DCNL5_MOUSE
ID DCNL5_MOUSE Reviewed; 237 AA.
AC Q9CXV9; Q5XKI2; Q9CUS4;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=DCN1-like protein 5 {ECO:0000305};
DE Short=DCNL5 {ECO:0000303|PubMed:29958295};
DE AltName: Full=DCUN1 domain-containing protein 5;
DE AltName: Full=Defective in cullin neddylation protein 1-like protein 5;
DE AltName: Full=Squamous cell carcinoma-related oncogene 5 {ECO:0000250|UniProtKB:Q9BTE7};
GN Name=Dcun1d5 {ECO:0000312|MGI:MGI:1924113};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryonic head, Head, and Olfactory bulb;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II, and FVB/N; TISSUE=Mammary tumor;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP 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 [5]
RP PHOSPHORYLATION AT SER-41, IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF SER-41; ASP-195 AND ALA-219.
RX PubMed=29958295; DOI=10.1371/journal.pone.0199197;
RA Thomas Y., Scott D.C., Kristariyanto Y.A., Rinehart J., Clark K., Cohen P.,
RA Kurz T.;
RT "The NEDD8 E3 ligase DCNL5 is phosphorylated by IKK alpha during Toll-like
RT receptor activation.";
RL PLoS ONE 13:e0199197-e0199197(2018).
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 is necessary for
CC the activation of cullin-RING E3 ubiquitin ligases (CRLs). May play a
CC role in DNA damage response and may participate in cell proliferation
CC and anchorage-independent cell growth. {ECO:0000250|UniProtKB:Q9BTE7}.
CC -!- SUBUNIT: Part of a complex that contains DCUN1D5, CUL1 and RBX1; this
CC interaction is bridged by CUL1. Interacts (via the DCUN1 domain) with
CC the unneddylated cullins: interacts with CUL1, CUL2, CUL3, CUL4A, CUL4B
CC and CUL5; these interactions promote the cullin neddylation and the
CC identity of the cullin dictates the affinity of the interaction.
CC Interacts (via DCUN1 domain) with UBE2M (N-terminally acetylated form)
CC and probably with UBE2F (N-terminally acetylated form). May also
CC interact with regulators or subunits of cullin-RING ligases such as
CC RBX1, RNF7, ELOB and DDB1; these interactions are bridged by cullins.
CC Interacts with CAND1; this interaction is bridged by cullins and
CC strongly inhibits the neddylation of cullins. These CAND-cullin-DCNL
CC complexes can only be neddylated in the presence of a substrate
CC adapter. {ECO:0000250|UniProtKB:Q9BTE7}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:29958295}. Cytoplasm,
CC cytoskeleton, spindle {ECO:0000250|UniProtKB:Q9BTE7}. Note=Subcellular
CC localization is independent of the interaction with cullins.
CC {ECO:0000250|UniProtKB:Q9BTE7}.
CC -!- TISSUE SPECIFICITY: Highly expressed in testis (PubMed:26906416). Lower
CC expressed in skin, thymus, spleen, lymph nodes and lung
CC (PubMed:26906416). {ECO:0000269|PubMed:26906416}.
CC -!- DOMAIN: The DCUN1 domain, also known as PONY domain, mediates the
CC interaction with different cullins. The DCUN1 domain mediates the
CC interaction with the N-terminally acetylated NEDD8-conjugating E2s
CC enzyme leading to the NEDD8 transfer from N-terminally acetylated
CC NEDD8-conjugating E2s enzyme to different cullin C-terminal domain-RBX
CC complexes; the neddylation efficiency correlates with the DCUN1D5-
CC cullin and DCUN1D5-E2 interaction affinities.
CC {ECO:0000250|UniProtKB:Q9BTE7}.
CC -!- PTM: Phosphorylation at Ser-41 is independent of cullin's interaction
CC and neddylation (PubMed:29958295). Phosphorylated in response to both
CC TICAM1 and MYD88 dependent Toll-like receptor (TLR) pathway activation
CC (PubMed:29958295). Phosphorylated in response to IL1B stimulation (By
CC similarity). {ECO:0000250|UniProtKB:Q9BTE7,
CC ECO:0000269|PubMed:29958295}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BC020048; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK013933; BAB29066.1; -; mRNA.
DR EMBL; AK014737; BAB29526.2; -; mRNA.
DR EMBL; AK134862; BAE22318.1; -; mRNA.
DR EMBL; BC020048; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC020089; AAH20089.1; -; mRNA.
DR CCDS; CCDS40529.1; -.
DR RefSeq; NP_084051.1; NM_029775.2.
DR AlphaFoldDB; Q9CXV9; -.
