KEGG; hsa:54492; -.
DR   MANE-Select; ENST00000369800.6; ENSP00000358815.5; NM_001142651.3; NP_001136123.1.
DR   UCSC; uc003mbt.4; human. [A8MQ27-1]
DR   AGR; HGNC:35422; -.
DR   DisGeNET; 54492; -.
DR   GeneCards; NEURL1B; -.
DR   HGNC; HGNC:35422; NEURL1B.
DR   HPA; ENSG00000214357; Low tissue specificity.
DR   MIM; 615893; gene.
DR   neXtProt; NX_A8MQ27; -.
DR   OpenTargets; ENSG00000214357; -.
DR   PharmGKB; PA164723819; -.
DR   VEuPathDB; HostDB:ENSG00000214357; -.
DR   eggNOG; KOG4172; Eukaryota.
DR   eggNOG; KOG4625; Eukaryota.
DR   GeneTree; ENSGT00940000157079; -.
DR   HOGENOM; CLU_090535_0_0_1; -.
DR   InParanoid; A8MQ27; -.
DR   OMA; THGPDIN; -.
DR   OrthoDB; 5471056at2759; -.
DR   PhylomeDB; A8MQ27; -.
DR   TreeFam; TF314368; -.
DR   PathwayCommons; A8MQ27; -.
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   SIGNOR; A8MQ27; -.
DR   UniPathway; UPA00143; -.
DR   BioGRID-ORCS; 54492; 12 hits in 1184 CRISPR screens.
DR   ChiTaRS; NEURL1B; human.
DR   GenomeRNAi; 54492; -.
DR   Pharos; A8MQ27; Tdark.
DR   PRO; PR:A8MQ27; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   RNAct; A8MQ27; Protein.
DR   Bgee; ENSG00000214357; Expressed in ileal mucosa and 179 other cell types or tissues.
DR   GO; GO:0015629; C:actin cytoskeleton; IDA:HPA.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0005769; C:early endosome; ISS:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0061630; F:ubiquitin protein ligase activity; ISS:UniProtKB.
DR   GO; GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW.
DR   GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR   GO; GO:0070086; P:ubiquitin-dependent endocytosis; ISS:UniProtKB.
DR   CDD; cd16786; mRING-HC-C3HC5_NEU1B; 1.
DR   Gene3D; 2.60.120.920; -; 2.
DR   Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 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:SF10; E3 UBIQUITIN-PROTEIN LIGASE NEURL1B; 1.
DR   PANTHER; PTHR12429; NEURALIZED; 1.
DR   Pfam; PF07177; Neuralized; 2.
DR   Pfam; PF13920; zf-C3HC4_3; 1.
DR   SMART; SM00588; NEUZ; 2.
DR   SUPFAM; SSF57850; RING/U-box; 1.
DR   PROSITE; PS51065; NHR; 2.
DR   PROSITE; PS50089; ZF_RING_2; 1.
DR   Genevisible; A8MQ27; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cytoplasm; Metal-binding; Notch signaling pathway;
KW   Phosphoprotein; Reference proteome; Repeat; Transferase;
KW   Ubl conjugation pathway; Zinc; Zinc-finger.
FT   CHAIN           1..555
FT                   /note="E3 ubiquitin-protein ligase NEURL1B"
FT                   /id="PRO_0000349382"
FT   DOMAIN          38..194
FT                   /note="NHR 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00400"
FT   DOMAIN          279..433
FT                   /note="NHR 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00400"
FT   ZN_FING         503..543
FT                   /note="RING-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT   REGION          436..493
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        436..480
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         199
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   VAR_SEQ         11..192
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:19723503"
FT                   /id="VSP_044404"
FT   VAR_SEQ         191..430
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:19723503"
FT                   /id="VSP_044405"
SQ   SEQUENCE   555 AA;  59270 MW;  228B459336279423 CRC64;
     MGNTVHRTLP DPSPPARLLA TRPCCGPGPE RRPVLGEAPR FHAQAKGKNV RLDGHSRRAT
     RRNSFCNGVT FTQRPIRLYE QVRLRLVAVR PGWSGALRFG FTAHDPSLMS AQDIPKYACP
     DLVTRPGYWA KALPENLALR DTVLAYWADR HGRVFYSVND GEPVLFHCGV AVGGPLWALI
     DVYGITDEVQ LLESAFADTL TPARLSQARF SACLPPSSHD AANFDNNELE NNQVVAKLGH
     LALGRAPGPP PADAAAAAIP CGPRERPRPA SSPALLEADL RFHATRGPDV SLSADRKVAC
     APRPDGGRTL VFSERPLRPG ESLFVEVGRP GLAAPGALAF GITSCDPGVL RPNELPADPD
     ALLDRKEYWV VARAGPVPSG GDALSFTLRP GGDVLLGING RPRGRLLCVD TTQALWAFFA
     VRGGVAGQLR LLGTLQSSPA TTTPSGSLSG SQDDSDSDMT FSVNQSSSAS ESSLVTAPSS
     PLSPPVSPVF SPPEPAGIKN GECTVCFDGE VDTVIYTCGH MCLCHSCGLR LKRQARACCP
     ICRRPIKDVI KIYRP
//