RN181_HUMAN
ID RN181_HUMAN Reviewed; 153 AA.
AC Q9P0P0; Q53H81;
DT 10-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=E3 ubiquitin-protein ligase RNF181 {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000269|PubMed:18331836, ECO:0000269|PubMed:24811749};
DE AltName: Full=RING finger protein 181 {ECO:0000303|PubMed:18331836};
GN Name=RNF181 {ECO:0000303|PubMed:24811749, ECO:0000312|HGNC:HGNC:28037};
GN ORFNames=HSPC238 {ECO:0000303|PubMed:11042152};
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 MRNA].
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for 300
RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor
RT cells.";
RL Genome Res. 10:1546-1560(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT HIS-118.
RC TISSUE=Brain;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 [6]
RP FUNCTION, INTERACTION WITH ITGA2B, TISSUE SPECIFICITY, AND
RP AUTOUBIQUITINATION.
RX PubMed=18331836; DOI=10.1016/j.bbrc.2008.02.142;
RA Brophy T.M., Raab M., Daxecker H., Culligan K.G., Lehmann I., Chubb A.J.,
RA Treumann A., Moran N.;
RT "RN181, a novel ubiquitin E3 ligase that interacts with the KVGFFKR motif
RT of platelet integrin alpha(IIb)beta3.";
RL Biochem. Biophys. Res. Commun. 369:1088-1093(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-153, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-153, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=24811749; DOI=10.1002/embj.201386906;
RA Besche H.C., Sha Z., Kukushkin N.V., Peth A., Hock E.M., Kim W., Gygi S.,
RA Gutierrez J.A., Liao H., Dick L., Goldberg A.L.;
RT "Autoubiquitination of the 26S proteasome on Rpn13 regulates breakdown of
RT ubiquitin conjugates.";
RL EMBO J. 33:1159-1176(2014).
CC -!- FUNCTION: E3 ubiquitin-protein ligase which accepts ubiquitin from an
CC E2 ubiquitin-conjugating enzyme in the form of a thioester and then
CC directly transfers the ubiquitin to targeted substrates
CC (PubMed:18331836). Catalyzes monoubiquitination of 26S proteasome
CC subunit PSMC2/RPT1 (PubMed:24811749). {ECO:0000269|PubMed:18331836,
CC ECO:0000269|PubMed:24811749}.
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:18331836,
CC ECO:0000269|PubMed:24811749};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:18331836, ECO:0000269|PubMed:24811749}.
CC -!- SUBUNIT: Directly interacts with ITGA2B and, as a result, with integrin
CC ITGA2B/ITGB3 (PubMed:18331836). There is no evidence that integrin
CC ITGA2B/ITGB3 is an endogenous substrate for RNF181-directed
CC ubiquitination (PubMed:18331836). {ECO:0000269|PubMed:18331836}.
CC -!- INTERACTION:
CC Q9P0P0; P51668: UBE2D1; NbExp=4; IntAct=EBI-2129136, EBI-743540;
CC Q9P0P0; Q9Y2X8: UBE2D4; NbExp=4; IntAct=EBI-2129136, EBI-745527;
CC -!- TISSUE SPECIFICITY: Widely expressed, with highest levels in liver and
CC heart and lowest levels in brain and skeletal muscle. Expressed in
CC platelets (at protein level). {ECO:0000269|PubMed:18331836}.
CC -!- PTM: Autoubiquitinated as part of the enzymatic reaction.
CC {ECO:0000269|PubMed:18331836}.
CC -!- SIMILARITY: Belongs to the RNF181 family. {ECO:0000305}.
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DR EMBL; AF151072; AAF36158.1; -; mRNA.
DR EMBL; CR457165; CAG33446.1; -; mRNA.
DR EMBL; AK222700; BAD96420.1; -; mRNA.
DR EMBL; AC016753; AAY24343.1; -; Genomic_DNA.
DR EMBL; BC002803; AAH02803.1; -; mRNA.
DR CCDS; CCDS1981.1; -.
DR RefSeq; NP_057578.1; NM_016494.3.
