TP8L3_HUMAN
ID TP8L3_HUMAN Reviewed; 292 AA.
AC Q5GJ75; Q6ZWD1;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2005, sequence version 1.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Tumor necrosis factor alpha-induced protein 8-like protein 3;
DE Short=TNF alpha-induced protein 8-like protein 3;
DE Short=TNFAIP8-like protein 3;
GN Name=TNFAIP8L3; Synonyms=TIPE3;
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].
RA Chen S., Guo J.H., Yu L.;
RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 58-292.
RC TISSUE=Amygdala;
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] OF 81-292.
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 [5]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=25479791; DOI=10.1369/0022155414564871;
RA Cui J., Hao C., Zhang W., Shao J., Zhang N., Zhang G., Liu S.;
RT "Identical expression profiling of human and murine TIPE3 protein reveals
RT links to its functions.";
RL J. Histochem. Cytochem. 63:206-216(2015).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 109-292, AND TISSUE SPECIFICITY.
RX PubMed=25242044; DOI=10.1016/j.ccr.2014.07.025;
RA Fayngerts S.A., Wu J., Oxley C.L., Liu X., Vourekas A., Cathopoulis T.,
RA Wang Z., Cui J., Liu S., Sun H., Lemmon M.A., Zhang L., Shi Y., Chen Y.H.;
RT "TIPE3 is the transfer protein of lipid second messengers that promote
RT cancer.";
RL Cancer Cell 26:465-478(2014).
CC -!- FUNCTION: Acts as a lipid transfer protein. Preferentially captures and
CC shuttles two lipid second messengers, i.e., phosphatidylinositol
CC 4,5- bisphosphate and phosphatidylinositol 3,4,5-trisphosphate and
CC increases their levels in the plasma membrane. Additionally, may also
CC function as a lipid-presenting protein to enhance the activity of the
CC PI3K-AKT and MEK-ERK pathways. May act as a regulator of tumorigenesis
CC through its activation of phospholipid signaling.
CC {ECO:0000250|UniProtKB:Q3TBL6}.
CC -!- INTERACTION:
CC Q5GJ75; Q9Y3M2: CBY1; NbExp=3; IntAct=EBI-14222571, EBI-947308;
CC Q5GJ75; O00560: SDCBP; NbExp=3; IntAct=EBI-14222571, EBI-727004;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:25479791}. Cell
CC membrane {ECO:0000250|UniProtKB:Q3TBL6}. Note=On PDGF activation,
CC translocates from cytoplasm to plasma membrane.
CC {ECO:0000250|UniProtKB:Q3TBL6}.
CC -!- TISSUE SPECIFICITY: Widely expressed (at protein level)
CC (PubMed:25479791). Highly expressed in most carcinoma cell lines
CC (PubMed:25479791, PubMed:25242044). {ECO:0000269|PubMed:25242044,
CC ECO:0000269|PubMed:25479791}.
CC -!- SIMILARITY: Belongs to the TNFAIP8 family. {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-89 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI27702.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAI27703.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAC85572.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=EAW77412.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AY517501; AAS76642.1; -; mRNA.
DR EMBL; AK123281; BAC85572.1; ALT_INIT; mRNA.
DR EMBL; CH471082; EAW77412.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC127701; AAI27702.1; ALT_INIT; mRNA.
DR EMBL; BC127702; AAI27703.1; ALT_INIT; mRNA.
DR CCDS; CCDS32241.1; -.
DR RefSeq; NP_001298104.1; NM_001311175.1.
DR RefSeq; NP_997264.2; NM_207381.3.
DR PDB; 4Q9V; X-ray; 2.30 A; A/B=109-292.
DR PDBsum; 4Q9V; -.
DR AlphaFoldDB; Q5GJ75; -.
DR SMR; Q5GJ75; -.
DR BioGRID; 132560; 2.
DR IntAct; Q5GJ75; 2.
DR STRING; 9606.ENSP00000328016; -.
DR iPTMnet; Q5GJ75; -.
DR PhosphoSitePlus; Q5GJ75; -.
DR BioMuta; TNFAIP8L3; -.
DR DMDM; 74707829; -.
DR EPD; Q5GJ75; -.
DR MassIVE; Q5GJ75; -.
DR PaxDb; Q5GJ75; -.
DR PeptideAtlas; Q5GJ75; -.
DR PRIDE; Q5GJ75; -.
DR ProteomicsDB; 62836; -.
DR Antibodypedia; 57338; 93 antibodies from 22 providers.
DR DNASU; 388121; -.
