RNF26_HUMAN
ID RNF26_HUMAN Reviewed; 433 AA.
AC Q9BY78; Q542Y8;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=E3 ubiquitin-protein ligase RNF26 {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000269|PubMed:25254379, ECO:0000269|PubMed:27368102, ECO:0000269|PubMed:33472082};
DE AltName: Full=RING finger protein 26 {ECO:0000305};
GN Name=RNF26 {ECO:0000312|HGNC:HGNC:14646};
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 [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=11352657; DOI=10.1006/bbrc.2001.4671;
RA Katoh M.;
RT "Molecular cloning and characterization of RNF26 on human chromosome 11q23
RT region, encoding a novel RING finger protein with leucine zipper.";
RL Biochem. Biophys. Res. Commun. 282:1038-1044(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Muscle;
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 INTERACTION WITH INCA1.
RX PubMed=21750715; DOI=10.1371/journal.pone.0021505;
RA Zhang F., Baeumer N., Rode M., Ji P., Zhang T., Berdel W.E.,
RA Mueller-Tidow C.;
RT "The inhibitor of growth protein 5 (ING5) depends on INCA1 as a co-factor
RT for its antiproliferative effects.";
RL PLoS ONE 6:E21505-E21505(2011).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF CYS-395; CYS-399 AND CYS-401.
RX PubMed=25254379; DOI=10.1371/journal.ppat.1004358;
RA Qin Y., Zhou M.T., Hu M.M., Hu Y.H., Zhang J., Guo L., Zhong B., Shu H.B.;
RT "RNF26 temporally regulates virus-triggered type I interferon induction by
RT two distinct mechanisms.";
RL PLoS Pathog. 10:E1004358-E1004358(2014).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF ILE-382.
RX PubMed=27368102; DOI=10.1016/j.cell.2016.05.078;
RA Jongsma M.L., Berlin I., Wijdeven R.H., Janssen L., Janssen G.M.,
RA Garstka M.A., Janssen H., Mensink M., van Veelen P.A., Spaapen R.M.,
RA Neefjes J.;
RT "An ER-associated pathway defines endosomal architecture for controlled
RT cargo transport.";
RL Cell 166:152-166(2016).
RN [8]
RP FUNCTION, INTERACTION WITH TMEM43; ENDOD1; TMEM33 AND TMED1, MUTAGENESIS OF
RP TYR-432, AND SUBCELLULAR LOCATION.
RX PubMed=32614325; DOI=10.7554/elife.57306;
RA Fenech E.J., Lari F., Charles P.D., Fischer R., Laetitia-Thezenas M.,
RA Bagola K., Paton A.W., Paton J.C., Gyrd-Hansen M., Kessler B.M.,
RA Christianson J.C.;
RT "Interaction mapping of endoplasmic reticulum ubiquitin ligases identifies
RT modulators of innate immune signalling.";
RL Elife 9:0-0(2020).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH UBE2J1, AND CATALYTIC
RP ACTIVITY.
RX PubMed=33472082; DOI=10.1016/j.celrep.2020.108659;
RA Cremer T., Jongsma M.L.M., Trulsson F., Vertegaal A.C.O., Neefjes J.,
RA Berlin I.;
RT "The ER-embedded UBE2J1/RNF26 ubiquitylation complex exerts spatiotemporal
RT control over the endolysosomal pathway.";
RL Cell Rep. 34:108659-108659(2021).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that plays a key role in endosome
CC organization by retaining vesicles in the perinuclear cloud
CC (PubMed:27368102). Acts as a platform for perinuclear positioning of
CC the endosomal system by mediating ubiquitination of SQSTM1 through
CC interaction with the ubiquitin conjugating enzyme UBE2J1
CC (PubMed:27368102, PubMed:33472082). Ubiquitinated SQSTM1 attracts
CC specific vesicle-associated adapters, forming a molecular bridge that
CC restrains cognate vesicles in the perinuclear region and organizes the
CC endosomal pathway for efficient cargo transport (PubMed:27368102,
CC PubMed:33472082). Also acts as a regulator of type I interferon
CC production in response to viral infection by mediating the formation of
CC 'Lys-11'-linked polyubiquitin chains on TMEM173/STING, leading to
CC stabilize TMEM173/STING (PubMed:25254379, PubMed:32614325). Also
CC required to limit type I interferon response by promoting autophagic
CC degradation of IRF3 (PubMed:25254379). {ECO:0000269|PubMed:25254379,
CC ECO:0000269|PubMed:27368102, ECO:0000269|PubMed:32614325,
CC ECO:0000269|PubMed:33472082}.
