NEU1B_HUMAN
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 03-AUG-2022, entry version 114.
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}.
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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; A8MQ27; -.
DR PeptideAtlas; A8MQ27; -.
DR PRIDE; A8MQ27; -.
DR ProteomicsDB; 1935; -. [A8MQ27-1]
DR ProteomicsDB; 7613; -.
DR ProteomicsDB; 7614; -.
DR Antibodypedia; 49674; 47 antibodies from 10 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 CTD; 54492; -.
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; NKNGECT; -.
DR OrthoDB; 1384219at2759; -.
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 UniPathway; UPA00143; -.
DR BioGRID-ORCS; 54492; 12 hits in 1106 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 177 other tissues.
DR Genevisible; A8MQ27; HS.
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:0070086; P:ubiquitin-dependent endocytosis; ISS:UniProtKB.
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 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