DR Ensembl; ENST00000327536.5; ENSP00000328016.5; ENSG00000183578.8.
DR GeneID; 388121; -.
DR KEGG; hsa:388121; -.
DR UCSC; uc001zyy.5; human.
DR CTD; 388121; -.
DR DisGeNET; 388121; -.
DR GeneCards; TNFAIP8L3; -.
DR HGNC; HGNC:20620; TNFAIP8L3.
DR HPA; ENSG00000183578; Tissue enhanced (endometrium, smooth muscle).
DR MIM; 616438; gene.
DR neXtProt; NX_Q5GJ75; -.
DR OpenTargets; ENSG00000183578; -.
DR PharmGKB; PA142670724; -.
DR VEuPathDB; HostDB:ENSG00000183578; -.
DR eggNOG; ENOG502QRE6; Eukaryota.
DR GeneTree; ENSGT00390000003488; -.
DR HOGENOM; CLU_085918_0_0_1; -.
DR InParanoid; Q5GJ75; -.
DR OrthoDB; 1284744at2759; -.
DR PhylomeDB; Q5GJ75; -.
DR TreeFam; TF323415; -.
DR PathwayCommons; Q5GJ75; -.
DR Reactome; R-HSA-1483255; PI Metabolism.
DR SignaLink; Q5GJ75; -.
DR BioGRID-ORCS; 388121; 7 hits in 1071 CRISPR screens.
DR GenomeRNAi; 388121; -.
DR Pharos; Q5GJ75; Tbio.
DR PRO; PR:Q5GJ75; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q5GJ75; protein.
DR Bgee; ENSG00000183578; Expressed in left uterine tube and 92 other tissues.
DR ExpressionAtlas; Q5GJ75; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0035091; F:phosphatidylinositol binding; ISS:UniProtKB.
DR GO; GO:0008526; F:phosphatidylinositol transfer activity; ISS:UniProtKB.
DR GO; GO:0048017; P:inositol lipid-mediated signaling; ISS:UniProtKB.
DR GO; GO:0006644; P:phospholipid metabolic process; TAS:Reactome.
DR GO; GO:0015914; P:phospholipid transport; ISS:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; ISS:UniProtKB.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISS:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; IEA:InterPro.
DR GO; GO:0019216; P:regulation of lipid metabolic process; ISS:UniProtKB.
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; Cell membrane; Cytoplasm; Lipid transport; Membrane;
KW Reference proteome; Transport.
FT CHAIN 1..292
FT /note="Tumor necrosis factor alpha-induced protein 8-like
FT protein 3"
FT /id="PRO_0000331424"
FT REGION 81..107
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 109..292
FT /note="Binding to phosphoinositides"
FT /evidence="ECO:0000250|UniProtKB:Q3TBL6"
FT VARIANT 38
FT /note="A -> T (in dbSNP:rs17647084)"
FT /id="VAR_042860"
FT HELIX 112..135
FT /evidence="ECO:0007829|PDB:4Q9V"
FT HELIX 139..156
FT /evidence="ECO:0007829|PDB:4Q9V"
FT HELIX 159..181
FT /evidence="ECO:0007829|PDB:4Q9V"
FT HELIX 187..212
FT /evidence="ECO:0007829|PDB:4Q9V"
FT HELIX 214..216
FT /evidence="ECO:0007829|PDB:4Q9V"
FT HELIX 219..237
FT /evidence="ECO:0007829|PDB:4Q9V"
FT HELIX 245..257
FT /evidence="ECO:0007829|PDB:4Q9V"
FT HELIX 259..266
FT /evidence="ECO:0007829|PDB:4Q9V"
FT HELIX 273..288
FT /evidence="ECO:0007829|PDB:4Q9V"
SQ SEQUENCE 292 AA; 32659 MW; 438700088C3DA6E3 CRC64;
MGKPRQNPST LVSTLCEAEP KGKLWVNGYA GTQGTRDATL QTRLIPLSFH LQRGKGLAAP
LSALSAPRLP ERPADGRVAV DAQPAARSMD SDSGEQSEGE PVTAAGPDVF SSKSLALQAQ
KKILSKIASK TVANMLIDDT SSEIFDELYK VTKEHTHNKK EAHKIMKDLI KVAIKIGILY
RNNQFSQEEL VIVEKFRKKL NQTAMTIVSF YEVEYTFDRN VLSNLLHECK DLVHELVQRH
LTPRTHGRIN HVFNHFADVE FLSTLYSLDG DCRPNLKRIC EGINKLLDEK VL
