ID PP1RB_HUMAN Reviewed; 126 AA. AC O60927; DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1998, sequence version 1. DT 29-MAY-2024, entry version 177. DE RecName: Full=E3 ubiquitin-protein ligase PPP1R11 {ECO:0000303|PubMed:27805901}; DE EC=2.3.2.27; DE AltName: Full=Hemochromatosis candidate gene V protein; DE Short=HCG V; DE AltName: Full=Protein phosphatase 1 regulatory subunit 11; DE AltName: Full=Protein phosphatase inhibitor 3; GN Name=PPP1R11; Synonyms=HCGV, TCTE5; 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 [GENOMIC DNA / MRNA], AND TISSUE SPECIFICITY. RC TISSUE=Duodenal mucosa; RX PubMed=8781118; DOI=10.1007/bf02602777; RA Giffon T., Lepourcelet M., Pichon L., Jezequel P., Bouric P., Carn G., RA Pontarotti P., Gall J.-Y., David V.; RT "Cloning of a human homologue of the mouse Tctex-5 gene within the MHC RT class I region."; RL Immunogenetics 44:331-339(1996). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=8938444; DOI=10.1006/geno.1996.0566; RA Lepourcelet M., Andrieux N., Giffon T., Pichon L., Hampe A., Galibert F., RA Mosser J.; RT "Systematic sequencing of the human HLA-A/HLA-F region: establishment of a RT cosmid contig and identification of a new gene cluster within 37 kb of RT sequence."; RL Genomics 37:316-326(1996). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Shiina S., Tamiya G., Oka A., Inoko H.; RT "Homo sapiens 2,229,817bp genomic DNA of 6p21.3 HLA class I region."; RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC TISSUE=Peripheral blood leukocyte; RA Shiina T., Ota M., Takasu M., Katsuyama Y., Hashimoto N., Tokunaga K., RA Inoko H.; RT "Genome diversity in HLA: a new strategy for detection of genetic RT polymorphisms in expressed genes within the HLA class III and class I RT regions."; RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 14-126, AND FUNCTION. RC TISSUE=Brain; RX PubMed=9843442; DOI=10.1021/bi981169g; RA Zhang J., Zhang L., Zhao S., Lee E.Y.C.; RT "Identification and characterization of the human HCG V gene product as a RT novel inhibitor of protein phosphatase-1."; RL Biochemistry 37:16728-16734(1998). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-73; SER-74; THR-75; SER-77 RP AND THR-109, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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 [9] RP IDENTIFICATION BY 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 [10] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [12] RP FUNCTION, MUTAGENESIS OF HIS-52; 60-CYS--CYS-62; CYS-85; HIS-87 AND HIS-94, RP REGION ZINC-FINGER DOMAIN, AND AUTOUBIQUITINATION. RX PubMed=27805901; DOI=10.7554/elife.18496; RA McKelvey A.C., Lear T.B., Dunn S.R., Evankovich J., Londino J.D., RA Bednash J.S., Zhang Y., McVerry B.J., Liu Y., Chen B.B.; RT "RING finger E3 ligase PPP1R11 regulates TLR2 signaling and innate RT immunity."; RL Elife 5:0-0(2016). CC -!- FUNCTION: Atypical E3 ubiquitin-protein ligase which ubiquitinates TLR2 CC at 'Lys-754' leading to its degradation by the proteasome. Plays a role CC in regulating inflammatory cytokine release and gram-positive bacterial CC clearance by functioning, in part, through the ubiquitination and CC degradation of TLR2 (PubMed:27805901). Inhibitor of protein phosphatase CC 1 (PubMed:9843442). {ECO:0000269|PubMed:27805901, CC ECO:0000269|PubMed:9843442}. 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: Interacts with TLR2 and UBE2D2. CC {ECO:0000250|UniProtKB:Q8K1L5}. CC -!