DCNL1_HUMAN
ID DCNL1_HUMAN Reviewed; 259 AA.
AC Q96GG9; B2RB37; Q7L3G9; Q8TEX7; Q9H6M1; Q9HCT3;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=DCN1-like protein 1 {ECO:0000305};
DE Short=DCNL1 {ECO:0000303|PubMed:23201271};
DE AltName: Full=DCUN1 domain-containing protein 1;
DE AltName: Full=Defective in cullin neddylation protein 1-like protein 1;
DE AltName: Full=Squamous cell carcinoma-related oncogene;
GN Name=DCUN1D1 {ECO:0000312|HGNC:HGNC:18184};
GN Synonyms=DCN1 {ECO:0000303|PubMed:28581483}, DCUN1L1, RP42, SCCRO;
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], AND TISSUE SPECIFICITY.
RC TISSUE=Telencephalon;
RX PubMed=10777668; DOI=10.1006/geno.2000.6126;
RA Mas C., Bourgeois F., Bulfone A., Levacher B., Mugnier C., Simonneau M.;
RT "Cloning and expression analysis of a novel gene, RP42, mapping to an
RT autism susceptibility locus on 6q16.";
RL Genomics 65:70-74(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lung carcinoma, and Squamous cell carcinoma;
RX PubMed=17018598; DOI=10.1158/0008-5472.can-06-2074;
RA Sarkaria I., O-charoenrat P., Talbot S.G., Reddy P.G., Ngai I., Maghami E.,
RA Patel K.N., Lee B., Yonekawa Y., Dudas M., Kaufman A., Ryan R.,
RA Ghossein R., Rao P.H., Stoffel A., Ramanathan Y., Singh B.;
RT "Squamous cell carcinoma related oncogene/DCUN1D1 is highly conserved and
RT activated by amplification in squamous cell carcinomas.";
RL Cancer Res. 66:9437-9444(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Trachea;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, and Skin;
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 OVEREXPRESSION IN SQUAMOUS CELL CARCINOMAS.
RX PubMed=12796399;
RA Estilo C.L., O-Charoenrat P., Ngai I., Patel S.G., Reddy P.G., Dao S.,
RA Shaha A.R., Kraus D.H., Boyle J.O., Wong R.J., Pfister D.G., Huryn J.M.,
RA Zlotolow I.M., Shah J.P., Singh B.;
RT "The role of novel oncogenes squamous cell carcinoma-related oncogene and
RT phosphatidylinositol 3-kinase p110alpha in squamous cell carcinoma of the
RT oral tongue.";
RL Clin. Cancer Res. 9:2300-2306(2003).
RN [7]
RP OVEREXPRESSION IN SQUAMOUS CELL CARCINOMAS.
RX PubMed=15123463; DOI=10.1245/aso.2004.03.014;
RA Talbot S.G., O-charoenrat P., Sarkaria I.S., Ghossein R., Reddy P.,
RA Ngai I., Cordeiro C.N., Wong R.J., Kris M.G., Rusch V.W., Singh B.;
RT "Squamous cell carcinoma related oncogene regulates angiogenesis through
RT vascular endothelial growth factor-A.";
RL Ann. Surg. Oncol. 11:530-534(2004).
RN [8]
RP OVEREXPRESSION IN BRONCHIOLOALVEOLAR CARCINOMAS.
RX PubMed=15511464; DOI=10.1016/j.athoracsur.2004.05.056;
RA Sarkaria I.S., Pham D., Ghossein R.A., Talbot S.G., Hezel M., Dudas M.E.,
RA Ebright M.I., Chuai S., Memoli N., Venkatraman E.S., Miller V.A.,
RA Kris M.G., Zakowski M.F., Rusch V.W., Singh B.;
RT "SCCRO expression correlates with invasive progression in
RT bronchioloalveolar carcinoma.";
RL Ann. Thorac. Surg. 78:1734-1741(2004).
RN [9]
RP LACK OF OVEREXPRESSION IN ADRENOCORTICAL CARCINOMAS.
