ID TP8L2_RABIT Reviewed; 184 AA.
AC B7NZC7;
DT 14-APR-2009, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2009, sequence version 1.
DT 24-JAN-2024, entry version 59.
DE RecName: Full=Tumor necrosis factor alpha-induced protein 8-like protein 2;
DE Short=TIPE2;
DE Short=TNF alpha-induced protein 8-like protein 2;
DE Short=TNFAIP8-like protein 2;
GN Name=TNFAIP8L2;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Antonellis A., Ayele K., Benjamin B., Blakesley R.W., Boakye A.,
RA Bouffard G.G., Brinkley C., Brooks S., Chu G., Coleman H., Engle J.,
RA Gestole M., Greene A., Guan X., Gupta J., Haghighi P., Han J., Hansen N.,
RA Ho S.-L., Hu P., Hunter G., Hurle B., Idol J.R., Kwong P., Laric P.,
RA Larson S., Lee-Lin S.-Q., Legaspi R., Madden M., Maduro Q.L., Maduro V.B.,
RA Margulies E.H., Masiello C., Maskeri B., McDowell J., Mojidi H.A.,
RA Mullikin J.C., Oestreicher J.S., Park M., Portnoy M.E., Prasad A., Puri O.,
RA Reddix-Dugue N., Schandler K., Schueler M.G., Sison C., Stantripop S.,
RA Stephen E., Taye A., Thomas J.W., Thomas P.J., Tsipouri V., Ung L.,
RA Vogt J.L., Wetherby K.D., Young A., Green E.D.;
RT "NISC comparative sequencing initiative.";
RL Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Acts as a negative regulator of innate and adaptive immunity
CC by maintaining immune homeostasis. Plays a regulatory role in the Toll-
CC like signaling pathway by determining the strength of LPS-induced
CC signaling and gene expression (By similarity). Inhibits TCR-mediated T-
CC cell activation and negatively regulate T-cell function to prevent
CC hyperresponsiveness (By similarity). Inhibits also autolysosome
CC formation via negatively modulating MTOR activation by interacting with
CC RAC1 and promoting the disassociation of the RAC1-MTOR complex (By
CC similarity). Plays an essential role in NK-cell biology by acting as a
CC checkpoint and displaying an expression pattern correlating with NK-
CC cell maturation process and by negatively regulating NK-cell maturation
CC and antitumor immunity (By similarity). Mechanistically, suppresses IL-
CC 15-triggered mTOR activity in NK-cells (By similarity).
CC {ECO:0000250|UniProtKB:Q6P589, ECO:0000250|UniProtKB:Q9D8Y7}.
CC -!- SUBUNIT: May interact with CASP8; however, such result is unclear since
CC could not reproduce the interaction with CASP8. Interacts with RAC1.
CC {ECO:0000250|UniProtKB:Q6P589}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q6P589}. Nucleus
CC {ECO:0000250|UniProtKB:Q6P589}. Lysosome
CC {ECO:0000250|UniProtKB:Q6P589}.
CC -!- DOMAIN: The central region was initially thought to constitute a DED
CC (death effector) domain. However, 3D-structure data reveal a previously
CC uncharacterized fold that is different from the predicted fold of a DED
CC (death effector) domain. It consists of a large, hydrophobic central
CC cavity that is poised for cofactor binding (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Phosphorylated by TAK1/MAP3K7; this phosphorylation triggers
CC association with BTRC and subsequent ubiquitination and degradation.
CC {ECO:0000250|UniProtKB:Q6P589}.
CC -!- PTM: Ubiquitinated in a BTRC-depdent manner; leading to degradation
CC mediated through the proteasome pathway.
CC {ECO:0000250|UniProtKB:Q6P589}.
CC -!- SIMILARITY: Belongs to the TNFAIP8 family. TNFAIP8L2 subfamily.
CC {ECO:0000305}.
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DR EMBL; DP001034; ACJ74009.1; -; Genomic_DNA.
DR RefSeq; NP_001164767.1; NM_001171296.1.
DR RefSeq; XP_008262236.1; XM_008264014.2.
DR RefSeq; XP_008262237.1; XM_008264015.2.
DR RefSeq; XP_017200998.1; XM_017345509.1.
DR AlphaFoldDB; B7NZC7; -.
DR SMR; B7NZC7; -.
DR STRING; 9986.ENSOCUP00000004072; -.
DR PaxDb; 9986-ENSOCUP00000004072; -.
DR Ensembl; ENSOCUT00000004713.1; ENSOCUP00000004072.1; ENSOCUG00000004719.1.
DR GeneID; 100328663; -.
DR KEGG; ocu:100328663; -.
DR CTD; 79626; -.
DR eggNOG; ENOG502QST4; Eukaryota.
DR GeneTree; ENSGT00390000003488; -.
DR HOGENOM; CLU_085918_1_0_1; -.
DR InParanoid; B7NZC7; -.
DR OMA; IRRVFDH; -.
DR OrthoDB; 5401401at2759; -.
DR TreeFam; TF323415; -.
DR Proteomes; UP000001811; Chromosome 13.
DR Bgee; ENSOCUG00000004719; Expressed in blood and 19 other cell types or tissues.
DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IEA:Ensembl.
DR GO; GO:0050868; P:negative regulation of T cell activation; IEA:Ensembl.
DR GO; GO:0042981; P:regulation of apoptotic process; IEA:InterPro.
DR GO; GO:0042110; P:T cell activation; IEA:Ensembl.
DR Gene3D; 1.20.1440.160; Tumor necrosis factor alpha-induced protein 8-like; 1.
DR InterPro; IPR008477; TNFAIP8-like.
DR InterPro; IPR038355; TNFAIP8_sf.
DR PANTHER; PTHR12757:SF4; TUMOR NECROSIS FACTOR ALPHA-INDUCED PROTEIN 8-LIKE PROTEIN 2; 1.
DR PANTHER; PTHR12757; TUMOR NECROSIS FACTOR INDUCED PROTEIN; 1.
DR Pfam; PF05527; DUF758; 1.
PE 3: Inferred from homology;
KW Cytoplasm; Immunity; Innate immunity; Lysosome; Nucleus; Phosphoprotein;
KW Reference proteome; Ubl conjugation.
FT CHAIN 1..184
FT /note="Tumor necrosis factor alpha-induced protein 8-like
FT protein 2"
FT /id="PRO_0000369395"
FT MOD_RES 3
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6P589"
SQ SEQUENCE 184 AA; 20522 MW; 64AD6FD07794CC30 CRC64;
MESFSSKSLA LQAEKKLLSK MVGRSAAHLF IDETSSEVLD ELYRVSKEYT HSRPQAQRVI
KDLIKVAVKV AVLHRSGCFG PSELALATRF RQKLRQGAMT ALSFGEVDFT FEAAVLAGLL
TECRDVLLEL VENHLTPKSH GRIRHVFDHF SDPGLLTALY GPDFTQHLGK ICDGLRKLLE
EGKL
//
