NEUL4_HUMAN
ID NEUL4_HUMAN Reviewed; 1562 AA.
AC Q96JN8; Q6GPI8; Q96IU9; Q9H0B0;
DT 21-AUG-2007, integrated into UniProtKB/Swiss-Prot.
DT 21-AUG-2007, sequence version 2.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Neuralized-like protein 4;
GN Name=NEURL4; Synonyms=KIAA1787;
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 [LARGE SCALE MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=11347906; DOI=10.1093/dnares/8.2.85;
RA Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XX. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 8:85-95(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 47-1562 (ISOFORM 2).
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 735-1562 (ISOFORM 2), AND VARIANT
RP HIS-1019.
RC TISSUE=Kidney, and Testis;
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-907, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [6]
RP FUNCTION, INTERACTION WITH CCP110, AND SUBCELLULAR LOCATION.
RX PubMed=22441691; DOI=10.1038/embor.2012.40;
RA Li J., Kim S., Kobayashi T., Liang F.X., Korzeniewski N., Duensing S.,
RA Dynlacht B.D.;
RT "Neurl4, a novel daughter centriole protein, prevents formation of ectopic
RT microtubule organizing centres.";
RL EMBO Rep. 13:547-553(2012).
RN [7]
RP INTERACTION WITH UBE3A AND MAPK6.
RX PubMed=22645313; DOI=10.1128/mcb.00201-12;
RA Martinez-Noel G., Galligan J.T., Sowa M.E., Arndt V., Overton T.M.,
RA Harper J.W., Howley P.M.;
RT "Identification and proteomic analysis of distinct UBE3A/E6AP protein
RT complexes.";
RL Mol. Cell. Biol. 32:3095-3106(2012).
RN [8]
RP FUNCTION, INTERACTION WITH CEP97; CCP110 AND HERC2, SUBCELLULAR LOCATION,
RP AND UBIQUITINATION.
RX PubMed=22261722; DOI=10.1074/mcp.m111.014233;
RA Al-Hakim A.K., Bashkurov M., Gingras A.C., Durocher D., Pelletier L.;
RT "Interaction proteomics identify NEURL4 and the HECT E3 ligase HERC2 as
RT novel modulators of centrosome architecture.";
RL Mol. Cell. Proteomics 11:M111.014233.01-M111.014233.14(2012).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-502, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [10]
RP STRUCTURE BY NMR OF 42-205.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the NEUZ domain in KIAA1787 protein.";
RL Submitted (JUN-2007) to the PDB data bank.
CC -!- FUNCTION: Promotes CCP110 ubiquitination and proteasome-dependent
CC degradation. By counteracting accumulation of CP110, maintains normal
CC centriolar homeostasis and preventing formation of ectopic microtubular
CC organizing centers. {ECO:0000269|PubMed:22261722,
CC ECO:0000269|PubMed:22441691}.
CC -!- SUBUNIT: Interacts with CCP110; this interaction propmotes CCP110
CC ubiquitination and degradation via the proteasome pathway. Via its
CC interaction with CCP110, may indirectly interact with CEP97. Interacts
CC with the E3 ubiquitin-protein ligase HERC2 and UBE3A. May interact with
CC MAPK6 and hence mediate MAPK6 interaction with UBE3A. Interaction with
CC UBE3A may be indirect and mediated by HERC2.
CC {ECO:0000269|PubMed:22261722, ECO:0000269|PubMed:22441691,
CC ECO:0000269|PubMed:22645313}.
CC -!- INTERACTION:
CC Q96JN8; O43303: CCP110; NbExp=9; IntAct=EBI-1053406, EBI-1566217;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing
CC center, centrosome, centriole {ECO:0000269|PubMed:22261722,
CC ECO:0000269|PubMed:22441691}. Note=Localizes to procentriole and
CC daughter centriole in growing and quiescent cells (PubMed:22441691).
CC May loose association with centrosomes during mitosis
CC (PubMed:22261722). {ECO:0000269|PubMed:22261722,
CC ECO:0000269|PubMed:22441691}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96JN8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96JN8-2; Sequence=VSP_027563;
CC -!- TISSUE SPECIFICITY: Widely expressed at high levels (including brain).
