DCNL2_HUMAN
ID DCNL2_HUMAN Reviewed; 259 AA.
AC Q6PH85; Q5JSA5; Q5JSA6; Q5JSA7; Q9NVJ1; Q9NXR6;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=DCN1-like protein 2 {ECO:0000305};
DE Short=DCNL2 {ECO:0000303|PubMed:23201271};
DE AltName: Full=DCUN1 domain-containing protein 2;
DE AltName: Full=Defective in cullin neddylation protein 1-like protein 2;
GN Name=DCUN1D2 {ECO:0000312|HGNC:HGNC:20328}; Synonyms=C13orf17, DCUN1L2;
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 2).
RC TISSUE=Colon, and Teratocarcinoma;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 INTERACTION WITH CUL1; CUL2; CUL3; CUL4A; CUL4B; CUL5 AND UBE2M, AND
RP 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 [5]
RP INTERACTION WITH CUL1; CUL2; CUL3; CUL4A; CUL4B; CUL5; CAND1; RBX1; RNF7;
RP ELOB AND DDB1, SUBCELLULAR LOCATION, FUNCTION, MUTAGENESIS OF ASP-211;
RP ALA-235 AND ASP-241, AND TISSUE SPECIFICITY.
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 [6]
RP X-RAY CRYSTALLOGRAPHY (3.28 ANGSTROMS) OF 62-259 IN COMPLEX WITH UBC12
RP PEPTIDE, FUNCTION, DOMAIN, AND INTERACTION WITH CUL1; CUL2; CUL3; CUL4A;
RP CUL4B; CUL5; UBE2M AND UBE2F.
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).
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 and plays an essential
CC role in the regulation of SCF (SKP1-CUL1-F-box protein)-type complexes
CC activity. {ECO:0000269|PubMed:19617556, ECO:0000269|PubMed:23201271,
CC 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, PubMed:19617556). May also interact with regulators or
CC subunits of cullin-RING ligases such as RBX1, RNF7, ELOB and DDB1;
CC these interactions are bridged by cullins (PubMed:26906416). Interacts
CC with CAND1; this interaction is bridged by cullins such as CUL3 and
CC strongly inhibits the neddylation of CUL3. These CAND-cullin-DCNL
CC complexes can only be neddylated in the presence of a substrate adapter
CC (PubMed:26906416). Interacts (via DCUN1 domain) with the N-terminally
CC acetylated form of UBE2M and UBE2F (PubMed:23201271, PubMed:19617556).
CC {ECO:0000269|PubMed:19617556, ECO:0000269|PubMed:23201271,
CC ECO:0000269|PubMed:26906416}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:26906416}. Nucleus
CC {ECO:0000269|PubMed:26906416}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6PH85-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6PH85-2; Sequence=VSP_015315, VSP_015316;
CC -!- TISSUE SPECIFICITY: Mostly expressed in liver, kidney and brain.
CC {ECO:0000269|PubMed:26906416}.
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=BAA90944.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK000099; BAA90944.1; ALT_INIT; mRNA.
DR EMBL; AK001566; BAA91760.1; -; mRNA.
DR EMBL; AL160251; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL442125; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC056669; AAH56669.1; -; mRNA.
DR CCDS; CCDS32013.1; -. [Q6PH85-1]
DR RefSeq; NP_001014305.1; NM_001014283.1. [Q6PH85-1]
DR PDB; 4GAO; X-ray; 3.28 A; A/B/D/G=62-259.
DR PDBsum; 4GAO; -.
DR AlphaFoldDB; Q6PH85; -.
DR SMR; Q6PH85; -.
DR BioGRID; 120504; 33.
DR DIP; DIP-60768N; -.
DR ELM; Q6PH85; -.
DR IntAct; Q6PH85; 12.
DR STRING; 9606.ENSP00000417706; -.
DR BindingDB; Q6PH85; -.
DR ChEMBL; CHEMBL4295866; -.
DR iPTMnet; Q6PH85; -.
DR PhosphoSitePlus; Q6PH85; -.
DR BioMuta; DCUN1D2; -.
DR DMDM; 73919224; -.
DR EPD; Q6PH85; -.
DR jPOST; Q6PH85; -.
DR MassIVE; Q6PH85; -.
DR MaxQB; Q6PH85; -.
DR PaxDb; Q6PH85; -.
DR PeptideAtlas; Q6PH85; -.
DR PRIDE; Q6PH85; -.
DR ProteomicsDB; 67123; -. [Q6PH85-1]
DR ProteomicsDB; 67124; -. [Q6PH85-2]
DR Antibodypedia; 48901; 98 antibodies from 15 providers.
DR DNASU; 55208; -.
DR Ensembl; ENST00000375403.6; ENSP00000364552.2; ENSG00000150401.15. [Q6PH85-2]
DR Ensembl; ENST00000478244.6; ENSP00000417706.1; ENSG00000150401.15. [Q6PH85-1]
DR GeneID; 55208; -.
