DCNL1_MOUSE
ID DCNL1_MOUSE Reviewed; 259 AA.
AC Q9QZ73; Q3TMX2; Q8CDZ7;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=DCN1-like protein 1 {ECO:0000305};
DE Short=DCNL1 {ECO:0000250|UniProtKB:Q96GG9};
DE AltName: Full=DCUN1 domain-containing protein 1;
DE AltName: Full=Defective in cullin neddylation protein 1-like protein 1;
DE AltName: Full=Testis-specific protein 3;
GN Name=Dcun1d1 {ECO:0000312|MGI:MGI:2150386}; Synonyms=Dcun1l1, Rp42, Tes3;
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 [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=10831844; DOI=10.1016/s0378-1119(00)00158-x;
RA Pourcel C., Jaubert J., Hadchouel M., Wu X., Schweizer J.;
RT "A new family of genes and pseudogenes potentially expressing testis-
RT specific and brain-specific leucine-zipper proteins in man and mouse.";
RL Gene 249:105-113(2000).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Colon, Head, and Stomach;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II; 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 [5]
RP DEVELOPMENTAL STAGE, AND FUNCTION.
RX PubMed=20563250; DOI=10.1593/neo.10202;
RA Broderick S.R., Golas B.J., Pham D., Towe C.W., Talbot S.G., Kaufman A.,
RA Bains S., Huryn L.A., Yonekawa Y., Carlson D., Hambardzumyan D.,
RA Ramanathan Y., Singh B.;
RT "SCCRO promotes glioma formation and malignant progression in mice.";
RL Neoplasia 12:476-484(2010).
CC -!- FUNCTION: Part of an E3 ubiquitin ligase complex for neddylation.
CC Promotes neddylation of cullin components of E3 cullin-RING ubiquitin
CC ligase complexes (By similarity). Acts by binding to cullin-RBX1
CC complexes in the cytoplasm and promoting their nuclear translocation,
CC enhancing recruitment of E2-NEDD8 (UBE2M-NEDD8) thioester to the
CC complex, and optimizing the orientation of proteins in the complex to
CC allow efficient transfer of NEDD8 from the E2 to the cullin substrates.
CC Involved in the release of inhibitory effets of CAND1 on cullin-RING
CC ligase E3 complex assembly and activity (By similarity). Acts also as
CC an oncogene facilitating malignant transformation and carcinogenic
CC progression (PubMed:20563250). {ECO:0000250|UniProtKB:Q96GG9,
CC ECO:0000269|PubMed:20563250}.
CC -!- SUBUNIT: Part of an E3 complex for neddylation composed of cullins,
CC RBX1, UBE2M and CAND1. Interacts (via the DCUN1 domain) with the
CC unneddylated cullins: interacts with CUL1, CUL2, CUL3, CUL4A, CUL4B and
CC CUL5; these interactions promote the cullin neddylation and the
CC identity of the cullin dictates the affinity of the interaction. Binds
CC neddylated CUL1. Interacts (via the C-terminus 50 AA) directly with
CC RBX1. Interacts (via DCUN1 domain) with the N-terminally acetylated
CC form of UBE2M and UBE2F. Interacts preferentially with UBE2M-NEDD8
CC thioester (via N-terminus 1-26 AA) than with free UBE2M. UBE2M N-
CC terminal acetylation increases the affinity of this interaction by
CC about 2 orders of magnitude. Interacts with CAND1; this interaction is
CC indirect and is bridged by cullins such as CUL1 and CUL3. May also
CC interact with regulators or subunits of cullin-RING ligases such as
CC RNF7, ELOB and DDB1; these interactions are bridged by cullins.
CC Component of VCB complex that contains at least DCUN1D1, CUL2 and VHL;
CC this complex triggers CUL2 neddylation and consequently cullin ring
CC ligase (CRL) substrates polyubiquitylation. Interacts with VHL; this
CC interaction triggers engagement of HIF1A in the VCB complex and is
CC independent of CUL2. Interacts with CUL2 independently of VHL.
CC Interacts with SOCS1 and SOCS2. Interacts with HIF1A; this interaction
CC increases the interaction between VHL and DCUN1D1. Interacts (via UBA-
CC like domain) with ARIH2; promotes DCUN1D1 ubiquitination.
CC {ECO:0000250|UniProtKB:Q96GG9}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q96GG9}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q96GG9}. Note=The ubiquitinated form is
CC localized in the cytoplasm. {ECO:0000250|UniProtKB:Q96GG9}.
CC -!- TISSUE SPECIFICITY: Highly expressed in testis. Also expressed in
CC brain, heart, liver, skeletal muscle and kidney. In brain,
CC preferentially expressed in the telencephalon ventricular and
CC subventricular zones, albeit at low levels. In adult testis, expressed
CC in cells above seminiferous tubules, but only weakly in spermatogonia.