CC {ECO:0000269|PubMed:11347906}.
CC -!- DOMAIN: The third NHR domain (NHR 3) is required for localization to
CC both mother and daughter centrioles. NHR 1 restricts targeting to
CC daughter centriole (PubMed:22441691). NHR 3 and 4 are required for
CC CCP110/CEP97-binding, but not for HERC2-binding. NHR 5 and 6 are
CC important for HERC2-binding and centrosomal localization
CC (PubMed:22261722). {ECO:0000269|PubMed:22261722,
CC ECO:0000269|PubMed:22441691}.
CC -!- PTM: Ubiquitinated; undergoes HERC2-dependent 'Lys-48' ubiquitination.
CC This ubiquitination leads to proteasomal degradation.
CC {ECO:0000269|PubMed:22261722}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH07227.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAB47416.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB058690; BAB47416.1; ALT_INIT; mRNA.
DR EMBL; AL136870; CAB66804.1; -; mRNA.
DR EMBL; BC007227; AAH07227.1; ALT_FRAME; mRNA.
DR EMBL; BC073134; AAH73134.1; -; mRNA.
DR CCDS; CCDS42251.1; -. [Q96JN8-1]
DR CCDS; CCDS42252.1; -. [Q96JN8-2]
DR RefSeq; NP_001005408.1; NM_001005408.1. [Q96JN8-2]
DR RefSeq; NP_115818.2; NM_032442.2. [Q96JN8-1]
DR PDB; 2E63; NMR; -; A=43-205.
DR PDBsum; 2E63; -.
DR AlphaFoldDB; Q96JN8; -.
DR SMR; Q96JN8; -.
DR BioGRID; 124095; 125.
DR CORUM; Q96JN8; -.
DR IntAct; Q96JN8; 171.
DR MINT; Q96JN8; -.
DR STRING; 9606.ENSP00000382390; -.
DR iPTMnet; Q96JN8; -.
DR PhosphoSitePlus; Q96JN8; -.
DR BioMuta; NEURL4; -.
DR DMDM; 156630938; -.
DR EPD; Q96JN8; -.
DR jPOST; Q96JN8; -.
DR MassIVE; Q96JN8; -.
DR MaxQB; Q96JN8; -.
DR PaxDb; Q96JN8; -.
DR PeptideAtlas; Q96JN8; -.
DR PRIDE; Q96JN8; -.
DR ProteomicsDB; 76995; -. [Q96JN8-1]
DR ProteomicsDB; 76996; -. [Q96JN8-2]
DR Antibodypedia; 48206; 15 antibodies from 7 providers.
DR DNASU; 84461; -.
DR Ensembl; ENST00000315614.11; ENSP00000319826.7; ENSG00000215041.10. [Q96JN8-2]
DR Ensembl; ENST00000399464.7; ENSP00000382390.2; ENSG00000215041.10. [Q96JN8-1]
DR Ensembl; ENST00000671847.1; ENSP00000500916.1; ENSG00000288301.1. [Q96JN8-1]
DR Ensembl; ENST00000673081.1; ENSP00000500667.1; ENSG00000288301.1. [Q96JN8-2]
DR GeneID; 84461; -.
DR KEGG; hsa:84461; -.
DR MANE-Select; ENST00000399464.7; ENSP00000382390.2; NM_032442.3; NP_115818.2.
DR UCSC; uc002gga.2; human. [Q96JN8-1]
DR CTD; 84461; -.
DR DisGeNET; 84461; -.
DR GeneCards; NEURL4; -.
DR HGNC; HGNC:34410; NEURL4.
DR HPA; ENSG00000215041; Low tissue specificity.
DR MIM; 615865; gene.
DR neXtProt; NX_Q96JN8; -.
DR OpenTargets; ENSG00000215041; -.
DR PharmGKB; PA164723835; -.
DR VEuPathDB; HostDB:ENSG00000215041; -.
DR eggNOG; KOG4625; Eukaryota.
DR GeneTree; ENSGT00940000159866; -.