RX PubMed=15657565; DOI=10.1016/j.surg.2004.06.041;
RA Sarkaria I.S., Stojadinovic A., Talbot S.G., Hoos A., Dudas M.E.,
RA Brennan M.F., Ghossein R.A., Singh B.;
RT "Squamous cell carcinoma-related oncogene is highly expressed in
RT developing, normal, and adenomatous adrenal tissue but not in aggressive
RT adrenocortical carcinomas.";
RL Surgery 136:1122-1128(2004).
RN [10]
RP OVEREXPRESSION IN THYROID CANCERS.
RX PubMed=15623817; DOI=10.1210/jc.2004-1337;
RA Jacques C., Baris O., Prunier-Mirebeau D., Savagner F., Rodien P.,
RA Rohmer V., Franc B., Guyetant S., Malthiery Y., Reynier P.;
RT "Two-step differential expression analysis reveals a new set of genes
RT involved in thyroid oncocytic tumors.";
RL J. Clin. Endocrinol. Metab. 90:2314-2320(2005).
RN [11]
RP IDENTIFICATION IN AN E3 LIGASE COMPLEX FOR NEDDYLATION, INTERACTION WITH
RP CUL1; CUL2; CUL3; CUL4; CUL5; UBE2M; CAND1 AND RBX1, AND MUTAGENESIS OF
RP ASP-241.
RX PubMed=18826954; DOI=10.1074/jbc.m804440200;
RA Kim A.Y., Bommelje C.C., Lee B.E., Yonekawa Y., Choi L., Morris L.G.,
RA Huang G., Kaufman A., Ryan R.J., Hao B., Ramanathan Y., Singh B.;
RT "SCCRO (DCUN1D1) is an essential component of the E3 complex for
RT neddylation.";
RL J. Biol. Chem. 283:33211-33220(2008).
RN [12]
RP INTERACTION WITH CUL1; CUL2; CUL3; CUL4A; CUL4B; CUL5 AND UBE2M,
RP MUTAGENESIS OF ASP-211; ALA-235 AND ASP-241, DOMAIN, AND FUNCTION.
RX PubMed=19617556; DOI=10.1073/pnas.0812528106;
RA Meyer-Schaller N., Chou Y.C., Sumara I., Martin D.D., Kurz T., Katheder N.,
RA Hofmann K., Berthiaume L.G., Sicheri F., Peter M.;
RT "The human Dcn1-like protein DCNL3 promotes Cul3 neddylation at
RT membranes.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:12365-12370(2009).
RN [13]
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 [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [15]
RP FUNCTION, MUTAGENESIS OF ASP-211; ALA-235 AND ASP-241, INTERACTION WITH
RP CUL2; VHL; SOCS2; SOCS1 AND HIF1A, AND COMPONENT OF VCB COMPLEX.
RX PubMed=23401859; DOI=10.1128/mcb.01342-12;
RA Heir P., Sufan R.I., Greer S.N., Poon B.P., Lee J.E., Ohh M.;
RT "DCNL1 functions as a substrate sensor and activator of cullin 2-RING
RT ligase.";
RL Mol. Cell. Biol. 33:1621-1631(2013).
RN [16]
RP DOMAIN, INTERACTION WITH CUL1; CUL2; CUL3; CUL4A; CUL4B; CUL5; UBE2M AND
RP UBE2F, 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 [17]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH UBE2M.
RX PubMed=25349211; DOI=10.1074/jbc.m114.585505;
RA Huang G., Stock C., Bommelje C.C., Weeda V.B., Shah K., Bains S., Buss E.,
RA Shaha M., Rechler W., Ramanathan S.Y., Singh B.;
RT "SCCRO3 (DCUN1D3) antagonizes the neddylation and oncogenic activity of
RT SCCRO (DCUN1D1).";
RL J. Biol. Chem. 289:34728-34742(2014).
RN [18]
RP INTERACTION WITH CUL1; CUL2; CUL3; CUL4A; CUL4B; CUL5; CAND1; RBX1; RNF7;
RP ELOB AND DDB1, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-211; ALA-235 AND
RP ASP-241, AND FUNCTION.
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 [19]
RP SUBCELLULAR LOCATION, UBIQUITINATION, DOMAIN, MUTAGENESIS OF PHE-15;
RP MET-16; PHE-44; PHE-45; ASP-211; ALA-235 AND ASP-241, AND INTERACTION WITH
RP CUL1; CUL2; CUL3; CUL4A; CUL4B; CUL5 AND ARIH2.
