RN187_HUMAN
ID RN187_HUMAN Reviewed; 235 AA.
AC Q5TA31; A6NL57; Q6P2J7; Q6PJR0;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 03-MAY-2011, sequence version 2.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=E3 ubiquitin-protein ligase RNF187;
DE EC=2.3.2.27;
DE AltName: Full=RING domain AP1 coactivator 1;
DE Short=RACO-1;
DE AltName: Full=RING finger protein 187;
DE AltName: Full=RING-type E3 ubiquitin transferase RNF187 {ECO:0000305};
GN Name=RNF187;
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 GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lymph, and 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 [3]
RP FUNCTION, INTERACTION WITH JUN, SUBCELLULAR LOCATION, IDENTIFICATION OF A
RP NON-AUG INITIATOR START CODON, UBIQUITINATION AT LYS-195; LYS-223 AND
RP LYS-224, AND MUTAGENESIS OF MET-1; CYS-12; CYS-15; LYS-195; LYS-223 AND
RP LYS-224.
RX PubMed=20852630; DOI=10.1038/ncb2098;
RA Davies C.C., Chakraborty A., Cipriani F., Haigh K., Haigh J.J., Behrens A.;
RT "Identification of a co-activator that links growth factor signalling to c-
RT Jun/AP-1 activation.";
RL Nat. Cell Biol. 12:963-972(2010).
RN [4]
RP SUBUNIT, AND METHYLATION AT ARG-98 AND ARG-109.
RX PubMed=23624934; DOI=10.1038/emboj.2013.98;
RA Davies C.C., Chakraborty A., Diefenbacher M.E., Skehel M., Behrens A.;
RT "Arginine methylation of the c-Jun coactivator RACO-1 is required for c-
RT Jun/AP-1 activation.";
RL EMBO J. 32:1556-1567(2013).
RN [5]
RP INTERACTION WITH TRIM7, UBIQUITINATION BY TRIM7, AND MUTAGENESIS OF ARG-98
RP AND ARG-109.
RX PubMed=25851810; DOI=10.1038/ncomms7782;
RA Chakraborty A., Diefenbacher M.E., Mylona A., Kassel O., Behrens A.;
RT "The E3 ubiquitin ligase Trim7 mediates c-Jun/AP-1 activation by Ras
RT signalling.";
RL Nat. Commun. 6:6782-6782(2015).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that acts as a coactivator of
CC JUN-mediated gene activation in response to growth factor signaling via
CC the MAP3K1 pathway, independently from MAPK8.
CC {ECO:0000269|PubMed:20852630}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Homodimer (PubMed:23624934). Interacts with JUN, independently
CC of JUN phosphorylation (PubMed:20852630). Interacts (via C-terminus)
CC with TRIM7 (PubMed:25851810). {ECO:0000269|PubMed:20852630,
CC ECO:0000269|PubMed:23624934, ECO:0000269|PubMed:25851810}.
CC -!- INTERACTION:
CC Q5TA31; Q8TAU3: ZNF417; NbExp=3; IntAct=EBI-6868977, EBI-740727;
CC Q5TA31; Q9Y2P0: ZNF835; NbExp=3; IntAct=EBI-6868977, EBI-5667516;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:20852630}. Nucleus
CC {ECO:0000269|PubMed:20852630}. Note=Predominantly located in the
CC cytoplasm. Shuttles between the cytoplasm and the nucleus.
CC -!- DOMAIN: The RING-type zinc finger domain is required for E3 ligase
CC activity.
CC -!- PTM: Ubiquitinated; undergoes 'Lys-48'-linked autoubiquitination in the
CC absence of growth factors and MAP3K1-induced 'Lys-63'-linked
CC polyubiquitination (PubMed:20852630). 'Lys-48'-autoubiquitination leads
CC to degradation by the proteasome, while MAP3K1-induced 'Lys-63'-linked
CC polyubiquitination results in the stabilization of the protein
CC (PubMed:20852630). 'Lys-48'- and 'Lys-63'-linked polyubiquitinations
CC occur most probably on the same 3 C-terminal lysine residues (Lys-195,
CC Lys-223 and Lys-224) and are thus mutually exclusive (PubMed:20852630).
CC Other sites of ubiquitination are not excluded (PubMed:20852630). 'Lys-
CC 63'-linked polyubiquitination by TRIM7 in response to growth factor
CC signaling via the MEK/ERK pathway enhances protein stability
CC (PubMed:25851810). {ECO:0000269|PubMed:20852630,
CC ECO:0000269|PubMed:25851810}.
CC -!- PTM: Arginine methylation by PRMT1 stabilizes RNF187 by facilitating
CC K63-linked ubiquitin chain formation, and enables dimerization, c-Jun
CC interaction and subsequent AP1 target gene expression.
CC {ECO:0000269|PubMed:20852630, ECO:0000269|PubMed:23624934}.
CC -!- CAUTION: This sequence initiates at a CTG codon.
CC {ECO:0000305|PubMed:20852630}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH12758.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH12758.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.; Evidence={ECO:0000305};
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DR EMBL; AL139288; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC012758; AAH12758.1; ALT_SEQ; mRNA.
DR EMBL; BC064481; AAH64481.1; -; mRNA.
DR CCDS; CCDS76271.1; -.
DR RefSeq; NP_001010858.2; NM_001010858.2.
DR AlphaFoldDB; Q5TA31; -.
DR SMR; Q5TA31; -.
DR BioGRID; 127223; 34.
DR IntAct; Q5TA31; 12.
DR MINT; Q5TA31; -.
DR STRING; 9606.ENSP00000306396; -.
DR iPTMnet; Q5TA31; -.
DR PhosphoSitePlus; Q5TA31; -.
