TP4AP_MOUSE
ID TP4AP_MOUSE Reviewed; 797 AA.
AC Q9JLV2; Q920J6; Q99L03;
DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 15-NOV-2002, sequence version 2.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Short transient receptor potential channel 4-associated protein {ECO:0000305};
DE Short=Trp4-associated protein {ECO:0000250|UniProtKB:Q8TEL6};
DE Short=Trpc4-associated protein {ECO:0000250|UniProtKB:Q8TEL6};
DE AltName: Full=Protein TAP1;
DE AltName: Full=Rabex-5/Rin2-interacting protein {ECO:0000303|Ref.4};
DE AltName: Full=TNF-receptor ubiquitous scaffolding/signaling protein {ECO:0000303|PubMed:14585990};
DE Short=Protein TRUSS {ECO:0000303|PubMed:14585990};
GN Name=Trpc4ap {ECO:0000312|MGI:MGI:1930751}; Synonyms=Trrp4ap;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, AND
RP INTERACTION WITH TNFRSF1A; TRADD; TRAF2; CHUK; IKBKB AND IKBKG.
RC STRAIN=BALB/cJ;
RX PubMed=14585990; DOI=10.1128/mcb.23.22.8334-8344.2003;
RA Soond S.M., Terry J.L., Colbert J.D., Riches D.W.H.;
RT "TRUSS, a novel tumor necrosis factor receptor 1 scaffolding protein that
RT mediates activation of the transcription factor NF-kappaB.";
RL Mol. Cell. Biol. 23:8334-8344(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Insulinoma;
RA Qian F., Philipson L.H.;
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 154-797 (ISOFORM 1).
RC STRAIN=BALB/cJ; TISSUE=Brain;
RA Scherrer D., Tsai M., Galli S.J., Tam S.-Y.;
RT "A novel Rabex-5/Rin2-interacting protein.";
RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION, AND INTERACTION WITH TRAF2.
RX PubMed=16876162; DOI=10.1016/j.febslet.2006.06.098;
RA Soond S.M., Terry J.L., Riches D.W.H.;
RT "TRUSS, a tumor necrosis factor receptor-1-interacting protein, activates
RT c-Jun NH(2)-terminal kinase and transcription factor AP-1.";
RL FEBS Lett. 580:4591-4596(2006).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP FUNCTION, AND INTERACTION WITH TRPC1; TRPC4 AND TRPC5.
RX PubMed=20458742; DOI=10.1002/jcp.22221;
RA Mace K.E., Lussier M.P., Boulay G., Terry-Powers J.L., Parfrey H.,
RA Perraud A.L., Riches D.W.H.;
RT "TRUSS, TNF-R1, and TRPC ion channels synergistically reverse endoplasmic
RT reticulum Ca2+ storage reduction in response to m1 muscarinic acetylcholine
RT receptor signaling.";
RL J. Cell. Physiol. 225:444-453(2010).
CC -!- FUNCTION: Substrate-recognition component of a DCX (DDB1-CUL4-X-box) E3
CC ubiquitin-protein ligase complex required for cell cycle control. The
CC DCX(TRPC4AP) complex specifically mediates the polyubiquitination and
CC subsequent degradation of MYC as part of the DesCEND (destruction via
CC C-end degrons) pathway. The DesCEND (destruction via C-end degrons)
CC pathway recognizes a C-degron located at the extreme C terminus of
CC target proteins, leading to their ubiquitination and degradation. The
CC DCX(TRPC4AP) complex specifically recognizes proteins with an arginine
CC at the minus 3 position (R-3 motif) at the C-terminus, such as MYC,
CC leading to their ubiquitination and degradation (By similarity). Also
CC participates in the activation of NFKB1 in response to ligation of
CC TNFRSF1A, possibly by linking TNFRSF1A to the IKK signalosome
CC (PubMed:14585990). Involved in JNK activation via its interaction with
CC TRAF2 (PubMed:16876162). Also involved in elevation of endoplasmic
CC reticulum Ca(2+) storage reduction in response to CHRM1
CC (PubMed:20458742). {ECO:0000250|UniProtKB:Q8TEL6,
CC ECO:0000269|PubMed:14585990, ECO:0000269|PubMed:16876162,
CC ECO:0000269|PubMed:20458742}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q8TEL6}.