RX PubMed=30587576; DOI=10.1074/jbc.ra118.005861;
RA Kelsall I.R., Kristariyanto Y.A., Knebel A., Wood N.T., Kulathu Y.,
RA Alpi A.F.;
RT "Coupled monoubiquitylation of the co-E3 ligase DCNL1 by Ariadne-RBR E3
RT ubiquitin ligases promotes cullin-RING ligase complex remodeling.";
RL J. Biol. Chem. 294:2651-2664(2019).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 62-259 IN COMPLEX WITH CUL1 AND
RP UBE2M.
RX PubMed=21940857; DOI=10.1126/science.1209307;
RA Scott D.C., Monda J.K., Bennett E.J., Harper J.W., Schulman B.A.;
RT "N-terminal acetylation acts as an avidity enhancer within an
RT interconnected multiprotein complex.";
RL Science 334:674-678(2011).
RN [21] {ECO:0007744|PDB:5V83, ECO:0007744|PDB:5V86, ECO:0007744|PDB:5V88}
RP X-RAY CRYSTALLOGRAPHY (1.37 ANGSTROMS) OF 62-259 IN COMPLEX WITH
RP INHIBITORS, FUNCTION, INTERACTION WITH UBE2M, MUTAGENESIS OF CYS-115, SITE,
RP AND DOMAIN.
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: Part of an E3 ubiquitin ligase complex for neddylation
CC (PubMed:18826954). Promotes neddylation of cullin components of E3
CC cullin-RING ubiquitin ligase complexes (PubMed:26906416,
CC PubMed:23201271, PubMed:19617556, PubMed:23401859). Acts by binding to
CC cullin-RBX1 complexes in the cytoplasm and promoting their nuclear
CC translocation, enhancing recruitment of E2-NEDD8 (UBE2M-NEDD8)
CC thioester to the complex, and optimizing the orientation of proteins in
CC the complex to allow efficient transfer of NEDD8 from the E2 to the
CC cullin substrates. Involved in the release of inhibitory effets of
CC CAND1 on cullin-RING ligase E3 complex assembly and activity
CC (PubMed:25349211, PubMed:28581483). Acts also as an oncogene
CC facilitating malignant transformation and carcinogenic progression (By
CC similarity). {ECO:0000250|UniProtKB:Q9QZ73,
CC ECO:0000269|PubMed:18826954, ECO:0000269|PubMed:19617556,
CC ECO:0000269|PubMed:23201271, ECO:0000269|PubMed:23401859,
CC ECO:0000269|PubMed:25349211, ECO:0000269|PubMed:26906416,
CC ECO:0000269|PubMed:28581483}.
CC -!- SUBUNIT: Part of an E3 complex for neddylation composed of cullins,
CC RBX1, UBE2M and CAND1 (PubMed:18826954). Interacts (via the DCUN1
CC domain) with the unneddylated cullins: interacts with CUL1, CUL2, CUL3,
CC CUL4A, CUL4B and CUL5; these interactions promote the cullin
CC neddylation and the identity of the cullin dictates the affinity of the
CC interaction (PubMed:26906416, PubMed:18826954, PubMed:23201271,
CC PubMed:19617556, PubMed:23401859, PubMed:30587576). Binds neddylated
CC CUL1. Interacts (via the C-terminus 50 AA) directly with RBX1
CC (PubMed:18826954, PubMed:26906416). Interacts (via DCUN1 domain) with
CC the N-terminally acetylated form of UBE2M and UBE2F (PubMed:28581483,
CC PubMed:23201271, PubMed:19617556). Interacts preferentially with UBE2M-
CC NEDD8 thioester (via N-terminus 1-26 AA) than with free UBE2M
CC (PubMed:18826954, PubMed:25349211). UBE2M N-terminal acetylation
CC increases the affinity of this interaction by about 2 orders of