DR SMR; Q9CXV9; -.
DR BioGRID; 218359; 1.
DR IntAct; Q9CXV9; 1.
DR MINT; Q9CXV9; -.
DR STRING; 10090.ENSMUSP00000034499; -.
DR iPTMnet; Q9CXV9; -.
DR PhosphoSitePlus; Q9CXV9; -.
DR EPD; Q9CXV9; -.
DR MaxQB; Q9CXV9; -.
DR PaxDb; Q9CXV9; -.
DR PeptideAtlas; Q9CXV9; -.
DR PRIDE; Q9CXV9; -.
DR ProteomicsDB; 279886; -.
DR Antibodypedia; 45452; 31 antibodies from 17 providers.
DR DNASU; 76863; -.
DR Ensembl; ENSMUST00000215683; ENSMUSP00000150564; ENSMUSG00000032002.
DR GeneID; 76863; -.
DR KEGG; mmu:76863; -.
DR UCSC; uc009ocf.1; mouse.
DR CTD; 84259; -.
DR MGI; MGI:1924113; Dcun1d5.
DR VEuPathDB; HostDB:ENSMUSG00000032002; -.
DR eggNOG; KOG3077; Eukaryota.
DR GeneTree; ENSGT00940000156155; -.
DR HOGENOM; CLU_047042_3_1_1; -.
DR InParanoid; Q9CXV9; -.
DR OMA; HERKCKI; -.
DR OrthoDB; 1418097at2759; -.
DR PhylomeDB; Q9CXV9; -.
DR TreeFam; TF354270; -.
DR Reactome; R-MMU-8951664; Neddylation.
DR BioGRID-ORCS; 76863; 4 hits in 75 CRISPR screens.
DR ChiTaRS; Dcun1d5; mouse.
DR PRO; PR:Q9CXV9; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q9CXV9; protein.
DR Bgee; ENSMUSG00000032002; Expressed in animal zygote and 284 other tissues.
DR ExpressionAtlas; Q9CXV9; baseline and differential.
DR Genevisible; Q9CXV9; MM.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005819; C:spindle; ISS:UniProtKB.
DR GO; GO:0000151; C:ubiquitin ligase complex; IBA:GO_Central.
DR GO; GO:0097602; F:cullin family protein binding; ISS: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:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:2000436; P:positive regulation of protein neddylation; ISS: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:0001558; P:regulation of cell growth; ISS:UniProtKB.
DR GO; GO:2000434; P:regulation of protein neddylation; ISS: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 PANTHER; PTHR12281; PTHR12281; 1.
DR Pfam; PF03556; Cullin_binding; 1.
DR PROSITE; PS51229; DCUN1; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Cytoskeleton; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..237
FT /note="DCN1-like protein 5"
FT /id="PRO_0000254172"
FT DOMAIN 46..232
FT /note="DCUN1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00574"
FT MOD_RES 41
FT /note="Phosphoserine; by IKKA"
FT /evidence="ECO:0000269|PubMed:29958295"
FT MUTAGEN 41
FT /note="S->A: Abolishes phosphoralation."
FT /evidence="ECO:0000269|PubMed:29958295"
FT MUTAGEN 195
FT /note="D->A: Does not affect phosphorylarion at Ser-41;
FT when associated with R-219."
FT /evidence="ECO:0000269|PubMed:29958295"
FT MUTAGEN 219
FT /note="A->R: Does not affect phosphorylarion at Ser-41;
FT when associated with A-195."
FT /evidence="ECO:0000269|PubMed:29958295"
FT CONFLICT 143
FT /note="R -> T (in Ref. 2; BC020048)"
FT /evidence="ECO:0000305"
FT CONFLICT 148
FT /note="F -> I (in Ref. 1; BAB29526)"
FT /evidence="ECO:0000305"
FT CONFLICT 171
FT /note="G -> A (in Ref. 1; BAB29526)"
FT /evidence="ECO:0000305"
FT CONFLICT 218
FT /note="G -> V (in Ref. 1; BAB29526)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 237 AA; 27579 MW; A3247168F317C794 CRC64;
MPVKKKRKAP GVAAAVAEDA GLKKCKIPSY CRSQPPARLI SGEEDFSRKK CLAWFYEYAG
PDEVVGPEGM EKFCEDIGVE PENIIMLVLA WKLEAESMGF FTKEEWLKGM TSLQCDCTEK
LQSRFDFLRS QLNDISSFKN IYRYAFDFAR DKDQRSLDID TAKSMLALLL GRTWPLFSVF
YQYLEQSKYR VMNKDQWYNV LEFSRTVHAD LSNYDEDGAW PVLLDEFVEW QKIRQTS
