ID DCNL4_HUMAN Reviewed; 292 AA. AC Q92564; B4DH25; Q7Z3F3; Q7Z6B8; DT 25-OCT-2005, integrated into UniProtKB/Swiss-Prot. DT 25-OCT-2005, sequence version 2. DT 27-MAR-2024, entry version 164. DE RecName: Full=DCN1-like protein 4 {ECO:0000305}; DE Short=DCNL4 {ECO:0000303|PubMed:23201271}; DE AltName: Full=DCUN1 domain-containing protein 4; DE AltName: Full=Defective in cullin neddylation protein 1-like protein 4; GN Name=DCUN1D4 {ECO:0000312|HGNC:HGNC:28998}; Synonyms=KIAA0276; 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). RC TISSUE=Brain; RX PubMed=9039502; DOI=10.1093/dnares/3.5.321; RA Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O., RA Tanaka A., Kotani H., Miyajima N., Nomura N.; RT "Prediction of the coding sequences of unidentified human genes. VI. The RT coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of RT cDNA clones from cell line KG-1 and brain."; RL DNA Res. 3:321-329(1996). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Retina; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Uterus; 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 [6] 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 [7] RP DOMAIN, INTERACTION WITH CUL1; CUL2; CUL3; CUL4A; CUL4B; CUL5; UBE2F AND RP UBE2M, AND FUNCTION. RX PubMed=23201271; DOI=10.1016/j.str.2012.10.013; RA Monda J.K., Scott D.C., Miller D.J., Lydeard J., King D., Harper J.W., RA Bennett E.J., Schulman B.A.; RT "Structural conservation of distinctive N-terminal acetylation-dependent RT interactions across a family of mammalian NEDD8 ligation enzymes."; RL Structure 21:42-53(2013). RN [8] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-95, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). RN [9] RP INTERACTION WITH CUL1; CUL2; CUL3; CUL5; CAND; RNF7 AND RBX1, SUBCELLULAR RP LOCATION, FUNCTION, AND MUTAGENESIS OF ASP-250; ALA-274 AND ASP-280. RX PubMed=26906416; DOI=10.1242/jcs.181784; RA Keuss M.J., Thomas Y., Mcarthur R., Wood N.T., Knebel A., Kurz T.; RT "Characterization of the mammalian family of DCN-type NEDD8 E3 ligases."; RL J. Cell Sci. 129:1441-1454(2016). RN [10] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-95, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [11] {ECO:0007744|PDB:5V89} RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 102-292 IN COMPLEX WITH CUL1. RX PubMed=28581483; DOI=10.1038/nchembio.2386; RA Scott D.C., Hammill J.T., Min J., Rhee D.Y., Connelly M., Sviderskiy V.O., RA Bhasin D., Chen Y., Ong S.S., Chai S.C., Goktug A.N., Huang G., Monda J.K., RA Low J., Kim H.S., Paulo J.A., Cannon J.R., Shelat A.A., Chen T., RA Kelsall I.R., Alpi A.F., Pagala V., Wang X., Peng J., Singh B., RA Harper J.W., Schulman B.A., Guy R.K.; RT "Blocking an N-terminal acetylation-dependent protein interaction inhibits RT an E3 ligase."; RL Nat. Chem. Biol. 13:850-857(2017). CC -!- FUNCTION: Contributes to the neddylation of all cullins by transferring CC NEDD8 from N-terminally acetylated NEDD8-conjugating E2s enzyme to CC different cullin C-terminal domain-RBX complexes which are necessary CC for the activation of cullin-RING E3 ubiquitin ligases (CRLs). CC {ECO:0000269|PubMed:23201271, ECO:0000269|PubMed:26906416}. CC -!- SUBUNIT: Interacts (via the DCUN1 domain) with the unneddylated CC cullins: interacts with CUL1, CUL2, CUL3, CUL4A, CUL4B and CUL5; these CC interactions promote the cullin neddylation and the identity of the CC cullin dictates the affinity of the interaction (PubMed:26906416, CC PubMed:23201271). Interacts with RBX1 and RNF7 (PubMed:26906416). CC Interacts with CAND1; this interaction is bridged by cullins such as CC CUL3 and strongly inhibits the neddylation of CUL3. These CAND-cullin- CC DCNL complexes can only be neddylated in the presence of a substrate CC adapter (PubMed:26906416). Interacts (via DCUN1 domain) with UBE2M (N- CC terminally acetylated form) and probably with UBE2F (N-terminally CC acetylated form) (PubMed:23201271). {ECO:0000269|PubMed:23201271, CC ECO:0000269|PubMed:26906416}. CC -!