CC magnitude (PubMed:21940857). Interacts with CAND1; this interaction is
CC indirect and is bridged by cullins such as CUL1 and CUL3
CC (PubMed:18826954, PubMed:26906416). May also interact with regulators
CC or subunits of cullin-RING ligases such as RNF7, ELOB and DDB1; these
CC interactions are bridged by cullins (PubMed:26906416). Component of VCB
CC complex that contains at least DCUN1D1, CUL2 and VHL; this complex
CC triggers CUL2 neddylation and consequently cullin ring ligase (CRL)
CC substrates polyubiquitylation (PubMed:23401859). Interacts with VHL;
CC this interaction triggers engagement of HIF1A in the VCB complex and is
CC independent of CUL2 (PubMed:23401859). Interacts with CUL2
CC independently of VHL (PubMed:23401859). Interacts with SOCS1 and SOCS2
CC (PubMed:23401859). Interacts with HIF1A; this interaction increases the
CC interaction between VHL and DCUN1D1 (PubMed:23401859). Interacts (via
CC UBA-like domain) with ARIH2; promotes DCUN1D1 ubiquitination
CC (PubMed:30587576). {ECO:0000269|PubMed:18826954,
CC ECO:0000269|PubMed:19617556, ECO:0000269|PubMed:21940857,
CC ECO:0000269|PubMed:23201271, ECO:0000269|PubMed:23401859,
CC ECO:0000269|PubMed:25349211, ECO:0000269|PubMed:26906416,
CC ECO:0000269|PubMed:28581483, ECO:0000269|PubMed:30587576}.
CC -!- INTERACTION:
CC Q96GG9; Q15018: ABRAXAS2; NbExp=3; IntAct=EBI-740086, EBI-1056583;
CC Q96GG9; Q96B67: ARRDC3; NbExp=10; IntAct=EBI-740086, EBI-2875665;
CC Q96GG9; Q9H305: CDIP1; NbExp=3; IntAct=EBI-740086, EBI-2876678;
CC Q96GG9; Q15038: DAZAP2; NbExp=9; IntAct=EBI-740086, EBI-724310;
CC Q96GG9; Q92567-2: FAM168A; NbExp=5; IntAct=EBI-740086, EBI-11978259;
CC Q96GG9; Q96IJ6: GMPPA; NbExp=3; IntAct=EBI-740086, EBI-750953;
CC Q96GG9; Q9BRK4: LZTS2; NbExp=6; IntAct=EBI-740086, EBI-741037;
CC Q96GG9; Q96CS7: PLEKHB2; NbExp=5; IntAct=EBI-740086, EBI-373552;
CC Q96GG9; Q92537: SUSD6; NbExp=3; IntAct=EBI-740086, EBI-2866213;
CC Q96GG9; Q8WW34-2: TMEM239; NbExp=3; IntAct=EBI-740086, EBI-11528917;
CC Q96GG9; Q13625-3: TP53BP2; NbExp=3; IntAct=EBI-740086, EBI-10175039;
CC Q96GG9; Q9HCM9: TRIM39; NbExp=4; IntAct=EBI-740086, EBI-739510;
CC Q96GG9; Q9HCM9-2: TRIM39; NbExp=7; IntAct=EBI-740086, EBI-11523450;
CC Q96GG9; Q9BYV2: TRIM54; NbExp=3; IntAct=EBI-740086, EBI-2130429;
CC Q96GG9; Q9BZR9: TRIM8; NbExp=3; IntAct=EBI-740086, EBI-2340370;
CC Q96GG9; P61081: UBE2M; NbExp=4; IntAct=EBI-740086, EBI-1041660;
CC Q96GG9; Q9H9H4: VPS37B; NbExp=3; IntAct=EBI-740086, EBI-4400866;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:25349211,
CC ECO:0000269|PubMed:26906416}. Cytoplasm {ECO:0000269|PubMed:26906416}.
CC Note=The ubiquitinated form is localized in the cytoplasm.
CC {ECO:0000269|PubMed:30587576}.
CC -!- TISSUE SPECIFICITY: Expressed in pancreas, kidney, placenta, brain and
CC heart. Weakly or not expressed in liver, skeletal muscle and lung.
CC Strongly overexpressed in thyroid tumors, bronchioloalveolar
CC carcinomas, and malignant tissues of squamous cell carcinoma of the
CC oral tongue. Not overexpressed in aggressive adrenocortical carcinomas.
