TP8L2_HUMAN
ID TP8L2_HUMAN Reviewed; 184 AA.
AC Q6P589; Q6I9Y0; Q9H2H7; Q9H5G2;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 134.
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;
DE AltName: Full=Inflammation factor protein 20;
GN Name=TNFAIP8L2;
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].
RX PubMed=18455983; DOI=10.1016/j.cell.2008.03.026;
RA Sun H., Gong S., Carmody R.J., Hilliard A., Li L., Sun J., Kong L., Xu L.,
RA Hilliard B., Hu S., Shen H., Yang X., Chen Y.H.;
RT "TIPE2, a negative regulator of innate and adaptive immunity that maintains
RT immune homeostasis.";
RL Cell 133:415-426(2008).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Xu X., Yang Y., Gao G., Xiao H., Chen Z., Han Z.;
RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Small intestine;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lymph node;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas;
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 [8]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS), AND LACK OF INTERACTION WITH CASP8.
RX PubMed=19079267; DOI=10.1038/nsmb.1522;
RA Zhang X., Wang J., Fan C., Li H., Sun H., Gong S., Chen Y.H., Shi Y.;
RT "Crystal structure of TIPE2 provides insights into immune homeostasis.";
RL Nat. Struct. Mol. Biol. 16:89-90(2009).
CC -!- FUNCTION: Acts as a negative regulator of innate and adaptive immunity
CC by maintaining immune homeostasis. Negative regulator of Toll-like
CC receptor and T-cell receptor function. Prevents hyperresponsiveness of
CC the immune system and maintains immune homeostasis. Inhibits JUN/AP1
CC and NF-kappa-B activation. Promotes Fas-induced apoptosis (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: May interact with CASP8; however, such result is unclear since
CC PubMed:19079267 could not reproduce the interaction with CASP8.
CC -!- INTERACTION:
CC Q6P589; P63000: RAC1; NbExp=2; IntAct=EBI-9073209, EBI-413628;
CC Q6P589; P63000-1: RAC1; NbExp=6; IntAct=EBI-9073209, EBI-7212896;
CC Q6P589; P15153: RAC2; NbExp=2; IntAct=EBI-9073209, EBI-489652;
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.
CC -!- SIMILARITY: Belongs to the TNFAIP8 family. TNFAIP8L2 subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG44785.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF548003; AAQ12262.1; -; mRNA.
DR EMBL; AF271774; AAG44785.1; ALT_FRAME; mRNA.
DR EMBL; AK027120; BAB15664.1; -; mRNA.
DR EMBL; CR457375; CAG33656.1; -; mRNA.
DR EMBL; AL833373; CAI46145.1; -; mRNA.
DR EMBL; AL592424; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC063014; AAH63014.1; -; mRNA.
DR CCDS; CCDS985.1; -.
DR RefSeq; NP_078851.2; NM_024575.4.
DR PDB; 3F4M; X-ray; 1.70 A; A=24-184.
DR PDBsum; 3F4M; -.
DR AlphaFoldDB; Q6P589; -.
DR SMR; Q6P589; -.
DR BioGRID; 122756; 6.
DR DIP; DIP-60326N; -.
DR IntAct; Q6P589; 3.
DR STRING; 9606.ENSP00000357906; -.
DR iPTMnet; Q6P589; -.
DR PhosphoSitePlus; Q6P589; -.
DR BioMuta; TNFAIP8L2; -.
DR DMDM; 74749120; -.
DR EPD; Q6P589; -.
DR jPOST; Q6P589; -.
DR MassIVE; Q6P589; -.
DR MaxQB; Q6P589; -.
DR PaxDb; Q6P589; -.
DR PeptideAtlas; Q6P589; -.
DR PRIDE; Q6P589; -.
DR ProteomicsDB; 66994; -.
DR Antibodypedia; 34053; 160 antibodies from 26 providers.
DR DNASU; 79626; -.
DR Ensembl; ENST00000368910.4; ENSP00000357906.3; ENSG00000163154.6.