- INTERACTION: CC Q92564; PRO_0000037946 [P29991]; Xeno; NbExp=3; IntAct=EBI-2654610, EBI-8826488; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:26906416}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q92564-1; Sequence=Displayed; CC Name=2; CC IsoId=Q92564-2; Sequence=VSP_016016; CC Name=3; CC IsoId=Q92564-3; Sequence=VSP_054381; CC -!- DOMAIN: The DCUN1 domain, also known as PONY domain, mediates the CC interaction with different cullins (PubMed:23201271). The DCUN1 domain CC mediates the interaction with the N-terminally acetylated NEDD8- CC conjugating E2s enzyme leading to the NEDD8 transfer from N-terminally CC acetylated NEDD8-conjugating E2s enzyme to different cullin C-terminal CC domain-RBX complexes; the neddylation efficiency correlates with the CC DCUN1D5-cullin and DCUN1D5-E2 interaction affinities (PubMed:23201271). CC {ECO:0000269|PubMed:23201271}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA13405.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=CAD97912.1; Type=Erroneous initiation; Evidence={ECO:0000305}; 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; D87466; BAA13405.1; ALT_INIT; mRNA. DR EMBL; AK294894; BAG57986.1; -; mRNA. DR EMBL; BX537944; CAD97912.1; ALT_INIT; mRNA. DR EMBL; AC027271; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC053897; AAH53897.2; -; mRNA. DR CCDS; CCDS33982.1; -. [Q92564-1] DR CCDS; CCDS3487.2; -. [Q92564-2] DR CCDS; CCDS75123.1; -. [Q92564-3] DR RefSeq; NP_001035492.1; NM_001040402.2. [Q92564-1] DR RefSeq; NP_001274684.1; NM_001287755.1. [Q92564-3] DR RefSeq; NP_001274686.1; NM_001287757.1. DR RefSeq; NP_055930.2; NM_015115.3. [Q92564-2] DR PDB; 5V89; X-ray; 1.55 A; A=102-292. DR PDBsum; 5V89; -. DR AlphaFoldDB; Q92564; -. DR SMR; Q92564; -. DR BioGRID; 116759; 25. DR IntAct; Q92564; 4. DR STRING; 9606.ENSP00000389900; -. DR BindingDB; Q92564; -. DR ChEMBL; CHEMBL4295914; -. DR GlyGen; Q92564; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q92564; -. DR PhosphoSitePlus; Q92564; -. DR BioMuta; DCUN1D4; -. DR DMDM; 78099237; -. DR EPD; Q92564; -. DR jPOST; Q92564; -. DR MassIVE; Q92564; -. DR MaxQB; Q92564; -. DR PaxDb; 9606-ENSP00000389900; -. DR PeptideAtlas; Q92564; -. DR ProteomicsDB; 4184; -. DR ProteomicsDB; 75320; -. [Q92564-1] DR ProteomicsDB; 75321; -. [Q92564-2] DR Pumba; Q92564; -. DR Antibodypedia; 23882; 137 antibodies from 17 providers. DR DNASU; 23142; -. DR Ensembl; ENST00000334635.10; ENSP00000334625.5; ENSG00000109184.15. [Q92564-1] DR Ensembl; ENST00000381441.7; ENSP00000370850.3; ENSG00000109184.15. [Q92564-2] DR Ensembl; ENST00000451288.6; ENSP00000389900.2; ENSG00000109184.15. [Q92564-3] DR GeneID; 23142; -. DR KEGG; hsa:23142; -. DR MANE-Select; ENST00000334635.10; ENSP00000334625.5; NM_001040402.3; NP_001035492.1. DR UCSC; uc003gze.5; human. [Q92564-1] DR AGR; HGNC:28998; -. DR CTD; 23142; -. DR DisGeNET; 23142; -. DR GeneCards; DCUN1D4; -. DR HGNC; HGNC:28998; DCUN1D4. DR HPA; ENSG00000109184; Low tissue specificity. DR MIM; 612977; gene. DR neXtProt; NX_Q92564; -. DR OpenTargets; ENSG00000109184; -. DR PharmGKB; PA142672010; -. DR VEuPathDB; HostDB:ENSG00000109184; -. DR eggNOG; KOG3077; Eukaryota. DR GeneTree; ENSGT00940000156935; -. DR HOGENOM; CLU_047042_3_1_1; -. DR InParanoid; Q92564; -. DR OMA; NMDQWLS; -. DR OrthoDB; 169757at2759; -. DR PhylomeDB; Q92564; -. DR TreeFam; TF354270; -. DR PathwayCommons; Q92564; -. DR Reactome; R-HSA-8951664; Neddylation. DR SignaLink; Q92564; -. DR BioGRID-ORCS; 23142; 20 hits in 1154 CRISPR screens. DR