- INTERACTION: CC O60927; P55212: CASP6; NbExp=3; IntAct=EBI-1048104, EBI-718729; CC O60927; O94985-2: CLSTN1; NbExp=3; IntAct=EBI-1048104, EBI-16041593; CC O60927; P22607: FGFR3; NbExp=3; IntAct=EBI-1048104, EBI-348399; CC O60927; Q8IY31-3: IFT20; NbExp=3; IntAct=EBI-1048104, EBI-9091197; CC O60927; P13473-2: LAMP2; NbExp=3; IntAct=EBI-1048104, EBI-21591415; CC O60927; Q96CV9: OPTN; NbExp=3; IntAct=EBI-1048104, EBI-748974; CC O60927; P62140: PPP1CB; NbExp=8; IntAct=EBI-1048104, EBI-352350; CC O60927; P36873: PPP1CC; NbExp=6; IntAct=EBI-1048104, EBI-356283; CC O60927; P62826: RAN; NbExp=3; IntAct=EBI-1048104, EBI-286642; CC O60927; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-1048104, EBI-741480; CC O60927; Q8IY57-5: YAF2; NbExp=3; IntAct=EBI-1048104, EBI-12111538; CC O60927; P62139: PPP1CA; Xeno; NbExp=2; IntAct=EBI-1048104, EBI-2008988; CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:8781118}. CC -!- PTM: Auto-ubiquitinated. {ECO:0000269|PubMed:27805901}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X81003; CAC16920.1; -; mRNA. DR EMBL; X89902; CAC16919.1; -; Genomic_DNA. DR EMBL; U53588; AAC52082.1; -; Genomic_DNA. DR EMBL; BA000025; BAB63334.1; -; Genomic_DNA. DR EMBL; AB088087; BAC54919.1; -; Genomic_DNA. DR EMBL; AB202082; BAE78601.1; -; Genomic_DNA. DR EMBL; AL669914; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL671859; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL845439; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC102010; AAI02011.1; -; mRNA. DR EMBL; BC102011; AAI02012.1; -; mRNA. DR EMBL; BC104750; AAI04751.1; -; mRNA. DR CCDS; CCDS4671.1; -. DR RefSeq; NP_068778.1; NM_021959.2. DR PDB; 8DWK; X-ray; 2.50 A; C/D=27-68. DR PDB; 8DWL; X-ray; 2.00 A; B/D=27-68. DR PDB; 8U5G; X-ray; 3.20 A; C=27-68. DR PDBsum; 8DWK; -. DR PDBsum; 8DWL; -. DR PDBsum; 8U5G; -. DR AlphaFoldDB; O60927; -. DR SMR; O60927; -. DR BioGRID; 112852; 25. DR IntAct; O60927; 19. DR MINT; O60927; -. DR STRING; 9606.ENSP00000365963; -. DR GlyCosmos; O60927; 1 site, 1 glycan. DR GlyGen; O60927; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; O60927; -. DR MetOSite; O60927; -. DR PhosphoSitePlus; O60927; -. DR BioMuta; PPP1R11; -. DR EPD; O60927; -. DR jPOST; O60927; -. DR MassIVE; O60927; -. DR MaxQB; O60927; -. DR PaxDb; 9606-ENSP00000365963; -. DR PeptideAtlas; O60927; -. DR ProteomicsDB; 49672; -. DR Pumba; O60927; -. DR TopDownProteomics; O60927; -. DR Antibodypedia; 26202; 126 antibodies from 22 providers. DR DNASU; 6992; -. DR Ensembl; ENST00000376772.8; ENSP00000365963.3; ENSG00000204619.8. DR Ensembl; ENST00000383612.8; ENSP00000373107.4; ENSG00000206501.8. DR Ensembl; ENST00000431424.6; ENSP00000411038.2; ENSG00000236560.6. DR Ensembl; ENST00000431977.6; ENSP00000407981.2; ENSG00000237829.6. DR Ensembl; ENST00000436591.6; ENSP00000414808.2; ENSG00000234058.6. DR Ensembl; ENST00000437937.6; ENSP00000394056.2; ENSG00000233314.6. DR Ensembl; ENST00000448378.6; ENSP00000403557.2; ENSG00000237403.6. DR Ensembl; ENST00000452679.6; ENSP00000412297.2; ENSG00000227720.6. DR GeneID; 6992; -. DR KEGG; hsa:6992; -. DR MANE-Select; ENST00000376772.8; ENSP00000365963.3; NM_021959.3; NP_068778.1. DR UCSC; uc003npb.4; human. DR AGR; HGNC:9285; -. DR CTD; 6992; -. DR DisGeNET; 6992; -. DR GeneCards; PPP1R11; -. DR HGNC; HGNC:9285; PPP1R11. DR HPA; ENSG00000204619; Low tissue specificity. DR MIM; 606670; gene. DR neXtProt; NX_O60927; -. DR OpenTargets; ENSG00000204619; -. DR PharmGKB; PA33614; -. DR VEuPathDB; HostDB:ENSG00000204619; -. DR eggNOG; KOG4102; Eukaryota. DR GeneTree; ENSGT00390000001153; -. DR HOGENOM; CLU_098333_6_2_1; -. DR InParanoid; O60927; -. DR