REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
InVivoMAb anti-mouse TNF (neutralizing) (clone XT3.11)	BioXcell	Cat#BE0058; RRID: AB_1107764
InVivoMAb anti-mouse IL-6 (neutralizing) (clone MP5-20F3)	BioXcell	Cat#BE0046; RRID: AB_1107709
anti-mouse G-CSF (neutralizing) (clone 67604)	R&D Systems	Cat#MAB414; RRID: AB_2085954
InVivoMAb Rat IgG1 isotype control (clone HRPN)	BioXcell	Cat#BE0088; RRID: AB_1107775
anti-B220 conjugated to FITC (clone RA3-6B2)	eBioscience	Cat#11-0452-81; RRID: AB_465053
anti-CD3ε conjugated to FITC (clone 145-2C11)	BioLegend	Cat#17-0031-81; RRID: AB_312670
anti-CD3ε conjugated to PE-Cy7 (clone 145-2C11)	BioLegend	Cat#100319; RRID: AB_312684
anti-CD3ε conjugated to APC (clone 145-2C11)	eBioscience	Cat#17-0031; RRID: AB_469314
anti-CD4 conjugated to Alexafluor700 (clone GK1.5)	eBioscience	Cat#56-0041-82; RRID: AB_493999
anti-CD4 conjugated to Alexafluor647 (clone GK1.5)	eBioscience	Cat#50-0041-82; RRID: AB_469773
anti-CD4 conjugated to biotin (clone GK1.5)	BioLegend	Cat#100403; RRID: AB_312688
anti-CD4 conjugated to FITC (clone H129.19)	BD Biosciences	Cat#561831; RRID: AB_10892800
anti-CD4 conjugated to BrilliantViolet785 (clone RM4-5)	BioLegend	Cat#100551; RRID: AB_11218992
anti-CD5 conjugated to BrilliantViolet-510 (clone 53-7.3)	BioLegend	Cat#100627; RRID: AB_2563930
anti-CD5 conjugated to FITC (clone 53-7.3)	BD Biosciences	Cat#553020; RRID: AB_394558
anti-CD8α conjugated to FITC (clone 53-6.7)	eBioscience	Cat#11-0081-81; RRID: AB_464914
anti-CD8α conjugated to APC (clone 53-6.7)	eBioscience	Cat#17-0081-81; RRID: AB_469334
anti-CD8α conjugated to PE-Cy7 (clone 53-6.7)	eBioscience	Cat#25-0081-81; RRID: AB_469583
anti-CD8α conjugated to PE (clone 53-6.7)	eBioscience	Cat#12-0081-81; RRID: AB_465529
anti-CD8α conjugated to biotin (clone 53-6.7)	eBioscience	Cat#13-0081-81; RRID: AB_466345
anti-CD11b conjugated to PE-Cy7 (clone M1/70)	eBioscience	Cat#25-0112-81; RRID: AB_469587
anti-CD11b conjugated to eFluor-450 (clone M1/70)	eBioscience	Cat#48-0112-82; RRID: AB_1582236
anti-CD11b conjugated to BrilliantViolet-421 (clone M1/70)	BioLegend	Cat#101235; RRID: AB_10897942
anti-CD11b conjugated to FITC (clone M1/70)	BioLegend	Cat#101205; RRID: AB_312788
anti-CD11c conjugated to PE (clone N418)	BioLegend	Cat#117307; RRID: AB_313776
anti-CD11c conjugated to FITC (clone N418)	eBioscience	Cat#11-0114-81; RRID: AB_464939
anti-CD19 conjugated to FITC (clone eBio1D3)	eBioscience	Cat#11-0193-81; RRID: AB_657667
anti-CD19 conjugated to PerCP-Cy5.5 (clone eBio1D3)	eBioscience	Cat#45-0193-82; RRID: AB_1106999
anti-CD19 conjugated to Alexafluor700 (clone 6D5)	BioLegend	Cat#115528; RRID: AB_493735
anti-CD21/CD35 conjugated to APC (clone 7E9)	BioLegend	Cat#123411; RRID: AB_940395
anti-CD23 conjugated to PE-Cy7 (clone B3B4)	eBioscience	Cat#25-0232-81; RRID: AB_469603
anti-CD25 conjugated to BrilliantViolet-421 (clone PC61)	BioLegend	Cat#102033; RRID: AB_10895908
anti-CD43 conjugated to PE (clone S7)	BD Biosciences	Cat#553271; RRID: AB_394748