DR AlphaFoldDB; Q9P0P0; -.
DR SMR; Q9P0P0; -.
DR BioGRID; 119411; 137.
DR IntAct; Q9P0P0; 29.
DR MINT; Q9P0P0; -.
DR STRING; 9606.ENSP00000306906; -.
DR iPTMnet; Q9P0P0; -.
DR MetOSite; Q9P0P0; -.
DR PhosphoSitePlus; Q9P0P0; -.
DR BioMuta; RNF181; -.
DR DMDM; 74761852; -.
DR EPD; Q9P0P0; -.
DR jPOST; Q9P0P0; -.
DR MassIVE; Q9P0P0; -.
DR MaxQB; Q9P0P0; -.
DR PaxDb; Q9P0P0; -.
DR PeptideAtlas; Q9P0P0; -.
DR PRIDE; Q9P0P0; -.
DR ProteomicsDB; 83589; -.
DR Antibodypedia; 31897; 102 antibodies from 23 providers.
DR DNASU; 51255; -.
DR Ensembl; ENST00000306368.9; ENSP00000306906.4; ENSG00000168894.10.
DR GeneID; 51255; -.
DR KEGG; hsa:51255; -.
DR MANE-Select; ENST00000306368.9; ENSP00000306906.4; NM_016494.4; NP_057578.1.
DR UCSC; uc002spv.2; human.
DR CTD; 51255; -.
DR DisGeNET; 51255; -.
DR GeneCards; RNF181; -.
DR HGNC; HGNC:28037; RNF181.
DR HPA; ENSG00000168894; Low tissue specificity.
DR MIM; 612490; gene.
DR neXtProt; NX_Q9P0P0; -.
DR OpenTargets; ENSG00000168894; -.
DR PharmGKB; PA162401586; -.
DR VEuPathDB; HostDB:ENSG00000168894; -.
DR eggNOG; KOG0800; Eukaryota.
DR GeneTree; ENSGT00940000160552; -.
DR HOGENOM; CLU_144247_0_0_1; -.
DR InParanoid; Q9P0P0; -.
DR OMA; EHLHGAM; -.
DR OrthoDB; 1249953at2759; -.
DR PhylomeDB; Q9P0P0; -.
DR TreeFam; TF332127; -.
DR BRENDA; 2.3.2.27; 2681.
DR PathwayCommons; Q9P0P0; -.
DR Reactome; R-HSA-8866654; E3 ubiquitin ligases ubiquitinate target proteins.
DR SignaLink; Q9P0P0; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 51255; 27 hits in 1110 CRISPR screens.
DR ChiTaRS; RNF181; human.
DR GenomeRNAi; 51255; -.
DR Pharos; Q9P0P0; Tbio.
DR PRO; PR:Q9P0P0; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9P0P0; protein.
DR Bgee; ENSG00000168894; Expressed in kidney epithelium and 183 other tissues.
DR ExpressionAtlas; Q9P0P0; baseline and differential.
DR Genevisible; Q9P0P0; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:FlyBase.
DR GO; GO:0051865; P:protein autoubiquitination; IDA:FlyBase.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF13639; zf-RING_2; 1.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Metal-binding; Phosphoprotein; Reference proteome; Transferase;
KW Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..153
FT /note="E3 ubiquitin-protein ligase RNF181"
FT /id="PRO_0000295174"
FT ZN_FING 76..117
FT /note="RING-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 127..153
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 127..143
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 153
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT VARIANT 118
FT /note="Y -> H (in dbSNP:rs6643)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_033323"
SQ SEQUENCE 153 AA; 17909 MW; AF0CEC8D438FF0AB CRC64;
MASYFDEHDC EPSDPEQETR TNMLLELARS LFNRMDFEDL GLVVDWDHHL PPPAAKTVVE
NLPRTVIRGS QAELKCPVCL LEFEEEETAI EMPCHHLFHS SCILPWLSKT NSCPLCRYEL
PTDDDTYEEH RRDKARKQQQ QHRLENLHGA MYT