CC {ECO:0000269|PubMed:10777668}.
CC -!- DOMAIN: The DCUN1 domain, also known as PONY domain, mediates the
CC interaction with different cullins (PubMed:23201271, PubMed:19617556).
CC The DCUN1 domain mediates the interaction with the N-terminally
CC acetylated NEDD8-conjugating E2s enzyme leading to the NEDD8 transfer
CC from N-terminally acetylated NEDD8-conjugating E2s enzyme to different
CC cullin C-terminal domain-RBX complexes; the neddylation efficiency
CC correlates with the DCUN1D1-cullin and DCUN1D1-E2 interaction
CC affinities (PubMed:23201271, PubMed:28581483). The UBA-like domain
CC mediates interaction with autoubiquitylated ARIH2 leading to ubiquitin
CC ligation to DCUN1D1 (PubMed:30587576). {ECO:0000269|PubMed:19617556,
CC ECO:0000269|PubMed:23201271, ECO:0000269|PubMed:28581483,
CC ECO:0000269|PubMed:30587576}.
CC -!- PTM: Mono- and poly-ubiquitinated by ARIH2 and ARIH1.
CC Monoubiquitination by ARIH2 is mediated by an interaction between
CC autoubiquitinated ARIH2 and the UBA-like domain. The monoubiquitinated
CC form preferentially interacts with non-neddylated cullins and modulates
CC cullin RING ligase (CRL) complex composition and activity.
CC {ECO:0000269|PubMed:30587576}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB15235.1; Type=Erroneous initiation; Note=Truncated N-terminus.; 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; AF292100; AAG00606.2; -; mRNA.
DR EMBL; AF456425; AAL78672.1; -; mRNA.
DR EMBL; AF456426; AAL78673.1; -; mRNA.
DR EMBL; AK025764; BAB15235.1; ALT_INIT; mRNA.
DR EMBL; AK056335; BAG51680.1; -; mRNA.
DR EMBL; AK314480; BAG37084.1; -; mRNA.
DR EMBL; CH471052; EAW78342.1; -; Genomic_DNA.
DR EMBL; BC009478; AAH09478.1; -; mRNA.
DR EMBL; BC013163; AAH13163.2; -; mRNA.
DR CCDS; CCDS3240.1; -.
DR RefSeq; NP_001295030.1; NM_001308101.1.
DR RefSeq; NP_065691.2; NM_020640.3.
DR PDB; 3TDU; X-ray; 1.50 A; A/B=62-259.
DR PDB; 3TDZ; X-ray; 2.00 A; A/B=62-259.
DR PDB; 4P5O; X-ray; 3.11 A; E/F=62-259.
DR PDB; 5UFI; X-ray; 2.58 A; A/B/C/D=58-259.
DR PDB; 5V83; X-ray; 2.00 A; A=62-259.
DR PDB; 5V86; X-ray; 1.37 A; A=62-259.
DR PDB; 5V88; X-ray; 1.60 A; A=62-259.
DR PDB; 6B5Q; X-ray; 2.16 A; A/B=58-259.
DR PDB; 6BG3; X-ray; 1.05 A; A=62-259.
DR PDB; 6BG5; X-ray; 1.10 A; A=62-259.
DR PDB; 6P5V; X-ray; 1.40 A; A=62-259.
DR PDB; 6P5W; X-ray; 1.69 A; A=62-259.
DR PDB; 6XOL; X-ray; 2.39 A; A=62-259.
DR PDB; 6XOM; X-ray; 2.10 A; A=62-259.
DR PDB; 6XON; X-ray; 2.80 A; A=62-259.
DR PDB; 6XOO; X-ray; 2.06 A; A=62-259.
DR PDB; 6XOP; X-ray; 2.07 A; A=62-259.
DR PDB; 6XOQ; X-ray; 2.07 A; A=62-259.
DR PDB; 7KWA; X-ray; 1.57 A; A=62-259.
DR PDBsum; 3TDU; -.
DR PDBsum; 3TDZ; -.
DR PDBsum; 4P5O; -.
DR PDBsum; 5UFI; -.
DR PDBsum; 5V83; -.
DR PDBsum; 5V86; -.