anti-CD44 conjugated to PE (clone IM7)	eBioscience	Cat#12-0441-81; RRID: AB_465663
anti-CD45.1 conjugated to eFluor-450 (clone A20)	eBioscience	Cat#48-0453-82; RRID: AB_1272189
anti-CD45.1 conjugated to BrilliantViolet-510 (clone A20)	BioLegend	Cat#110741; RRID: AB_2563378
anti-CD45.2 conjugated to Alexafluor700 (clone 104)	eBioscience	Cat#56-0454-81; RRID: AB_657753
and anti-CD62L conjugated to BrilliantViolet-421 (clone MEL-14)	BioLegend	Cat#104435; RRID: AB_10900082
anti-cKit/CD117 conjugated to PerCP-Cy5.5 (clone 2B8)	BioLegend	Cat#105823; RRID: AB_2131598
anti-FcεRIα conjugated to FITC (clone MAR-1)	BioLegend	Cat#134305; RRID: AB_1626102
anti-IgD conjugated to BrilliantViolet-650 (clone 11-26c.2a)	BioLegend	Cat#405721; RRID: AB_2562731
anti-IgM conjugated to PerCP-Cy5.5 (clone RMM-1)	BioLegend	Cat#406511; RRID: AB_2075944
anti-Ly6G/Gr-1 conjugated to FITC (clone RB6-8C5)	eBioscience	Cat#11-5931-81; RRID: AB_465313
anti-Ly6G/Gr-1 conjugated to PE (clone RB6-8C5)	eBioscience	Cat#12-5931-81; RRID: AB_466044
anti-Ly6G/Gr-1 conjugated to APC (clone RB6-8C5)	eBioscience	Cat#17-5931-81; RRID: AB_469475
anti-NK1.1 conjugated to BrilliantViolet-421 (clone PK136)	BioLegend	Cat#108731; RRID: AB_10895916
anti-NK1.1 conjugated to FITC (clone PK136)	BioLegend	Cat#108705; RRID: AB_313392
anti-Sca1 conjugated to PE-Cy7 (clone D7)	eBioscience	Cat#25-5981-81; RRID: AB_469668
anti-Ter-119 conjugated to FITC (clone TER-119)	eBioscience	Cat#11-5921; RRID: AB_2206887
anti-A20	Cell Signaling Technology	Cat#4625; RRID: AB_2204524
anti-Actin (clone C4)	Millipore	Cat#MAB1501R; RRID: AB_94235
anti-CYLD	Santa Cruz Biotechnology	Cat#sc-74435; RRID: AB_1122022
anti-GAPDH	Ambion	Cat#AM4300; RRID: AB_437392
anti-HOIL-1/RBCK1	Novus Biologicals	Cat#NBP2-27105; RRID: AB_2576210
anti-HOIL-1/RBCK1	Santa Cruz Biotechnology	Cat#sc-49718; RRID: AB_2175281
anti-HOIP/RNF31	Abcam	Cat#46322; RRID: AB_945269
anti-mouse HOIP/RNF31	Laboratory of Kazuhiro Iwai	Tokunaga et al., 2011; RRID: N/A
anti-IκBα	Cell Signaling Technology	Cat#9242; RRID: AB_10694550
anti-IRF-3	Santa Cruz Biotechnology	Cat#sc-9082; RRID: AB_2264929
anti-phospho-IRF-3 (pS396)	Cell Signaling Technology	Cat#4947; RRID: AB_823547
anti-Lys63-linked ubiquitin (clone Apu3)	Millipore	Cat#05-1308; RRID: AB_1587580
anti-Lys48-linked ubiquitin (clone Apu2)	Millipore	Cat#05-1307; RRID: AB_1587578
anti-Met1-linked/linear ubiquitin (clone LUB9)	LifeSensors	Cat#AB130; RRID: AB_2576211
anti-Met1-linked/linear ubiquitin (clone 1E3)	Millipore	Cat#MABS199; RRID: AB_2576212
anti-NIK	Santa Cruz Biotechnology	Cat#sc-8417; RRID: AB_628021
anti-NEMO/IKKγ	Santa Cruz Biotechnology	Cat#sc-8330; RRID: AB_2124846
anti-OTULIN	Cell Signaling Technology	Cat#14127; RRID: AB_2576213
anti-p38 (clone M138)	Abcam	Cat#ab31828; RRID: AB_881839
anti-phospho-p38 (pT180/pY182) (clone ERP18120)	Abcam	Cat#ab195049; RRID: AB_2576214
anti-p65/RelA	Cell Signaling Technology	Cat#8242; RRID: AB_10860244
anti-phospho-p65/RelA (pS563) (clone 93H1)	Cell Signaling Technology	Cat#3033; RRID: AB_331284