DR KEGG; hsa:55208; -.
DR MANE-Select; ENST00000478244.6; ENSP00000417706.1; NM_001014283.2; NP_001014305.1.
DR UCSC; uc001vtr.2; human. [Q6PH85-1]
DR CTD; 55208; -.
DR DisGeNET; 55208; -.
DR GeneCards; DCUN1D2; -.
DR HGNC; HGNC:20328; DCUN1D2.
DR HPA; ENSG00000150401; Tissue enhanced (heart muscle, skeletal muscle, tongue).
DR neXtProt; NX_Q6PH85; -.
DR OpenTargets; ENSG00000150401; -.
DR PharmGKB; PA134941036; -.
DR VEuPathDB; HostDB:ENSG00000150401; -.
DR eggNOG; KOG3077; Eukaryota.
DR GeneTree; ENSGT00940000157453; -.
DR HOGENOM; CLU_047042_0_2_1; -.
DR InParanoid; Q6PH85; -.
DR OMA; NEDQAWP; -.
DR OrthoDB; 1418097at2759; -.
DR PhylomeDB; Q6PH85; -.
DR TreeFam; TF313332; -.
DR PathwayCommons; Q6PH85; -.
DR Reactome; R-HSA-8951664; Neddylation.
DR SignaLink; Q6PH85; -.
DR BioGRID-ORCS; 55208; 8 hits in 1076 CRISPR screens.
DR ChiTaRS; DCUN1D2; human.
DR GenomeRNAi; 55208; -.
DR Pharos; Q6PH85; Tchem.
DR PRO; PR:Q6PH85; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; Q6PH85; protein.
DR Bgee; ENSG00000150401; Expressed in apex of heart and 186 other tissues.
DR ExpressionAtlas; Q6PH85; baseline and differential.
DR Genevisible; Q6PH85; HS.
DR GO; GO:0005737; C:cytoplasm; IMP:UniProtKB.
DR GO; GO:0005634; C:nucleus; IMP:UniProtKB.
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: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 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; Alternative splicing; Cytoplasm; Nucleus; Phosphoprotein;
KW Reference proteome; Ubl conjugation pathway.
FT CHAIN 1..259
FT /note="DCN1-like protein 2"
FT /id="PRO_0000129501"
FT DOMAIN 8..45
FT /note="UBA-like"
FT DOMAIN 60..248
FT /note="DCUN1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00574"
FT MOD_RES 55
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8BZJ7"
FT VAR_SEQ 174..186
FT /note="DLEMAVAYWKLVL -> GSPPFLNVKALHH (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_015315"
FT VAR_SEQ 187..259
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_015316"
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."
FT /evidence="ECO:0000269|PubMed:26906416"
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."
FT /evidence="ECO:0000269|PubMed:26906416"
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 with A-211 and R-235."
FT /evidence="ECO:0000269|PubMed:26906416"
FT HELIX 62..70
FT /evidence="ECO:0007829|PDB:4GAO"
FT STRAND 77..81
FT /evidence="ECO:0007829|PDB:4GAO"
FT HELIX 83..92
FT /evidence="ECO:0007829|PDB:4GAO"
FT HELIX 100..109
FT /evidence="ECO:0007829|PDB:4GAO"
FT HELIX 119..128
FT /evidence="ECO:0007829|PDB:4GAO"
FT HELIX 134..146
FT /evidence="ECO:0007829|PDB:4GAO"
FT HELIX 147..149
FT /evidence="ECO:0007829|PDB:4GAO"
FT HELIX 151..165
FT /evidence="ECO:0007829|PDB:4GAO"
FT STRAND 171..174
FT /evidence="ECO:0007829|PDB:4GAO"
FT HELIX 175..185
FT /evidence="ECO:0007829|PDB:4GAO"
FT TURN 187..189
FT /evidence="ECO:0007829|PDB:4GAO"
FT HELIX 193..202
FT /evidence="ECO:0007829|PDB:4GAO"
FT HELIX 210..222
FT /evidence="ECO:0007829|PDB:4GAO"
FT HELIX 238..247
FT /evidence="ECO:0007829|PDB:4GAO"
FT HELIX 249..251
FT /evidence="ECO:0007829|PDB:4GAO"
SQ SEQUENCE 259 AA; 30179 MW; B12A33F80D419A28 CRC64;
MHKLKSSQKD KVRQFMACTQ AGERTAIYCL TQNEWRLDEA TDSFFQNPDS LHRESMRNAV
DKKKLERLYG RYKDPQDENK IGVDGIQQFC DDLSLDPASI SVLVIAWKFR AATQCEFSRK
EFLDGMTELG CDSMEKLKAL LPRLEQELKD TAKFKDFYQF TFTFAKNPGQ KGLDLEMAVA
YWKLVLSGRF KFLDLWNTFL MEHHKRSIPR DTWNLLLDFG NMIADDMSNY DEEGAWPVLI
DDFVEYARPV VTGGKRSLF