CC {ECO:0000269|PubMed:10777668, ECO:0000269|PubMed:10831844}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the developing forebrain, midbrain
CC and hindbrain at early stages of neuronal development.
CC {ECO:0000269|PubMed:20563250}.
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 DCUN1D1-
CC cullin and DCUN1D1-E2 interaction affinities. The UBA-like domain
CC mediates interaction with autoubiquitylated ARIH2 leading to ubiquitin
CC ligation to DCUN1D1. {ECO:0000250|UniProtKB:Q96GG9}.
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:0000250|UniProtKB:Q96GG9}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC26390.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF198092; AAF04863.1; -; mRNA.
DR EMBL; AK008657; BAB25813.1; -; mRNA.
DR EMBL; AK029314; BAC26390.1; ALT_INIT; mRNA.
DR EMBL; AK155081; BAE33033.1; -; mRNA.
DR EMBL; AK165651; BAE38318.1; -; mRNA.
DR EMBL; BC020161; AAH20161.1; -; mRNA.
DR EMBL; BC031666; AAH31666.1; -; mRNA.
DR EMBL; BC037431; AAH37431.1; -; mRNA.
DR CCDS; CCDS57207.1; -.
DR RefSeq; NP_001192290.1; NM_001205361.1.
DR AlphaFoldDB; Q9QZ73; -.
DR SMR; Q9QZ73; -.
DR BioGRID; 227901; 23.
DR STRING; 10090.ENSMUSP00000113594; -.
DR iPTMnet; Q9QZ73; -.
DR PhosphoSitePlus; Q9QZ73; -.
DR EPD; Q9QZ73; -.
DR MaxQB; Q9QZ73; -.
DR PaxDb; Q9QZ73; -.
DR PRIDE; Q9QZ73; -.
DR ProteomicsDB; 279603; -.
DR DNASU; 114893; -.
DR Ensembl; ENSMUST00000108182; ENSMUSP00000103817; ENSMUSG00000027708.
DR GeneID; 114893; -.
DR KEGG; mmu:114893; -.
DR UCSC; uc008oyw.2; mouse.
DR CTD; 54165; -.
DR MGI; MGI:2150386; Dcun1d1.
DR VEuPathDB; HostDB:ENSMUSG00000027708; -.
DR eggNOG; KOG3077; Eukaryota.
DR GeneTree; ENSGT00940000154552; -.
DR InParanoid; Q9QZ73; -.
DR OrthoDB; 1418097at2759; -.
DR PhylomeDB; Q9QZ73; -.
DR Reactome; R-MMU-8951664; Neddylation.
DR BioGRID-ORCS; 114893; 6 hits in 72 CRISPR screens.
DR ChiTaRS; Dcun1d1; mouse.
DR PRO; PR:Q9QZ73; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q9QZ73; protein.
DR Bgee; ENSMUSG00000027708; Expressed in animal zygote and 253 other tissues.
DR ExpressionAtlas; Q9QZ73; baseline and differential.
DR Genevisible; Q9QZ73; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0000151; C:ubiquitin ligase complex; ISO:MGI.
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: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:2000434; P:regulation of protein neddylation; ISS:UniProtKB.
DR GO; GO:0031396; P:regulation of protein ubiquitination; 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 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 2: Evidence at transcript level;
KW Acetylation; Cytoplasm; Nucleus; Proto-oncogene; Reference proteome;
KW Ubl conjugation; Ubl conjugation pathway.
FT CHAIN 1..259
FT /note="DCN1-like protein 1"
FT /id="PRO_0000129499"
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:0000250|UniProtKB:Q96GG9"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q96GG9"
FT CONFLICT 13
FT /note="R -> S (in Ref. 3; BAC26390)"
FT /evidence="ECO:0000305"
FT CONFLICT 115
FT /note="C -> F (in Ref. 3; BAC26390)"
FT /evidence="ECO:0000305"
FT CONFLICT 259
FT /note="V -> L (in Ref. 3; BAC26390)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 259 AA; 30097 MW; 06E095D5F58EF20A CRC64;
MNKLKSSQKD KVRQFMIFTQ SSEKTAVSCL SQNDWKLDVA TDNFFQNPEL YIRESVKGSL
DRKKLEQLYT RYKDPQDENK IGIDGIQQFC DDLALDPASI SVLIIAWKFR AATQCEFSKQ
EFMDGMTELG CDSIEKLKAQ IPKMEQELKE PGRFKDFYQF TFNFAKNPGQ KGLDLEMAIA
YWNLVLNGRF KFLDLWNKFL LEHHKRSIPK DTWNLLLDFS SMIADDMSNY DEEGAWPVLI
DDFVEFARPQ IAGTKSTTV