DR PDBsum; 5V88; -.
DR PDBsum; 6B5Q; -.
DR PDBsum; 6BG3; -.
DR PDBsum; 6BG5; -.
DR PDBsum; 6P5V; -.
DR PDBsum; 6P5W; -.
DR PDBsum; 6XOL; -.
DR PDBsum; 6XOM; -.
DR PDBsum; 6XON; -.
DR PDBsum; 6XOO; -.
DR PDBsum; 6XOP; -.
DR PDBsum; 6XOQ; -.
DR PDBsum; 7KWA; -.
DR AlphaFoldDB; Q96GG9; -.
DR SMR; Q96GG9; -.
DR BioGRID; 119920; 257.
DR DIP; DIP-42121N; -.
DR ELM; Q96GG9; -.
DR IntAct; Q96GG9; 220.
DR MINT; Q96GG9; -.
DR STRING; 9606.ENSP00000292782; -.
DR BindingDB; Q96GG9; -.
DR ChEMBL; CHEMBL4105838; -.
DR GlyGen; Q96GG9; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q96GG9; -.
DR MetOSite; Q96GG9; -.
DR PhosphoSitePlus; Q96GG9; -.
DR BioMuta; DCUN1D1; -.
DR DMDM; 73919222; -.
DR EPD; Q96GG9; -.
DR jPOST; Q96GG9; -.
DR MassIVE; Q96GG9; -.
DR MaxQB; Q96GG9; -.
DR PaxDb; Q96GG9; -.
DR PeptideAtlas; Q96GG9; -.
DR PRIDE; Q96GG9; -.
DR ProteomicsDB; 76634; -.
DR Antibodypedia; 18885; 273 antibodies from 32 providers.
DR DNASU; 54165; -.
DR Ensembl; ENST00000292782.9; ENSP00000292782.4; ENSG00000043093.15.
DR GeneID; 54165; -.
DR KEGG; hsa:54165; -.
DR MANE-Select; ENST00000292782.9; ENSP00000292782.4; NM_020640.4; NP_065691.2.
DR UCSC; uc003fld.2; human.
DR CTD; 54165; -.
DR DisGeNET; 54165; -.
DR GeneCards; DCUN1D1; -.
DR HGNC; HGNC:18184; DCUN1D1.
DR HPA; ENSG00000043093; Tissue enriched (testis).
DR MIM; 605905; gene.
DR neXtProt; NX_Q96GG9; -.
DR OpenTargets; ENSG00000043093; -.
DR PharmGKB; PA142672008; -.
DR VEuPathDB; HostDB:ENSG00000043093; -.
DR eggNOG; KOG3077; Eukaryota.
DR GeneTree; ENSGT00940000154552; -.
DR HOGENOM; CLU_047042_0_1_1; -.
DR InParanoid; Q96GG9; -.
DR OMA; FTQTGEQ; -.
DR OrthoDB; 1418097at2759; -.
DR PhylomeDB; Q96GG9; -.
DR TreeFam; TF313332; -.
DR BioCyc; MetaCyc:ENSG00000043093-MON; -.
DR PathwayCommons; Q96GG9; -.
DR Reactome; R-HSA-8951664; Neddylation.
DR SignaLink; Q96GG9; -.
DR BioGRID-ORCS; 54165; 43 hits in 1045 CRISPR screens.
DR ChiTaRS; DCUN1D1; human.
DR GeneWiki; DCUN1D1; -.
DR GenomeRNAi; 54165; -.
DR Pharos; Q96GG9; Tchem.
DR PRO; PR:Q96GG9; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q96GG9; protein.
DR Bgee; ENSG00000043093; Expressed in left testis and 197 other tissues.
DR ExpressionAtlas; Q96GG9; baseline and differential.
DR Genevisible; Q96GG9; HS.
DR GO; GO:0005737; C:cytoplasm; IMP:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IMP:UniProtKB.
DR GO; GO:0000151; C:ubiquitin ligase complex; IDA:UniProtKB.
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:0051443; P:positive regulation of ubiquitin-protein transferase activity; IBA:GO_Central.
DR GO; GO:0045116; P:protein neddylation; IBA:GO_Central.