CC -!- SUBUNIT: Component of the DCX(TRPC4AP) E3 ubiquitin ligase complex, at
CC least composed of CUL4A, DDB1, TRPC4AP/TRUSS and RBX1 (By similarity).
CC Interacts with MYC (By similarity). Constitutively associated with
CC TNFRSF1A (PubMed:14585990). Directly interacts with TRADD, TRAF2, CHUK,
CC IKBKB and IKBKG (PubMed:16876162, PubMed:14585990). Interacts with
CC TRPC1, TRPC4 and TRPC5 (PubMed:20458742).
CC {ECO:0000250|UniProtKB:Q8TEL6, ECO:0000269|PubMed:14585990,
CC ECO:0000269|PubMed:16876162, ECO:0000269|PubMed:20458742}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:Q8TEL6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9JLV2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9JLV2-2; Sequence=VSP_003983;
CC -!- TISSUE SPECIFICITY: Widely expressed, with high levels in heart, liver
CC and testis. {ECO:0000269|PubMed:14585990}.
CC -!- PTM: Phosphorylated by GSK3B; phosphorylation is required for
CC ubiquitination. {ECO:0000250|UniProtKB:Q8TEL6}.
CC -!- PTM: Ubiquitinated by a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-
CC protein ligase containing SKP2, leading to its degradation.
CC Phosphorylation by GSK3B is required for ubiquitination.
CC {ECO:0000250|UniProtKB:Q8TEL6}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL08422.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF509881; AAM46938.1; -; mRNA.
DR EMBL; AF130458; AAF36513.1; -; mRNA.
DR EMBL; BC003931; AAH03931.1; -; mRNA.
DR EMBL; BC033274; AAH33274.1; -; mRNA.
DR EMBL; BC057330; AAH57330.1; -; mRNA.
DR EMBL; AF093589; AAL08422.1; ALT_INIT; mRNA.
DR CCDS; CCDS16952.1; -. [Q9JLV2-2]
DR CCDS; CCDS50769.1; -. [Q9JLV2-1]
DR RefSeq; NP_001156924.1; NM_001163452.1. [Q9JLV2-1]
DR RefSeq; NP_062802.2; NM_019828.2. [Q9JLV2-2]
DR AlphaFoldDB; Q9JLV2; -.
DR STRING; 10090.ENSMUSP00000037574; -.
DR iPTMnet; Q9JLV2; -.
DR PhosphoSitePlus; Q9JLV2; -.
DR EPD; Q9JLV2; -.
DR MaxQB; Q9JLV2; -.
DR PaxDb; Q9JLV2; -.
DR PRIDE; Q9JLV2; -.
DR ProteomicsDB; 258958; -. [Q9JLV2-1]
DR ProteomicsDB; 258959; -. [Q9JLV2-2]
DR Antibodypedia; 25963; 195 antibodies from 30 providers.
DR DNASU; 56407; -.
DR Ensembl; ENSMUST00000041059; ENSMUSP00000037574; ENSMUSG00000038324. [Q9JLV2-1]
DR Ensembl; ENSMUST00000103140; ENSMUSP00000099429; ENSMUSG00000038324. [Q9JLV2-2]
DR GeneID; 56407; -.
DR KEGG; mmu:56407; -.
DR UCSC; uc008nlc.2; mouse. [Q9JLV2-1]
DR UCSC; uc012che.1; mouse. [Q9JLV2-2]
DR CTD; 26133; -.
DR MGI; MGI:1930751; Trpc4ap.
DR VEuPathDB; HostDB:ENSMUSG00000038324; -.
DR eggNOG; ENOG502QQ1C; Eukaryota.
DR GeneTree; ENSGT00390000018330; -.
DR HOGENOM; CLU_015792_1_0_1; -.
DR InParanoid; Q9JLV2; -.
DR OMA; EMTKGNW; -.
DR PhylomeDB; Q9JLV2; -.
DR TreeFam; TF329145; -.
DR Reactome; R-MMU-3295583; TRP channels.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 56407; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Trpc4ap; mouse.
DR PRO; PR:Q9JLV2; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q9JLV2; protein.