OMA; CILGHSR; -. DR OrthoDB; 4807at2759; -. DR PhylomeDB; O60927; -. DR TreeFam; TF352541; -. DR PathwayCommons; O60927; -. DR SignaLink; O60927; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 6992; 673 hits in 1173 CRISPR screens. DR ChiTaRS; PPP1R11; human. DR GeneWiki; PPP1R11; -. DR GenomeRNAi; 6992; -. DR Pharos; O60927; Tbio. DR PRO; PR:O60927; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; O60927; Protein. DR Bgee; ENSG00000204619; Expressed in rectum and 100 other cell types or tissues. DR ExpressionAtlas; O60927; baseline and differential. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0019902; F:phosphatase binding; IPI:DisProt. DR GO; GO:0008157; F:protein phosphatase 1 binding; IBA:GO_Central. DR GO; GO:0004864; F:protein phosphatase inhibitor activity; IDA:DisProt. DR GO; GO:0004865; F:protein serine/threonine phosphatase inhibitor activity; IBA:GO_Central. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB. DR GO; GO:0050830; P:defense response to Gram-positive bacterium; ISS:UniProtKB. DR GO; GO:0001818; P:negative regulation of cytokine production; ISS:UniProtKB. DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IMP:UniProtKB. DR DisProt; DP00219; -. DR InterPro; IPR011107; PPI_Ypi1. DR PANTHER; PTHR20835:SF0; E3 UBIQUITIN-PROTEIN LIGASE PPP1R11; 1. DR PANTHER; PTHR20835; E3 UBIQUITIN-PROTEIN LIGASE PPP1R11-RELATED; 1. DR Pfam; PF07491; PPI_Ypi1; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Phosphoprotein; Protein phosphatase inhibitor; KW Reference proteome; Transferase; Ubl conjugation; Ubl conjugation pathway. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:22814378" FT CHAIN 2..126 FT /note="E3 ubiquitin-protein ligase PPP1R11" FT /id="PRO_0000239619" FT REGION 1..25 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 52..62 FT /note="Atypical RING finger domain 1" FT /evidence="ECO:0000269|PubMed:27805901" FT REGION 70..126 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 85..94 FT /note="Atypical RING finger domain 2" FT /evidence="ECO:0000269|PubMed:27805901" FT COMPBIAS 9..25 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 106..126 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:22814378" FT MOD_RES 73 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 74 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 75 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 77 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 109 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648" FT MUTAGEN 52 FT /note="H->A: Loss of function in inducing TLR2 FT degradation." FT /evidence="ECO:0000269|PubMed:27805901" FT MUTAGEN 60..62 FT /note="CCC->SSS: Loss of function in inducing TLR2 FT degradation." FT /evidence="ECO:0000269|PubMed:27805901" FT MUTAGEN 85 FT /note="C->S: Loss of function in inducing TLR2 FT degradation." FT /evidence="ECO:0000269|PubMed:27805901" FT MUTAGEN 87 FT /note="H->A: Loss of function in inducing TLR2 FT degradation." FT /evidence="ECO:0000269|PubMed:27805901" FT MUTAGEN 89..90 FT /note="HC->AS: Loss of function in inducing TLR2 FT degradation." FT /evidence="ECO:0000269|PubMed:27805901" FT MUTAGEN 94 FT /note="H->A: Loss of function in inducing TLR2 FT degradation." FT /evidence="ECO:0000269|PubMed:27805901" FT TURN 51..54 FT /evidence="ECO:0007829|PDB:8DWK" FT STRAND 57..59 FT /evidence="ECO:0007829|PDB:8DWL" SQ SEQUENCE 126 AA; 13953 MW; D6788A5AAC073549 CRC64; MAEAGAGLSE TVTETTVTVT TEPENRSLTI KLRKRKPEKK VEWTSDTVDN EHMGRRSSKC CCIYEKPRAF GESSTESDEE EEEGCGHTHC VRGHRKGRRR ATLGPTPTTP PQPPDPSQPP PGPMQH //