ChiTaRS; DCUN1D4; human. DR GeneWiki; DCUN1D4; -. DR GenomeRNAi; 23142; -. DR Pharos; Q92564; Tchem. DR PRO; PR:Q92564; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; Q92564; Protein. DR Bgee; ENSG00000109184; Expressed in calcaneal tendon and 200 other cell types or tissues. DR ExpressionAtlas; Q92564; baseline and differential. DR GO; GO:0005634; C:nucleus; IDA:LIFEdb. DR GO; GO:0000151; C:ubiquitin ligase complex; IBA:GO_Central. DR GO; GO:0097602; F:cullin family protein binding; IMP:UniProtKB. DR GO; GO:0031624; F:ubiquitin conjugating enzyme binding; IBA:GO_Central. DR GO; GO:0032182; F:ubiquitin-like protein binding; IBA:GO_Central. DR GO; GO:2000436; P:positive regulation of protein neddylation; IMP:UniProtKB. DR GO; GO:0045116; P:protein neddylation; IBA:GO_Central. DR Gene3D; 1.10.238.200; Cullin, PONY binding domain; 1. DR Gene3D; 1.10.238.10; EF-hand; 1. DR InterPro; IPR014764; DCN-prot. DR InterPro; IPR042460; DCN1-like_PONY. DR InterPro; IPR005176; PONY_dom. DR PANTHER; PTHR12281:SF8; DCN1-LIKE PROTEIN 4; 1. DR PANTHER; PTHR12281; RP42 RELATED; 1. DR Pfam; PF03556; Cullin_binding; 1. DR PROSITE; PS51229; DCUN1; 1. DR Genevisible; Q92564; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Isopeptide bond; Nucleus; KW Reference proteome; Ubl conjugation. FT CHAIN 1..292 FT /note="DCN1-like protein 4" FT /id="PRO_0000129503" FT DOMAIN 101..287 FT /note="DCUN1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00574" FT REGION 43..83 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 43..57 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 60..83 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT CROSSLNK 95 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25218447, FT ECO:0007744|PubMed:28112733" FT VAR_SEQ 1..9 FT /note="MHSDAAAVN -> MEVEAALGCSGQGRGCGGVAPAGRGRERASERGTRVRIS FT KGLSGAGGSVRKAD (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_054381" FT VAR_SEQ 206..240 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_016016" FT MUTAGEN 250 FT /note="D->A: Does not affect localization at nucleus; when FT associated with R-274 and A-280." FT /evidence="ECO:0000269|PubMed:26906416" FT MUTAGEN 274 FT /note="A->R: Does not affect localization at nucleus; when FT associated with A-250 and A-280." FT /evidence="ECO:0000269|PubMed:26906416" FT MUTAGEN 280 FT /note="D->A: Does not affect localization at nucleus; when FT associated with A-250 and R-274." FT /evidence="ECO:0000269|PubMed:26906416" FT HELIX 104..114 FT /evidence="ECO:0007829|PDB:5V89" FT TURN 115..118 FT /evidence="ECO:0007829|PDB:5V89" FT HELIX 122..132 FT /evidence="ECO:0007829|PDB:5V89" FT STRAND 136..138 FT /evidence="ECO:0007829|PDB:5V89" FT HELIX 139..147 FT /evidence="ECO:0007829|PDB:5V89" FT HELIX 158..167 FT /evidence="ECO:0007829|PDB:5V89" FT HELIX 173..177 FT /evidence="ECO:0007829|PDB:5V89" FT HELIX 180..185 FT /evidence="ECO:0007829|PDB:5V89" FT HELIX 186..188 FT /evidence="ECO:0007829|PDB:5V89" FT HELIX 190..204 FT /evidence="ECO:0007829|PDB:5V89" FT STRAND 211..213 FT /evidence="ECO:0007829|PDB:5V89" FT HELIX 214..225 FT /evidence="ECO:0007829|PDB:5V89" FT TURN 226..228 FT /evidence="ECO:0007829|PDB:5V89" FT HELIX 232..241 FT /evidence="ECO:0007829|PDB:5V89" FT STRAND 245..248 FT /evidence="ECO:0007829|PDB:5V89" FT HELIX 249..261 FT /evidence="ECO:0007829|PDB:5V89" FT HELIX 277..289 FT /evidence="ECO:0007829|PDB:5V89" SQ SEQUENCE 292 AA; 34068 MW; 1927AA612E075E9C CRC64; MHSDAAAVNF QLNSHLSTLA NIHKIYHTLN KLNLTEDIGQ DDHQTGSLRS CSSSDCFNKV MPPRKKRRPA SGDDLSAKKS RHDSMYRKYD STRIKTEEEA FSSKRCLEWF YEYAGTDDVV GPEGMEKFCE DIGVEPENVV MLVLAWKLDA QNMGYFTLQE WLKGMTSLQC DTTEKLRNTL DYLRSFLNDS TNFKLIYRYA FDFAREKDQR SLDINTAKCM LGLLLGKIWP LFPVFHQFLE QSKYKVINKD QWCNVLEFSR TINLDLSNYD EDGAWPVLLD EFVEWYKDKQ MS //