DR GO; GO:2000434; P:regulation of protein neddylation; IMP:UniProtKB.
DR GO; GO:0031396; P:regulation of protein ubiquitination; IMP:UniProtKB.
DR Gene3D; 1.10.238.200; -; 1.
DR InterPro; IPR014764; DCN-prot.
DR InterPro; IPR042460; DCN1-like_PONY.
DR InterPro; IPR005176; PONY_dom.
DR InterPro; IPR009060; UBA-like_sf.
DR PANTHER; PTHR12281; PTHR12281; 1.
DR Pfam; PF03556; Cullin_binding; 1.
DR SUPFAM; SSF46934; SSF46934; 1.
DR PROSITE; PS51229; DCUN1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Nucleus; Proto-oncogene;
KW Reference proteome; Ubl conjugation; Ubl conjugation pathway.
FT CHAIN 1..259
FT /note="DCN1-like protein 1"
FT /id="PRO_0000129498"
FT DOMAIN 8..45
FT /note="UBA-like"
FT DOMAIN 60..248
FT /note="DCUN1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00574"
FT SITE 115
FT /note="Essential for interaction with UBE2M"
FT /evidence="ECO:0000269|PubMed:28581483"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MUTAGEN 15
FT /note="F->A: Loss of ubiquitin binding; when associated
FT with A-16, A-44 and A-45."
FT /evidence="ECO:0000269|PubMed:30587576"
FT MUTAGEN 16
FT /note="M->A: Loss of ubiquitin binding; when associated
FT with A-15, A-44 and A-45."
FT /evidence="ECO:0000269|PubMed:30587576"
FT MUTAGEN 44
FT /note="F->A: Loss of ubiquitin binding; when associated
FT with A-15, A-16 and A-45."
FT /evidence="ECO:0000269|PubMed:30587576"
FT MUTAGEN 45
FT /note="F->A: Loss of ubiquitin binding; when associated
FT with A-15, A-16 and A-44."
FT /evidence="ECO:0000269|PubMed:30587576"
FT MUTAGEN 115
FT /note="C->A,G,I,L,T,V: Loss of ability to stimulate cullin
FT neddylation."
FT /evidence="ECO:0000269|PubMed:28581483"
FT MUTAGEN 211
FT /note="D->A: Loss of interaction with CUL1, CUL2, CUL3,
FT CULA4, CULA5 CAND1 and RBX1; when associated with R-235 and
FT A-241. Does not affect both nucleus and cytoplasm
FT localization; when associated with R-235 and A-241. Reduces
FT cullin neddylation; when associated with R-235 and A-241.
FT Loss of interaction with CUL1, CUL2, CUL3, CULA4 and CULA4;
FT when associated with R-235 and A-241. Loss of CUL2
FT interaction; when associated with R-235 and A-241. Reduces
FT neddylation on CUL2; when associated with R-235 and A-241.
FT Reduces interaction with VHL and HIF1A; when associated
FT with R-235 and A-241. Does not affect interaction with
FT SOCS1; when associated with R-235 and A-241. Does not
FT affect DCUN1D1 monoubiquitylation; when associated with R-
FT 235 and A-241."
FT /evidence="ECO:0000269|PubMed:23401859,
FT ECO:0000269|PubMed:26906416, ECO:0000269|PubMed:30587576"
FT MUTAGEN 235
FT /note="A->R: Loss of interaction with CUL1, CUL2, CUL3,
FT CULA4, CULA5 CAND1 and RBX1; when associated with A-211 and
FT A-241.Does not affect both nucleus and cytoplasm
FT localization; when associated with A-211 and A-241. Reduces
FT cullin neddylation; when associated with A-211 and A-241.
FT Loss of interaction with CUL1, CUL2, CUL3, CULA4 and CULA4;
FT when associated with A-211 and A-241. Loss of CUL2
FT interaction; when associated with A-211 and A-241. Reduces
FT neddylation on CUL2; when associated with A-211 and A-241.
FT Reduces interaction with VHL and HIF1A; when associated
FT with A-211 and A-241. Does not affect interaction with
FT SOCS1; when associated with A-211 and A-241. Does not
FT affect DCUN1D1 monoubiquitylation; when associated with A-
FT 211 and A-241."