DR InParanoid; Q96JN8; -.
DR OMA; TTHNPAV; -.
DR OrthoDB; 74097at2759; -.
DR PhylomeDB; Q96JN8; -.
DR PathwayCommons; Q96JN8; -.
DR SignaLink; Q96JN8; -.
DR BioGRID-ORCS; 84461; 17 hits in 1079 CRISPR screens.
DR EvolutionaryTrace; Q96JN8; -.
DR GenomeRNAi; 84461; -.
DR Pharos; Q96JN8; Tdark.
DR PRO; PR:Q96JN8; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q96JN8; protein.
DR Bgee; ENSG00000215041; Expressed in right hemisphere of cerebellum and 95 other tissues.
DR ExpressionAtlas; Q96JN8; baseline and differential.
DR Genevisible; Q96JN8; HS.
DR GO; GO:0005814; C:centriole; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR Gene3D; 2.60.120.920; -; 6.
DR InterPro; IPR043136; B30.2/SPRY_sf.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR InterPro; IPR037962; Neuralized.
DR InterPro; IPR006573; NHR_dom.
DR PANTHER; PTHR12429; PTHR12429; 1.
DR Pfam; PF07177; Neuralized; 6.
DR SMART; SM00588; NEUZ; 6.
DR SUPFAM; SSF49899; SSF49899; 2.
DR PROSITE; PS51065; NHR; 6.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Cytoskeleton;
KW Phosphoprotein; Reference proteome; Repeat; Ubl conjugation;
KW Ubl conjugation pathway.
FT CHAIN 1..1562
FT /note="Neuralized-like protein 4"
FT /id="PRO_0000299105"
FT DOMAIN 41..207
FT /note="NHR 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00400"
FT DOMAIN 317..484
FT /note="NHR 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00400"
FT DOMAIN 520..686
FT /note="NHR 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00400"
FT DOMAIN 716..884
FT /note="NHR 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00400"
FT DOMAIN 913..1086
FT /note="NHR 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00400"
FT DOMAIN 1131..1294
FT /note="NHR 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00400"
FT REGION 1..48
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 207..236
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 691..716
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1086..1123
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 207..225
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 699..714
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1086..1104
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 502
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 907
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT VAR_SEQ 863..864
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11230166,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_027563"
FT VARIANT 1019
FT /note="Q -> H (in dbSNP:rs3809813)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_049527"
FT CONFLICT 228
FT /note="T -> S (in Ref. 2; CAB66804)"
FT /evidence="ECO:0000305"
FT CONFLICT 359
FT /note="D -> G (in Ref. 2; CAB66804)"
FT /evidence="ECO:0000305"