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:0000269|PubMed:25254379,
CC ECO:0000269|PubMed:27368102};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:25254379, ECO:0000269|PubMed:27368102}.
CC -!- SUBUNIT: Interacts with INCA1 (PubMed:21750715). Interacts with TMEM43,
CC ENDOD1, TMEM33 and TMED1 to form a complex capable of modulating innate
CC immune signaling through the cGAS-STING pathway (PubMed:32614325).
CC Interacts with UBE2J1; this interaction is important for SQSTM1
CC ubiquitination (PubMed:33472082). {ECO:0000269|PubMed:21750715,
CC ECO:0000269|PubMed:32614325, ECO:0000269|PubMed:33472082}.
CC -!- INTERACTION:
CC Q9BY78; Q0VD86: INCA1; NbExp=2; IntAct=EBI-2129375, EBI-6509505;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:25254379, ECO:0000269|PubMed:27368102,
CC ECO:0000269|PubMed:32614325}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. Up-regulated in several cancer cell
CC lines. {ECO:0000269|PubMed:11352657}.
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DR EMBL; AB055622; BAB40955.1; -; mRNA.
DR EMBL; AK075379; BAC11580.1; -; mRNA.
DR EMBL; CH471065; EAW67479.1; -; Genomic_DNA.
DR EMBL; BC000058; AAH00058.1; -; mRNA.
DR EMBL; BC007534; AAH07534.1; -; mRNA.
DR CCDS; CCDS8419.1; -.
DR PIR; JC7678; JC7678.
DR RefSeq; NP_114404.1; NM_032015.4.
DR AlphaFoldDB; Q9BY78; -.
DR BioGRID; 122549; 69.
DR IntAct; Q9BY78; 19.
DR STRING; 9606.ENSP00000312439; -.
DR iPTMnet; Q9BY78; -.
DR PhosphoSitePlus; Q9BY78; -.
DR BioMuta; RNF26; -.
DR DMDM; 20139692; -.
DR EPD; Q9BY78; -.
DR jPOST; Q9BY78; -.
DR MassIVE; Q9BY78; -.
DR PaxDb; Q9BY78; -.
DR PeptideAtlas; Q9BY78; -.
DR PRIDE; Q9BY78; -.
DR ProteomicsDB; 79600; -.
DR Antibodypedia; 18819; 112 antibodies from 22 providers.
DR DNASU; 79102; -.
DR Ensembl; ENST00000311413.5; ENSP00000312439.4; ENSG00000173456.5.
DR GeneID; 79102; -.
DR KEGG; hsa:79102; -.
DR MANE-Select; ENST00000311413.5; ENSP00000312439.4; NM_032015.5; NP_114404.1.
DR UCSC; uc001pwh.4; human.
DR CTD; 79102; -.
DR DisGeNET; 79102; -.
DR GeneCards; RNF26; -.
DR HGNC; HGNC:14646; RNF26.
DR HPA; ENSG00000173456; Low tissue specificity.
DR MIM; 606130; gene.
DR neXtProt; NX_Q9BY78; -.
DR OpenTargets; ENSG00000173456; -.
DR PharmGKB; PA34430; -.
DR VEuPathDB; HostDB:ENSG00000173456; -.
DR eggNOG; KOG4265; Eukaryota.
DR GeneTree; ENSGT00390000016584; -.
DR HOGENOM; CLU_057705_0_0_1; -.
DR InParanoid; Q9BY78; -.