DR BioMuta; RNF187; -.
DR DMDM; 332278146; -.
DR EPD; Q5TA31; -.
DR jPOST; Q5TA31; -.
DR MassIVE; Q5TA31; -.
DR MaxQB; Q5TA31; -.
DR PaxDb; Q5TA31; -.
DR PeptideAtlas; Q5TA31; -.
DR PRIDE; Q5TA31; -.
DR ProteomicsDB; 64824; -.
DR Antibodypedia; 34669; 56 antibodies from 12 providers.
DR DNASU; 149603; -.
DR Ensembl; ENST00000305943.9; ENSP00000306396.9; ENSG00000168159.15.
DR Ensembl; ENST00000643372.3; ENSP00000495836.2; ENSG00000285426.4.
DR GeneID; 149603; -.
DR KEGG; hsa:149603; -.
DR MANE-Select; ENST00000305943.9; ENSP00000306396.9; NM_001010858.3; NP_001010858.2.
DR UCSC; uc057qfa.1; human.
DR CTD; 149603; -.
DR DisGeNET; 149603; -.
DR GeneCards; RNF187; -.
DR HGNC; HGNC:27146; RNF187.
DR HPA; ENSG00000168159; Low tissue specificity.
DR MIM; 613754; gene.
DR neXtProt; NX_Q5TA31; -.
DR OpenTargets; ENSG00000168159; -.
DR PharmGKB; PA142671058; -.
DR VEuPathDB; HostDB:ENSG00000168159; -.
DR eggNOG; KOG2177; Eukaryota.
DR GeneTree; ENSGT00390000009510; -.
DR HOGENOM; CLU_1175118_0_0_1; -.
DR InParanoid; Q5TA31; -.
DR OMA; CQSAPRD; -.
DR OrthoDB; 423686at2759; -.
DR TreeFam; TF351093; -.
DR PathwayCommons; Q5TA31; -.
DR SignaLink; Q5TA31; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 149603; 20 hits in 359 CRISPR screens.
DR ChiTaRS; RNF187; human.
DR GenomeRNAi; 149603; -.
DR Pharos; Q5TA31; Tbio.
DR PRO; PR:Q5TA31; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q5TA31; protein.
DR Bgee; ENSG00000168159; Expressed in right frontal lobe and 97 other tissues.
DR ExpressionAtlas; Q5TA31; baseline and differential.
DR Genevisible; Q5TA31; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; IDA:UniProtKB.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IMP:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Isopeptide bond; Metal-binding; Methylation; Nucleus;
KW Reference proteome; Transferase; Ubl conjugation; Ubl conjugation pathway;
KW Zinc; Zinc-finger.
FT CHAIN 1..235
FT /note="E3 ubiquitin-protein ligase RNF187"
FT /id="PRO_0000278241"
FT ZN_FING 12..53
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT MOD_RES 98
FT /note="Asymmetric dimethylarginine; by PRMT1"
FT /evidence="ECO:0000269|PubMed:23624934"
FT MOD_RES 109
FT /note="Asymmetric dimethylarginine; by PRMT1"
FT /evidence="ECO:0000269|PubMed:23624934"
FT CROSSLNK 195
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000305|PubMed:20852630"
FT CROSSLNK 223
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000305|PubMed:20852630"
FT CROSSLNK 224
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000305|PubMed:20852630"
FT MUTAGEN 1
FT /note="M->A: Loss of protein expression."
FT /evidence="ECO:0000269|PubMed:20852630"
FT MUTAGEN 12
FT /note="C->A: Increased RNF187 stability and reduced
FT polyubiquitination; when associated with A-15."
FT /evidence="ECO:0000269|PubMed:20852630"
FT MUTAGEN 15
FT /note="C->A: Increased RNF187 stability and reduced
FT polyubiquitination; when associated with A-12."
FT /evidence="ECO:0000269|PubMed:20852630"
FT MUTAGEN 98
FT /note="R->K: Abolishes ubiquitination by TRIM7; when
FT associated with K-109."
FT /evidence="ECO:0000269|PubMed:25851810"
FT MUTAGEN 109
FT /note="R->K: Abolishes ubiquitination by TRIM7; when
FT associated with K-98."
FT /evidence="ECO:0000269|PubMed:25851810"
FT MUTAGEN 195
FT /note="K->R: No detectable effect on ubiquitination. Marked
FT decrease in ubiquitination, but no effect on subcellular
FT location; when associated with R-223 and R-224."
FT /evidence="ECO:0000269|PubMed:20852630"
FT MUTAGEN 223
FT /note="K->R: No detectable effect on ubiquitination. Marked
FT decrease in ubiquitination, but no effect on subcellular
FT location; when associated with R-195 and R-224."
FT /evidence="ECO:0000269|PubMed:20852630"
FT MUTAGEN 224
FT /note="K->R: No detectable effect on ubiquitination. Marked
FT decrease in ubiquitination, but no effect on subcellular
FT location; when associated with R-195 and R-223."
FT /evidence="ECO:0000269|PubMed:20852630"
SQ SEQUENCE 235 AA; 26190 MW; 6C16442F7419CD25 CRC64;
MALPAGPAEA ACALCQRAPR EPVRADCGHR FCRACVVRFW AEEDGPFPCP ECADDCWQRA
VEPGRPPLSR RLLALEEAAA APARDGPASE AALQLLCRAD AGPLCAACRM AAGPEPPEWE
PRWRKALRGK ENKGSVEIMR KDLNDARDLH GQAESAAAVW KGHVMDRRKK ALTDYKKLRA
FFVEEEEHFL QEAEKEEGLP EDELADPTER FRSLLQAVSE LEKKHRNLGL SMLLQ