FT CONFLICT 637
FT /note="T -> A (in Ref. 2; CAB66804)"
FT /evidence="ECO:0000305"
FT CONFLICT 1262
FT /note="G -> A (in Ref. 3; AAH07227)"
FT /evidence="ECO:0000305"
FT STRAND 50..54
FT /evidence="ECO:0007829|PDB:2E63"
FT STRAND 56..58
FT /evidence="ECO:0007829|PDB:2E63"
FT STRAND 60..64
FT /evidence="ECO:0007829|PDB:2E63"
FT TURN 66..68
FT /evidence="ECO:0007829|PDB:2E63"
FT STRAND 86..94
FT /evidence="ECO:0007829|PDB:2E63"
FT STRAND 103..109
FT /evidence="ECO:0007829|PDB:2E63"
FT HELIX 120..122
FT /evidence="ECO:0007829|PDB:2E63"
FT STRAND 125..139
FT /evidence="ECO:0007829|PDB:2E63"
FT STRAND 141..145
FT /evidence="ECO:0007829|PDB:2E63"
FT HELIX 150..152
FT /evidence="ECO:0007829|PDB:2E63"
FT STRAND 159..163
FT /evidence="ECO:0007829|PDB:2E63"
FT STRAND 169..175
FT /evidence="ECO:0007829|PDB:2E63"
FT STRAND 177..182
FT /evidence="ECO:0007829|PDB:2E63"
FT STRAND 189..194
FT /evidence="ECO:0007829|PDB:2E63"
FT STRAND 199..204
FT /evidence="ECO:0007829|PDB:2E63"
SQ SEQUENCE 1562 AA; 166907 MW; CB25753A5D127246 CRC64;
MAAGSGGSGG SGGGPGPGPG GGGGPSGSGS GPGSNGGLGS GGELHPRTGR LVSLSACGRT
ARRQQPGQEF NHGLVLSREP LRDGRVFTVR IDRKVNSWSG SIEIGVTALD PSVLDFPSSA
TGLKGGSWVV SGCSVLRDGR SVLEEYGQDL DQLGEGDRVG VERTVAGELR LWVNGRDCGV
AATGLPPRVW AVVDLYGKCT QITVLPPEPG FSPPTPIPTP PLEPLAPTED SALAEQGTSA
DEAFMVSPAQ ARPETFPNSL ESHNDFANME LSEVVSNTIL SAYNGGLLNV NLSSPPAGEG
LGSSGAATSP ILTSNDALLF HEKCGTLIKL SNNNKTAERR RPLDEFNNGV VMTNRPLRDN
EMFEIRIDKL VDKWSGSIEI GVTTHNPNSL EYPATMTNLQ SGTIMMSGCG ILTNGKGTRR
EYCEFSLDEL QEGDHIGLTR KSNSALHFFI NGIDQGVATP LTPPVVYGVV DLYGMAVKVT
IVHNNNHSDR LRRNNAILRA LSPEGALRRA APAAQAEPER LLFHPNCGQK AAITHEGRTA
LRPHATDDFN HGVVLSSRAL RDGEVFQVRI DKMVDKWAGS IEIGVTTHNP AYLQLPSTMT
NLRSGTWMMT GNGVMHNGTT ILDEYGHNLD RLKAGDTVGV VRREDGTLHF FVNGMTQGPA
AWNVPPGVYA VVDLYGQAAQ ATIVDDVEVA PVPEPLPEGN NQVSPSSPSS GAGGSDLRFH
QLHGSNAVIT NGGRTALRHN CRSEFNDAIV ISNRALRDGE LFEIVIQKMV DRWSGSIEAG
VTAIRPEDLE FPNTMTDIDY DTWMLSGTAI MQDGNTMRNN YGCDLDALGT GARIGMMRTA
KGDLHYFING QDQGAACSGL PPGKEVYAVV DLYGQCVQVS ITNATGPMDN SLATSNTATE
KSFPLHSPVA GVAHRFHSTC GKNVTLEEDG TRAVRAAGYA HGLVFSTKEL RAEEVFEVKV
EELDEKWAGS LRLGLTTLAP GEMGPGAGGG GPGLPPSLPE LRTKTTWMVS SCEVRRDGQL
QRMNYGRNLE RLGVGSRVGV RRGADDTMHI LVDGEDMGPA ATGIAKNVWA VLDLYGPVRG
VSIVSSTRLE ESEGTQPPSP SSDTGSEGEE DDEGEEHGLG GQNEVGIIPT TLEFLENHGK
NILLSNGNRT ATRVASYNQG IVVINQPLVP QLLVQVRIDF LNRQWTSSLV LGVITCAPER
LNFPASACAL KRAAWLLRGR GVFHNGLKIC EKFGPNLDTC PEGTILGLRL DSSGGLHLHV
NGVDQGVAVP DVPQPCHALV DLYGQCEQVT IVNPEPGAAS GKSAGTQGDM EKADMVDGIK
ESVCWGPPPA ASPLKSCEYH ALCSRFQELL LLPEDYFMPP PKRSLCYCES CRKLRGDEAH
RRRGEPPREY ALPFGWCRFN LRVNPRLEAG TLTKKWHMAY HGSNVAAVRR VLDRGELGAG
TASILSCRPL KGEPGVGFEE PGENCAPPRE EQPPPVLLSP SLQYAGAETL ASKVQFRDPK
SQRTHQAQVA FQVCVRPGSY TPGPPSAALG EPPDPHFSPA ELEWVTKEKG ATLLCALLVR
VE
