RN139_PONAB
ID RN139_PONAB Reviewed; 664 AA.
AC Q5RBT7;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 25-MAY-2022, entry version 91.
DE RecName: Full=E3 ubiquitin-protein ligase RNF139;
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q8WU17};
DE AltName: Full=RING finger protein 139;
DE AltName: Full=RING-type E3 ubiquitin transferase RNF139 {ECO:0000305};
DE AltName: Full=Translocation in renal carcinoma on chromosome 8 protein;
GN Name=RNF139;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: E3-ubiquitin ligase; acts as a negative regulator of cell
CC proliferation through mechanisms involving G2/M arrest and cell death.
CC Required for MHC class I ubiquitination in cells expressing the
CC cytomegalovirus protein US2 before dislocation from the endoplasmic
CC reticulum (ER). Affects SREBP processing by hindering the SREBP-SCAP
CC complex translocation from the ER to the Golgi, thereby reducing SREBF2
CC target gene expression. Involved in the sterol-accelerated degradation
CC of HMGCR. This is achieved through binding to INSIG1 and/or INSIG2 at
CC the ER membrane. In addition, interaction of RNF139 with AUP1
CC facilitates interaction of RNF139 with ubiquitin-conjugating enzyme
CC UBE2G2 and ubiquitin ligase AMFR, leading to ubiquitination of HMGCR.
CC The ubiquitinated HMGCR is then released from the ER by the complex
CC into the cytosol for subsequent destruction. Required for INSIG1
CC ubiquitination. May be required for EIF3 complex ubiquitination.
CC {ECO:0000250|UniProtKB:Q8WU17}.
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; Evidence={ECO:0000250|UniProtKB:Q8WU17};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q8WU17}.
CC -!- SUBUNIT: Interacts with VHL. Interacts with MHC class I and HM13.
CC Component of SCAP-SREBP complex composed of SREBF2, SCAP and RNF139;
CC the complex hampers the interaction between SCAP and SEC24B, thereby
CC reducing SREBF2 proteolytic processing. Interacts with SREBF2 (via C-
CC terminal domain). Interacts with SCAP; the interaction inhibits the
CC interaction of SCAP with SEC24B and hampering the ER to Golgi transport
CC of the SCAP-SREBP complex. Interacts with SEC24B. Interacts with INSIG1
CC and INSIG2. Interacts with EIF3F and EIF3H; the interaction leads to
CC protein translation inhibitions in a ubiquitination-dependent manner.
CC Interacts with XBP1; the interaction induces ubiquitination and
CC degradation of XBP1. Interacts with AUP1, AMFR and UBE2G2; interaction
CC with AUP1 facilitates interaction of RNF139 with ubiquitin-conjugating
CC enzyme UBE2G2 and ubiquitin ligase AMFR/gp78, leading to sterol-induced
CC ubiquitination of HMGCR and its subsequent proteasomal degradation.
CC {ECO:0000250|UniProtKB:Q8WU17}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q8WU17}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q8WU17}.
CC -!- DOMAIN: The RING-type zinc finger domain may be essential for ubiquitin
CC ligase activity. {ECO:0000250}.
CC -!- PTM: Autoubiquitinated. Ubiquitination is induced by sterol and leads
CC to ist degradation via the ubiquitin-proteasome pathway.
CC {ECO:0000250|UniProtKB:Q8WU17}.
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DR EMBL; CR858546; CAH90773.1; -; mRNA.
DR AlphaFoldDB; Q5RBT7; -.
DR SMR; Q5RBT7; -.
DR STRING; 9601.ENSPPYP00000021168; -.
DR eggNOG; KOG0802; Eukaryota.
DR InParanoid; Q5RBT7; -.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0031648; P:protein destabilization; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR025754; TRC8_N_dom.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR011016; Znf_RING-CH.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF13705; TRC8_N; 1.
DR Pfam; PF13639; zf-RING_2; 1.
DR SMART; SM00184; RING; 1.
DR SMART; SM00744; RINGv; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Endoplasmic reticulum; Membrane; Metal-binding;
KW Phosphoprotein; Receptor; Reference proteome; Transferase; Transmembrane;
KW Transmembrane helix; Ubl conjugation; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q8WU17"
FT CHAIN 2..664
FT /note="E3 ubiquitin-protein ligase RNF139"
FT /id="PRO_0000284916"
FT TRANSMEM 51..71
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 85..105
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 125..145
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 154..174
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 178..198
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 293..313
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 323..343
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 356..376
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 390..410
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 420..440
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 469..489
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 495..512
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ZN_FING 547..586
FT /note="RING-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 599..664
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q8WU17"
FT MOD_RES 634
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8WU17"
FT MOD_RES 635
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8WU17"
FT MOD_RES 663
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8WU17"
SQ SEQUENCE 664 AA; 75941 MW; 51F0E0C0068813D6 CRC64;
MAAVGPPQQQ VRMAHRQVWA ALEVALRVPC LYIIDAIFNS YPDSSQSRFC IVLQIFLRLL
GIFVSSIVLI LSQRSLFKFY MYSSAFLLAA TSVLVNYYAS LHIDFYGAYN TSAFGIELLP
RKGPSLWMAL IVLQLTFGIG YVTLLQIHSI YSQLIILDLL VPVIGLITEL PLHIRETLVF
TSSLILTLNT VLVLAVKLKW FYYSTRYVYL LVRHMYRIYG LQLLMEDTWK RIRFPDILRV
FWLTRVTAQA TVLMYILRMA NETDSFFISW DDFWDLICNL IISGCDSTLT VLGMSAVISS
VAHYLGLGIL AFIGSTEEDD RRLGFVAPVL FFILALQTGL SGLRPEERLI RLSRNMCLLL
TAVLHFIHGM TDPVLMSLSA SHVSSFRRHF PVLFVSACLF ILPVLLSYVL WHHYALNTWL
FAATAFCVEL CLKVIVSLTV YTLFMIDGYY NVLWEKLDNY VYYVRSTGSI IVFIFGVVMF
GNGAYTMMFE SGSKIRAFMM CLHAYFNIYL QAKNGWKTFM NRRTAVKKIN SLPEIKGSRL
QEINDVCAIC YHEFTTSARI TPCNHYFHAL CLRKWLYIQD TCPMCHQKVY IEDDIKDNSN
VSNNNGFTPP NETPEEAVRE AAAESDRELN EDDSTDCDDD VQRERNGVIQ HTGAAAEEFN
DDTD