FT /evidence="ECO:0000269|PubMed:23401859,
FT ECO:0000269|PubMed:26906416, ECO:0000269|PubMed:30587576"
FT MUTAGEN 241
FT /note="D->A: Loss of interaction with CUL1, CUL2, CUL3,
FT CULA4, CULA5 CAND1 and RBX1; when associated with A-211 and
FT R-235.Does not affect both nucleus and cytoplasm
FT localization; when associated withA-211 and R-235. Reduces
FT cullin neddylation; when associated with A-211 and R-235.
FT Loss of interaction with CUL1, CUL2, CUL3, CULA4 and CULA4;
FT when associated with A-211 and R-235. Loss of CUL2
FT interaction; when associated with A-211 and R-235. Reduces
FT neddylation on CUL2; when associated with A-211 and R-235.
FT Reduces interaction with VHL and HIF1A; when associated
FT with A-211 and R-235. Does not affect interaction with
FT SOCS1; when associated with A-211 and R-235. Does not
FT affect DCUN1D1 monoubiquitylation; when associated with A-
FT 211 and R-235."
FT /evidence="ECO:0000269|PubMed:23401859,
FT ECO:0000269|PubMed:26906416, ECO:0000269|PubMed:30587576"
FT MUTAGEN 241
FT /note="D->N: Loss of binding to CAND1 and CUL-RBX1 complex
FT but retains binding to UBE2M."
FT /evidence="ECO:0000269|PubMed:18826954"
FT CONFLICT 134
FT /note="I -> T (in Ref. 2; AAL78673)"
FT /evidence="ECO:0000305"
FT CONFLICT 136
FT /note="K -> Q (in Ref. 1; AAG00606)"
FT /evidence="ECO:0000305"
FT CONFLICT 191..192
FT /note="KF -> RL (in Ref. 2; AAL78673)"
FT /evidence="ECO:0000305"
FT HELIX 62..72
FT /evidence="ECO:0007829|PDB:6BG3"
FT STRAND 77..81
FT /evidence="ECO:0007829|PDB:6BG3"
FT HELIX 83..92
FT /evidence="ECO:0007829|PDB:6BG3"
FT HELIX 100..108
FT /evidence="ECO:0007829|PDB:6BG3"
FT STRAND 116..118
FT /evidence="ECO:0007829|PDB:4P5O"
FT HELIX 119..128
FT /evidence="ECO:0007829|PDB:6BG3"
FT HELIX 134..147
FT /evidence="ECO:0007829|PDB:6BG3"
FT STRAND 148..151
FT /evidence="ECO:0007829|PDB:4P5O"
FT HELIX 153..165
FT /evidence="ECO:0007829|PDB:6BG3"
FT STRAND 171..174
FT /evidence="ECO:0007829|PDB:6BG3"
FT HELIX 175..186
FT /evidence="ECO:0007829|PDB:6BG3"
FT TURN 187..189
FT /evidence="ECO:0007829|PDB:6BG3"
FT HELIX 193..202
FT /evidence="ECO:0007829|PDB:6BG3"
FT HELIX 210..222
FT /evidence="ECO:0007829|PDB:6BG3"
FT STRAND 234..236
FT /evidence="ECO:0007829|PDB:6XOM"
FT HELIX 238..247
FT /evidence="ECO:0007829|PDB:6BG3"
FT HELIX 248..255
FT /evidence="ECO:0007829|PDB:6P5V"
SQ SEQUENCE 259 AA; 30124 MW; F3709235E0610C54 CRC64;
MNKLKSSQKD KVRQFMIFTQ SSEKTAVSCL SQNDWKLDVA TDNFFQNPEL YIRESVKGSL
DRKKLEQLYN RYKDPQDENK IGIDGIQQFC DDLALDPASI SVLIIAWKFR AATQCEFSKQ
EFMDGMTELG CDSIEKLKAQ IPKMEQELKE PGRFKDFYQF TFNFAKNPGQ KGLDLEMAIA
YWNLVLNGRF KFLDLWNKFL LEHHKRSIPK DTWNLLLDFS TMIADDMSNY DEEGAWPVLI
DDFVEFARPQ IAGTKSTTV