DR OMA; CDVCAIA; -.
DR OrthoDB; 670633at2759; -.
DR PhylomeDB; Q9BY78; -.
DR TreeFam; TF331813; -.
DR PathwayCommons; Q9BY78; -.
DR SignaLink; Q9BY78; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 79102; 25 hits in 1118 CRISPR screens.
DR ChiTaRS; RNF26; human.
DR GenomeRNAi; 79102; -.
DR Pharos; Q9BY78; Tbio.
DR PRO; PR:Q9BY78; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9BY78; protein.
DR Bgee; ENSG00000173456; Expressed in ileal mucosa and 170 other tissues.
DR Genevisible; Q9BY78; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; NAS:UniProtKB.
DR GO; GO:0007032; P:endosome organization; IDA:UniProtKB.
DR GO; GO:0050687; P:negative regulation of defense response to virus; IDA:UniProtKB.
DR GO; GO:0070979; P:protein K11-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:1905719; P:protein localization to perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0032479; P:regulation of type I interferon production; IDA:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR CDD; cd16788; mRING-HC-C3HC5_RNF26; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR040089; RNF26_mRING-HC-C3HC5.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Membrane; Metal-binding; Reference proteome;
KW Transferase; Transmembrane; Transmembrane helix; Ubl conjugation pathway;
KW Zinc; Zinc-finger.
FT CHAIN 1..433
FT /note="E3 ubiquitin-protein ligase RNF26"
FT /id="PRO_0000056068"
FT TRANSMEM 24..44
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 60..80
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 147..169
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 183..203
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 220..240
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ZN_FING 380..422
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT MUTAGEN 382
FT /note="I->R: Strongly decreased E3 ubiquitin-protein ligase
FT activity due to impaired interaction with E2 enzymes.
FT Impaired ability to retain vesicles in the perinuclear
FT cloud."
FT /evidence="ECO:0000269|PubMed:27368102"
FT MUTAGEN 395
FT /note="C->S: Strongly decreased E3 ubiquitin-protein ligase
FT activity. Impaired ability to mediate ubiquitination of
FT TMEM173/STING."
FT /evidence="ECO:0000269|PubMed:25254379"
FT MUTAGEN 399
FT /note="C->S: Strongly decreased E3 ubiquitin-protein ligase
FT activity. Impaired ability to mediate ubiquitination of
FT TMEM173/STING."
FT /evidence="ECO:0000269|PubMed:25254379"
FT MUTAGEN 401
FT /note="C->S: Strongly decreased E3 ubiquitin-protein ligase
FT activity. Impaired ability to mediate ubiquitination of
FT TMEM173/STING."
FT /evidence="ECO:0000269|PubMed:25254379"
FT MUTAGEN 432
FT /note="Y->A: About 4-fold increase of stability (from 30
FT min to 2 hours)."
FT /evidence="ECO:0000269|PubMed:32614325"
SQ SEQUENCE 433 AA; 47737 MW; C23E36A66C3677E7 CRC64;
MEAVYLVVNG LGLVLDVLTL VLDLNFLLVS SLLASLAWLL AFVYNLPHTV LTSLLHLGRG
VLLSLLALIE AVVRFTCGGL QALCTLLYSC CSGLESLKLL GHLASHGALR SREILHRGVL
NVVSSGHALL RQACDICAIA MSLVAYVINS LVNICLIGTQ NLFSLVLALW DAVTGPLWRM
TDVVAAFLAH ISSSAVAMAI LLWTPCQLAL ELLASAARLL ASFVLVNLTG LVLLACVLAV
TVTVLHPDFT LRLATQALSQ LHARPSYHRL REDVMRLSRL ALGSEAWRRV WSRSLQLASW
PNRGGAPGAP QGDPMRVFSV RTRRQDTLPE AGRRSEAEEE EARTIRVTPV RGRERLNEEE
PPGGQDPWKL LKEQEERKKC VICQDQSKTV LLLPCRHLCL CQACTEILMR HPVYHRNCPL
CRRGILQTLN VYL