anti-SHARPIN	Proteintech	Cat#14626-1-AP; RRID: AB_2187734
anti-ubiquitin (clone UBI-1)	Novus Biologicals	Cat#NB300-130; RRID: AB_2238517
anti-mouse CD19-coupled MACS MicroBeads	Miltenyi Biotec	Cat#130-052-201; RRID: N/A
anti-mouse CD11b-couple MACS MicroBeads	Miltenyi Biotec	Cat#130-049-601; RRID: N/A
anti-Biotin-coupled MACS MicroBeads	Miltenyi Biotec	Cat#130-090-485; RRID: N/A
Chemicals, Peptides, and Recombinant Proteins
Recombinant mouse M-CSF	R&D Systems	Cat#416-ML-050
Recombinant mouse TNF	GIBCO	Cat#PMC3014
Ultrapure LPS from E. coli K12	InvivoGen	Cat#tlrl-peklps
Staurosporine from Streptomyces sp.	Sigma-Aldrich	Cat#S6942; CAS 62996-74-1
MG132 (Z-Leu-Leu-Leu-al)	Sigma-Aldrich	Cat#C2211; CAS 133407-82-6
Tamoxifen	Sigma	Cat#T5648-1G; CAS 10540-29-1
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliym bromide (MTT)	Sigma	Cat#M2128-250MG; CAS 298-93-1
Collagenase D	Roche	Cat#11088866001
Liberase	Roche	Cat#5401020001
DNase I	Sigma-Aldrich	Cat#D5025
Percoll PLUS	GE Healthcare	Cat#17-5445-02
Recombinant OTULIN-WT	Laboratory of David Komander	Keusekotten et al., 2013
Recombinant OTULIN-C129A/L272P	This paper	N/A
Critical Commercial Assays
MILLIPLEX MAP Cytokine/Chemokune Magnetic Bead Panel – Premixed 25-plex	Merck Millipore	Cat#MCYTOMAG-70K-PMX
Mouse BAFF/BLyS/TNFSF13B Quantikine ELISA kit	R&D Systems	Cat#MBLYS0
Mouse G-CSF Quantikine ELISA kit	R&D Systems	Cat#MCS00
Mouse anti-nuclear antigen/ENA IgA+G+M ELISA kit	Alpha Diagnostics	Cat#5210
Mouse anti-Smith antigen IgA+G+M ELISA kit	Alpha Diagnostics	Cat#5405
Mouse anti-dsDNA IgA+G+M ELISA kit	Alpha Diagnostics	Cat#5110
Mouse Total IgG Ready-Set-Go ELISA kit	eBioscience	Cat#88-50400-22
IgG Mouse ELISA kit	Abcam	Cat#ab151276
Mouse Isotyping Panel 1 multiplex sandwich electrochemiluminescence immunoassay kit	Meso Scale Discovery	Cat#K15183-1
MACS Dead Cell Removal Kit	Miltenyi Biotec	Cat#130-090-101
Experimental Models: Organisms/Strains
Mouse: ACTB-FLPe	Laboratory of Susan M. Dymeki	Rodríguez et al., 2000
Mouse: ROSA26-CreERT2	Laboratory of Ernesto Bockamp	Hameyer et al., 2007
Mouse: LysM-Cre	Laboratory of Irmgard Förster	Clausen et al., 1999
Mouse: Mb1-Cre	Laboratory of Michael Reth	Hobeika et al., 2006
Mouse: Cd4-Cre	Laboratory of Christopher B. Wilson	Lee et al., 2001
Experimental Models: Cell Lines
Otulin/Fam105b-targeted JM8A3.N1 ES cells	EuMMCR	Fam105btm1a(EUCOMM)Hmgu
HEK293	N/A	N/A
Recombinant DNA
pEGFP-N1-OTULIN-WT	Laboratory of David Komander	Keusekotten et al., 2013.
pEGFP-N1-OTULIN-L272P	This paper	N/A
Sequence-Based Reagents
For primer sequences, please see Table S8.
Software and Algorithms
HomozygosityMapper	Seelow et al., 2009	http://www.homozygositymapper.org/
Annovar / wAnnovar	Yang and Wang, 2015	http://wannovar.usc.edu/index.php
SAMtools	Li et al., 2009	http://samtools.sourceforge.net/
Other
Exome Variant Server	NHLBI GO Exome Sequencing Project (ESP)	http://evs.gs.washington.edu/EVS/
EXaC Browser	Exome Aggregation Consortium	http://exac.broadinstitute.org/gene/ENSG00000154124