DR Bgee; ENSMUSG00000038324; Expressed in spermatocyte and 246 other tissues.
DR ExpressionAtlas; Q9JLV2; baseline and differential.
DR Genevisible; Q9JLV2; MM.
DR GO; GO:0080008; C:Cul4-RING E3 ubiquitin ligase complex; ISS:UniProtKB.
DR GO; GO:0031464; C:Cul4A-RING E3 ubiquitin ligase complex; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0019902; F:phosphatase binding; ISS:UniProtKB.
DR GO; GO:1990756; F:ubiquitin ligase-substrate adaptor activity; ISS:UniProtKB.
DR GO; GO:0048820; P:hair follicle maturation; IMP:MGI.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0140627; P:ubiquitin-dependent protein catabolic process via the C-end degron rule pathway; ISS:UniProtKB.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR022162; TRPC4AP.
DR PANTHER; PTHR31743; PTHR31743; 1.
DR Pfam; PF12463; DUF3689; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cytoplasm; Phosphoprotein;
KW Reference proteome; Ubl conjugation; Ubl conjugation pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q8TEL6"
FT CHAIN 2..797
FT /note="Short transient receptor potential channel 4-
FT associated protein"
FT /id="PRO_0000072642"
FT REGION 2..400
FT /note="Interaction with TNFRSF1A"
FT /evidence="ECO:0000269|PubMed:14585990"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q8TEL6"
FT VAR_SEQ 351..358
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_003983"
FT CONFLICT 11..14
FT /note="GASR -> LPYW (in Ref. 2; AAF36513)"
FT /evidence="ECO:0000305"
FT CONFLICT 158
FT /note="I -> L (in Ref. 2; AAF36513)"
FT /evidence="ECO:0000305"
FT CONFLICT 193
FT /note="F -> L (in Ref. 2; AAF36513)"
FT /evidence="ECO:0000305"
FT CONFLICT 359
FT /note="G -> S (in Ref. 1; AAM46938)"
FT /evidence="ECO:0000305"
FT CONFLICT 532
FT /note="R -> K (in Ref. 1; AAM46938)"
FT /evidence="ECO:0000305"
FT CONFLICT 769
FT /note="L -> V (in Ref. 4; AAL08422)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 797 AA; 90727 MW; 8BC3453A7658A234 CRC64;
MAAAPAAAGA GASRGRRLAA TAAAWGGWGG RPRPGNILLQ LRQGQLTGRG LVRAVQFTET
FLTERDKLSK WSGIPQLLLK LYATSHLHSD FVECQSILKE ISPLLSMEAM AFVTEDRKFT
QEATYPNTYI FDLFGGVDLL VEILMRPTIS IRGQKLKISD EMSKDCLSIL YNTCVCTEGV
TKRLAEKNDF VIFLFTLMTS KKTFLQTATL IEDILGVKKE MIRLDEVPNL SSLVSNFDQQ
QLANFCRILA VTISEMDTGN DDKHTLLAKN AQQKKSLSLG PSAAEINQAA LLSIPGFVER
LCKLATRKVS ESTGTASFLQ ELEEWYTWLD NALVLDALMR VANEESEHNQ APTVFPSLGT
SEEGGLPHTS ARAQLPQSMK IMHEIMYKLE VLYVLCVLLM GRQRNQVHRM IAEFKLIPGL
NNLFDKLIWR KHSASALVLH GHNQNCDCSP DITLKIQFLR LLQSFSDHHE NKYLLLNNQE
LNELSAISLK ANIPEVEAVL NTDRSLVCDG KRGLLTRLLQ VMKKEPAESS FRFWQARAVE
SFLRGTTSYA DQMFLLKRGL LEHILYCIVD SECKSRDVLQ SYFDLLGELM KFNVDAFKRF
NKYINTDAKF QVFLKQINSS LVDSNMLVRC VTLSLDRFEN QVDMKVAEVL SECRLLAYIS
QVPTQMSFLF RLINIIHVQT LTQENVSCLN TSLVILMLAR RKERLPLYLR LLQRMEHSKK
YPGFLLNNFH NLLRFWQQHY LHKDKDSTCL ENSSCISFSY WKETVSILLN PDRQSPSALV
SYIEEPYMDI DRDFTEE