DR GeneID; 79626; -.
DR KEGG; hsa:79626; -.
DR MANE-Select; ENST00000368910.4; ENSP00000357906.3; NM_024575.5; NP_078851.2.
DR UCSC; uc001ewx.2; human.
DR CTD; 79626; -.
DR DisGeNET; 79626; -.
DR GeneCards; TNFAIP8L2; -.
DR HGNC; HGNC:26277; TNFAIP8L2.
DR HPA; ENSG00000163154; Tissue enhanced (lymphoid).
DR MIM; 612112; gene.
DR neXtProt; NX_Q6P589; -.
DR OpenTargets; ENSG00000163154; -.
DR PharmGKB; PA142670723; -.
DR VEuPathDB; HostDB:ENSG00000163154; -.
DR eggNOG; ENOG502QST4; Eukaryota.
DR GeneTree; ENSGT00390000003488; -.
DR HOGENOM; CLU_085918_1_0_1; -.
DR InParanoid; Q6P589; -.
DR OMA; IRRVFDH; -.
DR PhylomeDB; Q6P589; -.
DR TreeFam; TF323415; -.
DR PathwayCommons; Q6P589; -.
DR Reactome; R-HSA-1483255; PI Metabolism.
DR SignaLink; Q6P589; -.
DR BioGRID-ORCS; 79626; 15 hits in 1058 CRISPR screens.
DR EvolutionaryTrace; Q6P589; -.
DR GenomeRNAi; 79626; -.
DR Pharos; Q6P589; Tbio.
DR PRO; PR:Q6P589; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q6P589; protein.
DR Bgee; ENSG00000163154; Expressed in granulocyte and 109 other tissues.
DR Genevisible; Q6P589; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IBA:GO_Central.
DR GO; GO:0050868; P:negative regulation of T cell activation; IBA:GO_Central.
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; -; 1.
DR InterPro; IPR008477; TNFAIP8-like.
DR InterPro; IPR038355; TNFAIP8_sf.
DR PANTHER; PTHR12757; PTHR12757; 1.
DR Pfam; PF05527; DUF758; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Immunity; Innate immunity; Reference proteome.
FT CHAIN 1..184
FT /note="Tumor necrosis factor alpha-induced protein 8-like
FT protein 2"
FT /id="PRO_0000285771"
FT CONFLICT 48
FT /note="E -> G (in Ref. 4; CAG33656)"
FT /evidence="ECO:0000305"
FT CONFLICT 103
FT /note="S -> T (in Ref. 3; BAB15664)"
FT /evidence="ECO:0000305"
FT HELIX 33..50
FT /evidence="ECO:0007829|PDB:3F4M"
FT HELIX 53..75
FT /evidence="ECO:0007829|PDB:3F4M"
FT HELIX 81..104
FT /evidence="ECO:0007829|PDB:3F4M"
FT HELIX 113..131
FT /evidence="ECO:0007829|PDB:3F4M"
FT TURN 132..134
FT /evidence="ECO:0007829|PDB:3F4M"
FT HELIX 137..150
FT /evidence="ECO:0007829|PDB:3F4M"
FT HELIX 153..159
FT /evidence="ECO:0007829|PDB:3F4M"
FT HELIX 162..164
FT /evidence="ECO:0007829|PDB:3F4M"
FT HELIX 165..180
FT /evidence="ECO:0007829|PDB:3F4M"
SQ SEQUENCE 184 AA; 20556 MW; D76EAEF5E24D3895 CRC64;
MESFSSKSLA LQAEKKLLSK MAGRSVAHLF IDETSSEVLD ELYRVSKEYT HSRPQAQRVI
KDLIKVAIKV AVLHRNGSFG PSELALATRF RQKLRQGAMT ALSFGEVDFT FEAAVLAGLL
TECRDVLLEL VEHHLTPKSH GRIRHVFDHF SDPGLLTALY GPDFTQHLGK ICDGLRKLLD
EGKL
